Risk of venous congestion in live donors of extended right liver graft.

AIM: To investigate middle hepatic vein (MHV) management in adult living donor liver transplantation and safer remnant volumes (RV). METHODS: There were 59 grafts with and 12 grafts without MHV (including 4 with MHV-5/8 reconstructions). All donors underwent our five-step protocol evaluation containing a preoperative protocol liver biopsy Congestive vs non-congestive RV, remnant-volume-body-weight ratios (RVBWR) and postoperative outcomes were evaluated in 71 right graft living donors. Dominant vs non-dominant MHV anatomy in total liver volume (d-MHV/TLV vs nd-MHV/TLV) was constellated with large/small congestion volumes (CV-index). Small for size (SFS) and non-SFS remnant considerations were based on standard cut-off- RVBWR and RV/TLV. Non-congestive RVBWR was based on non-congestive RV. RESULTS: MHV and non-MHV remnants showed no significant differences in RV, RV/TLV, RVBWR, total bilirubin, or INR. SFS-remnants with RV/TLV < 30% and non-SFS-remnants with RV/TLV ≥ 30% showed no significant differences either. RV and RVBWR for non-MHV (n = 59) and MHV-containing (n = 12) remnants were 550 ± 95 mL and 0.79 ± 0.1 mL vs 568 ± 97 mL and 0.79 ± 0.13, respectively (P = 0.423 and P = 0.919. Mean left RV/TLV was 35.8% ± 3.9%. Non-MHV (n = 59) and MHV-containing (n = 12) remnants (34.1% ± 3% vs 36% ± 4% respectively, P = 0.148. Eight SFS-remnants with RVBWR < 0.65 had a significantly smaller RV/TLV than 63 non-SFS-remnants with RVBWR ≥ 0.65 [SFS: RV/TLV 32.4% (range: 28%-35.7%) vs non-SFS: RV/TLV 36.2% (range: 26.1%-45.5%), P < 0.009. Six SFS-remnants with RV/TLV < 30% had significantly smaller RVBWR than 65 non-SFS-remnants with RV/TLV ≥ 30% (0.65 (range: 0.6-0.7) vs 0.8 (range: 0.6-1.27), P < 0.01. Two (2.8%) donors developed reversible liver failure. RVBWR and RV/TLV were concordant in 25%-33% of SFS and in 92%-94% of non-SFS remnants. MHV management options including complete MHV vs MHV-4A selective retention were necessary in n = 12 vs n = 2 remnants based on particularly risky congestive and non-congestive volume constellations. CONCLUSION: MHV procurement should consider individual remnant congestive- and non-congestive volume components and anatomy characteristics, RVBWR-RV/TLV constellation enables the identification of marginally small remnants.

The "carving" liver partitioning technique for graft hepatectomy in live donor liver transplantation: a single-center experience.

BACKGROUND: In adult live donor liver transplantation, postoperative venous congestion of graft and remnant livers can lead to life-threatening complications. The purpose of this study was to evaluate the safety and benefits of our 3-dimensional, computed tomographic, computer-assisted donor hepatectomy using the "carving" partitioning technique. METHODS: Eighty-three consecutive adult live donor liver transplantations were performed based on data obtained from individualized preoperative 3-dimensional, computed tomographic reconstructions and virtual graft hepatectomies. RESULTS: There were 71 right and 12 left grafts. Small grafts (graft volume body weight ratio, <1.0) were used in 20 cases. We observed no clinically important differences in postoperative function between right and left grafts. Four recipients developed lethal small-for-size syndrome. Reversible small-for-size syndrome was observed in a right graft recipient and in 2 right graft donors. CONCLUSION: Preoperative 3-dimensional, computed tomographic, computer-assisted planning using virtual liver partitioning allowed for: (1) an individualized carving technique based on specific donor anatomic characteristics, (2) donor safety based on individualized patterns of venous outflow, and (3) optimized drainage of the medial area of the graft based on the preferential inclusion of the middle hepatic vein.

Computer-assisted surgical planning in adult-to-adult live donor liver transplantation: how much does it help? A single center experience.

BACKGROUND: Preoperative imaging and donor selection are cardinal components of adult-to-adult live donor liver transplantation (ALDLT). The purpose of this study was to evaluate our three-dimensional (3D) computed tomography image-derived computer-assisted surgical planning (3D CASP) in ALDLT. METHODS: Eighty-three consecutive ALDLTs (71 right and 12 left) were planned with 3D CASP. Graft, remnant, and total liver volume compliance were calculated and compared with actual intraoperative values. Computed risk analysis encompassing territorial liver mapping, functional (safely drained) volumes, and outflow congestion volumes in grafts and remnants allowed for the individualized management of the middle hepatic vein (MHV). RESULTS: Graft volume compliance was 13.5%±4.4%. Three small-for-size (SFS) grafts with lethal SFS syndrome (SFSS) had nonsignificant volume compliance with maximal graft volume-body weight ratios of less than 0.83. Seven SFS grafts with reversible or absent SFSS showed maximal graft volume-body weight ratios of 0.9 to 1.16. Significant differences were identified for (a) virtual graft and remnant congestion volumes of risky versus nonrisky MHV types (49%±6% and 34%±7% vs. 29%±8% and 33%±12%, P<0.001 and P<0.02, respectively) and (b) virtual mean functional versus surgical volumes of grafts (527±119 vs. 963±176 mL, P<0.0001) and remnants (419±182 vs. 640±213 mL, P<0.001). CONCLUSIONS: CASP allowed for (a) prevention of SFSS in extremely small grafts by predicting donor liver plasticity and (b) individualized MHV management for both donors and recipients based on functional graft/remnant volume analysis.

Liver transplantation for unresectable hepatocellular carcinoma in normal livers.

BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. METHODS: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. RESULTS: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8 cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation < 12 months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival. CONCLUSIONS: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients ≥ 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC.

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.

Hemostatic efficacy of TachoSil in liver resection compared with argon beam coagulator treatment: an open, randomized, prospective, multicenter, parallel-group trial.

BACKGROUND: The aim of this trial was to confirm previous results demonstrating the efficacy and safety of a fixed combination tissue sealant versus argon beam coagulation (ABC) treatment in liver resection. METHODS: This trial was designed as an international, multicenter, randomized, controlled surgical trial with 2 parallel groups. Patients were eligible for intra-operative randomization after elective resection of ≥ 1 liver segment and primary hemostasis. The primary end point was the time to hemostasis after starting the randomized intervention to obtain secondary hemostasis. Secondary end points were drainage duration, volume, and content. Adverse events were collected to evaluate the safety of treatments. The trial was registered internationally (Eudract number 2008-006407-23). RESULTS: Among 119 patients (60 TachoSil and 59 ABC) randomized in 10 tertiary care centers in Europe, the mean time to hemostasis was less when TachoSil was used (3.6 minutes) compared with ABC (5.0 minutes; P = .0018). The estimated ratio of mean time to hemostasis for TachoSil/ABC was 0.61 (95% confidence interval, 0.47-0.80; P = .0003). Postoperative drainage volume, drainage fluid, and drainage duration did not differ between the 2 groups. Mortality (2 vs 4 patients) and adverse reactions (24 vs 28 patients) for TachoSil versus ABC did not differ. CONCLUSION: This trial confirmed that TachoSil achieved significantly faster hemostasis after liver resection compared with ABC. Postoperative morbidity and mortality remained unchanged between both groups.

"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.

Ala499Val (C>T) and Lys939Gln (A>C) polymorphisms of the XPC gene: their correlation with the risk of primary gallbladder adenocarcinoma--a case-control study in China.

Genetic variations in the gene XPC may be associated with increased risk for gallbladder cancer (GBC). In this study, we detected two non-synonymous polymorphisms in XPC (Ala499Val and Lys939Gln) in 334 cases of GBC and 329 subjects of hospital-based age- and sex frequency-matched controls in China using a polymerase chain reaction-restriction fragment length polymorphism assay. Allelic association analysis for the two single-nucleotide polymorphisms (SNPs) showed that the risk allele T of Ala499Val was significantly associated with GBC [odds ratio (OR)=1.40, 95% confidence interval (CI): 1.11-1.76, P=0.005), with a population attributive risk of 5.3%. Logistic regression analysis revealed that Ala499Val CT heterozygote (OR=1.56, 95% CI: 1.13-2.14, P=0.002) and TT homozygote (OR=1.93, 95% CI: 1.04-3.55, P=0.048) had a significantly increased risk compared with CC homozygotes. Genetic analysis suggested that either the SNPs directly exert an effect or the linked functional gene impact of the disease trait likely follows an additive or dominant model. Gene interaction analysis demonstrated that the effects of XPC diplotypes (defined as the number of risk genotypes at the two SNP loci) were highly dependent on gallstone. The data from this case-control study indicated that XPC exonic variants contributed to the risk of GBC in this Chinese population.

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.

Hepatic venous drainage: how much can we learn from imaging studies? Anatomic-functional classification derived from three-dimensional computed tomography reconstructions.

BACKGROUND: The knowledge of "venous dominance" is essential to prevent serious venous congestion in live donor liver transplantation and extended liver resections. AIMS: The purpose of our study was to delineate our proposed anatomic-functional classification of hepatic venous drainage. METHODS: One hundred forty consecutive live liver donor candidates underwent three-dimensional computed tomography reconstructions and three-dimensional virtual hepatectomies. Five different venous dominance types were defined on drainage volumes or territories. "Risky" configurations were identified and classified. RESULTS: The right hepatic vein (RHV) was dominant for the entire liver and right hemiliver (RHH) in most (83.5%) cases irrespective of the presence of inferior (accessory) hepatic veins (IHVs). The middle hepatic vein (MHV) was dominant for the total liver (TL) in 15.5% of cases and for the RHH in 27% of cases. The left hepatic vein was almost always (92%) dominant for the left hemiliver. When associated with a large IHV drainage volume, a RHV/IHV complex dominant for the TL led to a RHH dominant MHV (mean 59.5%RHH) if the IHV was not reconstructed. CONCLUSIONS: Our proposed anatomic-functional classification provides a valuable insight into hepatic vein dominance patterns. RHH venous drainage patterns at "high risk" for venous congestion include (1) a dominant MHV for the TL and (2) a dominant RHV/IHV complex with a large IHV drainage volume.

Procalcitonin as a prognostic marker for infectious complications in liver transplant recipients in an intensive care unit.

Clinically significant infections (CSIs) are life-threatening but difficult to diagnose after liver transplantation (LTx). This study investigates the value of procalcitonin (PCT) in addition to c-reactive protein (CRP) and the leukocyte count (LC) as a prognostic marker for CSIs in LTx recipients. The clinical course of 135 LTx recipients was prospectively studied. CSIs were defined as pulmonary, bloodstream, or intra-abdominal infections. Independent risk factors for CSIs were determined by Cox proportional hazard analysis. The concordance statistics (c-statistics) were used to assess the discrimination effect of PCT. Thirty recipients (22%) experienced a CSI. They had significantly higher peak PCT (27.2 versus 12.7 ng/mL, P = 0.014) and peak CRP (13.7 versus 9.9 mg/dL, P < 0.001) and a tendency toward a higher peak LC (19.3 versus 14.2 cells/nL, P = 0.051) in comparison with recipients without CSIs. Independent risk factors for CSIs were male sex [hazard ratio (HR) = 6.4], a body mass index (BMI) < 20 kg/m(2) (versus a BMI > 25 kg/m(2), HR = 13.8), acute liver failure as an indication for LTx (HR = 7.1), a cold ischemic time > 420 minutes (HR = 3.5), and peak CRP (HR = 1.1) but not peak PCT. The addition of peak PCT marginally improved the c-statistic from 0.815 to 0.827. In conclusion, although peak PCT differed significantly between recipients with and without CSIs, it was not an independent risk factor for CSIs and added little prognostic accuracy. Interestingly, the parameters peak CRP, male sex, low BMI, acute liver failure, and long cold ischemic time were independent risk factors for CSIs. They could serve as risk stratifiers directing medical therapy in clinical practice.

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.

Deregulation of HIF1-alpha and hypoxia-regulated pathways in hepatocellular carcinoma and corresponding non-malignant liver tissue--influence of a modulated host stroma on the prognosis of HCC.

PURPOSE: The aim of this study was to elucidate the role of HIF1A expression in hepatocellular carcinoma (HCC) and the corresponding non-malignant liver tissue and to correlate it with the clinical outcome of HCC patients after curative liver resection. METHODS: HIF1A expression was determined by quantitative RT-PCR in HCC and corresponding non-malignant liver tissue of 53 patients surgically treated for HCC. High-density gene expression analysis and pathway analysis was performed on a selected subset of patients with high and low HIF1A expression in the non-malignant liver tissue. RESULTS: HIF1A over-expression in the apparently non-malignant liver tissue was a predictor of tumor recurrence and survival. The estimated 1-year and 5-year disease-free survival was significantly better in patients with low HIF1A expression in the non-malignant liver tissue when compared to those patients with high HIF1 expression (88.9% vs. 67.9% and 61.0% vs. 22.6%, respectively, p = 0.008). Based on molecular pathway analysis utilizing high-density gene-expression profiling, HIF1A related molecular networks were identified that contained genes involved in cell migration, cell homing, and cell-cell interaction. CONCLUSION: Our study identified a potential novel mechanism contributing to prognosis of HCC. The deregulation of HIF1A and its related pathways in the apparently non-malignant liver tissue provides for a modulated environment that potentially enhances or allows for HCC recurrence after curative resection.

Neurologic complications in adult living donor liver transplant patients: an underestimated factor?

Liver transplantation is the only curative treatment in patients with end-stage liver disease. Neurological complications (NC) are increasingly reported to occur in patients after cadaveric liver transplantation. This retrospective cohort study aims to evaluate the incidence and causes of NC in living donor liver transplant (LDLT) patients in our transplant center. Between August 1998 and December 2005, 121 adult LDLT patients were recruited into our study. 17% of patients experienced NC, and it occurred significantly more frequently in patients with alcoholic cirrhosis (42%) and autoimmune hepatitis (43%) as compared with patients with hepatitis B or C (9/10%, P = 0.013). The most common NC was encephalopathy (47.6%) followed by seizures (9.5%). The choice of immunosuppression by calcineurin inhibitor (Tacrolimus or Cyclosporin A) showed no significant difference in the incidence of NC (19 vs. 17%). The occurrence of NC did not influence the clinical outcome, since mortality rate, median ICU stay and length of hospital stay were similar between the two groups. Most patients who survived showed a nearly complete recovery of their NC. NCs occur in approximately 1 in 6 patients after LDLT and seem to be predominantly transient in nature, without major impact on clinical outcome.

Predictive factors of outcome in patients transplanted for hepatitis B.

BACKGROUND: This study aimed to (1) identify the variables that affect graft and patient survival in recipients transplanted for hepatitis B virus (HBV) disease; and (2) assess factors associated with an increased risk of graft cirrhosis at 5 years after liver transplantation (LT). METHODS AND RESULTS: A total of 104 chronically infected HBV patients were considered for this study and all received tacrolimus- or cyclosporine A (CSA)-based immunosuppressive regimens. The overall 5-year patient and graft survival rates were 80% and 73%, respectively. Univariate Cox proportional hazards regression analysis indicated that older recipient age and higher body mass index (BMI) at LT, LT more than or equal to 1998, arterial hypertension, hyperlipidemia, and CSA-based immunosuppression correlated with decreased patient survival. In the multivariate model, advanced recipient age, higher BMI, CSA-based immunosuppressive therapy, and increasing cold ischemia time were associated with worse patient survival. Recipient age and BMI at time of LT and posttransplant hypertriglyceridemia also affected graft survival. Log-rank analysis showed that a viral load of more than 10 copies/mL and antiviral therapy at LT, post-LT biliary complications, HBV recurrence, nucleos(t)ide analogue monoprophylaxis (without hepatitis B immunoglobulin), and short-term (< or = 1 year) mycophenolate mofetil therapy were significant risk factors for graft cirrhosis within 5 years of LT. CONCLUSION: Various recipient factors at the time of LT and post-LT virological status, antiviral prophylaxis, cholestasis, cardiovascular risk profile, and immunosuppressive regimen affect the outcome of HBV patients after LT. Prospective studies are warranted to define optimal immunosuppression for recipients transplanted for hepatitis B.

Impact of KIT and PDGFRA gene mutations on prognosis of patients with gastrointestinal stromal tumors after complete primary tumor resection.

INTRODUCTION: To investigate the impact of KIT and PDGFRA gene mutations on the prognosis of gastrointestinal stromal tumors (GIST). MATERIAL AND METHODS: Tumor tissue from 184 patients with primary GIST was submitted to mutational analysis of exons 9, 11, 13, and 17 of the KIT gene and exons 12 and 18 of the PDGFRA gene. Clinical and pathological parameters were analyzed and correlated to the risk of recurrence and disease-free survival (DFS). RESULTS AND DISCUSSION: The authors found that somatic mutations were detected in 162 tumors (88.0%). Age, clinical stage, mitotic count, and tumor size were of prognostic relevance on both univariate and multivariate analysis. Five-year DFS was 41.9%. While the presence of a KIT or PDGFRA mutation per se was not associated with tumor recurrence and/or disease-free survival, exon 11 deletion and hemizygous mutation status were both independent factors highly predictive for poor survival. CONCLUSION: The authors conclude that KIT exon 11 deletions and somatic loss of the wild-type KIT identified patients with poor prognosis. Age, clinical stage, tumor size, and mitotic count were standard clinicopathologic features that significantly influenced the prognosis. Mutation type of the mitogen receptor c-kit has a potential for predicting the course of the disease and might contribute to management individualization of GIST patients.

Prognostic impact of intrahepatic lymphatic and microvascular involvement in cases of colorectal liver metastases.

OBJECTIVE: The purpose of this study was to evaluate the effect of intrahepatic microvascular and lymphatic infiltration on survival in cases of colorectal liver metastases. MATERIALS AND METHODS: Prospectively collected data of 331 patients were analyzed for microvascular invasion (V), lymphatic infiltration (L), and resection margins (R) with respect to overall and disease-free survival. RESULTS: One-, 3-, and 5-year overall survival rates for R0 resected patients were 89%, 64%, and 39%, respectively. The corresponding survival rates for R1 resected patients were 83%, 42%, and 24% (p < 0.001). The sole presence of microvascular invasion (V1) or lymphatic infiltration (L1) was not associated with a diminished overall survival (p > 0.05). However, patients with a combination of L1V1 had a significantly worse overall survival of 68%, 20%, and 0% when compared to L0V0 patients. This difference was not influenced by the status of the resection margin. No other parameter investigated was found to be of predictive value. CONCLUSIONS: The presence of combined lymphatic and vascular invasion (L1V1) constitutes a predictor of poor overall and disease-free survival. This subgroup of patients might benefit from adjuvant strategies such as chemotherapeutic treatment.