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Purpose To investigate surveillance strategies for initial recurrent hepatocellular carcinoma (irHCC) after ablation to support clinical decision making, as there is no consensus regarding the monitoring strategy for irHCC after ablation. Materials and Methods Data from patients with irHCC who received ablation were retrospectively collected at 2 medical centers. The risk of tumor relapse in each month was calculated through random survival forest methodology, and follow-up schedules were arranged thereafter to maximize the capability of relapse detection at each visit. Results The cumulative 0.5-, 1-, 1.5-, and 2-year risk-adjusted probabilities in the training/validation cohorts were 26.2%/21.5%, 42.3%/39.4%, 55.5%/52.6%, and 61.3%/63.2%, respectively, with the highest recurrence rate occurring in the second month (maximum, 7.9%/7.4%). The surveillance regime primarily concentrated on the first year after treatment, especially the initial 6 months. The delay in detecting tumor recurrence gradually decreased when the total number of follow-up visits increased from 4 to 8. Compared with the control strategies, this schedule (follow-up visits at 2, 4, 6, 9, 12, and 18 months) reduced the delay in detection. The benefits of this surveillance regime were evident when the patients were followed up 6 times. The proposed 6-visit surveillance strategy significantly decreased the delay in detection compared with the control 7-visit approach (1.32 months vs 1.82 months, respectively; P Conclusions The proposed new surveillance schedule minimized the delay in detecting recurrence in patients with irHCC after ablation. The risk-related machine learning method described in this study could be applied to develop follow-up strategies for other patients with hepatocellular carcinoma.

Rationale: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains a major therapeutic challenge. In recent years, new molecular-targeted therapies, such as cabozantinib, have been approved for the treatment of advanced HCC. However, clinical experience with these new drugs in the treatment of HCC in the LT setting is very limited. Patient concerns: In 2003, a 36-year-old woman was referred to the hospital with right upper abdominal pain. Diagnosis: An initial ultrasound of the liver demonstrated a large unclear lesion of the left lobe of the liver. The magnet resonance imaging findings confirmed a multifocal inoperable HCC in a non-cirrhotic liver. Seven years after receiving a living donor LT, pulmonary and intra-hepatic recurrence of the HCC was radiologically diagnosed and histologically confirmed. Interventions: Following an interdisciplinary therapy concept consisting of surgical, interventional-radiological (with radiofrequency ablation [RFA]) as well as systemic treatment, the patient achieved a survival of more than 10 years after tumor recurrence. As systemic first line therapy with sorafenib was accompanied by grade 3 to 4 toxicities, such as mucositis, hand-foot skin reaction, diarrhea, liver dysfunction, and hyperthyroidism, it had to be discontinued. After switching to cabozantinib from June 2018 to April 2020, partial remission of all tumor manifestations was achieved. The treatment of the remaining liver metastasis could be completed by RFA. The therapy with cabozantinib was well tolerated, only mild arterial hypertension and grade 1 to 2 mucositis were observed. Liver transplant function was stable during the therapy, no drug interaction with immunosuppressive drugs was observed. Outcomes: More than 10 years survival after recurrence of HCC after living-donor LT due to intensive multimodal therapy concepts, including surgery, RFA, and systemic therapy with cabozantinib in the second line therapy. Lessons: In conclusion, this report highlights the tolerability and effectiveness of cabozantinib for the treatment of HCC recurrence after LT. We show that our patient with a late recurrence of HCC after LT benefitted from intensive multimodal therapy concepts, including surgery, RFA, and systemic therapy.

// Tae Hyun Kim 1, * , Joong-Won Park 1, * , Bo Hyun Kim 1, * , Dae Yong Kim 1 , Sung Ho Moon 1 , Sang Soo Kim 1 , Ju Hee Lee 1 , Sang Myung Woo 1 , Young-Hwan Koh 1 , Woo Jin Lee 1 and Chang-Min Kim 1 1 Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea * These authors contributed equally to this work Correspondence to: Tae Hyun Kim, email: k2onco@naver.com Keywords: hepatocellular carcinoma; tumour response; proton beam therapy Received: June 10, 2017 Accepted: November 26, 2017 Published: December 19, 2017 ABSTRACT Objective: To evaluate the optimal time of tumour response and effectiveness of hypofractionated proton beam therapy (PBT) for hepatocellular carcinoma (HCC). Results: Overall, treatment was well tolerated with no grade toxicity ≥3. Of 71 patients, 66 patients (93%) eventually reached complete response (CR) after PBT: 93.9% (62 of 66) of patients who reached CR within 12 months, and the remaining 4 patients (6.1%) reached CR at 12.5, 16.2, 19.1 and 21.7 months, respectively. The three-year local progression-free survival (LPFS), relapse-free survival (RFS) and OS rates were 89.9%, 26.8%, and 74.4%, respectively. Multivariate analysis revealed that the tumour response was an independent prognostic factor for LPFS, RFS, and OS. Conclusion: Most CR was achieved within 1 year after PBT and further salvage treatments in PBT field might be postponed up to approximately 18–24 months. Hypofractionated PBT could be good alternative for HCC patients who are unsuitable for surgical or invasive treatments with curative intent. Materials and Methods: Seventy-one inoperable or recurrent HCC patients underwent hypofractionated PBT using 66 GyE in 10 fractions. The tumour responses were defined as the maximal tumour response observed during the follow-up period using the modified Response Evaluation Criteria in Solid Tumors criteria.

The salvage liver transplantation (LT) strategy was conceived for initially resectable and transplantable hepatocellular carcinoma (HCC) to obviate upfront transplantation, with salvage LT in the case of recurrence. The longterm outcomes of a second resection for recurrent HCC have improved. The aim of this study was to perform an intention-to-treat analysis of overall survival (OS) comparing these 2 strategies for initially resectable and transplantable recurrent HCC. From 1994 to 2011, 391 patients with HCC who underwent salvage LT (n = 77) or a second resection (n = 314) were analyzed. Of 77 patients in the salvage LT group, 21 presented with resectable and transplantable recurrent HCC and 18 underwent transplantation. Of 314 patients in the second resection group, 81 presented with resectable and transplantable recurrent HCC and 81 underwent a second resection. The 5-year intention-to-treat OS rates, calculated from the time of primary hepatectomy, were comparable between the 2 strategies (72% for salvage transplantation versus 77% for second resection; P = 0.57). In patients who completed the salvage LT or second resection procedure, the 5-year OS rates, calculated from the time of the second surgery, were comparable between the 2 strategies (71% versus 71%; P = 0.99). The 5-year disease-free survival (DFS) rates were 72% following transplantation and 18% following the second resection (P

To retrospectively compare the efficacy and safety of combined radiofrequency ablation and percutaneous ethanol injection (RFA-PEI) with repeat hepatectomy for elderly patients with initial recurrent hepatocellular carcinoma (HCC) after hepatic surgery.From January 2009 to June 2015, 105 elderly patients (≥70 years) who underwent RFA-PEI (n = 57) or repeated hepatectomy (n = 48) for recurrent HCC ≤ 5.0 cm were included in the study. The overall survival (OS) and recurrence-free survival (RFS) were analysed with the Kaplan-Meier method and compared by the log-rank test. Non-tumour-related death, complications and hospital stays were assessed. Univariate and multivariate analyses were performed to identify the prognostic significance of the variables in predicting the OS and RFS.OS rates were 78.2%, 40.8% and 36.7% at 1, 3 and 5 years after RFA-PEI and 76.3%, 52.5% and 42.6% after repeat hepatectomy, respectively (p = 0.413). Correspondingly, the 1-, 3- and 5-year RFS rates after RFA-PEI and repeat hepatectomy were 69.5%, 37.8%, 33.1% and 73.1%, 49.7%, 40.7%, respectively (p = 0.465). Non-tumour-related deaths in the RFA-PEI group (2/57) were significantly fewer than those in the repeat hepatectomy group (10/48) (p = 0.016). RFA-PEI was superior to repeat hepatectomy regarding the major complication rates and length of in-hospital stay (both p 0.001). Multivariate analysis showed that the tumour number was the significant prognostic factor for the OS (hazard ratio (HR) = 1.961, 95% CI = 1.043-3.686, p = 0.037) and RFS (HR = 1.866, 95% CI = 1.064-3.274, p = 0.030).RFA-PEI provides comparable OS and RFS to repeat hepatectomy for elderly patients with small recurrent HCC after hepatectomy but with fewer non-tumour-related deaths, major complications and shorter hospital stays.

Because liver fibrosis can be treated, it is important to diagnose liver fibrosis noninvasively and monitor response to treatment. Although ultrasound (grayscale and Doppler) can diagnose cirrhosis, it does so unreliably using morphologic and sonographic features and cannot diagnose the earlier, treatable stages of hepatic fibrosis. Transient elastography, ultrasound elastography with acoustic radiation force impulse, and MR elastography are modalities that can assess for hepatic fibrosis. Although all international organizations recommend ultrasound for screening for hepatocellular carcinoma, ultrasound is particularly limited for identifying hepatocellular carcinoma in patients with obesity, nonalcoholic fatty liver disease, and nodular cirrhotic livers. In these patient groups as well as patients who are on the liver transplant wait list, ultrasound is so limited that consideration can be made for screening for hepatocellular carcinoma with either MRI or multiphase CT. Additionally, patients who have been previously diagnosed with and treated for hepatocellular carcinoma require continued surveillance for recurrent hepatocellular carcinoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

There is controversy concerning whether radiofrequency ablation (RFA) or surgical resection (SR) is a better treatment option for recurrent HCC after resection. In Kaohsiung Veteran General Hospital, from January 2002 to September 2014, a total of 100 consecutive patients who developed recurrent HCCs with a tumor size ≦ 3 cm and tumor numbers ≦ 3 after surgical resection were enrolled. Among these patients, 57 patients received RFA and 43 patients underwent repeated SR. Baseline characteristics at the time of recurrence after hepatic resection and clinical outcomes following treatment of recurrent HCC were compared between the two groups. The baseline data of initial HCC and the first recurrence of HCC were comparable in both groups. The 1-, 3-, 5-year overall survival rates following treatment of the first recurrence of HCC were 97.6%, 82.7%, 56.4% in the repeated SR group and 98.2%, 77.2%, 52.6% in the RFA group (p = 0.69). The 1-, 3-, 5-year disease-free survival rates were 57.0%, 32.1%, 28.6% in the repeated SR group and 60.8%, 26.6%, 16.6% in the RFA group ((p = 0.89). There was a trend whereby patients who underwent repeated SR had more procedure-related morbidity than patients who underwent RFA (16% vs. 7%, p = 0.14). The median total hospital days were longer in the repeated SR group than that in the RFA group (13 vs. 5 days, p < 0.05). In the small recurrent HCCs after SR, RFA achieved similar overall survival and disease-free survival than those with repeated SR as well as having a shorter hospital stay.

Objective The optimal treatment strategy for patients with recurrent hepatocellular carcinoma (HCC) remains unclear. This study was designed to investigate the outcomes of salvage liver transplantation (SLT) and re-resection (RR)/radiofrequency ablation (RFA) with respect to the time to recurrence after initial curative resection. Methods Between 2007 and 2016, 756 patients underwent curative hepatectomy for HCC in accordance with the Milan criteria. Among them, 152 experienced an intrahepatic recurrence and underwent SLT (n = 36) and RR/RFA (n = 116). Clinical data, overall survival (OS), and disease-free survival (DFS) (including subgroup analyses) according to the time to recurrence were statistically compared between the 2 groups, and prognostic factors were identified. Results The DFS of the patients who underwent SLT was much better than that of the patients who underwent RR/RFA (P = 0.002), particularly those with late recurrence (more than 12 months, P = 0.004). The time to recurrence from initial hepatectomy was found to be an independent predictor of OS and DFS. Conclusions SLT, rather than re-resection or RFA, should be the preferred treatment option for patients with late recurrence.

Caudate lobe is located in the deep dorsal area of the liver between the portal triad and the inferior vena cava (IVC). Torrential bleeding can occur from the IVC and short hepatic veins during dissection. Isolated total caudate lobe resection is still rare and technically demanding. We herein present a video on the technical aspect of laparoscopic total caudate lobectomy.A 61-year-old woman was admitted for recurrent hepatocellular carcinoma detected on imaging. She had history of multifocal hepatocellular carcinoma in July 2015 and underwent open cholecystectomy, segment 6 and segment 8 tumorectomy. Ten months later, the computed tomography scan and magnetic resonance imaging showed a 1 cm arterial enhancing lesion in segment I (S1) with no other foci of recurrence. Laparoscopic total caudate lobectomy was contemplated.The operative time was 270 minutes. The intraoperative blood loss was 200 mL and blood transfusion was not necessary. The patient was discharged on the fourth postoperative day without any complications.This report showed the safety and feasibility of laparoscopic total caudate lobectomy. Nonetheless, it is a technically demanding procedure. It should be performed in carefully selected patients and by experienced hepatobiliary surgeons proficient in laparoscopic liver resection.

Microvascular invasion (mvi) is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. However, mvi is difficult to detect preoperatively. The aim of this study was to clarify the risk factors of postoperative recurrence and investigate predictive factors of mvi before hepatectomy for HCC classified within the Milan criteria. One hundred fifty-nine patients with hepatocellular carcinoma (HCC) classified within the Milan criteria, who underwent hepatectomy, were enrolled in this study. We investigated the risk factors of recurrence. In addition, we divided them into two groups: mvi-negative group and mvi-positive group, based on pathological findings after surgery. We compared the clinicopathological factors between the two groups and determined the risk factors for mvi. Overall survival rate at 1, 3, and 5 years were 91.6%, 80.5%, and 74.9%, and the recurrence-free survival rate at 1, 3, and 5-years were 72.3%, 51.6%, and 37.2%. Risk factor analysis for tumor recurrence revealed that total bilirubin, albumin, ICGR15, AFP-L3, tumor number, mvi, and tumor stage had a significant predictive value. Multivariate analysis revealed that tumor number and mvi were significant independent risk factors for tumor recurrence. Predictive analysis for risk factors of mvi revealed that multiple tumors and AFP-L3 > 10% were significant independent risk factors for mvi in HCC classified within the Milan criteria. The mvi was one of the independent risk factors for tumor recurrence in HCC classified within the Milan criteria. Multiple tumors and high AFP-L3 value were independent predictive factors for mvi.

The management of recurrent hepatocellular carcinoma untreatable with surgical options is based on systemic therapy with sorafenib. Due to the high rates of adverse events connected to the therapy with sorafenib, metronomic capecitabine seems a promising strategy for these patients. We analyzed the data of 38 patients with hepatocellular carcinoma recurrent after liver transplantation performed at our center. We compared the outcome of 17 patients receiving metronomic capecitabine versus 20 patients experiencing best supportive care and versus the data of the literature about treatment with sorafenib. In the group treated with metronomic capecitabine we observed an increased survival after tumor recurrence at the univariate and multivariate analysis compared to the group of best supportive care (median 22 months vs. 7 months, p

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and extrahepatic metastases are typically found during disease progression. The incidence of adrenal metastasis (AM) from HCC in autopsy series ranges from 4.6 to 12.5%, and it is the second most common site of metastasis after the lungs. To date, there have been few reports of patients who underwent adrenalectomy for isolated AM from HCC after liver transplantation (LT). A woman aged 55 years was referred to our clinic for the evaluation of a right adrenal mass that was detected by abdominal ultrasonography at another center. She had undergone liver transplantation secondary to HCC and acute liver failure due to cryptogenic liver cirrhosis 138 months previously. She had been followed up for 5 years following LT after which she declined to continue with further follow-up. After radiologic and biochemical evaluation, she underwent adrenalectomy and the histopathologic examination revealed a 10 × 8 × 7-cm adrenal mass, which was considered to be an isolated AM from HCC. To our knowledge, this is the first case of isolated AM from HCC in the literature that was diagnosed 138 months after liver transplantation. Isolated AM from HCC after LT is rare and might be detected a long time after LT. Curative surgical resection of isolated metachronous AM from HCC in the absence of disseminated disease might provide for an acceptable disease-free period after adrenalectomy.

To evaluate predictors of mortality and impact of treatment in patients developing recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT).Despite well-described clinicopathologic predictors of posttransplant HCC recurrence, data on prognosis following recurrence are scarce.Multivariate predictors of mortality following HCC recurrence were identified to develop a risk score model to stratify prognostic subgroups among 106 patients developing posttransplant recurrence from 1984 to 2014, including analysis of recurrence treatment modality on survival.Of 857 patients undergoing LT, 106 (12.4%) developed posttransplant HCC recurrence (median 15.8 months following LT) with a median post-recurrence survival of 10.6 months. Patients receiving surgical therapy (n = 25) had a median survival of 27.8 months, significantly superior to patients receiving nonsurgical therapy (10.6 months) and best supportive care (3.7 months, P0.001). Multivariate predictors of mortality following recurrence included model for end-stage liver disease at LT23, time to recurrence,3 recurrent nodules, maximum recurrence size, bone recurrence, alphafetoprotein at recurrence, donor serum sodium, and pretransplant recipient neutrophil-lymphocyte ratio. A risk score model based on multivariate predictors accurately stratified recurrent HCC patients into prognostic subgroups, with low-risk patients (10 points) demonstrating excellent median survival of 70.6 months, significantly superior to the medium-risk (12.2 months, 10-16 points) and high-risk (3.4 months,16 points) groups (C-statistic 0.75, P0.001).In the largest single-center report of recurrent HCC following LT, surgical treatment in well-selected patients is associated with significantly improved survival and should be pursued. A risk score model accurately stratifies prognostic subgroups, and may help guide treatment strategies.

Background Intrahepatic recurrence of hepatocellular carcinoma (HCC) following resection is common. However, no current consensus guidelines exist to inform management decisions in these patients. Systematic review and meta-analysis of survival following different treatment modalities may allow improved treatment selection. This review aimed to identify the optimum treatment strategies for HCC recurrence. Methods A systematic review, up to September 2016, was conducted in accordance with MOOSE guidelines. The primary outcome was the hazard ratio for overall survival of different treatment modalities. Meta-analysis of different treatment modalities was carried out using a random-effects model, with further assessment of additional prognostic factors for survival. Results Nineteen cohort studies (2764 patients) were included in final data analysis. The median 5-year survival rates after repeat hepatectomy (525 patients), ablation (658) and transarterial chemoembolization (TACE) (855) were 35·2, 48·3 and 15·5 per cent respectively. Pooled analysis of ten studies demonstrated no significant difference between overall survival after ablation versus repeat hepatectomy (hazard ratio 1·03, 95 per cent c.i. 0·68 to 1·55; P = 0·897). Pooled analysis of seven studies comparing TACE with repeat hepatectomy showed no statistically significant difference in survival (hazard ratio 1·61, 0·99 to 2·63; P = 0·056). Conclusion Based on these limited data, there does not appear to be a significant difference in survival between patients undergoing repeat hepatectomy or ablation for recurrent HCC. The results also identify important negative prognostic factors (short disease-free interval, multiple hepatic metastases and large hepatic metastases), which may influence choice of treatment.

Treatment of unresectable recurrent hepatocellular carcinoma (HCC) in patients who recur after resection or orthotopic liver transplantation (OLT) remains a clinical challenge. One option is sorafenib, although little is known about its safety and tolerance in this unique patient population; therefore, we analyzed patients who underwent prior surgical resection and/or OLT and were treated with sorafenib in US cohort of GIDEON registry. In US, 645 patients were enrolled; 553 for intent to treat and 563 for safety. Data were analyzed in the safety population of 479 patients no surgery and 56 for resection or OLT. Forty-one patients underwent resection prior to the initiation of sorafenib, 15 patients had previously received an OLT, and 6 patients had both resection and OLT. Initial low starting doses (400 mg/day) were observed for more patients with prior OLT (71%) than prior resection (36%), resection and OLT (50%), concomitant OLT (25%), and no surgery (36%). Most AEs occurred in the first 4 weeks of treatment. Drug-related AEs were higher in patients with prior resection (87%), prior OLT (100%), or both (100%) than in patients with concomitant OLT (63%) or no surgery (70%). However, incidence of AEs resulting in permanent discontinuation were similar in all groups (19–38%).

// Xia Ying 1, 2 , Su-xia Han 3 , Chen-chen He 3 , Cong-ya Zhou 1 , Yi-ping Dong 3 , Meng-jiao Cai 1 , Xin Sui 3 , Cheng-xian Ma 1 , Xiao Sun 3 , Yuan-yuan Zhang 1 , Wen-li Gou 4 , Clifford Mason 5 , Qing Zhu 1 1 Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi’an, Shannxi, P.R. China 2 Department of Gynecological Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China 3 Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University Medical College, Xi’an, Shannxi, P.R. China 4 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University Medical College, Xi’an, Shannxi, P.R. China 5 Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, Kansas, USA Correspondence to: Qing Zhu, email: newzhuqing1972@yahoo.com Keywords: heptocellular carcinoma (HCC), tumor associated antigens (TAA), proteomics, autoantibodies, biomarker Received: June 03, 2016 Accepted: December 05, 2016 Published: February 08, 2017 ABSTRACT Purpose: To identify Heptocellular carcinoma (HCC) associated antigens by proteomics, and validate whether autoantibodies against tumor-associated antigens (TAAs) could be used for diagnosis and conditional monitoring. Results: The 78 kDa glucose regulated protein (GRP78) was selected as a candidate TAA. The titers of autoantibodies against 78 kDa glucose regulated protein (GRP78) from patients with HCC, liver cirrhosis (LC), and chronic hepatitis (CH) were significantly higher than that from normal controls ( P

Background Redo hepatic resection (RHR) and radiofrequency ablation (RFA) are salvage treatment choices for recurrent hepatocellular carcinoma (RHCC). As yet, it is unclear as to which treatment modality is superior in terms of long term survival. The aim of this study was to compare the survival benefits and treatment efficacy of RHR and RFA for recurrent HCC. Methods A literature review using the EMBASE, Medline, Google scholar, and Cochrane databases was performed. Meta-analyses were performed using an inference of variance, random effects model for 1, 3 and 5-year Disease Free Survival (DFS) and Overall Survival (OS). Secondary outcomes were major morbidity and mortality. Results Five retrospective studies including 639 patients were eligible. Overall, there were no differences in 1, 3 and 5-year DFS or OS for patients undergoing RHR or RFA for recurrent HCC. Comparison between the two groups demonstrated similar 5-year DFS (HR 0.86, 95% CI 0.67–1.11, p = 0.250) and 5-year OS (HR 1.03, 95% CI 0.83–1.27, p = 0.082). However, RFA had a lower morbidity rate (2%) compared with RHR (17%, p Conclusion This study demonstrates, neither RHR nor RFA appeared to be superior in terms of DFS and OS. Well-constructed, randomised, multicenter trials will be required to determine if a true difference exists.

Background: Intrahepatic recurrence of hepatocellular carcinoma (HCC) is frequently noted in patients after hepatectomy of HCC. Recurrence HCC is usually diagnosed as small nodule ≤ 2 cm in diameter due to the frequent postoperative check up with US, dynamic CT, or dynamic EOB-MRI. Radiofrequency ablation (RFA) is recommended for these small HCCs, because RFA is minimally invasive, effective, and repeatedly performed. Purpose: To investigate the long-term outcome and prognostic factors of RFA in recurrent HCC after heaptectomy. Material and Methods: Between February 2002 and October 2011, 75 patients with initial intrahepatic recurrence of HCC after hepatectomy underwent RFA. The 57 patients were men and 18 women, whose age ranged from 44 years to 83 years (median, 69 years). Sixty-nine patients had a single nodule and 6 patients had two nodules. The size of the 81 nodules ranged 5 - 30 mm (median, 15 mm). Regular follow-up after RFA was performed to evaluate rates of local tumor progression, overall survival rates, and disease-free survival rates. Prognostic factors related to overall survivals and disease-free survivals were evaluated, too. Results: During follow-up periods after RFA (3 to 151 months, median, 55 months), local recurrence was noted in 10 nodules of 10 patients (10/81 nodules = 12.3%). The rates of local recurrence of 1-yr, 3-yr, 5-yr, and 8-yr were 7.6%, 12.0%, 12.0%, and 12.0%, respectively. During the follow-up periods, 36 patients were alive and 39 died. The cumulative overall survival rates of 1-yr, 3-yr, 5-yr, and 10-yr were 97.3%, 79.1%, 56.6%, and 32.2%, respectively. The cumulative disease-free survival rates of 1-yr, 3-yr, and 5-yr were 42.7%, 18.8%, and 12.6%, respectively. Child-Pugh Class (A or B) before RFA for a recurrent HCC was a significant prognostic predictor of overall survival rates (p = 0.007), and Child-Pugh class (A or B) before hepatectomy was that of disease-free survival rates (p = 0.004). Conclusion: RFA was an effective, useful therapeutic option for treatment of recurrent HCC after hepatectomy. Child-Pugh Class (A or B) before RFA was a significant prognostic predictor of long-term survival, and Child-Pugh class (A or B) before hepatectomy was a significant prognostic predictor of disease-free survival.

There is presently no evidence-based recommendation for surveillance of recurrent hepatocellular carcinoma after liver transplantation (LT). We aim to evaluate and develop evidence-based alternate surveillance imaging schedules for post-LT hepatocellular carcinoma patients.Imaging and pathologic reports for consecutive post-LT patients followed up by regular surveillance imaging from a single institution's prospective database were evaluated with institutional review board approval. Outcome variable was time to diagnosis of first recurrence post-LT by surveillance imaging. Recurrence-free survival times from alternative surveillance schedules were compared with the existing schedule (every 3 months) using a parametric frailty model. Expected delay (EpD) in diagnosis compared to the existing schedule was also computed for the alternate surveillance schedules. A P value less than 0.05 was considered to indicate a significant difference.One hundred twenty-five patients (108 men; 59.4 ± 16.6 years) underwent 1953 computed tomography and 255 magnetic resonance imaging scans. Recurrence-free survival time was not significantly different in the first 5 years after LT when the imaging interval was extended from current every 3 months to every 6 months (P = 0.786, EpD = 55 days). This alternative schedule incurred 10 (50.0%) fewer surveillance scans than the 20 in the original schedule, and a corresponding reduction in radiation dose (if involved) and cost during the 5-year follow-up period.In conclusion, modeled alternative surveillance schedules have the potential to reduce the frequency of scans without compromising surveillance benefits.

The incidence of hepatocellular carcinoma in pregnancy is rare, and we present the first reported case of a pregnancy complicated by pre-existing advanced hepatocellular carcinoma. We describe the case of a 39-year-old woman in her second pregnancy, with a diagnosis of hepatocellular carcinoma. This was discovered in 2013 incidentally following hepato-splenectomy and pancreatectomy for a presumed hepatic adenoma in the context of multiple arterio-venous malformations. Recurrent hepatocellular carcinoma, in conjunction with co-existing pulmonary hypertension was successfully managed in a multi-disciplinary setting, resulting in a spontaneous vaginal delivery of a live female infant with maternal and neonatal survival six months following delivery.

International audience; Background & aims: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs.Methods: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies.Results: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up.Conclusions: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients.Lay summary: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up.

Background and aims The optimal treatment strategy for recurrent hepatocellular carcinoma (HCC) remains unclear. Therefore, we aimed to compare the outcomes of repeat hepatic resection (RHR) and radiofrequency ablation (RFA) for recurrent HCC. Method From December 2004 to December 2015, 138 patients who underwent RHR and 194 patients who underwent RFA were enrolled. Propensity score matching (PSM) was performed to establish 1:1 RHR‐RFA group matching. Clinical outcomes were compared before and after matching. Results Before matching, the 1‐, 3‐, and 5‐year postrecurrence survival (PRS) rates were 91.8%, 82.0%, and 72.9% for the RHR group (n = 138) and 94.4%, 75.4%, and 61.7% for the RFA group (n = 194), respectively (P = .380). After matching, the PRS rates at 1, 3, and 5 years were 90.5%, 81.5%, and 71.8% for the RHR group (n = 120) and 91.0%, 61.0%, and 41.7% for the RFA group (n = 120), respectively (P = .002). In the subgroup analysis, the PRS rates for the RHR group were better than those for the RFA group for patients who relapsed within 2 years (P = .004) or patients with primary tumor burden beyond the Milan criteria (P = .004). Multivariate analysis showed that treatment allocation was identified as an independent prognostic factor for PRS. Conclusion Compared with RFA, RHR provided a survival advantage for recurrent HCC, especially for patients who relapsed within 2 years and those with primary tumor burden beyond the Milan criteria., Compared with RFA, repeat hepatic resection provided a survival advantage for recurrent HCC, especially for patients relapsed within 2 years and patients with primary tumor burden beyond Milan criteria.

Repeat laparoscopic hepatectomy (LRH) offers an option for recurrent tumors in liver remnants following an initial liver resection of recurrent hepatocellular carcinoma (HCC), colorectal liver metastasis (CRLM) and cholangiocellular carcinoma (CCC), showing advantages in some outcomes. The objective of the study was to evaluate the feasibility, safety, and potential benefits of LRH in comparison with repeat open hepatectomy (ORH) for recurrent liver cancer.A systematic review was performed in compliance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) and AMSTAR (Assessing the methodological quality of systematic reviews) guidelines. We performed a systematic search of PubMed, Embase, Cochrane Library, and Web of Science to identify studies that compared LRH with ORH from inception to September 30, 2019. Outcomes of interest included operation time, intraoperative estimated blood loss, length of hospital stay, complication rate, transfusion and R0 resection rate. The protocol was registered with the PROSPERO register of systematic reviews.10 retrospective observational studies were suitable for this analysis, involving 767 patients with 334 undergoing LRH (43.5%) and 433 undergoing ORH (56.5%). Compared with ORH, LRH had less intraoperative blood loss (SMD = -1.03; 95% CI: 1.48~-0.59, P 0.001), less overall postoperative complications (OR = 0.40; 95% CI: 0.16-0.99, P = 0.048), less major complications (OR = 0.31, 95% CI: 0.15-0.62, P = 0.001), shorter hospital stay (SMD = -0.98; 95% CI: 1.41~-0.54, P 0.001) and higher R0 resection rate (OR = 2.30, 95% CI: 1.39-3.81, P = 0.001). It was comparable in operation time (WMD = -7.66; 95% CI: 52.50-37.19, P = 0.738), transfusion rate (OR = 0.33; 95% CI:0.11-1.05, P = 0.060), and mortality (OR = 0.76; 95% CI: 0.27-2.18, P = 0.615) between LRH and ORH.Our results indicate that LRH is a safe and effective technique. Benefits, especially less intra-operative blood loss, less complications rate, shorter hospital stay and higher R0 resection, might be offered in the laparoscopic approach.

OBJECTIVE To explore prognostic factors by comparing the efficacy of salvage liver transplantation (sLT) and rehepatectomy (RH) for the treatment of recurrent hepatocellular carcinoma after hepatectomy. METHODS Clinical data were collected for 124 patients treated at our center from January 2012 to August 2018. The median follow-up time for the patients was 39 months. By analyzing the clinical data between the sLT group (46 cases) and RH group (78 cases), the factors affecting the prognosis of patients were compared. RESULTS The proportion of alpha-fetoprotein (AFP) ≥ 100 µg/L in the recurrence group was significantly higher than that in the recurrence-free group (70.0% vs 22.2%, P = .014). The postoperative overall survival (OS) and recurrence-free survival (RFS) were better in the sLT group than in the RH group (81.2% vs 36.9%, P

The treatment of hepatocellular carcinoma after liver transplantation (LT) is controversial because of its high recurrence rate and low survival rate. Here, we report a case of early diffuse bilateral lung metastasis after LT beyond the Milan transplantation criteria (d = 18 cm, α-fetoprotein >24,000 ng/mL) that successfully achieved 1-year tumor-free remission survival with sirolimus combined with regorafenib. The donor source of the liver is legal, and this study followed the guidelines of the Helsinki Congress in this LT. To the best of our knowledge, this is the first report of the use of regorafenib as a first-line agent combined with sirolimus to treat recurrent hepatocellular carcinoma after LT, and this case expands the indications for LT.

Sorafenib resistance is one of the main obstacles to the treatment of advanced/recurrent hepatocellular carcinoma (HCC). Here, sorafenib-resistant HCC cells and xenografts in nude mice were used as experimental models. A cohort of patients with advanced recurrent HCC who were receiving sorafenib therapy was used to assess the clinical significance of this therapy. Our data showed that 14-3-3η maintained sorafenib resistance in HCC. An analysis of the underlying molecular mechanisms revealed that 14-3-3η stabilizes hypoxia-inducible factor 1α (HIF-1α) through the inhibition of ubiquitin-dependent proteasome protein degradation, which leads to the maintenance of cancer stem cell (CSC) properties. We further found that microRNA-16 (miR-16) is a competent miRNA that reverses sorafenib resistance by targeting the 3′-UTR of 14-3-3η and thereby inhibits 14-3-3η/HIF-1α/CSC properties. In HCC patients, significant negative correlations were found between the expression of miR-16 and 14-3-3η, HIF-1α, or CSC properties. Further analysis showed that low miR-16 expression but high 14-3-3η expression can prognosticate sorafenib resistance and poor survival. Collectively, our present study indicated that miR-16/14-3-3η is involved in sorafenib resistance in HCC and that these two factors could be potential therapeutic targets and biomarkers for predicting the response to sorafenib treatment.

Background Recurrent hepatocellular carcinoma (HCC) with a tumor thrombus (TT) extending into the inferior vena cava (IVC)/right atrium (RA) is generally regarded as a terminal-stage condition and there is no worldwide consensus on the proper management of this situation. In the present study, we report the efficacy of hypofractionated radiotherapy (HFRT) as a salvage treatment for recurrent HCC with IVC/RA TT. Methods We retrospectively reviewed 75 HCC patients with an IVC/RA TT who were referred for HFRT at three institutions between 2008 and 2016. 57 cases had a TT located in the IVC (IVC group), and 18 cases had a TT located in the IVC and RA (IVC + RA group). HFRT was designed to focus on the TT with or without the primary intrahepatic tumors. Results In all cases, the TT completely disappeared (CR) in 17 patients (22.7%), 55 patients (73.3%) had a partial response (PR), and 3 patients (4.0%) had a stable disease (SD). There were no cases of progressive disease (PD). The 1-, 2-, and 3-year overall survival rates of the 75 patients were 38.7% (29/75), 13.3% (10/75) and 5.3% (4/75), respectively. The overall median survival time was 10 months. The mean survival times for the IVC group and IVC+ RA group were 13.8 ± 1.1 and 11.6 ± 2.5 months, respectively. There was no significant difference in survival between the two groups (p = 0.205). Log-rank test revealed that factors predicting poor survival were Child-Pugh B liver function classification, AFP ≥ 400 μg/L, intrahepatic multiple tumors, distant metastases, only the TT as the target, a biological effective dose (BED)

Small recurrent hepatocellular carcinoma (HCC) can show atypical imaging patterns, and a specific diagnostic algorithm for HCC is lacking. This study aimed to better characterize postoperative recurrent HCCs

Background We aimed to investigate the optimal treatment modality between radiofrequency ablation (RFA) and repeated hepatectomy in the treatment of solitary recurrent HCC (rHCC) after hepatectomy, considering the influence of tumor size and location. Methods From Jan 2009 to Dec 2016, 630 consecutive patients with solitary small rHCC (≤3.0 cm) after initial hepatectomy who underwent RFA or repeated hepatectomy were enrolled in three tertiary referral centers. Patients were divided into four groups according to tumor size (≤ 2.0 cm or >2.0 cm) and location (central or peripheral) respectively. Overall survival (OS) and recurrence-free survival (RFS) rates were compared between RFA and repeated hepatectomy in these four groups. Results For central rHCC ≤ 2.0 cm, the OS and RFS rates at 5 years after RFA were significantly higher than those after repeated hepatectomy (69.9% vs 53.1%, P=0.001; 56.2% vs 42.6%, P=0.038). For central rHCC >2.0 cm, the 5-year OS and RFS rates were not significantly different between repeated hepatectomy and RFA (55.9% vs 48.2%, P=0.080; 27.0% vs 19.2%, P=0.103). For peripheral tumors ≤ 2.0 cm (58.8% vs. 47.7%, P=0.001; 45.2% vs. 25.6%, P=0.001) or >2.0 cm (62.6% vs. 45.4%, P=0.001; 44.7% vs. 21.1%, P=0.010), the OS and RFS rates at 5 years after repeated hepatectomy were both significantly higher than those after RFA. Complications were more common in patients after repeated hepatectomy than RFA, especially for central tumors. Conclusions RFA might be the optimal treatment for patients with central rHCC ≤ 2.0 cm whereas repeated hepatectomy should be recommended for patients with peripheral tumors.

Background Early detection of recurrent hepatocellular carcinoma (HCC) can make early intervention available. This study aimed to find radiomics features to improve the performance of detecting recurrence based on computer tomography (CT). Methods The retrospective study included a training cohort of 35 patients and a validation cohort of 62 patients. A series of follow-up CT images of patients with primary HCC after surgical resection or ablation were collected from January 2009 to April 2018. Tumor and liver regions of interest (ROI) were manually delineated on CT1 (within one month after resection or ablation), CT2 (when suspicious recurrence was observed) and CT3 (when confirmed recurrence was observed). Radiomics features were extracted and a radiomics algorithm, ‘difference-in-difference’ (DD) was established for detecting recurrence. Folded cross validation (CV) was used. Results A total of 256 follow-up images were available for analysis. The training cohort was divided into recurrence and no recurrence group, with 18 patients and 17 patients, respectively. Our radiomics algorithm selected 17 DD radiomics features for detecting recurrence using univariable analysis. Principle component analysis showed that an Area Under the Receiver Operator Characteristic Curve (AUC) of the first principle component of 17 selected DD features achieved 0.97 (95% CI: 0.92–1.00). Leave-one-out CV produced an error of 18.2% and 10-fold CV with a highest error as 19.1%. Incorporating post-treatment alpha-fetoprotein (AFP), there was no significant increase in AUC compared with the first principal component of 17 DD features alone (0.97 vs 0.97, Z=0.346, P=0.730). In the validation cohort, univariable analysis showed that the variation trend of radiomics features was suggestive of recurrence. Conclusions Difference-in-difference of CT radiomics features improved performance of conventional CT and was superior to AFP in detecting recurrence of HCC.

Background Treatment strategies for recurrent hepatocellular carcinoma (rHCC) are controversial. We used the status of microvascular invasion (MVI) at primary resection as a marker to choose the appropriate treatment options for rHCC patients in Barcelona Clinic Liver Cancer (BCLC) stage B-C. Methods From Jun 2009 to Jun 2017, a consecutive 241 patients with postsurgical recurrence at BCLC stage B-C who received re-resection (RR), radiofrequency ablation (RFA) or transarterial chemoembolization(TACE), were enrolled. Multivariate COX regression analysis was performed to identify the prognostic factors for post-recurrence survival (PRS). PRS, overall survival (OS) and costs were compared between RR/RFA and TACE according to MVI status. A one-to-one propensity score matching analysis was performed to reduce bias. Results For MVI(-) patients, the median PRS was 88.1 months for the RR/RFA group (n=20) and 21.1 months for the TACE group (n=49) with the HR=0.40 (P=0.014). The corresponding OS were 98.1 and 26.6 months, respectively (HR=0.34, P=0.003). For MVI(+) patients, the median PRS in RR/RFA group (n=35) and TACE group (n=137) were 15.9 and 10.7 months, respectively (HR=0.67, P=0.105). The corresponding OS were 23.5 and 16.8 months, respectively (HR=0.66, P=0.087). After matching, the dominance of RR/RFA over TACE remained in MVI(-) patients for both PRS (62.3 vs 18.5 months; HR=0.37, 95%CI=0.15–0.96; P=0.033) and OS (98.1 vs 33.3 months; HR=0.31, P=0.008). No significant difference was found in MVI(+) patients for either PRS (15.9 vs 15.6 months; HR=0.83, 95%CI=0.44–1.55; P=0.554) or OS (23.5 vs 28.1 months; HR=0.90, P=0.752). The cost of TACE group was significant lower than that of the RR/RFA group for both MVI-positive patients (P=0.007) and MVI-negative patients (P Conclusions For MVI-negative patients, RR/RFA provided better survival than TACE while for MVI-positive patients, TACE was recommended.

Background The evidence of combining sorafenib with transarterial chemoembolization (TACE) for intermediate-stage recurrent hepatocellular carcinoma (HCC) is limited. Patient responses to this treatment varied because of the heterogeneous nature of intermediate-stage recurrent HCC, making it important to identify patients who are most likely to benefit from this combination therapy. Purpose To compare sorafenib administered in combination with TACE versus TACE alone in the treatment of recurrent intermediate-stage HCC after initial hepatectomy and to determine the relationship of microvascular invasion (MVI) to survival. Materials and Methods In this retrospective multicenter study, 3652 consecutive patients were found to have intrahepatic recurrences after initial hepatectomy of primary HCC from January 2010 to December 2016. Of these, 260 patients with intermediate-stage recurrent HCC underwent combination treatment with sorafenib and TACE or TACE alone. Overall survival (OS) and progression-free survival (PFS) were compared between these two treatments according to MVI status by using log-rank tests. Results A total of 128 patients were administered combination therapy (mean age, 55 years ± 7.6 [standard deviation]; 107 men) and 132 patients were administered TACE alone (mean age, 56 years ± 8.3; 110 men). The 5-year OS and PFS were higher in the combination group than in the TACE group (OS: 38.9% vs 20.5%, respectively, P = .01; PFS, 37.5% vs 18.7%, respectively, P = .003). For patients with MVI-positive lesions, the median OS and PFS after combination treatment (n = 55) were longer than those after TACE alone (n = 72; OS: 17.2 months vs 12.1 months, respectively, P = .02; PFS: 17.0 months vs 11.0 months, respectively, P = .02). Multivariable analysis showed that tumor number, MVI status, and treatment allocation were significant predictors of OS and PFS, whereas tumor size was a prognostic factor for PFS. Conclusion Patients with recurrent intermediate-stage hepatocellular carcinoma and lesions positive for microvascular invasion (MVI) had longer survival times by using a combined treatment of sorafenib with transarterial chemoembolization (TACE) compared with TACE alone; patients with MVI-negative lesions did not show survival benefit from combined therapy. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Malloy in this issue.

OBJECTIVE To evaluate the long-term outcomes of surgery for recurrent hepatocellular carcinoma (HCC). BACKGROUND HCC recurs with high incidence after liver resection. Little is known about long-term outcomes of patients undergoing surgery for recurrent HCC. METHODS Among 989 patients who underwent R0/R1 liver resection for HCC between 1995 and 2014, 676 patients who exhibited recurrence were included. Repeat surgery was performed in 128 patients (RS group), and not in the remaining 548 patients (NS group). Prognostic value after repeat surgery was evaluated by comparing survival after recurrence (SAR) between the RS and NS groups. Subgroup analyses according to the 3 recurrence patterns [intrahepatic recurrence (IHR), extrahepatic recurrence (EHR), and intra plus extrahepatic recurrence (IHR + EHR)] were performed. RESULTS Seventy-three of 430 patients (17.0%) with IHR, 17 of 57 patients (29.8%) with EHR, and 38 of 189 patients (20.1%) with IH + EHR underwent repeat surgery. Compared with the NS group, the RS group had better liver function and their time to recurrence was significantly longer (16.5 vs 11.4 months; P < 0.001). In the overall and 3 recurrence patterns, the 5-year SAR rate was better in the RS group compared with the NS group (RS vs NS group; overall, 53.0% vs 25.7%; IHR, 73.8% vs 37.2%; EHR, 30.0% vs 0%; IHR + EHR, 34.1% vs 10.6%; all P < 0.001, respectively). On multivariate analysis, repeat surgery was identified as an independent factor for better SAR (P < 0.001). CONCLUSION Surgery for recurrent HCC may yield long-term survival for not only IHR but also for EHR in selected patients.

There is lack of data for identifying optimal local therapy for the management of recurrent hepatocellular carcinoma (HCC) after hepatic resection. A retrospective study was performed to compare the effectiveness of transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with that of TACE alone for recurrent HCC. From 2007 to 2013, patients with recurrent HCC ≤ 5 cm were treated with either TACE plus RFA (n = 96) or TACE (n = 63). Inverse probability of treatment weighting was used to make allowances for imbalances in treatment assignment. The disease-free survival (DFS) and overall survival (OS) were retrospectively analyzed. The TACE group had lower pretreatment Child–Pugh class (P = 0.025) and shorter pretreatment interval of recurrence (P = 0.028). The 1-, 3-, and 5-year DFS rates for the TACE-RFA group were 55.1%, 22.5%, and 9.7%, respectively, and 41.1%, 9.9%, and 4.9%, respectively, for the TACE group. The OS rates at 1, 3, and 5 years were 82.3%, 42.7%, and 16.5%, respectively, in the TACE-RFA group, and 75.9%, 30.7%, and 11.3%, respectively, in the TACE group. Cirrhosis was significantly associated with disease progression (hazard ratio [HR] 1.53; 95% CI 1.09–2.14; P = 0.014). In patients with recurrent HCC ≤ 5 cm, TACE-RFA shows better DFS than TACE alone as a first-line local therapy.

Background/aimsIt is important to identify patients who are refractory to transarterial chemoembolization (TACE), which is performed for the treatment of hepatocellular carcinoma (HCC). We investigated the predictors of poor treatment outcomes in patients with recurrent HCC treated who were treated with TACE after curative resection.Methods428 patients with recurrent HCC after curative resection who were treated with TACE were enrolled.ResultsThe median age of the study population was 59.2 years. On multivariate analysis, ≥2 TACE procedures within 6 months (hazard ratio [HR] = 1.898), and the des-gamma carboxyprothrombin level (HR = 1.000) independently predicted the progression to Barcelona Clinic Liver Cancer (BCLC) stage C in patients with BCLC stage 0-B HCC (both PConclusionsMore than 2 TACE procedures within 6 months might be associated with the refractoriness to TACE in patients with recurrent HCC after curative resection.

Repeat liver resection is an effective treatment approach for patients with recurrent hepatocellular cell carcinoma (HCC). However, the surgical feasibility and oncological significance of repeat laparoscopic liver resection (r-LLR) remain unproven. This study evaluates and compares the clinical outcomes of non-anatomic r-LLR applied towards recurrent HCC, with those of primary LLR (p-LLR) for primary HCC. This retrospective study reports 104 patients with HCC, treated with LLR between 2014 and 2018. Twenty eight of these patients underwent r-LLR for recurrent HCC. The clinical and surgical variables were reviewed for all cases. The analysis was limited to non-anatomic resection across both groups (r-LLR: 89% (25/28) vs. p-LLR: 80% (61/76)). There were no statistically significant differences about patient background between the two groups, with the exception of Child–Pugh classification. r-LLR surgical techniques included single-site laparoscopic adhesiolysis (32%, 8/25), Pringle maneuver (8%, 2/25), and crush–clamp method using BiClamp for hepatic parenchymal transection (72%, 18/25). No severe postoperative complications were observed in the r-LLR group. Postoperative hospital stays and procedure-related postoperative survival were similar for both groups. Non-anatomical r-LLR renders comparable surgical and oncological outcomes. Our data suggest that non-anatomical r-LLR is a safe and feasible therapeutic approach to recurrent HCC.

To compare the efficacy of magnetic resonance imaging (MRI) with hepatobiliary agents (HBA-MRI) and MRI with extracellular contrast agents (ECA-MRI) for detection of recurrent hepatocellular carcinoma (HCC) after multiple treatments. The institutional review board approved this retrospective study and waived the requirement for informed patient consent. A total of 135 patients with suspected HCC recurrence after 2–5 treatments (surgery, transarterial chemoembolization, and/or radiofrequency ablation) underwent both HBA-MRI and ECA-MRI within a 1 month interval. HBA-MRI and ECA-MRI were analyzed for HCC detection by two observers using a five-point scale. The diagnostic performances according to MRI modality were compared. A total of 136 liver lesions (121 HCCs and 15 benign lesions; median size, 1.9 cm) were identified. ECA-MRI showed greater sensitivity (90.9% vs. 76.9% for observer 1; 91.7% vs. 78.5% for observer 2) and accuracy (91.2% vs. 78.7% for observer 1; 91.9% vs. 80.2% for observer 2) than HBA-MRI for both observers (P = 0.002, 0.003). Fifteen (12.4%) HCCs were correctly diagnosed with ECA-MRI but not with HBA-MRI by both observers. Interobserver agreement was excellent (0.885) for ECA-MRI and substantial (0.749) for HBA-MRI. For detection of recurrent HCC, ECA-MRI was superior to HBA-MRI in terms of sensitivity and accuracy. Therefore, ECA-MRI could be the preferred imaging modality over HBA-MRI for assessing HCC recurrence following multiple treatments.

This study sought to investigate the clinical impact of repeated interventions for recurrent hepatocellular carcinoma (HCC) and to establish a new surrogate measure for survival: the time-to-interventional failure (TIF). Based on a retrospective review of 1158 patients who underwent curative resection for HCC, the abilities of recurrence-free survival (RFS) and TIF, which was defined as the elapsed time from resection to unresectable/unablatable recurrence, to predict overall survival (OS) were compared. Within a median follow-up period of 84.9 months, 676 (59.0%) recurrence events occurred, 78.1% of which were resectable/ablatable recurrences. Of these, 99.1% of the patients underwent repeated treatments. TIF had a stronger correlation than RFS (r = 0.921 vs. r = 0.631) in prediction of OS. Patients who underwent curative-intent treatment (i.e., resection or ablation) for recurrence showed significantly better survival outcomes compared with those who underwent non-curative treatment (e.g., TACE, chemotherapy) (median OS, 89.1 months vs. 55.0 months; P