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.

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.

Recipient Criteria Predictive of Graft Failure in Kidney Transplantation.

Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables. This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics. All U.S. kidney transplant recipients between October 25,1999 and January 1, 2007 were reviewed. Cox proportional hazards regression was used to model time until graft failure. Death-censored and nondeath-censored graft survival models were generated for recipients of live and deceased donor organs. Recipient age, gender, body mass index (BMI), presence of cardiac risk factors, peripheral vascular disease, pulmonary disease, diabetes, cerebrovascular disease, history of malignancy, hepatitis B core antibody, hepatitis C infection, dialysis status, panel-reactive antibodies (PRA), geographic region, educational level, and prior kidney transplant were evaluated in all kidney transplant recipients. Among the 88,284 adult transplant recipients the following groups had increased risk of graft failure: younger and older recipients, increasing PRA (hazard ratio [HR],1.03-1.06], increasing BMI (HR, 1.04-1.62), previous kidney transplant (HR, 1.17-1.26), dialysis at the time of transplantation (HR, 1.39-1.51), hepatitis C infection (HR, 1.41-1.63), and educational level (HR, 1.05-1.42). Predictive criteria based on recipient characteristics could guide organ allocation, risk stratification, and patient expectations in planning kidney transplantation.

Surgical Therapy of Cholangiocarcinoma.

BACKGROUND: The majority of patients with cholangiocarcinoma present with advanced disease that is often challenging to diagnose and to treat. The optimal preoperative evaluation requires a coordinated multidisciplinary approach. Surgical resection is the mainstay of therapy. METHODS: This systematic review delineates surgical treatment strategies for cholangiocarcinoma in general as well as special considerations concerning the particular tumor localization. A literature search (see keywords) was conducted using PubMed and publications between 1990 and 2016 regarding resectable and advanced cholangiocarcinoma were reviewed. Selected studies were utilized based on their significance and innovation. RESULTS: The type and extent of resection performed depends on the location of the cholangiocarcinoma within the liver or biliary tree and the extent of local tumor invasion. The common surgical strategy contains: (i) for intrahepatic tumors: tailored partial hepatectomy combined with extended hilar, suprapancreatic, celiac axis lymphadenectomy, (ii) for hilar tumors: complete resection of the extrahepatic biliary tree combined with extended hepatectomy inclusive of segment I, resection of portal vein bifurcation, and systematic N1/N2 lymphadenectomy, and (iii) for distal tumors: en bloc pancreatoduodenectomy combined with complete resection of the extrahepatic bile duct below the hepatic confluence and systematic N1/N2 lymphadenectomy. Pathologic confirmation is not required prior to resection. Preoperative biliary drainage and remnant liver volume augmentation are necessary in selected patients with intrahepatic or hilar cholangiocarcinoma considered for extensive liver resection. CONCLUSION: Cure for cholangiocarcinoma requires complete surgical resection with histologically negative margins. R0 resection provides a satisfactory long-term outcome in patients with lymph node-negative stage. Neoadjuvant treatment followed by liver transplantation provides long-term survival in highly selected cases with localized, unresectable, lymph node-negative hilar cholangiocarcinoma.

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.

Donor-Specific Anti-HLA Antibodies and Endothelial C4d Deposition-Association With Chronic Liver Allograft Failure.

BACKGROUND: The significance of humoral immune response for allograft survival after liver transplantation (LT) is still a matter of debate. The aim of this cross-sectional study was to assess immunological and clinical factors associated with advanced fibrosis (F3-F4) and chronic graft failure in LT recipients. METHODS: Serum samples from 174 patients prospectively enrolled and followed up for 12 months were tested for anti-HLA antibodies and compared against donor HLA types. Immunohistochemical C4d staining was performed on formalin-fixed, paraffin-embedded liver tissue. RESULTS: Mean time period from LT to enrollment was 66.9 ± 51.9 months. Independent predictive factors for graft failure included donor-positive cytomegalovirus serostatus (P = 0.02), donor-specific antibodies (DSA) against HLA class II (P = 0.03), donor age (P = 0.01), hepatitis C virus allograft reinfection (P = 0.0008), and biliary complications (P = 0.003). HLA class II DSA and HLA class I antibody positivity, hepatitis C virus reinfection, and mycophenolate mofetil-free regimens were significant risk factors for advanced fibrosis after LT. There was a significant association between C4d deposition on allograft endothelial cells and presence of class II DSA (P < 0.0001). Patients with C4d deposits had a 4.3 times higher risk of graft failure than those with negative staining and a significantly lower median time to graft failure (94.6 months [range, 3.6-158.9 months] vs 176.4 months [range, 9.4-217.8 months], P < 0.0001). CONCLUSIONS: Screening for HLA DSA might be useful for early identification of LT recipients at increased risk of graft failure who could benefit from closer surveillance and tailored immunosuppressive regimens.

Comparison of different magnetic resonance cholangiography techniques in living liver donors including Gd-EOB-DTPA enhanced T1-weighted sequences.

OBJECTIVES: Preoperative evaluation of potential living liver donors (PLLDs) includes the assessment of the biliary anatomy to avoid postoperative complications. Aim of this study was to compare T2-weighted (T2w) and Gd-EOB-DTPA enhanced T1-weighted (T1w) magnetic resonance cholangiography (MRC) techniques in the evaluation of PLLDs. MATERIALS AND METHODS: 30 PLLDs underwent MRC on a 1.5 T Magnetom Avanto (Siemens, Erlangen, Germany) using (A) 2D T2w HASTE (Half Fourier Acquisition Single Shot Turbo Spin Echo) fat saturated (fs) in axial plane, (B) 2D T2w HASTE fs thick slices in coronal plane, (C) free breathing 3D T2w TSE (turbo spin echo) RESTORE (high-resolution navigator corrected) plus (D) maximum intensity projections (MIPs), (E) T2w SPACE (sampling perfection with application optimized contrasts using different flip angle evolutions) plus (F) MIPs and (G) T2w TSE BLADE as well as Gd-EOB-DTPA T1w images without (G) and with (H) inversion recovery. Contrast enhanced CT cholangiography served as reference imaging modality. Two independent reviewers evaluated the biliary tract anatomy on a 5-point scale subjectively and objectively. Data sets were compared using a Mann-Whitney-U-test. Kappa values were also calculated. RESULTS: Source images and maximum intensity projections of 3D T2w TSE sequences (RESTORE and SPACE) proved to be best for subjective and objective evaluation directly followed by 2D HASTE sequences. Interobserver variabilities were good to excellent (k = 0.622-0.804). CONCLUSIONS: 3D T2w sequences are essential for preoperative biliary tract evaluation in potential living liver donors. Furthermore, our results underline the value of different MRCP sequence types for the evaluation of the biliary anatomy in PLLDs including Gd-EOB-DTPA enhanced T1w MRC.

Bile duct evaluation of potential living liver donors with Gd-EOB-DTPA enhanced MR cholangiography: Single-dose, double dose or half-dose contrast enhanced imaging.

INTRODUCTION: Detailed knowledge of the biliary anatomy is essential to avoid complications in living donor liver transplantation. The aim of this study was to determine the optimal dosage of Gd-EOB-DTPA for contrast-enhanced magnetic resonance cholangiography (ce-MRC) with reference to contrast-enhanced CT cholangiography (ce-CTC). MATERIALS AND METHODS: 30 potential living liver donors (PLLD) underwent both ce-CTC and ce-MRC. Ten candidates each received single, double or half-dose Gd-EOB-DTPA. Ce-MRC images with and without inversion recovery pulses (T1w±IR) were acquired 20-30min after intravenous contrast injection. Image data was quantitatively and qualitatively reviewed by two radiologists based on a on a 5-point scale. Data sets were compared using a Mann-Whitney-U-test or Wilcoxon-rank-sum-test. Kappa values were also calculated. RESULTS: All image series provided sufficient diagnostic information both showing normal biliary anatomy and variant bile ducts. Ce-CTC showed statistically significant better results compared to all ce-MRC data sets. T1w MRC with single dose Gd-EOB-DTPA proved to be superior to half and double dose in subjective and objective evaluation without a statistically significant difference. CONCLUSIONS: Ce-MRC is at any dosage inferior to ce-CTC. As far as preoperative planning of bile duct surgery is focused on the central biliary anatomy, ce-MRC can replace harmful ce-CTC strategies, anyway. Best results were seen with single dose GD-EOB-DTPA on T1w MRC+IR.

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.

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.

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.

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.

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.

"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.

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.

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.