Whole liver transplantation in children under 10 kg: How to minimize the high risks of a still challenging procedure.

BACKGROUND: Whole liver transplantation in infants <10 kg is a rare procedure with moderate outcomes (67%-79% graft survival at 1 year) and high rates of vascular complications (hepatic artery thrombosis 5-26%). METHODS: Retrospective single-center analysis of whole liver transplantation in infants <10 kg and systematic review of the literature focused on survival rates and surgical complications. RESULTS: Between January 2005 and December 2020, 175 liver transplantations in 173 children were performed at our center. A total of 92 (53%) children weighed less than 10 kg; 19 (21%) of them underwent WLT and constitute the study population. Median age of the recipients was 10 months (21 days-24 months) and median body weight 6.5 (3.1-9.8) kg. Median age of the donors was 5 (1-84) months and median body weight 6.1 (4-21) kg. Median donor-to-recipient body weight ratio was 1.2 (range: 0.6-4.5). Postoperatively, neither hepatic artery nor portal vein thrombosis occurred. A biliary complication occurred in 4 cases: 1 bile leak (early), 3 anastomotic stenoses (1 delayed and 2 late), and 1 non-anastomotic stenosis (late). Patient survival rate at 1, 5, and 10 years was 100%, 92%, and 92%, respectively. Overall, death-censored graft survival after 1, 5, and 10 was 100%. CONCLUSION: Our results are excellent in terms of complications and graft and patient survival. This involves not only high-end surgical performance but also close interdisciplinary perioperative cooperation based on strong standard operating procedures and mainly focused on fluid management, hemostasiology, and strict monitoring of vessel patency.

MicroRNA-101 inhibits human hepatocellular carcinoma progression through EZH2 downregulation and increased cytostatic drug sensitivity.

BACKGROUND & AIMS: Oncogene polycomb group protein enhancer of zeste homolog 2 (EZH2) has been proposed to be a target gene of putative tumor suppressor microRNA-101 (miR-101). The aim of our study was to investigate the functional role of both miR-101 and EZH2 in human hepatocellular carcinoma (HCC). METHODS: MiR-101 and EZH2 expressions were evaluated in tumor tissues of 99 HCC patients and 7 liver cancer cell lines by real-time PCR. Luciferase reporter assay was employed to validate whether EZH2 represents a target gene of miR-101. The effect of miR-101 on HCC growth as well as programmed cell death was studied in vitro and in vivo. RESULTS: MiR-101 expression was significantly downregulated in most of HCC tissues and all cell lines, whereas EZH2 was significantly overexpressed in most of HCC tissues and all cell lines. There was a negative correlation between expression levels of miR-101 and EZH2. Luciferase assay results confirmed EZH2 as a direct target gene of miR-101, which negatively regulates EZH2 expression in HCC. Ectopic overexpression of miR-101 dramatically repressed proliferation, invasion, colony formation as well as cell cycle progression in vitro and suppressed tumorigenicity in vivo. Furthermore, miR-101 inhibited autophagy and synergized with either doxorubicin or fluorouracil to induce apoptosis in tumor cells. CONCLUSION: Tumor suppressor miR-101 represses HCC progression through directly targeting EZH2 oncogene and sensitizes liver cancer cells to chemotherapeutic treatment. Our findings provide significant insights into molecular mechanisms of hepatocarcinogenesis and may have clinical relevance for the development of novel targeted therapies for HCC.

Calcineurin inhibitors in liver transplantation - still champions or threatened by serious competitors?

Current strategies for immunosuppression in liver transplant (LT) recipients include the design of protocols targeting a more individualized approach to reduce risk factors such as renal failure, cardiovascular complications and malignancies. Renal injury in LT recipients may be often multifactorial and is associated with increased risk of post-transplant morbidity and mortality. The quest for low toxicity immunosuppressive regimens has been challenging and resulted in CNI minimization protocols or CNI withdrawal and conversion to mycophenolate mofetil (MMF) and/or mammalian target of rapamycin inhibitor-based immunosuppressive regimens. Use of antibody induction to delay CNI administration may be an option in particular in immunocompromized, critically ill patients with high MELD scores. Protocols including MMF introduction and concomitant CNI minimization have the potential to recover renal function even in the medium and long term after LT. We review on hot topics in the prevention and management of acute and chronic renal injury in LT patients. For this purpose, we present and critically discuss results from immunosuppressive studies published in the current literature or presented at recent LT meetings.

Long-term follow-up after right hepatectomy for adult living donation and attitudes toward the procedure.

OBJECTIVES: To determine the long-term health status of donors after right hepatectomy for adult live donor liver transplantation (ALDLT). BACKGROUND: The long-term outcomes for ALDLT donors are unknown. METHODS: ALDLT donors undergoing right hepatectomy from April 1998 to June 2007 were invited to complete a questionnaire regarding health status, satisfaction (1-10/worst-best scale), self-esteem, willingness to donate again, and suggestions for improvement. In addition, donor files and cholecystectomy specimens were reviewed. Fisher's exact test, Kaplan-Meier and logistic regression analyses were performed. RESULTS: Eighty-three donors were contacted (median age: 36 years; median follow-up: 69 months). 39 (47%) were free of symptoms. The remaining 44 (53%) reported: intolerance to fatty meals and diarrhea (31%), gastroesophageal reflux associated with left liver hypertrophy (9%), incisional discomfort requiring pain medications (6%), severe depression requiring hospitalization (4%), rib pain affecting lifestyle (2%), and exacerbation of psoriasis (1%). Median satisfaction score was 8. Self-esteem diminished in 5%. Thirty-nine (47%) recommended improvements particularly more detailed informed donor consent and a centralized living donor liver registry. Seventy-eight (94%) were willing to donate again. There were no differences between donors with and without complaints with respect to: donor age, gender, early complications and follow-up time, young-to-old donation, recipient diagnosis of malignancy and death of the recipient. Noninflamed donor cholecystectomy specimens correlated with intolerance to fatty meals and diarrhea (P = 0.001). CONCLUSIONS: ALDLT donors are at risk for long-term complaints that are neither reflected nor related to early complications. This information should be included in both the donor evaluation and the ALDLT decision-making process.

"Anatomical" versus "territorial" belonging of the middle hepatic vein: virtual imaging and clinical repercussions.

BACKGROUND: Venous drainage patterns are of vital importance in live donor liver transplantation. The purpose of this study was to delineate "anatomical-topographical" and "territorial-physiologic" patterns of the middle hepatic vein (MHV) in a 3-D liver model as determined by the Pringle line and its drainage volume of the right and left hemilivers. METHODS: One hundred thirty-seven consecutive live donor candidates were evaluated by 3-D CT reconstructions and virtual hepatectomies. Based on right (R) and left (L), anatomical (A) and territorial (T) belonging patterns of the MHV, each individual was assigned to one of four possible types: type I:A(R)-T(R); type II:A(L)-T(L); type III:A(R)-T(L); type IV:A(L)-T(R). Couinaud's anatomical MHV variants A-C were subsequently included in our combined anatomical/territorial MHV belonging classification. RESULTS: The MHV showed a significant predominance of right "anatomical" (59.1%) and left "territorial" belonging patterns (65.7%). The paradoxical combinations A(R)-T(L) (type III) and A(L)-T(R) (type IV) were encountered in 36.5% and 11.7% of cases, respectively. The constellations Couinaud's A-belonging type IV and Couinaud's C-belonging type IV were predictive of right hemiliver venous congestion. CONCLUSIONS: (1) Almost half of all livers in our series had paradoxical "anatomical"/"territorial" MHV belonging patterns that placed them at risk for right and left hepatectomies. (2) The proposed combined "anatomical"/"territorial" MHV belonging types (I-IV) provide useful preoperative information. (3) Combined types III and IV as well as Couinaud's A-IV, and Couinaud's C-IV should be considered particularly risky for venous congestion in right hemiliver grafts and in extended left hepatectomies.

Efficacy, safety, and immunosuppressant adherence in stable liver transplant patients converted from a twice-daily tacrolimus-based regimen to once-daily tacrolimus extended-release formulation.

The aim of this study was to determine the efficacy, safety, and immunosuppressant adherence in 125 stable liver transplant (LT) patients converted from twice-daily tacrolimus (TAC BID) to once-daily TAC (TAC OD). Tacrolimus trough levels, laboratory parameters, metabolic disorders, selected patient reported outcomes, and adverse events were assessed. Mean TAC trough level concentration was 6.1 ± 2.3 ng/ml at study entry, decreased to 5.5 ± 2.1 ng/ml (P = 0.016) and 5.5 ± 2.2 ng/ml (P = 0.019) after 1 and 2 weeks, respectively, and tended to equal the baseline value during further follow-up. At week 1, TAC concentrations were lower in 62.4% of patients and higher in 36.0% when compared with baseline. Renal and cardiovascular risk factors remained stable and no rejection episodes occurred over 12 months. Adverse events were consistent with the safety profile known from previous studies with TAC BID. Nonadherence measured by the "Basel Assessment of Adherence Scale to Immunosuppressives" was evident in 66.4% at study entry and decreased to 30.9% postconversion (P < 0.0001). Prevalence of nonadherence at baseline was significantly higher in patients converted >2 years after LT and in those ≤60 years of age. Conversion to TAC OD is safe, enhances immunosuppressant adherence and should be accompanied by a close TAC level monitoring during the initial period.

Drainage patterns of right and accessory hepatic veins: anatomical-functional classification derived from 3-dimensional CT reconstructions.

BACKGROUND/AIMS: Inadequate knowledge of the right (RHV) and accessory (IHV) hepatic 'venous drainage' territories can lead to severe postoperative venous congestion after right graft live donor liver transplantation. The purpose of our study was to define the anatomical-functional RHV and IHV drainage territories. METHODOLOGY: One hundred and forty consecutive live liver donor candidates were evaluated by means of 3-D CT reconstructions and 3-D virtual hepatectomies. Three RHV/IHV drainage patterns were identified and 'risky' configurations for right graft resections were defined. RESULTS: Livers with 'small' IHV drainage volumes (90.1±63.2mL) had dominant type IRHV/ IHV or non-dominant type III-RHV/IHV total liver (TL) complexes. All other cases had 'large' IHV volumes (294.7±115.5mL, p<0.001) with dominant type II-RHV/IHV TL complexes. Loss of IHV drainage volume (such as with no IHV reconstruction) in these cases was associated with a 'dominance transition' from right (RHV) to middle (MHV) hepatic veins, placing the grafts at 'high risk' for venous congestion. CONCLUSIONS: Type II-RHV/IHV complexes with large IHV drainage volumes are at 'high risk' for venous congestion in live donor liver transplantation.

Prediction of late allograft dysfunction following liver transplantation by immunological blood biomarkers.

BACKGROUND: An accelerated course of hepatic fibrosis may occur in liver transplantation (LT) patients despite normal or slightly abnormal liver blood tests. AIM: To identify screening tools based on blood biomarkers to predict late allograft dysfunction in LT recipients. METHODS: 174 LT recipients were enrolled. Liver biopsy, liver functional tests, cytokine quantitation in serum, as well as soluble MHC class I polypeptide-related sequence A and B (sMICA/sMICB) and soluble UL16 binding protein 2 (sULBP2) were performed. RESULTS: Patients with late graft dysfunction had a significantly higher donor age, lower albumin level, higher alanine (ALT) and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin and alkaline phosphatase (ALP), higher sMICA, sULBP2, higher interleukin (IL) 6, interferon γ and lower IL10 in serum as compared to recipients without allograft dysfunction. In order to provide a better statistical accuracy for discriminating 5-year allograft dysfunction from other less progressive subtype of allograft injury, we established a predictive model, based on 7 parameters (serum ALP, ALT, AST, GGT, sMICA, IL6 and albumin) which provided an Area Under the Receiver Operating Characteristics (AUROC) curve of 0.905. CONCLUSIONS: Blood-based biomarkers can significantly improve prediction of late liver allograft outcome in LT patients. The new developed score comprising serum parameters, with an excellent AUROC, can be reliably used for diagnosing late allograft dysfunction in transplanted patients.

Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion.

BACKGROUND: Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion. METHODS: Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR) analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis. RESULTS: A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells. CONCLUSIONS: Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC.

The impact of 68Ga-DOTATOC positron emission tomography/computed tomography on the multimodal management of patients with neuroendocrine tumors.

OBJECTIVE: To evaluate the impact of 68Ga-DOTATOC positron emission tomography (PET)/computed tomography (CT) on the multimodal management of neuroendocrine tumors (NET). BACKGROUND: Establishment of the extent and progression of NET are necessary to decide which treatment option to choose. However, morphological imaging with CT or magnetic resonance imaging (MRI) is often inadequate in identifying the primary tumor and/or in detecting small metastatic lesions. METHODS: In total, 52 patients (27 women and 25 men) with histologically proven NET could be included in the protocol of comparison between 68Ga-DOTATOC PET/CT and CT and/or MRI. The examinations were performed in terms of tumor staging and, in some instances, also of primary tumor site identification to evaluate the patient's eligibility for treatment. Each patient presented with either CT and/or MRI performed elsewhere and consecutively underwent 68Ga-DOTATOC PET/CT in our institution. RESULTS: In all 52 patients, 68Ga-DOTATOC PET/CT demonstrated pathologically increased uptake for at least 1 tumor site, yielding a sensitivity of 100% on a patient basis. In 3 of 4 patients with unknown primary tumor site, 68Ga-DOTATOC PET/CT visualized the primary tumor region (jejunum, ileum, and pancreas, respectively) not identified on CT and/or MRI. 68Ga-DOTATOC PET/CT detected additional hepatic and/or extrahepatic metastases in 22 of the 33 patients diagnosed with hepatic metastases on CT and/or MRI. Of the 15 patients evaluated for liver transplantation, we omitted 7 (46.6%) from further screening because of evidence of metastatic deposits not seen by conventional imaging. Overall, 68Ga-DOTATOC PET/CT altered our treatment decision based on CT and/or MRI alone, in 31 (59.6%) of the 52 patients. CONCLUSIONS: In this study, 68Ga-DOTATOC PET/CT proved clearly superior to CT and/or MRI for detection and staging of NET. More important, 68Ga-DOTATOC PET/CT impacted our treatment decision in more than every second patient.

Computer-assisted surgery planning for complex liver resections: when is it helpful? A single-center experience over an 8-year period.

OBJECTIVE: The purpose of this study was (1) to compare 2-dimensional computed tomographic (2D-CT) and 3D-CT computer-assisted preoperative surgical planning, and (2) to define the indications for the latter method. BACKGROUND: The determination of functional residual liver volumes and the imaging of intrahepatic anatomy are critical when planning complex liver resections. PATIENTS AND METHODS: Prospective study of 202 consecutive patients who underwent high-risk procedures (extended right/left hepatectomies, central resections, polysegmentectomies, large atypical resections, repeated resections, and hepatectomies in the setting of abnormal liver parenchyma). Preoperative evaluation included 3D-CT computer-assisted surgical planning (3D-CASP) and conventional 2D-CT imaging. Endpoints of the study were (1) determination of resectability and (2) changes in operative strategy (resection modifications/extensions/intrahepatic vascular reconstructions). RESULTS: Thirty-four of 202 cases were considered nonresectable on the basis of both 2D and 3D imaging results. In 56 (33%) instances, 3D-CASP either changed the 2D strategy (expansion of resection, n = 40; intrahepatic vascular reconstructions, n = 13) or provided an entirely different approach (n = 3). Eleven (5.4%) cases were considered unresectable at laparotomy on the basis of poor liver quality (n = 8) or unfeasible vascular reconstructions resulting in remnants too small to sustain physiologic function (n = 3). Significant differences between resectional 2D and functional 3D remnant liver volumes were observed in extended left hepatectomies and left trisectionectomies. CONCLUSIONS: 3D-CASP was particularly helpful in patients with unconventional resection planes and in those with central left tumors. Its main advantages were the individualized inflow/outflow virtual analyses and the accurate determination of safely perfused/drained retained liver volumes.

Multicentric evaluation of a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas.

OBJECTIVE: To develop a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas (ICC). PATIENTS: Two hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing the data set from Essen University and then applied to the data sets from Mount Sinai Medical Center and Chiba University for validation. Eighteen potential prognostic factors were evaluated. Statistical analysis included multivariable regression analyses with the Cox proportional hazard model, power analysis, internal validation with structural equation modelling bootstrapping and external validation. The prognostic scoring model was based mainly in pathological and demographical variables, whereas the clinical scoring model was based mainly in radiological and demographical variables. RESULTS: Gender (P=0.0086), UICC stage (P=0.0140) and R-class (P=0.0016) were predictive of survival for the prognostic scoring model, while gender (P=0.0023), CA 19-9 levels (P=0.0153) and macrovascular invasion (P=0.0067) were predictive of survival for the clinical scoring model. Prognostic points were assigned as follows: female:male=1:2 points, UICC (I-II):UICC (III-IV)=1:2 points and R0:R1=1:2 points. Clinical points were allocated as follows: female:male=1:2 points, CA 19-9 (<100 U/ml):CA 19-9 (> or =100 U/ml)=1:2 points and no macrovascular invasion:macrovascular invasion=1:2 points. Prognostic groups with 3-4, 5 and 6 points (P=0.000001) and clinical groups with 3-4 and 5-6 points (P=0.0103) achieved statistically significant difference. CONCLUSIONS: We propose a clinical and prognostic scoring system predictive of long-term survival after surgical resections for ICC.

Minimally invasive versus open esophagectomy: meta-analysis of outcomes.

BACKGROUND: A meta-analysis of the current literature was performed to compare the perioperative outcome measures and oncological impact between minimally invasive and open esophagectomy. METHODS: Using the electronic databases Medline, Embase, Pubmed and the Cochrane Library, we performed a meta-analysis pooling the effects of outcomes of 1,008 patients enrolled into eight comparative studies, using classic and modern meta-analytic methods. RESULTS: Two comparisons were considered for this systematic review: (I) open thoracotomy vs. VATS/laparoscopy esophagectomy and (II) open thoracotomy vs. VATS esophagectomy. In comparison I: both procedures report equally comparable outcomes (removed lymph nodes, 30-day mortality, 3-year survival) with the exception of overall morbidity (P = 0.038; in favor of the MIE arm) and anastomotic stricture (P < 0.001; in favor of the open thoracotomy arm). In comparison II: No differences were noted between treatment arms concerning postoperative outcomes and survival. CONCLUSIONS: In summary, both arms were comparable with regard to perioperative results and prognosis. Further prospective comparative or randomized-controlled trials focusing on the oncological impact of MIE are needed.

The use of self-expanding stents in esophageal and gastroesophageal junction cancer palliation: a meta-analysis and meta-regression analysis of outcomes.

BACKGROUND: The objective of this study was to examine the impact of self-expanding stents versus locoregional treatment modalities in the setting of esophageal cancer palliation. METHODS: The present meta-analysis pooled the effects of outcomes of 1,027 patients enrolled in 16 randomized controlled trials. RESULTS: The meta-analysis revealed an advantage to the use of stents compared to locoregional modality treatments with respect to the number of patients requiring reinterventions, although the latter treatment arm had a higher 1-year survival. No difference was observed between the use of the antireflux stents and conventional stents in relieving reflux. Previous chemoradiotherapy had no impact on complications, procedural deaths, and overall patient survival. Differences in outcomes among stents were minimal. CONCLUSIONS: Conventional self-expanding stents and anti-reflux stents are equally effective. Although the risk difference for 1-year survival favoured locoregional palliative treatment modalities, the latter were associated with a higher number of patients requiring reintervention.

Does long-term ventilation with PEEP > or = 10mbar influence graft-function in patients following liver transplantation?

BACKGROUND/AIMS: Long-term positive end-expiratory pressure (PEEP) ventilation, particular with PEEP up to 15 mbar may impair graft-function in liver transplant (LT) patients. The aim of our study was to evaluate the impact of long-term high PEEP (at least 48 hours) on liver graft function. We retrospectively reviewed the records of 50 patients, who required artificial ventilation for at least 1 week with a PEEP level > or = 10mbar due to pulmonary complication caused mainly by sepsis (n = 19), pneumonia (n = 7) and lung edema associated with reperfusion syndrome or primary non-function of the graft (n = 13). Patients who required a PEEP > or = 10mbar within the first two days after transplantation (group A, n = 23) showed significant decrease of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin on day 3 and day 7 after initiation of high PEEP, whereas prothrombin time (PT) significantly increased on day 7. Group B (patients ventilated with PEEP > or = 10mbar after more than 2 days after transplantation, n = 27) showed a significant decrease of bilirubine and a significantly increase of PT on day 7. CONCLUSION: Long-term ventilation with PEEP levels of at least 10mbar does not harm graft function in patients following LT.

Corticosteroid-free immunosuppression in liver transplantation: a meta-analysis and meta-regression of outcomes.

To examine the impact of steroid withdrawal from the immunosuppression protocols in liver transplantation. The electronic databases Medline, Embase, Pubmed and the Cochrane Library were searched. Meta-analysis pooled the effects of outcomes of a total of 2590 patients enrolled into 21 randomized controlled trials (RCTs), using classic and modern meta-analytic methods. Meta-analysis of RCTs addressing patients transplanted for any indication showed no differences between corticosteroid-free immunosuppression and steroid-based protocols in most of the analyzed outcomes. More importantly, steroid-free cohorts appeared to benefit in terms of de novo diabetes mellitus development [R.R = 1.86 (1.43, 2.41)], Cytomegalovirus (CMV) infection [R.R = 1.47 (0.99, 2.17)], cholesterol levels [WMD = 19.71 (13.7, 25.7)], the number of patients that received the allocated treatment [O.R = 1.55 (1.17, 2.05)], severe acute rejection [R.R = 1.71 (1.14, 2.54)] and overall acute rejection [R.R = 1.31 (1.09, 1.58)] (when steroids were replaced in the steroid-free arm). Taking RCTs into account independently when steroids were not replaced, overall acute rejection was favoring the steroid-based arm [R.R = 0.75 (0.58, 0.98)]. Studies addressing exclusively transplanted HCV patients demonstrated a significant advantage of steroid-free protocols considering HCV recurrence [R.R = 1.15 (1.01, 1.13)], acute graft hepatitis [O.R = 3.15 (1.18, 8.40)], and treatment failure [O.R = 1.87 (1.33, 2.63)]. No unfavorable effects were observed after steroid withdrawal during short-term follow-up. On the contrary, significant advantages were documented.

R0 liver resections for primary malignant liver tumors in the noncirrhotic liver: a diagnosis-related analysis.

BACKGROUND: Primary liver cancer constitutes an increasingly malignancy in the Western world and one of the leading causes of cancer-related deaths worldwide. The purpose of this study was to evaluate and compare long-term outcomes after R0 resections in noncirrhotic livers for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 1998 and May 2006 a total of 102 patients with either ICC (n = 41, group 1) or HCC (n = 61, group 2) in the absence of cirrhosis underwent curative liver resection in our department. Demographic characteristics, operative details, perioperative complications, pathologic findings, tumor recurrence and survival were analyzed. RESULTS: Gender (P = 0.007), extent of liver resection (P = 0.036), additional surgical procedures (P < 0.001) and operative morbidity (P = 0.018) differed among the two groups. Following resection, after a median follow-up of 28 months, the calculated 5-year survival was 44% and 40% for ICC and HCC, respectively (P = 0.38). The corresponding recurrence-free survival was 25% for both ICC and HCC (P = 0.66). UICC stage was found to predict overall and recurrence-free survival in both types of tumors. Multifocality in the case of ICC, and tumor differentiation and vascular invasion in the case of HCC, were predictive factors for overall and recurrence-free survival, respectively. In multivariable analyses, vascular invasion for HCC was predictive for overall and recurrence-free survival, whereas in the case of ICC significant differences were detected in the recurrence analysis for multifocality and UICC stage. CONCLUSIONS: R0 resections for both ICC and HCC result to similar long-term outcomes, which are characterized by good overall and acceptable recurrence-free survival rates.

Liberal policy in living donor liver transplantation for hepatocellular carcinoma: lessons learned.

BACKGROUND: Living donor liver transplantation (LDLT) in cases of hepatocellular carcinoma (HCC) that do not fulfil accepted tumor criteria continues to be a matter of controversy. The aim of this study was to evaluate survival and prognostic factors associated with a liberal exclusionary policy. MATERIAL AND METHODS: This is an analysis of data collected prospectively on 57 HCC patients who underwent LDLT at our institution between April 1998 and January 2007. RESULTS: Overall 3-year survival was 62%; this increased to 71% when 45-day mortality was excluded from the analysis. Age proved to be a predictor of survival irrespective of the 45-day mortality. In contrast, the Model for End stage Liver Disease (MELD) score predicted survival only when 45-day mortality was included in the analysis, while alpha fetoprotein (AFP) level predicted survival only when it was excluded. Significant cut-off values were patient age of over 60 years, MELD score above 22, and AFP level greater than 400 ng/ml. A scoring system was developed. Survival rate at 3 years--including 45-day mortality--was 72% for score =2 and 41% for score >2 (P = 0.0146). When 45-day mortality was excluded, the survival rate at 3 years was 90% for score =2 and 32% for score >2 (P = 0.00002). CONCLUSIONS: Our results could further enhance current guidelines on age, MELD score, and AFP level for patients with HCC being evaluated to undergo LDLT.

Liver transplantation, liver resection, and transarterial chemoembolization for hepatocellular carcinoma in cirrhosis: which is the best oncological approach?

The aim of the study was to evaluate our institutional experience with monotherapies for hepatocellular carcinoma (HCC) in the setting of cirrhosis. A retrospective cohort study was carried out at the tertiary care academic referral center and involved 185 consecutive HCC patients with cirrhosis and no previous treatment who underwent resection (n = 61), transarterial chemoembolization (TACE) (n = 64), or liver transplantation (LT) (n = 60). Long-term survival and survival according to the Milan criteria were the main outcomes measured. Median survival after resection, TACE, and LT was 11, 14, and 23 months, respectively. Five-year cumulative survival after resection, TACE, and LT was 23, 10, and 59%, respectively (P = 0.001). Five-year cumulative disease-free survival after resection and LT was 15% and 77%, respectively (P = 0.002). The presence of complications in the resection group (P = 0.004), MELD score (P = 0.0003), and maximum tumor diameter (P = 0.05) in the TACE group, and tumor grade (P = 0.01) and complications (P = 0.004) in the LT group were found to be independent predictors of survival. Five-year survival for patients within the Milan criteria after resection, TACE, and LT was 26, 37, and 66%, respectively. Five-year survival for patients outside the Milan criteria for patients undergoing LT was 53%. The results suggest that LT represents the best oncological treatment option for patients with HCC in the setting of cirrhosis, even for those beyond the Milan criteria. Considering the scarcity of available organs, liver resection remains the best alternative option. TACE remains a potential therapy in patients within the Milan criteria, where it may be more beneficial than resection.

Vascular and biliary anatomy of the right hilar window: its impact on recipient morbidity and mortality for right graft live donor liver transplantation.

BACKGROUND: Intrahepatic anatomic variations have been associated with both morbidity and mortality associated with live donor liver transplantation. The aim of our study was to evaluate central hilar and peripheral segmental vascular/biliary anatomy in right graft living donor liver transplantation. METHODS: From January 2003 to August 2007, three-dimensional (3D) computed tomography (CT) reconstructions and virtual 3D hepatectomies were performed in 71 consecutive right graft live liver donors. A combined two-level classification system addressing the four possible combinations of normal (N) and abnormal (A) central hilar and peripheral features based on both the existing classification and our own classification for portal (portal vein, PV), arterial (hepatic artery, HA) and biliary (bile duct, BD) systems was defined as follows: type I, N/N; type II, N/A; type III, A/N; and type IV, A/A. RESULTS: A simultaneous normal central hilar and peripheral segmental (N/N) anatomy for each system (PV, HA, BD) was found in <50% of grafts. The highest incidence of complex vascular and biliary reconstructions was observed with grafts having abnormal central (type III) or combined abnormal central/peripheral (type IV) anatomy. Central hilar arterial and biliary anomalies were predictors of morbidity by both univariable and multivariable analyses. CONCLUSIONS: Our two-level classification and 3D imaging techniques allowed a cautious surgical approach in high-risk cases. Central hilar anatomic variants of the arterial and biliary systems were associated with increased morbidity. Further randomized trials will help determine the precise extent of our observations.