Predictors of Long-Term Outcomes After Liver Transplantation for Unresectable Metastatic Neuroendocrine Tumors.

BACKGROUND Malignant and benign neuroendocrine tumors (NET) share many histopathological features. Liver transplantation (LT) is one of the liver-directed therapies for neuroendocrine liver metastases (NELM). The aim of this study was to determine the outcomes of patients undergoing LT for NELM. MATERIAL AND METHODS This was a retrospective study that included 19 patients who underwent LT for unresectable NELM between December 1989 and December 2022 in the Department of General, Transplant, and Liver Surgery of the Medical University of Warsaw. Kaplan-Meier estimator and Cox proportional hazards regression were used for statistical analyses. RESULTS The primary tumor was located most frequently in the pancreas. The median follow-up was 72.5 months. The overall survival (OS) was 94.7%, 88.0%, 88.0%, 70.4%, and 49.3% after 1, 3, 5, 10, and 15 years, respectively. Accordingly, the recurrence-free survival (RFS) rates were 93.8%, 72.9%, 64.8%, 27.8%, and 27.8% after 1, 3, 5, 10, and 15 years, respectively. Ki-67 index ≥5% was found as a risk factor for both worse OS (hazard ratio (HR) 7.13, 95% confidence intervals (95% CI) 1.32-38.63, P=0.023) and RFS (HR 13.68, 95% CI 1.54-121.52, P=0.019). Recipient age ≥55 years was a risk factor for worse RFS (P=0.046, HR 5.47, 95% CI 1.03-29.08). Multivariable analysis revealed Ki-67 ≥5% as the sole independent factor for worse OS (HR 13.78, 95% CI 1.48-128.56, P=0.021). CONCLUSIONS Patients with unresectable NELM achieve great OS and satisfying RFS after LT. The risk factors associated with worse outcomes are attributed to primary tumor aggressiveness.

Stapled Anastomosis for Side-to-Side Cavo-Cavostomy in Orthotopic Liver Transplantation.

In liver transplantation, a side-to-side anastomosis is one of the commonly performed techniques of the inferior vena cava reconstruction. The authors report a case of an application of an endoscopic vascular linear stapler for a side-to-side caval anastomosis during deceased-donor liver transplantation. The back table procedure was performed in a standard fashion for a side-to-side anastomosis. The linear vascular stapler was introduced during the temporary clamping of the recipient's inferior vena cava and the anastomosis was created without problems. Suturing of the resulting defect completed the anastomosis. The use of the stapler resulted in a shortening of the anastomosis time. The staple line after the reperfusion of the graft was completely sealed. The patient's postoperative course was uncomplicated and post-operative ultrasound and computed tomography confirmed the patency of the anastomosis. This case demonstrates a novel approach to a side-to-side caval reconstruction during liver transplantation that enables a shortening of the implantation time and may improve the quality of anastomoses.

Routine End-ischemic Hypothermic Oxygenated Machine Perfusion in Liver Transplantation From Donors After Brain Death: A Randomized Controlled Trial.

OBJECTIVE: To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD). BACKGROUND: There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors. METHODS: In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 hours or SCS (1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity (ClinicalTrials. gov, NCT04812054). RESULTS: Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS groups ( P =0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P =0.18). Median Comprehensive Complication Index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS ( P =0.19). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs 6.31; P =0.037) and lower median Comprehensive Complication Index (4.35 vs 22.6; P =0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values. CONCLUSION: Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.

Skin Autofluorescence Measurement as Initial Assessment of Hepatic Parenchyma Quality in Patients Undergoing Liver Resection.

Skin autofluorescence (SAF) can detect advanced glycation end products (AGEs) that accumulate in tissues over time. AGEs reflect patients' general health, and their pathological accumulation has been associated with various diseases. This study aimed to determine whether its measurements can correlate with the liver parenchyma quality. This prospective study included 186 patients who underwent liver resections. Liver fibrosis and/or steatosis > 10% were found in almost 30% of the patients. ROC analysis for SAF revealed the optimal cutoff point of 2.4 AU as an independent predictor for macrovesicular steatosis ≥ 10% with an AUC of 0.629 (95% CI 0.538−0.721, p = 0.006), 59.9% sensitivity, 62.4% specificity, and positive (PPV) and negative (NPV) predictive values of 45.7% and 74.1%, respectively. The optimal cutoff point for liver fibrosis was 2.3 AU with an AUC of 0.613 (95% CI 0.519−0.708, p = 0.018), 67.3% sensitivity, 55.2% specificity, and PPV and NPV of 37.1% and 81.2%, respectively. In the multivariable logistic regression model, SAF ≥ 2.4 AU (OR 2.16; 95% CI 1.05−4.43; p = 0.036) and BMI (OR 1.21; 95% CI 1.10−1.33, p < 0.001) were independent predictors of macrovesicular steatosis ≥ 10%. SAF may enhance the available non-invasive methods of detecting hepatic steatosis and fibrosis in patients prior to liver resection.

Predictors of Long-Term Outcomes After Liver Transplantation Depending on the Length of Cold Ischemia Time.

BACKGROUND: Cold ischemia time (CIT) is one of the most significant variables affecting graft survival after liver transplantation. The aim of this study was to identify other predictors of worse graft survival depending on the duration of cold ischemia. METHODS: This retrospective cohort study included data of liver transplant recipients and donors in the period from 2014 to 2019. A total of 724 patients were analyzed after excluding retransplatations and urgent operations. Using receiver operating characteristic analysis, we identified CIT value which divides into 2 clinically different subgroups with respect to 5-year graft loss. Within those 2 subgroups, we performed Cox proportional hazard analysis with time to graft loss as endpoint. RESULTS: The optimal cut-off point for CIT was identified as 496 minutes. Model of end-stage liver disease score, recipient body mass index, and donor sodium concentration showed no significant effect on time to graft loss in either subgroup. For 3 factors we observed a significant effect on time to graft loss in subgroup CIT ≥496 min: transfused red cell concentrate units (hazard ratio [HR] 1.05; 95% confidence interval [CI] 1.00-1.09; P = .02), transfused fresh frozen plasma units (HR 1.04; 95% CI 1.00-1.08; P = .08), and a recipient age of >60 years (HR 1.81; 95% CI 1.10-2.98; P = .02). CONCLUSIONS: Predictive ability of well-known risk factors for worse outcomes after liver transplantation depend on the length of cold ischemia.

The Effect of Early Retransplantation on Early and Late Survival After Liver Transplantation.

BACKGROUND: Early liver retransplantation after liver transplantation (LT) is the ultimate salvage procedure for irreversible graft failure. The aim of this study was to assess the impact of early retransplantation on 90-day and 5-year patient survival. METHODS: This retrospective cohort study included 2185 patients after LT in the period between 1997 and 2019. First, the patients undergoing first retransplantation within 6 months after initial LT were compared with naïve LT patients for early mortality (within 90 days). Second, to assess late survival, the patients who had retransplantation and survived at least 90 days post LT were compared with naïve LT patients for 5-year overall survival. The patients undergoing late retransplantation (>6 months) were excluded from analyses. Fisher's exact test was used to compare groups for early survival and log-rank test for late survival. RESULTS: The cumulative 1-, 3-, and 5-year overall survival was 87.0%, 79.9%, 75.0%, respectively, and did not differ significantly between the groups. The patients undergoing early retransplantation had lower 90-day survival rate of 89.2% as compared to 95.7% for naïve LT patients (P < .001). CONCLUSIONS: The early liver retransplantation has profound impact on post-LT 90-day survival; however, patients who survive that period can achieve long overall survival comparable with naïve LT patients.

Early Postoperative Transaminase Activities Affecting Early and Late Liver Graft Survival.

BACKGROUND: This study aimed to examine the effect of transaminases' activities in the first posttransplant day on early (90-day) and late (5-year) graft survival. METHODS: This retrospective cohort study included 612 patients after liver transplantation (LT) in the period between 2015 and 2019. Patients with acute liver failure and with vascular complications after LT were excluded. The natural logarithms of alanine transaminase (ALT) and aspartate transaminase (AST) were used for analyses using the logistic regression and Cox proportional hazards regression models. The optimal cut-off point for transaminases was determined using receiver operating characteristic curves. The 5-year graft survival was calculated after previously excluding the patients with 90-day graft loss. RESULTS: The ALT and AST were risk factors for 90-day graft loss (odds ratio 2.16; 95% CI 1.45-3.23; P < .001 and 2.23; 95% CI 1.55-3.19; P < .001, respectively). The optimal cut-off for ALT and AST in prediction of 90-day graft loss was ≥1030 and ≥3899 U/L; area under the curve 0.694 (95% CI 0.602-0.786; P < .001), with 11.3% and 97.1% positive predictive value (PPV) and negative predictive (NPV) value, and 0.673 (95% CI 0.575-0.772; P < .001), with 18.4% PPV and 95.6% NPV, respectively. The activities of AST and ALT on first posttransplant day were not identified as risk factors for late graft loss (P = .924 and P = .629, respectively). CONCLUSIONS: Early post-transplant transaminase activities can be used to determine early liver graft loss; however, their utility is lost for assessing the late graft survival.

The Utility of Early Allograft Dysfunction Components in Determining 90-Day Liver Graft Survival.

BACKGROUND: Early allograft dysfunction (EAD) had been established as a useful tool to asses graft and patient survival after liver transplant. We wanted to evaluate effect of EAD components on early graft survival. METHODS: This retrospective study included 264 patients with EAD after liver transplant in the period between 2015 and 2019. The patients with retransplants were excluded from analyses. The EAD was determined with Olthoff criteria. The logistic regression model was used for analyses. The 90-day graft survival was set as a primary outcome measure. RESULTS: The main indications for transplant in the analyzed group were hepatitis C virus infection (53 patients, 20.1%), hepatitis B infection (22, 8.3%), primary sclerosing cholangitis (28, 10.1%), and alcoholic liver disease (62, 23.5%), with a median model for end-stage liver disease score of 13.5 points. The 90-day graft loss occurred in 51 patients (19.3%). Each of the components used in EAD diagnosis was found to be correlated with 90-day graft loss. The bilirubin concentration on day 7 (odds ratio [OR], 3.1; 95% CI, 1.4-6.7; P < .001), international normalized ratio on day 7 (OR, 179; 95% CI, 39-815; P < .001), and the natural logarithm of alanine aminotransferase (OR, 3.1; 95% CI, 1.6-6.4) and aspartate aminotransferase (OR, 1.4; 95% CI, 0.4-4.9) predicted 90-day graft loss. CONCLUSIONS: In patients with EAD, international normalized ratio ≥ 1.6 on day 7 was the strongest predictor of early graft-loss among all EAD components.

Early results of the implementation of laparoscopic major liver resection program.

BACKGROUND: Laparoscopic liver resections offer potential benefits but may require advanced laparoscopic skills and are volume dependent. METHODS: This retrospective study included 12 patients who underwent major laparoscopic resection and 24 patients after open major liver resection for liver malignancy in the time period between September 2020 and May 2021. The primary outcomes were complications according to Clavien-Dindo classification and duration of hospital stay. RESULTS: Median duration of hospital stay in laparoscopic resection group (6 days) was significantly shorter than in open resection group (8 days) (p = 0.046). Complications classified as grade II or higher were significantly less frequent in the laparoscopic resection group (2 patients) versus open resection group (13 patients) (p = 0.031). CONCLUSIONS: Although laparoscopic major liver resections should be limited to expert hepatobiliary centers and are characterized by long learning curve, this approach may offer favorable short-term outcomes even during launching a new program.

Skin autofluorescence as a novel predictor of acute kidney injury after liver resection.

BACKGROUND: Skin autofluorescence (SAF) reflects accumulation of advanced glycation end-products (AGEs). The aim of this study was to evaluate predictive usefulness of SAF measurement in prediction of acute kidney injury (AKI) after liver resection. METHODS: This prospective observational study included 130 patients undergoing liver resection. The primary outcome measure was AKI. SAF was measured preoperatively and expressed in arbitrary units (AU). RESULTS: AKI was observed in 32 of 130 patients (24.6%). SAF independently predicted AKI (p = 0.047), along with extent of resection (p = 0.019) and operative time (p = 0.046). Optimal cut-off for SAF in prediction of AKI was 2.7 AU (area under the curve [AUC] 0.611), with AKI rates of 38.7% and 20.2% in patients with high and low SAF, respectively (p = 0.037). Score based on 3 independent predictors (SAF, extent of resection, and operative time) well stratified the risk of AKI (AUC 0.756), with positive and negative predictive values of 59.3% and 84.0%, respectively. In particular, SAF predicted AKI in patients undergoing major and prolonged resections (p = 0.010, AUC 0.733) with positive and negative predictive values of 81.8%, and 62.5%, respectively. CONCLUSIONS: AGEs accumulation negatively affects renal function in patients undergoing liver resection. SAF measurement may be used to predict AKI after liver resection, particularly in high-risk patients.

Incisional Surgical Site Infections After Mass and Layered Closure of Upper Abdominal Transverse Incisions: First Results of a Randomized Controlled Trial.

OBJECTIVE: To compare the early results of mass and layered closure of upper abdominal transverse incisions. SUMMARY OF BACKGROUND DATA: Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking. METHODS: This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727). RESULTS: A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13-0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12-0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P <0.001) with median closure times of 27.5 and 25.0 minutes (P =0.044) for layered and mass closures, respectively. CONCLUSIONS: Layered closure of upper abdominal transverse incisions should be preferred due to lower risk of incisional-SSIs and higher SWLR, despite clinically irrelevant longer duration.

Long-Term Effects of Pedicle Clamping during Major Hepatectomy for Colorectal Liver Metastases.

The use of the Pringle maneuver (PM) varies widely among surgical departments. Its use depends on the operator and type of liver resection. The aim of this study was to determine the impact of the PM on patient outcomes when undergoing major liver resections. This retrospective study comprised 179 colorectal liver metastasis patients from two liver centers from Leeds and Warsaw. Only right or right extended hepatectomies with negative oncological margins were included. The primary outcome measure was the 5-year overall survival (OS). The PM was applied during 60 (33.5%) major hepatectomies included in the study and was associated with a higher peak 3-day postoperative bilirubin concentration (p = 0.002), yet not with the peak 3-day alanine aminotransferase activity (p = 0.415). The 5-year OS after liver resections with the PM and without the PM were 55.0% and 33.4%, respectively (p = 0.019). Following stratification by the Tumor Burden Score, after resections with the use of the PM, superior survival was particularly found in the subgroup of patients at intermediate risk of recurrence (p = 0.004). However, the use of the PM had no significant effect on the 5-year overall survival following adjustment for the confounding effect of the carcinoembryonic antigen concentration (p = 0.265). The use of the PM had no negative effects on the long-term outcomes in patients undergoing major, oncologically radical liver resections for colorectal metastases.

Analysis of Patients With Incidental Perihilar Cholangiocarcinoma: An Old and a Persistent Burden for Liver Transplantation.

BACKGROUND: Selected patients with unresectable perihilar cholangiocarcinoma (p-CCA) are now considered as candidates for liver transplant, provided they fulfill a strict perioperative treatment and staging protocol. The aim of this study was to examine the outcomes of patients after liver transplant with incidental p-CCA found in the liver explants. METHODS: A cohort of 10 patients with incidental p-CCA after liver transplant in the period between 1994 and 2019 was included in this retrospective analysis. All patients with this diagnosis were scheduled for transplant because of primary sclerosing cholangitis. The primary and secondary endpoints comprised patient's death and tumor recurrence, respectively, assessed over a 5-year postoperative period. RESULTS: Patient median age was 35 years (range, 32-42 years). Median size of the tumor was 3.0 cm (range, 2.5-4.0 cm). Five patients (50%) had metastases to local lymph nodes. Overall survival was 100%, 37.5%, and 18.8% after the first, third, and fifth postoperative year, respectively, with median survival of 21 months. Patient age (P = .827), R1 resection status (P = .144), tumor diameter (P = .432), and presence of lymph node metastases (P = .663) were not significantly associated with overall survival. Recurrence-free survival was 60.0% after the first postoperative year and 22.5% after the third and fifth postoperative years, with median recurrence-free survival of 13.6 months. No significant predictors of tumor recurrence were found. CONCLUSIONS: Incidental p-CCA in patients with primary sclerosing cholangitis undergoing liver transplant is associated with universally very high risk of postoperative tumor recurrence and short expected survival.

Unsatisfactory Long-term Results of Liver Transplant in Patients With Intrahepatic Cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is the primary liver tumor forming from the biliary epithelium. Two major subtypes of this disease are distinguished because of the initial location: the extra- and intrahepatic form. The latter disease is currently a controversial indication for liver transplant (LT). The aim of this study was to evaluate the outcomes of LT of patients with intrahepatic cholangiocarcinoma. METHODS: Based on postoperative histopathologic examination of the explanted liver, 8 patients with intrahepatic cholangiocarcinoma were identified from all LT recipients in the period between 1994 and 2019 and included in this retrospective cohort study. Four of the patients received transplants with a preoperative diagnosis of hepatocellular carcinoma; the remaining tumors were incidental findings. Patient survival was the primary outcome measure. RESULTS: Six recipients had solitary lesion with a maximum tumor diameter of 6 cm. The median carbohydrate antigen 19-9 concentration prior to LT was 52.3 U/mL. The overall survival was 75.0%, 37.5%, and 25% after the first, third, and fifth year, respectively, with a median survival of 18 months. Age (P = .758), carbohydrate antigen 19-9 (P = .282), largest tumor size (P = .862), and the sum of the number of lesions and diameter of the largest tumor (P = .530) were not significantly associated with overall survival. Recurrence-free survival was 71.4% after 1 year and 28.6% after 3 and 5 years. Correspondingly, no significant predictors of worse recurrence-free survival were found. CONCLUSIONS: Intrahepatic cholangiocarcinoma remains associated with a very high risk of recurrence and dismal survival after LT irrespective of macroscopic disease burden.

A Comparison of Intrathecal and Intravenous Morphine for Analgesia After Hepatectomy: A Randomized Controlled Trial.

BACKGROUND: Effective analgesia is essential for patient recovery after liver resection. This study aimed to evaluate the effects of the addition of preoperative intrathecal morphine to multimodal intravenous analgesia in patients undergoing liver resection. METHODS: In this single-blind randomized controlled trial, patients undergoing liver resection were randomly assigned to the patient-controlled analgesia with (ITM-IV) or without (IV) preoperative intrathecal morphine groups. All patients received acetaminophen and dexketoprofen. The primary outcome was pain severity at rest over three postoperative days, assessed using the numerical rating scale (NRS). RESULTS: The study included 36 patients (18 in each group). The mean maximum daily NRS scores over the first three postoperative days in the ITM-IV and IV groups were 1.3, 1.1, and 0.3 and 1.6, 1.1, and 0.7, respectively (p = 0.580). No differences were observed in pain severity while coughing, with corresponding scores of 2.8, 2.1, and 1.1, respectively, in the ITM-IV group and 2.3, 2.2, and 1.5, respectively, in the IV group (p = 0.963). Proportions of patients reporting clinically significant pain at rest and while coughing were 11.1% and 44.4%, respectively, in the ITM-IV group, and 16.7% and 44.4%, respectively, in the IV group (both p > 0.999). Cumulative morphine doses in the ITM-IV and IV groups were 26 mg and 17 mg, respectively (p = 0.257). Both groups also showed similar time to mobilization (p = 0.791) and solid food intake (p = 0.743), sedation grade (p = 0.584), and morbidity (p = 0.402). CONCLUSIONS: Preoperative intrathecal morphine administration provides no benefits to multimodal analgesia in patients undergoing liver resection. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov Identifier: NCT03620916.

Hepatic Epithelioid Hemangioendothelioma: A Rare Disease With Favorable Outcomes After Liver Transplantation.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor with indolent behavior in terms of malignancy. The treatment of choice is either resection in the case of resectable lesions or liver transplantation (LT) for the disseminated intrahepatic form. The aim of this study was to investigate the outcomes of patients with HEHE treated by LT. MATERIAL AND METHODS: There were 18 patients with HEHE who underwent LT between 2002 and 2018 included in this retrospective study. The study group was comprised of young recipients (median age of 39 years) and mainly women (15 of 18; 83.3%). Two recipients had concomitant tumors of epithelioid hemangioendothelioma in the liver and lungs prior to LT. The survival probability was calculated using the Kaplan-Meier estimator. RESULTS: According to histopathological data, none of the patients had a macrovascular invasion. In 4 patients (22.2%), the disease had spread to the hilar lymph nodes. The maximum diameter of the tumor in the studied group was 18 cm. The survival probability after 1, 5, and 15 years was 94.0%, 82.6%, and 41.3%, respectively. No disease recurrence was observed during a median follow-up of 65.9 months. CONCLUSION: Liver transplantation provides favorable outcomes for selected patients with a hepatic form of epithelioid hemangioendothelioma.

Shadows Behind Using Simple Risk Models in Selection of Hepatocellular Carcinoma Patients for Liver Transplantation.

OBJECTIVE: To assess the potential influence of replacing Milan criteria with simple risk scores on outcomes of hepatocellular carcinoma (HCC) patients undergoing liver transplantation. SUMMARY BACKGROUND DATA: Several risk scores combining morphological and biological features were recently proposed for precise selection of HCC patients for transplantation. METHODS: This retrospective study included 282 HCC liver transplant recipients. Recurrence-free survival (RFS), the primary outcome measure, was evaluated according to Metroticket 2.0 model and French AFP model with Milan criteria serving as benchmark. RESULTS: Patients were well stratified with respect to RFS by Milan criteria, Metroticket 2.0 criteria, and AFP model cut-off ≤2 points (all P < 0.001) with c-statistics of 0.680, 0.695, and 0.681, respectively. Neither Metroticket 2.0 criteria (0.014, Z = 0.023; P = 0.509) nor AFP model (-0.014, Z = -0.021; P = 0.492) provided significant net reclassification improvement. Both patients within the Metroticket 2.0 criteria and AFP model ≤2 points exhibited heterogeneous recurrence risk, dependent upon alpha-fetoprotein (P = 0.026) and tumor number (P = 0.024), respectively. RFS of patients beyond Milan but within Metroticket 2.0 criteria (75.3%) or with AFP model ≤2 points (74.1%) was inferior to that observed for patients within Milan criteria (87.1%; P = 0.067 and P = 0.045, respectively). Corresponding microvascular invasion rates were 37.2% and 50.0%, compared with 13.6% in patients within Milan criteria (both P < 0.001). Moreover, Milan-out status was associated with significantly higher recurrence risk in subgroups within Metroticket 2.0 criteria (P = 0.021) or AFP model ≤2 points (P = 0.014). CONCLUSION: Utilization of simple risk scores for liver transplant eligibility assessment leads to selection of patients at higher risk of posttransplant HCC recurrence.

Prognostic Relevance of a Complete Pathologic Response in Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: A complete pathologic response (CPR) after neoadjuvant treatment is reported to be associated with an exceptionally low risk of recurrence after liver transplantation for hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic role of CPR in liver transplantation for HCC. METHODS: This retrospective cohort study was based on 222 HCC transplant recipients. Incidence of recurrence and survival at 5 years were the primary and secondary outcome measures, respectively. Competing risk analyses were applied to evaluate recurrence incidence and its predictors. Propensity score matching was performed to compare the outcomes for patients after neoadjuvant treatment with and without CPR. RESULTS: Neoadjuvant treatment was performed for 127 patients, 32 of whom achieved CPR (25.2%). Comparison of baseline characteristics showed that the patients with CPR were at lowest baseline recurrence risk, followed by treatment-naïve patients and patients without CPR. Adjusted for potential confounders, CPR did not have any significant effects on tumor recurrence. No significant net reclassification improvement was noted after addition of CPR to existing criteria. Neoadjuvant treatment without CPR was associated with increased risk of recurrence in subgroups within the Milan criteria (p = 0.016), with alpha-fetoprotein concentration (AFP) model not exceeding 2 points (p = 0.021) and within the Warsaw criteria (p = 0.007) compared with treatment-naïve patients who were at risk similar to those with CPR. The 5-year incidences of recurrence in propensity score-matched patients with and without CPR were respectively 14.0% and 15.9% (p = 0.661), with corresponding survival rates of 73.2% and 67.4%, respectively (p = 0.329). CONCLUSIONS: The findings showed that CPR is not independently associated with long-term outcomes after liver transplantation for HCC.

Fulminant liver failure following a marathon: Five case reports and review of literature.

BACKGROUND: The growing popularity of marathon and half-marathon runs has led to an increased number of patients presenting with exertion-induced heat stroke. Mild hepatic involvement is often observed in these patients; however, fulminant liver failure may occur in approximately 5% of all cases. Liver transplantation is a potentially curative approach for exertion-induced liver failure, although there is a lack of consensus regarding the criteria and optimal timing of this intervention. CASE SUMMARY: This paper describes 5 patients (4 men and 1 woman) who were referred to the department where this study was performed with the diagnosis of exertion-induced acute liver failure. Three patients underwent liver transplantation, 1 recovered spontaneously, and 1 patient died on day 11 following the exertion. CONCLUSION: Exertion-induced heat stroke may present as fulminant liver failure. These patients may recover with conservative treatment, may require liver transplantation, or may die. No definitive criteria are available to determine patient suitability for a conservative vs surgical approach.

Extremes of Liver Transplantation for Hepatocellular Carcinoma.

The aim of this retrospective observational study was to evaluate outcomes of patients with extremely advanced hepatocellular carcinoma (HCC) after liver transplantation. A total of 285 HCC patients after liver transplantation were screened for eligibility based on either intrahepatic dissemination (≥10 tumors) or macrovascular invasion. Tumor recurrence was the primary end-point. The study cohort comprised 26 patients. Median recurrence-free survival was 23.2 months with hepatitis B virus (HBV) infection (p = 0.038), higher AFP model score (p = 0.001), prolonged graft ischemia (p = 0.004), and younger donor age (p = 0.016) being significant risk factors. Median recurrence-free survival of HBV-negative and HBV-positive patients was 29.8 and 9.3 months, respectively (p = 0.053). In patients with macrovascular invasion, recurrence-free survival at 3 years was 46.3% with no specific predictors. Tumor size (p = 0.044), higher AFP model score (p = 0.019), prolonged graft ischemia (p = 0.016), and younger donor age (p = 0.041) were significant risk factors in patients with intrahepatic dissemination. Superior 3-year outcomes were observed in patients with intrahepatic dissemination and tumor size <3.5 cm (83.3%, p = 0.027) and HBV-negative patients with ischemia <9.7 h (85.7%, p = 0.028). In conclusion, patients with extremely advanced HCCs are remarkably heterogeneous with respect to their profile of tumor recurrence risk. This heterogeneity is largely driven by factors other than standard predictors of post-transplant HCC recurrence.