Anterior approach with or without liver hanging maneuver versus conventional approach in major liver resections. A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The anterior approach (AA), whether or not associated with the liver hanging maneuver (LHM), has been advocated to improve survival and postoperative outcomes in HCC patients undergoing major liver resection. This systematic review and meta-analysis of randomized controlled trials aims to explore intra/perioperative and long-term survival outcomes of AA ± LHM compared to CA regardless of tumor histology. METHODS: The study was conducted according to the Cochrane recommendations searching the PubMed, Scopus, and EMBASE databases until January 27, 2024 (PROSPERO ID: CRD42024507060). Only English-language RCTs were included. The primary outcome, expressed as hazard ratio (HR) and 95 % confidence intervals (CI), was the overall and disease-free survival. Random effects models were developed to assess heterogeneity. The risk of bias in included studies was assessed with the RoB 2 tool. The certainty of evidence was assessed following GRADE recommendations. RESULTS: Six RCTs, for a total of 736 patients were included. A significant survival benefit was highlighted for patients undergoing AA ± LHM in terms of overall (HR: 0.65; 95 % CI: 0.62-0.68; p < 0.0001) and disease-free survival (HR: 0.65; 95 % CI: 0.63-0.68; p < 0.0001). AA ± LHM was associated with a longer duration of surgery (WMD: 29.5 min; 95 % CI: 17.72-41.27; p = 0.004), and a lower intraoperative blood loss (WMD: 24.3; 95 % CI: 31.1 to -17.5; p = 0.0014). No difference was detected for other postoperative outcomes. The risk of bias was low. CONCLUSION: AA ± LHM provides better survival outcomes compared to CA. Furthermore, AA ± LHM is related to a modest reduction in intraoperative blood loss, at the price of a slightly longer duration of hepatectomy. Regarding other postoperative outcomes, the two techniques appear comparable.

Three-dimensional reconstruction technology in the preoperative workup of complex hepatic resections. Our experience on 11 consecutive cases.

Three-dimensional liver modeling can be a useful tool when planning the preoperative strategy in liver surgery. The present study aims to review our case series of patients requiring complex hepatic resections for primary and secondary liver tumors, and for whom 3D models were built, to add further evidence in this direction. All consecutive patients undergoing complex liver resection were enrolled. Cross-sectional triphasic CT images were obtained for each patient. DICOM images were processed, and full virtual 3D models were generated. The additional details provided by 3D models were employed to better understand the anatomy, to define the most adequate surgical pathway, and, in case, to switch to a different surgical procedure. From January 2020 to September 2022, 11 complex hepatic resections requiring 3D reconstruction technology were performed. Eight 3D models scored ≥ 15 points in the quality control system. A detailed analysis of each case was reported. In three cases (27%) 3DVT helped to understand the anatomy and/or to detect vascular abnormalities. In six cases (54.5%) 3DVT led to a variation of the surgical planning. 3DVT may be helpful in planning preoperatively the most appropriate surgical procedure. Further large-scale, well-designed studies are needed to prove its true effectiveness in HPB surgical oncology.

Undifferentiated Embryonal Sarcoma of the Liver with Epithelioid Features: A Case Report of an Exceptional Histological Heterogeneity among Rare Diseases.

INTRODUCTION: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignant tumor, with nonspecific clinical symptoms and radiological features. Less than 150 cases have been reported in adults across the world. PRESENTATION OF CASE: We report a case of an extremely rare subtype of UESL with epithelioid features in a 29-year-old woman, presenting as a cystic lesion of 27 × 17 cm, completely subverting the right hepatic lobe. She underwent a right hepatectomy with anterior approach, complete hilum lymphadenectomy and partial diaphragmatic resection for local infiltration, followed by systemic chemotherapy. She remains with no evidence of disease and liver mass has been restored after 6 months. DISCUSSION: The present case report represents the second case of UESL with epithelioid features described across the world. The immunohistochemical expression pattern, cytokeratin (CK)19 + and CK7 -, strongly suggests an origin of this epithelioid component from native biliary cells and not from a reshaped ductal plate. Due to the rarity of this form, to date it is impossible to define the prognostic impact of this subtype of UESL, and treatment remains challenging. CONCLUSION: UESL is associated with a poor prognosis, especially in adults, but a comprehensive and multidisciplinary treatment based on radical resection and adjuvant therapy may provide a survival benefit. Surgical excision with negative margins remains mandatory to diagnose and treat UESL.

Dynamic surgical anatomy using 3D reconstruction technology in complex hepato-biliary surgery with vascular involvement. Results from an international multicentric survey.

INTRODUCTION: Three-dimensional liver modeling can lead to substantial changes in choosing the type and extension of liver resection. This study aimed to explore whether 3D reconstruction helps to better understand the relationship between liver tumors and neighboring vascular structures compared to standard 2D CT scan images. METHODS: Contrast-enhanced CT scan images of 11 patients suffering from primary and secondary hepatic tumors were selected. Twenty-three experienced HBP surgeons participated to the survey. A standardized questionnaire outlining 16 different vascular structures (items) having a potential relationship with the tumor was provided. Intraoperative and histopathological findings were used as the reference standard. The proper hypothesis was that 3D accuracy is greater than 2D. As a secondary endpoint, inter-raters' agreement was explored. RESULTS: The mean difference between 3D and 2D, was 2.6 points (SE: 0.40; 95 % CI: 1.7-3.5; p < 0.0001). After sensitivity analysis, the results favored 3D visualization as well (mean difference 1.7 points; SE: 0.32; 95 % CI: 1.0-2.5; p = 0.0004). The inter-raters' agreement was moderate for both methods (2D: W = 0.45; 3D: W = 0.44). CONCLUSION: 3D reconstruction may give a significant contribution to better understanding liver vascular anatomy and the precise relationship between the tumor and the neighboring structures.

The Role of Non-Peripancreatic Lymph Nodes in the Survival of Patients Suffering from Pancreatic Cancer of the Body and Tail: A Systematic Review and Meta-Analysis of High-Quality Studies.

Lymph nodes (LNs)' metastases have a well-known detrimental impact on the survival outcomes of patients suffering from pancreatic cancer of the body and tail. However, the extent of the lymphadenectomy for this tumor location is still debated. The aim of this study was to systematically review the current literature to explore the incidence and the prognostic impact of non-peripancreatic lymph nodes (PLNs) in patients suffering from pancreatic cancer of the body and tail. A systematic review was conducted according to PRISMA and MOOSE guidelines. The primary endpoint was to assess the impact of non-PLNs on overall survival (OS). As a secondary endpoint, the pooled frequencies of different non-PLN stations' metastatic patterns according to tumor location were explored. Eight studies were included in data synthesis. An increased risk of death for patients with positive non-PLNs was detected (HR: 2.97; 95% CI: 1.81-4.91; p < 0.0001). Meta-analysis of proportions pointed out a 7.1% pooled proportion of nodal infiltration in stations 8-9. The pooled frequency for station 12 metastasis was 4.8%. LN stations 14-15 were involved in 11.4% of cases, whereas station 16 represented a site of metastasis in 11.5% of cases. Despite its potential beneficial effect on survival outcome, a systematic extended lymphadenectomy could not be recommended yet for patients suffering from PDAC of the body/tail.

Kimura's vs Warshaw's technique for spleen preserving distal pancreatectomy: a systematic review and meta-analysis of high-quality studies.

BACKGROUND: Spleen preserving distal pancreatectomy (SPDP) represents a widely adopted procedure in the presence of benign or low-grade malignant tumors. Splenic vessels preservation and resection (Kimura and Warshaw techniques respectively) represent the two main surgical modalities to avoid splenic resection. Each one is characterized by strengths and drawbacks. The aim of the present study is to systematically review the current high-quality evidence regarding these two techniques and analyze their short-term outcomes. METHODS: A systematic review was conducted according to PRISMA, AMSTAR II and MOOSE guidelines. The primary endpoint was to assess the incidence of splenic infarction and splenic infarction leading to splenectomy. As secondary endpoints, specific intraoperative variables and postoperative complications were explored. Metaregression analysis was conducted to evaluate the effect of general variables on specific outcomes. RESULTS: Seventeen high-quality studies were included in quantitative analysis. A significantly lower risk of splenic infarction for patients undergoing Kimura SPDP (OR = 0.14; p < 0.0001). Similarly, splenic vessel preservation was associated with a reduced risk of gastric varices (OR = 0.1; 95% p < 0.0001). Regarding all secondary outcome variables, no differences between the two techniques were noticed. Metaregression analysis failed to identify independent predictors of splenic infarction, blood loss, and operative time among general variables. CONCLUSIONS: Although Kimura and Warshaw SPDP have been demonstrated comparable for most of postoperative outcomes, the former resulted superior compared to the latter in reducing the risk of splenic infarction and gastric varices. For benign pancreatic tumors and low-grade malignancies Kimura SPDP may be preferred.

Short-Term Outcomes after D2 Gastrectomy with Complete Mesogastric Excision in Patients with Locally Advanced Gastric Cancer: A Systematic Review and Meta-Analysis of High-Quality Studies.

Complete mesogastric excision (CME) has been advocated to allow for a more extensive retrieval of lymph nodes, as well as lowering loco-regional recurrence rates. This study aims to analyze the short-term outcomes of D2 radical gastrectomy with CME compared to standard D2 gastrectomy. A systematic review of the literature was conducted according to the Cochrane recommendations until 2 July 2023 (PROSPERO ID: CRD42023443361). The primary outcome, expressed as mean difference (MD) and 95% confidence intervals (CI), was the number of harvested lymph nodes (LNs). Meta-analyses of means and binary outcomes were developed using random effects models to assess heterogeneity. The risk of bias in included studies was assessed with the RoB 2 and ROBINS-I tools. There were 13 studies involving 2009 patients that were included, revealing a significantly higher mean number of harvested LNs in the CME group (MD: 2.55; 95% CI: 0.25-4.86; 95%; p = 0.033). The CME group also experienced significantly lower intraoperative blood loss, a lower length of stay, and a shorter operative time. Three studies showed a serious risk of bias, and between-study heterogeneity was mostly moderate or high. Radical gastrectomy with CME may offer a safe and more radical lymphadenectomy, but long-term outcomes and the applicability of this technique in the West are still to be proven.

Conversion Strategy in Left-Sided RAS/BRAF Wild-Type Metastatic Colorectal Cancer Patients with Unresectable Liver-Limited Disease: A Multicenter Cohort Study.

Colorectal cancer (CRC) patients frequently develop liver metastases. Different treatment strategies are available according to the timing of appearance, the burden of metastatic disease, and the performance status of the patient. Systemic treatment (ST) represents the cornerstone of metastatic disease management. However, in select cases, combined ST and surgical resection can lead to remarkable survival outcomes. In the present multicentric cohort study, we explored the efficacy of a conversion strategy in a selected population of left-sided RAS/BRAF wild-type CRC patients with liver-limited metastatic disease. Methods: The primary endpoint was to compare survival outcomes of patients undergoing ST not leading to surgery, liver resection after conversion ST, and hepatic resection with perioperative ST. Furthermore, we explored survival outcomes depending on whether the case was discussed within a multidisciplinary team. Results: Between 2012 and 2020, data from 690 patients respecting the inclusion criteria were collected. Among these, 272 patients were deemed eligible for the analysis. The conversion rate was 24.1% of cases. Fifty-six (20.6%) patients undergoing surgical resection after induction treatment (i.e., ultimately resectable) had a significant survival advantage compared to those receiving systemic treatment not leading to surgery (176 pts, 64.7%) (5-year OS 60.8% and 11.7%, respectively, Log Rank test p < 0.001; HR = 0.273; 95% CI: 0.16−0.46; p < 0.001; 5-year PFS 22.2% and 6.3%, respectively, Log Rank test p < 0.001; HR = 0.447; 95% CI: 0.32−0.63; p < 0.001). There was no difference in survival between ultimately resectable patients and those who had liver resection with perioperative systemic treatment (potentially resectable­40 pts) (5-year OS 71.1%, Log Rank test p = 0.311. HR = 0.671; 95% CI: 0.31−1.46; p = 0.314; 5-year PFS 25.7%, Log Rank test p = 0.305. HR = 0.782; 95% CI: 0.49−1.25; p = 0.306). Conclusions: In our selected population of left-sided RAS/BRAF wild-type colorectal cancer patients with liver-limited disease, a conversion strategy was confirmed to provide a survival benefit. Patients not deemed surgical candidates at the time of diagnosis and patients judged resectable with perioperative systemic treatment have similar survival outcomes.

Preoperative indocyanine green (ICG) clearance test: Can we really trust it to predict post hepatectomy liver failure? A systematic review of the literature and meta-analysis of diagnostic test accuracy.

INTRODUCTION: Post hepatectomy liver failure (PHFL) still represents a potentially fatal complication after major liver resection. Indocyanine green (ICG) clearance test represents one of the most widely adopted examinations in the preoperative workup. Despite a copious body of evidence which has been published on this topic, the role of ICG in predicting PHLF is still a matter of debate. METHODS: A systematic review of the literature was conducted according to PRISMA-DTA guidelines. The primary outcome was the assessment of diagnostic performance of ICG in predicting PHLF. The secondary outcome was the mean ICGR15 and ICGPDR in patients experiencing PHLF. RESULTS: Seventeen studies, for a total of 4852 patients, were deemed eligible. Sensitivity ranged from 25% to 83%; Specificity ranged from 66.1% to 93.8%. ICG clearance test pooled AUC was 0.673 (95% CI: 0.632-0.713). The weighted mean ICGR15 was 11 (95%CI: 8.3-13.7). The weighted mean ICGPDR was 16.5 (95%CI: 13.3-19.8). High risk of bias was detected in all examined domains. CONCLUSIONS: Preoperative ICG clearance test alone may not represent a reliable method to predict post hepatectomy liver failure. Its diagnostic significance should be framed within multiparametric models involving clinical and imaging features.

Prognostic impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients: A meta-analysis of randomized controlled trials.

BACKGROUND: gastric cancer patients frequently develop peritoneal metastases (PM) with a poor long-term prognosis. A solid body of evidence underlines the beneficial role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is a lack of consensus regarding the optimal strategy in the treatment of locally advanced primary tumors with or without peritoneal metastasis. The present meta-analysis aims to assess the impact of CRS + HIPEC on survival analyzing the results of randomized studies only. METHODS: A systematic review of articles was conducted according to PRISMA guidelines. Twelve studies were included in qualitative and quantitative analysis. RESULTS: A survival benefit for patients treated with CRS + HIPEC at all time points was highlighted. However, difference in survival was significant at all time points for patients treated for prophylaxis of PM, but no difference was found when considering resection with a curative intent. The 1, 2, 3 and 5-year survival rates (SR) for patients undergoing CRS + HIPEC were 86.9%, 70.5%, 63.7% and 55.7% respectively. CRS + HIPEC for the treatment rather than prophylaxis of PM was the only predictor of a reduced 3y SR. CONCLUSIONS: CRS + HIPEC may lead to improved prognosis for patients suffering from locally advanced gastric cancer in both prophylactic and curative settings. However, due to far from negligible postoperative morbidity and mortality rates, a strict patient selection is crucial to achieve the best results. The presence of extraperitoneal disease strongly limits the indication of this kind of surgery.

Indications and outcomes of enterovesical and colovesical fistulas: systematic review of the literature and meta-analysis of prevalence.

BACKGROUND: Entero-colovesical fistula is a rare complication of various benign and malignant diseases. The diagnosis is prominently based on clinical symptoms; imaging studies are necessary not only to confirm the presence of the fistula, but more importantly to demonstrate the extent and the nature of the fistula. There is still a lack of consensus regarding the if, when and how to repair the fistula. The aim of the study is to review the different surgical treatment options, focus on surgical indications, and explore cumulative recurrence, morbidity, and mortality rates of entero-vesical and colo-vesical fistula patients. METHODS: A systematic review of the literature was conducted according to PRISMA guidelines. Random effects meta-analyses of proportions were developed to assess primary and secondary endpoints. I2 statistic and Cochran's Q test were computed to assess inter-studies' heterogeneity. RESULTS: Twenty-two studies were included in the analysis with a total of 861 patients. Meta-analyses of proportions pointed out 5, 22.2, and 4.9% rates for recurrence, complications, and mortality respectively. A single-stage procedure was performed in 75.5% of the cases, whereas a multi-stage operation in 15.5% of patients. Palliative surgery was performed in 6.2% of the cases. In 2.3% of the cases, the surgical procedure was not specified. Simple and advanced repair of the bladder was performed in 84.3% and 15.6% of the cases respectively. CONCLUSIONS: Although burdened by a non-negligible rate of complications, surgical repair of entero-colovesical fistula leads to excellent results in terms of primary healing. Our review offers opportunities for significant further research in this field. Level of Evidence Level III according to ELIS (SR/MA with up to two negative criteria).

Surgical treatment of gastric cancer liver metastases: Systematic review and meta-analysis of long-term outcomes and prognostic factors.

The prognosis of patients with metastatic gastric cancer remains dismal, with palliative treatment as standard of care. However, encouraging results have been reported for surgical resection of liver only metastatic gastric cancer in carefully selected patients. A systematic review of articles published from 2000 onwards was conducted according to PRISMA guidelines. Twenty-nine studies were included in qualitative and quantitative analysis. Meta-analysis of proportions pointed out 29.1 % 5ySR (I 2 = 39 %). The pooled weighted median of MSTs was 31.1 months. T stage > 2, metastasis greatest dimension ≥ 5 cm, the presence of multiple metastases and bilobar disease resulted among the strongest predictors of mortality. Funnel plots, Egger's tests, and P-curve analyses failed to show significant publication bias. Based on strict selection criteria and robust statistical analyses, our results show that, in very carefully selected patients without extrahepatic disease, surgical resection with curative intent may significantly improve overall survival.

Angiotensin Receptor 1 Blockers Prolong Time to Recurrence after Radiofrequency Ablation in Hepatocellular Carcinoma patients: A Retrospective Study.

Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. Aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. Data on 215 patients were reviewed. The study population was classified into three groups: 113 (52.5%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 59 (27.4%) patients treated with angiotensin-converting enzyme inhibitors (group 2) and 43 (20.1%) patients treated with sartans (group 3). Survival outcomes were analyzed using Kaplan-Meier analysis and compared with log-rank test. In the whole study population, 85.6% of patients were in Child-Pugh A-class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10-40 mm) and alpha-fetoprotein was 25 (1.1-2100) IU/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (42-51) in group 1, 51 months (42-88) in group 2, and 63 months (51-84) in group 3 (p = 0.15). Child-Pugh stage and Model for End-staging Liver Disease (MELD) score resulted as significant predictors of overall survival in multivariate analysis. Median time to recurrence was 33 months (24-35) in group 1, 41 (23-72) in group 2 and 51 months (42-88) in group 3 (p = 0.001). Number of nodules and anti-angiotensin treatment were confirmed as significant predictors of time to recurrence in multivariate analysis. Sartans significantly improved time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients but did not improve overall survival.

Comparison Between Swan-Ganz Catheter and Minimally Invasive Hemodynamic Monitoring During Liver Transplantation: Report of a Monocentric Case Series.

INTRODUCTION: The aim of the present investigation was to retrospectively evaluate the utilization of Swan-Ganz catheter during orthotopic liver transplantation as opposed to FloTrac/Vigileo in selected cases, comparing a number of clinical outcomes across postoperative hospitalization. MATERIALS AND METHODS: Before 2015 all recipients received pulmonary artery catheter (Swan-Ganz group, n = 109). After 2015 Swan-Ganz was used only if coronary artery disease or high-grade portal hypertension or Child-Pugh C were present; the remaining recipients were assigned to FloTrac/Vigileo monitoring (Mini group, n =100). A number of clinical outcomes were considered. RESULTS: Donor's Risk Index was similar between groups (median value 1.7, P = .27). Anthropometric characteristics of the recipients were similar in the 2 groups. There were no significant differences in the proportion of patients with Child-Pugh C (P = .873), coronary artery disease (P = .18), and grade of portal hypertension (P = .733). The Model for End-Stage Liver Disease score was slightly higher in the Mini group: (9 [7-11] vs 9 [8-12], Swan-Ganz vs Mini, respectively, P < .035). Swan-Ganz utilization decreased over time (92% vs 26%, Swan-Ganz vs Mini, P < .001). Upon admission to the intensive care unit, patients of the Mini group presented a higher SAPS II score with similar values of Sequential Organ Failure Assessment score. Days on mechanical ventilation were similar between groups. The incidence of graft failure was similar between groups (2% vs 5%, Swan-Ganz and Mini group respectively, P = .376). Recipients' hospital length of stay was similar (13 days [11-19] vs 14 [11-20], P < .083). CONCLUSIONS: Our data suggest that the intraoperative utilization of FloTrac/Vigileo for oncologic patients with low grade end stage liver disease is reasonably safe.

Inducing tolerability of adverse events increases sorafenib exposure and optimizes patient's outcome in advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Various grades of adverse events are associated with sorafenib and have recently been considered as a surrogate of response in patients with advanced hepatocellular carcinoma. The aim of this prospective study was to measure the efficacy of a sorafenib dose reduction regimen, adjusted on patient's tolerability, and aimed at increasing the exposure to the drug. METHODS: A total of 73/140 patients with advanced hepatocellular carcinoma receiving sorafenib developed relevant adverse events (grade ≥2) and were managed with a tolerable-adverse-event-protocol consisting of a drug stepwise dose reduction adjusted on patient's tolerability. The remaining 67 patients with toxicity grade 0-1 (minor adverse event group) were managed conventionally with just symptomatic treatment. RESULTS: Median follow-up was 7 months. By adopting the tolerable-adverse-event-protocol, 48% of patients meant to transiently or definitively interrupt the drug were kept on treatment. Macrovascular invasion with/out extra-hepatic spread (HR = 1.9, 95% CI: 1.3-2.8; P = 0.001) and sorafenib exposure <2 months (HR = 4, 95% CI: 2.5-6.4; P < 0.0001) were independently related to a worse survival. Overall disease control rate, time to progression and survival were: 63.5%, 6 and 9.1 months respectively. The tolerable-adverse-event-protocol group experienced a more favourable outcome with respect to the minor adverse event group as for disease control rate (78% vs. 48%: P < 0.0001), time to progression (9.5 vs. 3 months; HR = 0.3, 95% CI: 0.2-0.5, P < 0.0001) and survival (12.5 vs. 5.7 months; HR = 0.4, 95% CI: 0.3-0.6; P < 0.0001). CONCLUSIONS: In patients with advanced hepatocellular carcinoma, sorafenib dose adjustments based on inducing tolerability of relevant adverse events prolong drug exposure and maximize survival.

Transhepatic anterior approach to the inferior vena cava in large retroperitoneal tumors resected en bloc with the right liver lobe.

BACKGROUND: The operative approach to large retrohepatic tumors can be challenging because of the difficulty in exposing the inferior vena cava (IVC) and controlling bleeding. The anterior approach to the IVC associated with the hanging maneuver for liver transection, originally described in large hepatic tumors, may also facilitate removal of large masses set behind the liver. METHODS: A prospective cohort of 10 patients with large retrohepatic tumors involving the IVC was selected according to restrictive criteria (ie, single low-grade tumor, sufficient liver remnant, normal hepatic function, absence of cholestasis, and symptoms secondary to lower vena cava obstruction). In all cases, the anterior approach and the hanging maneuver were applied intentionally to expose the IVC without any liver mobilization. Depending on tumor invasiveness, either IVC-preserving (n = 7) or IVC-removing (n = 3) strategies were applied. Our aim was to assess the safety of the technique and the possible benefits for patient outcome. RESULTS: The cohort represented less than 1% of a series of 1,168 major hepatectomies performed in our unit between 2005 and 2011. The median age of the patients was 58; adrenal tumors and retroperitoneal sarcomas accounted for 70% of the series. Total vascular liver exclusion was necessary in 3 patients. Median operative time was 420 min. R0 resection was obtained in all cases, with no mortality and 40% overall morbidity. Overall survival was 83% at 5 years. CONCLUSION: The transhepatic, anterior approach to the IVC is a safe procedure that improves vascular control, facilitates vein repair or reconstruction, and allows potentially curative resection of large retrohepatic tumors. This approach should be the preferred choice to be adopted in properly selected patients.

Comparative efficacy of sorafenib versus best supportive care in recurrent hepatocellular carcinoma after liver transplantation: a case-control study.

BACKGROUND & AIMS: The efficacy of sorafenib in the post-liver transplantation (LT) setting has been scarcely studied. The aim of this study was to evaluate the efficacy of sorafenib, compared to best supportive care (BSC), in two cohorts of patients which presented with hepatocellular carcinoma (HCC) recurrence after LT. METHODS: Data from patients who developed presentation or progression of HCC recurrence after LT not amenable to surgical/locoregional treatments (untreatable presentation/progression, UP) were retrieved. The cohort of patients receiving sorafenib starting from 2007 was compared to that of patients receiving BSC in the previous era. Disease outcome was investigated in terms of survival from recurrence or from UP by means of univariate and multivariate Cox regression models with event times left-truncated at the date of UP. RESULTS: Of a total of 39 patients, 24 received BSC and 15 sorafenib. The two groups were well matched at baseline, with time-related imbalances regarding mTOR-based immunosuppression and median time from LT to recurrence, significantly higher in the sorafenib group. Patients' outcome in the sorafenib group was significantly improved (median survival from recurrence 21.3 vs.11.8 months, HR=5.2, p=0.0009; median survival from UP 10.6 vs. 2.2 months, HR=21.1, p<0.0001). The only factor associated with survival after HCC recurrence in multivariate analysis was treatment with sorafenib (HR=4.0; p=0.0325). No severe adverse event was registered in this post-LT setting. CONCLUSIONS: Although the use of historical controls weakens final interpretation, sorafenib seems to be associated with an acceptable safety profile and benefit in survival in HCC patients suffering recurrence after LT.

The challenges of liver transplantation for hepatocellular carcinoma on cirrhosis.

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and liver transplantation (LT) has potentials to improve survival for patients with HCC. However, expansion of indications beyond Milan Criteria (MC) and use of bridging/downstaging procedures to convert intermediate-advanced stages of HCC within MC limits are counterbalanced by graft shortage and increasing use of marginal donors, partially limited by the use of donor-division protocols applied to the cadaveric and living-donor settings. Several challenges in technique, indications, pre-LT treatments and prioritization policies of patients on the waiting list have to be precised through prospective investigations that have to include individualization of prognosis, biological variables and pathology surrogates as stratification criteria. Also, liver resection has to be rejuvenated in the general algorithm of HCC treatment in the light of salvage transplantation strategies, while benefit of LT for HCC should be determined through newly designed composite scores that are able to capture both efficiency and equity endpoints. Innovative treatments such as radioembolization for HCC associated with portal vein thrombosis and molecular targeted compounds are likely to influence future strategies. Accepting this challenge has been part of the history of LT and will endure so also for the future.

Personalized molecular targeted therapy in advanced, recurrent hepatocellular carcinoma after liver transplantation: a proof of principle.

BACKGROUND & AIMS: The advent of molecular medicine that targets specific pathways is changing the therapeutic approach to hepatocellular carcinoma. For several aberrantly activated pathways in hepatocarcinoma, surrogate markers of activation can be assessed by immunohistochemistry, although associations with in vivo response to targeted therapies are still lacking. METHODS: A patient, who presented with hepatic and extra-hepatic hepatocarcinoma recurrence 11 years after liver transplantation, was assessed for beta-catenin, pERK, and pS6 in primary and secondary tumor specimens, in order to define a possible activation of the Wnt, Ras/MAPK and Akt/mTOR pathways and design a personalized targeted therapy in absence of alternative treatment options. Moreover, mutation analysis of the beta-catenin gene (CTNNB1) and DNA microsatellite analyses were performed. RESULTS: The identification of the same mutation in the beta-catenin gene, as well as the same microsatellite pattern in tumor tissues taken 11 years apart, proved that the observed hepatocarcinoma was a true recurrence. Nuclear beta-catenin and pS6 in tumor cells were positive, whereas pERK was positive only in the peritumoral endothelium. This pattern of immunohistochemistry, after failure of sorafenib alone, lead to the choice to add the mTOR inhibitor, everolimus, to sorafenib. Three months later a 50% tumor reduction was observed, and after 6 months a further reduction of tumor vital components was confirmed, while a grade II gastrointestinal bleeding episode occurred. CONCLUSIONS: A personalized approach aimed to treat recurrent hepatocarcinoma is possible through analysis of tumoral molecular pathways. Partial success of the selected combination of sorafenib and everolimus supports the pivotal role of mTOR signalling and highlights the importance of reliable biomarkers to route the best molecular-based therapeutic options in HCC.