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The article focuses on the findings of a study concerning the relationship between 31P metabolites and oncolytic viral therapy sensitivity in human colorectal cancer zenografts. It mentions that spectroscopic imaging was performed in colorectal flank tumours in nude mice. Moreover, the study determines that alterations in membrane phospholipid metabolites that relate to proliferation of cancer cells affect the efficacy of oncolytic viral therapy.

Background: Corroborating evidence for the use of hypothermic oxygenated machine perfusion (HOPE) prior to orthotopic liver transplantation (OLT) suggests a beneficial effect in regard to biliary complications. Here, the authors aim to evaluate whether perfusion via portal vein alone (sHOPE) or via additional perfusion of the hepatic artery (dHOPE) have diverging impact on outcomes after OLT when compared to the use of static cold storage (SCS)., Methods: Consecutive patients undergoing OLT at the Medical University of Vienna (2018-2023) were retrospectively analyzed. Donor organs were procured using SCS, or subjected to end-ischemic sHOPE or dHOPE. The severity of biliary complications was classified according to the degree of therapeutic intervention (endoscopic retrograde cholangiopancreatography or surgical revision)., Results: Two hundred forty-seven patients were included (69 SCS, 76 sHOPE, and 102 dHOPE). Hospitalization was shorter for patients after HOPE (median in days: SCS=25 vs HOPE=20, P =0.019). Biliary complications were less frequent in patients after HOPE (SCS=37.7% vs HOPE=22.5%, P =0.015). A significantly lower incidence of surgical revisions for biliary complications was observed in the HOPE cohort (24.6% vs 11.8%, P =0.012). When evaluating outcome according to HOPE-modality, a significant reduction in biliary complications ( P =0.006) and surgical revisions ( P =0.002) was only observed in dHOPE patients in comparison to SCS. Further, only dHOPE was significantly associated with a reduced need for surgical revision for biliary complications upon univariable and multivariable logistic regression (odds ratio=0.336, P =0.011)., Conclusion: HOPE leads to a reduction of biliary complications and associated surgical revisions. This effect seems to be primarily associated with use of dHOPE, while both methods appear as feasible options for preconditioning of donor grafts prior to OLT., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Liver transplantation (LT) in elderly recipients is controversially discussed in the literature with only little data on long-term outcome available. We aimed to evaluate the safety and efficiency of LT in elderly recipients (>65 years)., Methods: Between 1989-2016, 139 patients >65 years-old were listed for liver transplantation, and 76 (55%) were transplanted. Patient outcome and characteristics were evaluated separately for the time period before (1989-2004) and after (2005-2016) MELD-implementation. Post-transplant outcome was compared between the elderly cohort and LT-recipients aged 18-65 years (n = 1395)., Results: Overall survival of patients >65 years was better in the MELD-era compared to the earlier period (1- and 5-year-survival: 73%, 60% vs. 69%, 37%, respectively; p = 0.055). The main differences between the two groups included higher recipient age (p = 0.001) and BMI (p = 0.001), higher donor age (p < 0.001), less need of intraoperative red blood cells (p = 0.008) and a lower number of postoperative rejections (p = 0.03) after 2004. Comparing the overall survival of patients transplanted in the MELD-era aged 18-65 years vs. >65 years displayed comparable 1- and 5 year-survival rates (81%, 68% vs. 73% and 60%, respectively, p = 0.558)., Conclusion: In the modern era, outcome of patients receiving LT with >65 years is comparable to <65 year-old patients. After careful evaluation, patients >65 years old should be considered for LT., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Nonalcoholic fatty liver disease (NAFLD) can be considered the hepatic manifestation of the metabolic syndrome with nonalcoholic steatohepatitis (NASH) as its progressive form. With increasing prevalence of the metabolic syndrome, NASH cirrhosis is becoming a leading cause for liver transplantation. Some cases of orthotopic liver transplantation (OLT) due to cryptogenic cirrhosis (CC) might show typical features of NASH cirrhosis. Therefore, our aim was to assess recurrence of liver fibrosis in patients transplanted for NASH versus CC after OLT., Patients and Methods: Patients transplanted for CC or NASH between 1 January 2004 and 30 September 2015 were included. The histological NAFLD activity score and the NAFLD fibrosis score (NFS) were assessed., Results: In total, 15 and 12 patients underwent OLT because of NASH and CC, respectively. The case load for OLT because of NASH was constantly increasing (n=2 in 2004-2007 vs. n=9 in 2012-2015) whereas decreasing for CC (n=6 in 2004-2007 vs. n=2 in 2012-2015). Patient characteristics at OLT were similar, except for an older age and a higher BMI in NASH patients (59.1±2.2 vs. 51.8±2.9 years, P=0.05; 27.7±1.2 vs. 24.3±0.8 kg/m, P=0.035). Although post-OLT plasma lipid levels and incidence of de-novo hypertension, diabetes, and hyperlipidemia were similar between groups, the post-transplant NFS re-increased in the NASH group (but not in the CC: -0.1317 vs. -1.3645 at 12 months post-OLT, P=0.0400). Post-transplant survival was similar in NASH and CC patients., Conclusion: According to the NFS, some NASH patients show recurrence of fibrosis as early as 6-12 months after OLT.

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post-LT long-term observation is challenging, and biomarkers as carbohydrate-deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow-up was 73 months (0-213). One- and five-year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post-transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single-center analysis showed good post-transplant long-term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post-LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse., (© 2016 Steunstichting ESOT.)

Purpose: Traditionally, abdominal drainage (AD) is routinely inserted in patients after liver transplantation (LT) to drain ascites and to detect postoperative hemorrhage and bile leakage. However, the benefit of this surgical practice remains a matter of debate regarding potential drainage-associated morbidities., Methods: In a retrospective pair-matched analysis in a 1:1 ratio, 116 patients after LT were assessed with regards to benefits and risks of abdominal drainage under immunosuppression, respecting model for end-stage liver disease (MELD), age, and gender., Results: The indications for LT were comparable between the drain and the no-drain group. There was an increased rate of early bile leakage in patients with abdominal drainage (13.8 vs. 1.7%, p = 0.032). In addition, a significantly higher incidence of infections requiring antibiotic therapy was observed in the drain group (63.8 vs. 39.7%, p = 0.015). The contribution of drains as a diagnostic tool was marginal, as in the drain group, other diagnostic tools than the drain itself confirmed 50% of all early bile leakages and 60% of postoperative hemorrhages. Overall, there was no difference regarding the incidence of incisional hernia after LT (8.6 vs. 10.3%, p = 1.000), length of hospital stay (22.9 ± 18.7 vs. 18.6 ± 18.6 days, p = 0.215), and 1- and 5-year patient (p = 0.981) and graft survival (p = 0.092)., Conclusions: Equal results can be achieved with or without an abdominal drain in recipients with whole-liver grafts in spite of an increased risk of postoperative infection and biliary leakage in the former group. A benefit of AD as a diagnostic tool could not be demonstrated.

In this case report we have described a patient suffering from sclerosing cholangitis, diabetes mellitus type I, and consequent end-stage renal disease who was successfully treated with simultaneous pancreas and kidney transplantation 9 years after orthotopic liver transplantation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Oncolytic viruses show promise for treating cancer. However, to assess therapy and potential toxicity, a noninvasive imaging modality is needed. This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS., Methods: GLV-1h153 was modified from GLV-1h68 to encode the hNIS gene. Timing of cellular uptake of radioiodide (131)I in human pancreatic carcinoma cells PANC-1 was assessed using radiouptake assays. Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP) and bioluminescence. Timing characteristics of enhanced radiouptake in xenografts were assessed via (124)I-positron emission tomography (PET). Detection of systemic administration of virus was investigated with both (124)I-PET and 99m-technecium gamma-scintigraphy., Results: GLV-1h153 successfully facilitated time-dependent intracellular uptake of (131)I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P<0.05). In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 10(9) plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean %ID/gm of 3.82 ± 0.46 (P<0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via (124)I-PET and 99m-technecium-scintigraphy., Conclusion: GLV-1h153 is a promising oncolytic agent against pancreatic cancer with a promising biosafety profile. GLV-1h153 facilitated time-dependent hNIS-specific radiouptake in pancreatic cancer cells, facilitating detection by PET with both intratumoral and systemic administration. Therefore, GLV-1h153 is a promising candidate for the noninvasive imaging of virotherapy and warrants further study into longterm monitoring of virotherapy and potential radiocombination therapies with this treatment and imaging modality.

Objective: Morbid obesity is an increasingly common disease in the industrialized world and poses a great challenge to the medical community. Many obese adolescents have undergone various conservative treatment methods without adequate success so that a surgical approach became necessary. We report on 18 patients who underwent bariatric surgery as well as a long-term follow-up program., Methods: Eight patients received a laparoscopic adjustable gastric banding (LAGB). Four of these had to undergo a gastric bypass surgery (GByp) as second procedure due to insufficient weight loss. Nine patients primarily received a gastric bypass., Results: LAGB: Mean weight loss after 24 months was 20 ± 6.3 kg. Four of the patients showed a regain in weight leading to a mean weight loss of 9 kg compared to initial weight after 53.3 months mean in this group. These patients had to undergo an additional gastric bypass procedure and lost 31 ± 18.3 kg after 18 months. GByp: Mean weight loss in nine patients after gastric bypass (primary procedure) was 31 ± 10.2 kg after 12 months and 36 ± 30.1 kg at the end of the observation time. Sleeve: Initial weight in this patient was 232 kg with a weight loss of 38 kg after 24 months., Discussion and Conclusion: It is remarkable that in four of eight patients who underwent LAGB had to undergo a second surgical procedure (GByp). No previous indicator, neither from a psychological nor from a medical point of view, could be detected. More long-term studies including psychological aspects seem to be necessary.

The appropriate time point for starting immunosuppressive treatment with calcineurin inhibitors after orthotopic liver transplantation (OLT) has been a subject of debate. The aim of the study was to analyze the effects of anti-thymocyte globulin (ATG) induction therapy on rejection, renal function, infection, tumor rate, and survival. We retrospectively analyzed 391 patients after OLT who had either received calcineurin inhibitors immediately after OLT (n = 129) or after an initial short-term Thymoglobulin induction therapy (n = 262). The 1-year acute rejection rate was 14.5% vs. 31.8% in favor of ATG (P = 0.0008). Rejection grades and the need for treatment also differed significantly (7.3% vs. 23.3%; P = 0.001). Serum creatinine at transplantation was similar in both groups (1.14 mg/dL vs.1.18 mg/dL; P = NS). Postoperative hemofiltration was less frequently seen after induction therapy (P < 0.05). Reduced renal function at 1 year was commonly observed, but serum creatinine (1.26 mg/dL vs. 1.37mg/dL; P = 0.015) and glomerular filtration rate (81 mL/min vs. 75 mL/min; P = 0.02) were far better in the ATG group. Undesired side effects occurred at a similar rate in both groups. Five-year patient survival was also similar in the 2 groups (70.1% and 74.3%; P > 0.05). Short-term ATG induction therapy with delayed administration of calcineurin inhibitors led to a more favorable rejection rate and an improved clinical course in case of a rejection episode. It has beneficial effects on renal function immediately after OLT as well as later, and no additional harmful effects.

T-cell depletion is an essential aspect of clinical immunosuppression. The aim of the present study was to compare the efficacy of two dosage regimens in this setting. We retrospectively compared 246 patients (group 1) who received a 10-day antithymocyte globulin (ATG) induction protocol with 226 patients (group 2) who received a 3-day protocol. The 6-month rejection rate was 22.3% in group 1 and 12.7% in group 2 (P = 0.03). The sub-analysis showed a higher rejection rate in patients with cholestatic disease (P = 0.01), who were more numerous in group 1. This resulted in an overall difference between the groups. Rates of de novo malignancies and recurrent hepatocellular carcinoma were identical. Viral infection rates were 16% and 18%, respectively (P > 0.5). The rates of bacterial and fungal infection were also similar (37% vs. 42%, P > 0.1). However, infection and ATG administration are independent risk factors for survival. A lower rate of fatal infection was observed in group 2 (P = 0.01), while the 10-day ATG regimen had a detrimental effect on patients who had infection (P < 0.0001). Our results strongly support the application of 3-day ATG induction therapy regimen after orthotopic liver transplantation, as it is associated with the same rejection rate as long-term ATG induction therapy, without the negative survival effect of the latter due to lethal infection.

At the beginning of the 21st century, obesity has become an epidemic with the greatest prevalence in the western world. For morbidly obese patients, conservative treatment has yielded disappointing results: On the other hand, bariatric surgery offers a sustained substantial weight loss for these patients. Common bariatric procedures including results and complications are described. Different Bariatric procedures including Gastric Banding, Vertical Banded Gastroplasty, Gastric Bypass, Duodenal Switch and Gastric Pacing are introduced. Bariatric procedures can result in permanent excessive weight loss ranging from 25 to 78% and thus are an effective treatment for morbidly obese patients. Efficacy, morbidity and late term complications, however, should be considered in choosing the most effective bariatric approach.

Renal transplant rejection is caused by a lymphocyte-rich inflammatory infiltrate that attacks cortical tubules and endothelial cells. Immunosuppressive therapy reduces the number of infiltrating cells; however, their exit routes are not known. Here a >50-fold increase of lymphatic vessel density over normal kidneys in grafts with nodular mononuclear infiltrates is demonstrated by immunohistochemistry on human renal transplant biopsies using antibodies to the lymphatic endothelial marker protein podoplanin. Nodular infiltrates are constantly associated with newly formed, Ki-67-expressing lymphatic vessels and contain the entire repertoire of T and B lymphocytes to provide specific cellular and humoral alloantigenic immune responses, including Ki-67(+) CD4(+) and CD8(+) T lymphocytes, S100(+) dendritic cells, and Ki-67(+)CD20(+) B lymphocytes and lambda- and kappa-chain-expressing plasmacytoid cells. Numerous chemokine receptor CCR7(+) cells within the nodular infiltrates seemed to be attracted by secondary lymphatic chemokine (SLC/CCL21) that is produced and released by lymphatic endothelial cells in a complex with podoplanin. From these results, it is speculated that lymphatic neoangiogenesis not only contributes to the export of the rejection infiltrate but also is involved in the maintenance of a potentially detrimental alloreactive immune response in renal transplants and provides a novel therapeutic target.

Objective: We compared 3 different decellularization protocols in porcine heart valves for efficiency of complete cell removal and potential for recellularization., Methods: Porcine aortic and pulmonary roots were treated with trypsin, sodium-dodecyl-sulphate, or a new method using 0.25% tert-octylphenyl-polyoxyethylen in combination with sodium-deoxycholate. After a subsequent ribonuclease digestion, specimens were seeded with in vitro expanded human saphenous vein endothelial cells and myofibroblasts., Results: After treatment with trypsin and subsequent ribonuclease digestion, endothelial attachment took place; however, xenogenic cells were still visible within the matrix. Unexpectedly, when human cells were seeded onto specimens that had been decellularized with sodium-dodecyl-sulphate, the matrices were surrounded by nonviable endothelial cell fragments, indicating a toxic influence of the ionic detergent; 0.25% tert-octylphenyl-polyoxyethylen together with sodium-deoxycholate completely removed porcine cells and enabled host recellularization., Conclusion: Compared with trypsin and sodium-dodecyl-sulphate involving decellularization procedures, reported to be effective in cell removal and susceptible to recellularization with human cells, only the porcine matrix treated with a new detergent-based decellularization method using 0.25% tert-octylphenyl-polyoxyethylen/sodium-deoxycholate followed by nuclease digestion presented an excellent scaffold for recellularization with human cells.

Background and Aims: The hepatopulmonary syndrome (HPS) has been defined by chronic liver disease, arterial deoxygenation, and widespread intrapulmonary vasodilation. Mortality of patients with HPS is considered to be high, but the effect of HPS on survival in patients with cirrhosis remains unclear., Methods: A total of 111 patients with cirrhosis were studied prospectively by using transthoracic contrast echocardiography for detection of pulmonary vasodilation, blood gas analysis, and pulmonary function test. Twenty different clinical characteristics and survival times were noted., Results: Twenty-seven patients (24%) had HPS. Their mortality was significantly higher (median survival, 10.6 months) compared with patients without HPS (40.8 mo, P < 0.05), even after adjusting for liver disease severity (2.9 vs. 14.7 months in Child-Pugh class C with [n = 15] and without HPS [n = 35, P < 0.05]; 35.3 vs. 44.5 months in Child-Pugh class B with [n = 7] and without HPS [n = 23, P = NS]), and exclusion of patients who underwent liver transplantation during follow-up (median survival 4.8 vs. 35.2 months, P = 0.005). Causes of death were mainly nonpulmonary and liver-related in the 19 patients with and the 35 patients without HPS who died. In multivariate analysis, HPS was an independent predictor of survival besides age, Child-Pugh class, and blood urea nitrogen. Mortality correlates with severity of HPS., Conclusions: The presence of HPS independently worsens prognosis of patients with cirrhosis. This should influence patient management and scoring systems and accelerate the evaluation process for liver transplantation.