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

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

Postoperative Supplemental Oxygen in Liver Transplantation (PSOLT) does not reduce the rate of infections: results of a randomized controlled trial.

BACKGROUND: Despite inconsistent evidence, international guidelines underline the importance of perioperative hyperoxygenation in prevention of postoperative infections. Further, data on safety and efficacy of this method in liver transplant setting are lacking. The aim was to evaluate efficacy and safety of postoperative hyperoxygenation in prophylaxis of infections after liver transplantation. METHODS: In this randomized controlled trial, patients undergoing liver transplantation were randomly assigned to either 28% or 80% fraction of inspired oxygen (FiO2) for 6 postoperative hours. Infections occurring during 30-day post-transplant period were the primary outcome measure. Secondary outcome measures included 90-day mortality, 90-day severe morbidity, 30-day pulmonary complications, durations of hospital and intensive care unit stay, and 5-day postoperative bilirubin concentration, alanine and aspartate transaminase activity, and international normalized ratio (INR) (clinicatrials.gov NCT02857855). RESULTS: A total of 193 patients were included and randomized to 28% (n = 99) and 80% (n = 94) FiO2. With similar patient, operative, and donor characteristics in both groups, infections occurred in 34.0% (32/94) of patients assigned to 80% FiO2 as compared to 23.2% (23/99) of patients assigned to 28% FiO2 (p = 0.112). Patients randomized to 80% FiO2 more frequently developed severe complications (p = 0.035), stayed longer in the intensive care unit (p = 0.033), and had higher bilirubin concentration over first 5 post-transplant days (p = 0.043). No significant differences were found regarding mortality, duration of hospital stay, pulmonary complications, and 5-day aspartate and alanine transaminase activity and INR. CONCLUSIONS: Postoperative hyperoxygenation should not be used for prophylaxis of infections after liver transplantation due to the lack of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02857855. Registered 7 July 2016.

Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures.

OBJECTIVE: Despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). DESIGN: A prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. RESULTS: An initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. CONCLUSION: Implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.

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

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

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

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

[68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma.

PURPOSE: Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [68Ga]Ga-PSMA-11 in HCC and its impact on patient management. METHODS: Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, single-institution study. All patients underwent contrast-enhanced MRI/CT, [68Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions. RESULTS: No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [68Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUVmax) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [68Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC. CONCLUSION: [68Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.

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

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

Synergistic effects of extracellular vesicle phenotyping and AFP in hepatobiliary cancer differentiation.

BACKGROUND: Biliary cancer, comprising cholangio- and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation. METHODS: Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two-step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis. RESULTS: Two directly tumour-related antigen combinations (AnnV+ CD44v6+ and AnnV+ CD44v6+ CD133+ ) and two combinations related to progenitor cells from the tumour microenvironment (AnnV+ CD133+ gp38+ and AnnV+ EpCAM+ CD133+ gp38+ ) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV+ CD44v6+ EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively. CONCLUSIONS: EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.

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

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

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

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

Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma.

BACKGROUND & AIMS: Large extracellular vesicles, specifically AnnexinV+ EpCAM+ CD147+ tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection and monitoring of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Specifically, the aim of this study was to differentiate liver taMPs from other cancer taMPs, such as CRC and NSCLC. METHODS: Fluorescence-activated cell scanning (FACS) was applied to detect various taMP populations in patients' sera that were associated with the presence of a tumour (AnnexinV+ EpCAM+ CD147+ taMPs) or could discriminate between cirrhosis (due to HCV or HBV) and liver cancers (AnnexinV+ EpCAM+ ASGPR1+ taMPs). In total 172 patients with liver cancer (HCC or CCA), 54 with cirrhosis and no liver neoplasia, and 202 control subjects were enrolled. RESULTS: The results indicate that AnnexinV+ EpCAM+ CD147+ taMPs were elevated in HCC and CCA. Furthermore, AnnexinV+ EpCAM+ ASGPR1+ CD133+ taMPs allowed the distinction of liver malignancies (HCC or CCA) and cirrhosis from tumour-free individuals and, more importantly, from patients carrying other non-liver cancers. In addition, AnnexinV+ EpCAM+ ASGPR1+ taMPs were increased in liver cancer-bearing patients compared to patients with cirrhosis that lacked any detectable liver malignancy. The smallest sizes of successfully detected cancers were ranging between 11-15mm. AnnexinV+ EpCAM+ ASGPR1+ taMPs decreased at 7days after curative R0 tumour resection suggesting close correlations with tumour presence. ROC values, sensitivity/specificity scores and positive/negative predictive values (>78%) indicated a potent diagnostic accuracy of AnnexinV+ EpCAM+ ASGPR1+ taMPs. CONCLUSION: These data provide strong evidence that AnnexinV+ EpCAM+ ASGPR1+ taMPs are a novel biomarker of HCC and CCA liquid biopsy that permit a non-invasive assessment of the presence and possible extent of these cancers in patients with advanced liver diseases. LAY SUMMARY: Microparticles (MPs) are small vesicles that bleb from the membrane of every cell, including cancer cells, and are released to circulate in the bloodstream. Since their surface composition is similar to the surface of their underlying parental cell, MPs from the bloodstream can be isolated and by screening their surface components, the presence of their parental cells can be identified. This way, it was possible to detect and discriminate between patients bearing liver cancer and chronic liver cirrhosis.

Challenging the principle of utility as a barrier for wider use of liver transplantation for hepatocellular cancer.

BACKGROUND: Although transplant benefit appears superior for patients with advanced hepatocellular cancer (HCC), liver transplantation remains limited to selected low-risk HCC patients to keep their outcomes similar to heterogeneous group of non-HCC patients. The purpose of this study was to assess the rationale for current policy of restricting access to liver transplantation to minority of HCC patients based on utility principle. METHODS: This retrospective cohort study comprised 1246 liver transplant recipients, including 206 HCC and 1040 non-HCC patients. Patient survival was the primary outcome measure. Patients with HCC and benign diseases were divided into low-, moderate-, and high-risk subgroups basing on independent risk factors for disease-free survival and model for end-stage liver disease (MELD) score (<30, 30-40, >40), respectively. RESULTS: MELD (p < 0.001) and presence of HCC (p = 0.008) were independent risk factors for early and late mortality, respectively. Total tumor volume (p = 0.008) and alpha-fetoprotein (p = 0.013) were independent predictors of recurrence and mortality used for division of HCC patients into low-, moderate-, and high-risk subgroups, with disease-free survival rates of 74.9% (5 years), 51.7% (5 years), and 8.0% (3 years), respectively (p < 0.001). There were no differences in 5-year overall survival between low-risk HCC (74.9%) and non-HCC (81.9%) patients (p = 0.210), moderate-risk HCC (63.3%) and non-HCC (68.0%) patients (p = 0.372), and high-risk HCC (55.0%) and non-HCC (56.0%) patients (p = 0.559). CONCLUSIONS: The principle of utility is unequally applied for restriction of access to liver transplantation for HCC patients. The results provide rationale for discussion on reinitiation of liver transplantation for advanced HCCs.

The Warsaw Proposal for the Use of Extended Selection Criteria in Liver Transplantation for Hepatocellular Cancer.

BACKGROUND: Combination of the University of California, San Francisco (UCSF) and the up-to-7 criteria with alpha-fetoprotein (AFP) cutoff of 100 ng/ml was proposed as the Warsaw expansion of the Milan criteria in selection of hepatocellular cancer (HCC) patients for liver transplantation. The purpose of this retrospective study was to validate this proposal. METHODS: A total of 240 HCC patients after liver transplantation were included. Recurrence-free survival and overall survival at 5 years were set as the primary and secondary outcome measures, respectively. RESULTS: The Warsaw expansion increased transplant eligibility rate by 20.3 %. AFP >100 ng/ml significantly increased the recurrence risk in patients within the Milan criteria (p = 0.025) and in those beyond, yet within either the UCSF or the up-to-7 criteria (p < 0.001). Recurrence-free survival at 5 years was 90.8 % for patients within the Milan criteria, 100.0 % in patients within the Warsaw expansion, 54.9 % in patients beyond the Warsaw expansion but within either the UCSF or the up-to-7 criteria, and 45.1 % in patients beyond both the UCSF and the up-to-7 criteria (p < 0.001). The corresponding overall survival rates were 71.6, 82.4, 64.3, and 55.3 %, respectively (p = 0.027). CONCLUSIONS: The Warsaw expansion of the Milan criteria substantially increases the recipient pool without compromising outcomes.

Cystic echinococcosis in Poland: genetic variability and the first record of Echinococcus granulosus sensu stricto (G1 genotype) in the country.

Cystic echinococcosis is one of the most important zoonotic diseases affecting humans and livestock worldwide, and is endemic in Poland. A set of six isolates on larval stages of Echinococcus granulosus sensu lato tapeworms collected from three humans, two pigs and one sheep from Polish foci of CE was examined by DNA sequencing of two mitochondrial genes (cox1, rrnS). The results demonstrated the presence of E. canadensis and E. granulosus sensu stricto in the investigated hydatid cysts. The former species was found in all five isolates from pigs and humans derived from central Poland. In a sheep hydatid cyst originating from Lesser Poland Voivodeship in southern Poland, E. granulosus s. s. (G1 genotype) was identified. This is the first report of an unambiguously autochthonous infection with E. granulosus s. s. in Poland. The global distribution and host affiliations of the commonly occurring G1 microvariant with nucleotide change 56C/T in cox1, detected here in Polish sheep, are discussed. The finding that sheep harboured E. granulosus s. s. may have important consequences for developing effective hydatid control programmes in Poland due to its longer maturation rate in dogs compared with E. canadensis G7. This may lead to greater expenditures for purchasing anthelmintics to provide an appropriate dosing regime in sheep-raising areas of the country.

Good outcome following liver transplantation using pericardial-peritoneum window for hepato-atrial anastomosis to overcome advanced hepatic alveolar echinococcosis and secondary Budd-Chiari Syndrome - a case report.

BACKGROUND: This report presents a case of a 57- year old female with advanced Hepatic Alveolar Echinococcosis causing a secondary Budd-Chiari Syndrome due to infiltration of the suprahepatic inferior vena cava treated successfully by liver transplantation. CASE PRESENTATION: A temporary veno-venous bypass was introduced, but a typical end to end cavo-caval anastomosis wasn't possible in this case. In order to access a disease free part of the inferior vena cava, an oval window of the diaphragm was excised, providing communication between the peritoneum and pericardium. A vascular clamp was placed onto the right atrium which allowed for an atrial-caval anastomosis. The remainder of hepatectomy was performed in a conventional manner. In the post-operative period and during the 18 month follow-up there were no complications. The patient remains in good general condition with optimal graft function. CONCLUSIONS: A hepato-atrial anastomosis with a pericardial-peritoneum window during liver transplantation is feasible and extends the curability potential for patients with advanced Hepatic Alveolar Echinococcosis considered for liver transplantation.

Effects of Donor Age and Cold Ischemia on Liver Transplantation Outcomes According to the Severity of Recipient Status.

UNLABELLED: BackgroundProlonged cold ischemic time (CIT) and increased donor age are well-known factors negatively influencing outcomes after liver transplantation (LT). AIMS: The aim of this study was to evaluate whether the magnitude of their negative effects is related to recipient model for end-stage liver disease (MELD) score. METHODS: This retrospective study was based on a cohort of 1402 LTs, divided into those performed in low-MELD (<10), moderate-MELD (10­20), and high-MELD (>20) recipients. RESULTS: While neither donor age (p = 0.775) nor CIT (p = 0.561) was a significant risk factor for worse 5-year graft survival in low-MELD recipients, both were found to yield independent effects (p = 0.003 and p = 0.012, respectively) in moderate-MELD recipients, and only CIT (p = 0.004) in high-MELD recipients. However, increased donor age only triggered the negative effect of CIT in moderate-MELD recipients, which was limited to grafts recovered from donors aged ≥46 years (p = 0.019). Notably, utilization of grafts from donors aged ≥46 years with CIT ≥9 h in moderate-MELD recipients (p = 0.003) and those with CIT ≥9 h irrespective of donor age in high-MELD recipients (p = 0.031) was associated with particularly compromised outcomes. CONCLUSIONS: In conclusion, the negative effects of prolonged CIT seem to be limited to patients with moderate MELD receiving organs procured from older donors and to high-MELD recipients, irrespective of donor age. Varying effects of donor age and CIT according to recipient MELD score should be considered during the allocation process in order to avoid high-risk matches.

The Role of Computed Tomography in the Diagnostics of Diaphragmatic Injury After Blunt Thoraco-Abdominal Trauma.

BACKGROUND: Diaphragmatic injuries occur in 0.8-8% of patients with blunt trauma. The clinical diagnosis of diaphragmatic rupture is difficult and may be overshadowed by associated injuries. Diaphragmatic rupture does not resolve spontaneously and may cause life-threatening complications. The aim of this study was to present radiological findings in patients with diaphragmatic injury. MATERIAL/METHODS: The analysis of computed tomography examinations performed between 2007 and 2012 revealed 200 patients after blunt thoraco-abdominal trauma. Diaphragmatic rupture was diagnosed in 13 patients. Twelve of these patients had suffered traumatic injuries and underwent a surgical procedure that confirmed the rupture of the diaphragm. Most of diaphragmatic ruptures were left-sided (10) while only 2 of them were right-sided. In addition to those 12 patients there, another patient was admitted to the emergency department with left-sided abdominal and chest pain. That patient had undergone a blunt thoracoabdominal trauma 5 years earlier and complained of recurring pain. During surgery there was only partial relaxation of the diaphragm, without rupture. The most important signs of the diaphragmatic rupture in computed tomography include: segmental discontinuity of the diaphragm with herniation through the rupture, dependent viscera sign, collar sign and other signs (sinus cut-off sign, hump sign, band sign). RESULTS: In our study blunt diaphragmatic rupture occurred in 6% of cases as confirmed intraoperatively. In all patients, coronal and sagittal reformatted images showed herniation through the diaphragmatic rupture. In left-sided ruptures, herniation was accompanied by segmental discontinuity of the diaphragm and collar sign. In right-sided ruptures, predominance of hump sign and band sign was observed. Other signs were less common. CONCLUSIONS: The knowledge of the CT findings suggesting diaphragmatic rupture improves the detection of injuries in thoraco-abdominal trauma patients.

Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post-transplant year.

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long-term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post-transplant year (p = 0.655) but worse during the five subsequent years among the five-yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post-transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post-transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non-ALD recipients up to the fifth post-transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre-transplant diagnosis of ALD yields negative effects on post-transplant outcomes beyond the fifth post-transplant year, not attributable to recidivism.

Initial prevalence of anal human papilloma virus infection in liver transplant recipients.

Although liver transplant recipients are at increased risk of human papilloma virus (HPV)-related anal cancer, limited data are available regarding the initial prevalence of anal HPV infection in this population. Anal swabs collected from 50 liver transplant recipients within the first three postoperative weeks were subjected to real-time polymerase chain reaction for detection of the four HPV genotypes: 6, 11, 16, and 18. Predictors of any, low-risk, and high-risk anal HPV infection were evaluated. Overall, the prevalence of any anal HPV infection was 18.0%, with the corresponding rates for high- and low-risk HPV genotypes being 8.0% and 10.0%, respectively. Infection with any type of anal HPV was higher in patients with hepatitis B virus (HBV) infection (P = 0.027), ≥3 sexual partners (P = 0.031), and alcoholic liver disease (P = 0.063). HBV infection was the only factor significantly associated with high-risk HPV infection (P = 0.038). Male sex (P = 0.050), age ≥52 years (P = 0.016), ≥30 sexual partners (P = 0.003), age at first intercourse ≤18 years (P = 0.045), and time since first intercourse ≥38 years (P = 0.012) were identified as predictors of low-risk HPV infection. These results indicate that HPV vaccination of liver transplant candidates and screening for anal HPV infection in high-risk groups should be considered.