US-based Real-time Elastography for the Detection of Fibrotic Gut Tissue in Patients with Stricturing Crohn Disease.

PURPOSE: To assess whether ultrasonography (US)-based real-time elastography (RTE) can be used to detect gut fibrosis. MATERIALS AND METHODS: In this institutional review board-approved, prospective, proof-of-concept study, unaffected and affected gut segments in 10 patients with Crohn disease (four women, six men; median age, 49 years) were examined pre-, intra-, and postoperatively with US, including RTE to assess strain. Disease activity was scored by using the Limberg index on the basis of (a) bowel wall thickness and (b) size and extent of Doppler signal. After surgical resection, strain of full gut wall segments was measured with direct tensiometry. Gut wall layers, fibrosis, and collagen content were quantified histologically. Aggregated data per patient, disease status, and available measurements were assessed with mixed-effects models. RESULTS: Unaffected versus affected gut segments yielded higher RTE (mean ± standard deviation, 169.0 ± 27.9 vs 43.0 ± 25.9, respectively) and tensiometry (mean, 77.1 ± 21.4 vs 13.3 ± 11.2, respectively) values used to assess strain (both P < .001). There was good correlation between pre-, intra-, and postoperative RTE values of unaffected (intraclass correlation coefficient, 0.572) and affected (intraclass correlation coefficient, 0.830) segments. RTE was not associated with pre- or intraoperative Limberg scores (median, 1 vs 2; P = .255 and .382, respectively). Affected internal (median, 2011 vs 1363 µm; P = .011) and external (median, 929 vs 632 µm; P = .013) muscularis propria, serosa (median, 245 vs 64 µm; P = .019), and muscularis mucosae (median, 451 vs 80 µm; P = .031) were wider than unaffected segments. Width differences of internal muscularis propria and mucularis mucosae were associated with RTE-assessed strain (P = .044 and .012, respectively) and tensiometry-assessed strain (P = .006 and .014, respectively). Masson trichrome (median, 4 vs 0; P < .001) and elastica-van Gieson (median, 805 346 µm(2) vs 410 649 µm(2); P < .001) stains and western blotting (median, 2.01 vs 0.87; P = .009) demonstrated a higher collagen content in affected versus unaffected segments and were associated with RTE-assessed strain (both P < .001) and tensiometry-assessed strain (P < .001 and 0.025, respectively). CONCLUSION: RTE can be used to detect fibrosis in human Crohn disease. Online supplemental material is available for this article.

Prehospital fluid management of abdominal organ trauma patients--a matched pair analysis.

PURPOSE: Severe bleeding after trauma frequently leads to a poor outcome. Prehospital fluid replacement therapy is considered an important primary treatment option. We conducted a retrospective matched pair analysis to assess the influence of prehospital fluid replacement volume on the clinical course of patients with solid abdominal organ trauma. METHODS: Data were analyzed from 51,425 patients in TraumaRegister DGU® of the German Trauma Society. Inclusion criteria were as follows: injury severity score ≥ 16 points, primary admission, age ≥ 16 years, no isolated brain injury, transfusion of at least one unit of packed red blood cells (pRBCs), and systolic blood pressure ≥ 20 mmHg at the accident site. The patients were divided into "low-volume" (0-1000 ml) and "high-volume" (≥ 1,500 ml) groups according to the matched pair criteria. In each group, 68 patients met the inclusion criteria. RESULTS: Higher volume in fluid replacement was associated with increased need for transfusion (pRBCs: low-volume: 7.71 units, high-volume: 9.16 units; p = 0.074) and with by trend reduced clotting ability (prothrombin time: low-volume: 71.47 %, high-volume: 66.47 %; p = 0.27). The percentage of patients in shock (systolic blood pressure <90 mmHg) upon admission was equal in the two groups (25.0 %; p = 1). The mortality rate was discretely higher in the high-volume group (low-volume: 11.8 %, high-volume: 19.1 %; p = 0.089). CONCLUSIONS: Excessive prehospital fluid replacement is able to lead in an increased mortality rate in patients with solid abdominal organ injury. Our results support the concept of restrained fluid replacement in the preclinical treatment of severe trauma patients.

Increased T-helper 2 cytokines in bile from patients with IgG4-related cholangitis disrupt the tight junction-associated biliary epithelial cell barrier.

BACKGROUND & AIMS: IgG4-related cholangitis is a chronic inflammatory biliary disease that involves different parts of the pancreatobiliary system, but little is known about its mechanisms of pathogenesis. A T-helper (Th) 2 cell cytokine profile predominates in liver tissues from these patients. We investigated whether Th2 cytokines disrupt the barrier function of biliary epithelial cells (BECs) in patients with IgG4-related cholangitis. METHODS: We assessed the Th2 cytokine profile in bile samples and brush cytology samples from 16 patients with IgG4-related cholangitis and respective controls, and evaluated transcription of tight junction (TJ)-associated proteins in primary BECs from these patients. The effect of Th2 cytokines on TJ-mediated BEC barrier function and wound closure was examined by immunoblot, transepithelial resistance, charge-selective Na(+)/Cl(-) permeability, and 4-kDa dextran flux analyses. RESULTS: Bile samples from patients with IgG4-related cholangitis had significant increases in levels of Th2 cytokines, interleukin (IL)-4, and IL-5. IL-13 was not detected in bile samples, but polymerase chain reaction analysis of whole-brush cytology samples from patients with IgG4-related cholangitis revealed increased levels of IL-13 mRNA, compared with controls. BECs isolated from the brush cytology samples revealed decreased levels of claudin-1 and increased levels of claudin-2 mRNAs. In vitro, IL-4 and IL-13 significantly reduced TJ-associated BEC barrier function by activating claudin-2-mediated paracellular pore pathways. Th2 cytokines also impaired wound closure in BEC monolayers. CONCLUSIONS: Th2 cytokines predominate in bile samples from patients with IgG4-related cholangitis and disrupt the TJ-mediated BEC barrier in vitro. Subsequent increases in biliary leaks might contribute to the pathogenesis of chronic biliary inflammation in these patients.

Meeting report of the 2011 Joint International Congress of the International Liver Transplantation Society, the European Liver and Intestine Transplant Association, and the Liver Intensive Care Group of Europe.

The International Liver Transplantation Society held its yearly meeting as a joint conference with the European Liver and Intestine Transplant Association and the Liver Intensive Care Group of Europe at the Valencia Congress Center (Valencia, Spain) from June 22 to 25, 2011. Nearly 1500 registrants attended the meeting, which opened with a premeeting conference entitled "Global Challenges and Controversies in Liver Transplantation." This was followed by numerous oral and poster abstract sessions and topic sessions focused on medical, surgical, and intensive care aspects of liver transplantation (LT). This report summarizes key symposia and oral abstracts delivered at the meeting and is conveniently divided into subsections relevant to LT. It is not meant to be a critical or comprehensive evaluation of all the meeting presentations and is merely intended to highlight presentations and associated published literature dealing with key topics.

Galectins distinctively regulate central monocyte and macrophage function.

Monocytes and macrophages link the innate and adaptive immune systems and protect the host from the outside world. In inflammatory disorders their activation leads to tissue damage. Galectins have emerged as central regulators of the immune system. However, if they regulate monocyte/macrophage physiology is still unknown. Binding of Gal-1, Gal-2, Gal-3 and Gal-4 to monocytes/macrophages, activation, cytokine secretion and apoptosis were determined by FACS, migration by Transwell system and phagocytosis by phagotest. Supernatants from macrophages co-cultured with galectins revealed their influence on T-cell function. In our study Gal-1, Gal-2, Gal-4, and partly Gal-3 bound to monocytes/macrophages. Galectins prevented Salmonella-induced MHCII upregulation. Cytokine release was distinctly induced by different galectins. T-cell activation was significantly restricted by supernatants of macrophages co-cultured in the presence of Gal-2 or Gal-4. Furthermore, all galectins tested significantly inhibited monocyte migration. Finally, we showed for the first time that galectins induce potently monocyte, but not macrophage apoptosis. Our study provides evidence that galectins distinctively modulate central monocyte/macrophage function. By inhibiting T-cell function via macrophage priming, we show that galectins link the innate and adaptive immune systems and provide new insights into the action of sugar-binding proteins.

Liver damage and systemic inflammatory responses are exacerbated by the genetic deletion of CD39 in total hepatic ischemia.

Liver ischemia reperfusion injury is associated with both local damage to the hepatic vasculature and systemic inflammatory responses. CD39 is the dominant vascular endothelial cell ectonucleotidase and rapidly hydrolyses both adenosine triphosphate (ATP) and adenosine diphosphate to adenosine monophosphate. These biochemical properties, in tandem with 5'-nucleotidases, generate adenosine and potentially illicit inflammatory vascular responses and thrombosis. We have evaluated the role of CD39 in total hepatic ischemia reperfusion injury (IRI). Wildtype mice, Cd39-hemizygous mice (+/-) and matched Cd39-null mice (-/-); (n = 25 per group) underwent 45 min of total warm ischemia with full inflow occlusion necessitating partial hepatectomy. Soluble nucleoside triphosphate diphosphohydrolase (NTPDases) or adenosine/amrinone were administered to wildtype (n = 6) and Cd39-null mice (n = 6) in order to study protective effects in vivo. Parameters of liver injury, systemic inflammation, hepatic ATP determinations by P(31)-NMR and parameters of lung injury were obtained. All wildtype mice survived up to 7 days with minimal biochemical disturbances and minor evidence for injury. In contrast, 64% of Cd39+/- and 84% of Cd39-null mice required euthanasia or died within 4 h post-reperfusion with liver damage and systemic inflammation associated with hypercytokinemia. Hepatic ATP depletion was pronounced in Cd39-null mice posthepatic IRI. Soluble NTPDase or adenosine administration protected Cd39-deficient mice from acute reperfusion injury. We conclude that CD39 is protective in hepatic IRI preventing local injury and systemic inflammation in an adenosine dependent manner. Our data indicate that vascular CD39 expression has an essential protective role in hepatic IRI.

Evolving experience with prevention and treatment of splenic artery syndrome after orthotopic liver transplantation.

Impaired hepatic arterial perfusion after orthotopic liver transplantation (OLT) may lead to ischemic biliary tract lesions and graft-loss. Hampered hepatic arterial blood flow is observed in patients with hypersplenism, often described as arterial steal syndrome (ASS). However, arterial and portal perfusions are directly linked via the hepatic arterial buffer response (HABR). Recently, the term 'splenic artery syndrome' (SAS) was coined to describe the effect of portal hyperperfusion leading to diminished hepatic arterial blood flow. We retrospectively analyzed 650 transplantations in 585 patients. According to preoperative imaging, 78 patients underwent prophylactic intraoperative ligation of the splenic artery. In case of postoperative SAS, coil-embolization of the splenic artery was performed. After exclusion of 14 2nd and 3rd retransplantations and 83 procedures with arterial interposition grafts, SAS was diagnosed in 28 of 553 transplantations (5.1%). Twenty-six patients were treated with coil-embolization, leading to improved liver function, but requiring postinterventional splenectomy in two patients. Additionally, two patients with SAS underwent splenectomy or retransplantation without preceding embolization. Prophylactic ligation could not prevent SAS entirely (n = 2), but resulted in a significantly lower rate of complications than postoperative coil-embolization. We recommend prophylactic ligation of the splenic artery for patients at risk of developing SAS. Post-transplant coil-embolization of the splenic artery corrected hemodynamic changes of SAS, but was associated with a significant morbidity.

Biliary reconstruction using a side-to-side choledochocholedochostomy with or without T-tube in deceased donor liver transplantation: a prospective randomized trial.

OBJECTIVE: The biliary anastomosis is still one of the major causes for morbidity after orthotopic liver transplantation. The optimal method of reconstruction remains controversial. The aim of the study was to assess biliary complications after liver transplantation using a choledochocholedochostomy with or without a temporary T-tube. BACKGROUND DATA: Several reports have suggested that biliary reconstruction without T-tube is a safer method with a lower rate of biliary complications compared with T-tube insertion. METHODS: A total of 194 recipients of deceased donor liver grafts were randomized. In group 1 the biliary reconstruction was performed by side-to-side choledochocholedochostomy with (n = 99) and in group 2 (n = 95) without a T-tube. The T-tube was removed after 6 weeks. RESULTS: The overall biliary complication rate was significantly increased in group 2 (P < 0.0005). Biliary leaks occurred in 5 patients in group 1 and in 9 patients in group 2 (5.05% vs. 9.47%; P = 0.2756 ns). Anastomotic strictures of the bile duct were seen in 7 patients in group 1 and in 8 patients in group 2 (7.07% vs. 8.42%; P = 0.7923 ns). Two of the patients in group 1 and 5 patients in group 2 developed an ischemic type biliary lesion (2.02% vs. 5.26%; P = 0.2716 ns). The rate of reoperations was comparable in both groups. The rate of invasive interventions was higher in the group without T-tubes (9% vs. 18%, P = ns), as was the rate of cholangitis (5% vs. 11%. P = ns) and pancreatitis (4% vs. 14%, P = 0.0218). No complications after removal of the T-tube were observed. CONCLUSION: This study is a large prospective randomized trial to assess biliary complications that occur following liver transplantation, after anatomizing the bile duct with or without T-tubes. A significant increased rate of complications in the group without T-tube insertion was observed. In summary, our results indicate that the usage of T-tubes is safe and an excellent tool for the quality control of biliary anastomoses.

Long-term medical comorbidities and their management: hypertension/cardiovascular disease.

1. There is a high prevalence of cardiovascular risk factors in liver transplant recipients. 2. There is a high incidence of premature onset of cardiovascular disease. 3. The choice of calcineurin inhibitor shows no long-term impact. 4. Established cardiovascular risk scores may determine an individual's risk for cardiovascular events. 5. Posttransplant arterial hypertension is a major burden. 6. Strict surveillance guidelines are needed. 7. Threshold levels for arterial blood pressure according to recommendations for high-risk individuals should be applied. 8. Therapeutic lifestyle changes should be encouraged. 9. Escalating pharmacological treatment with respect to renal function is recommended. 10. Alterations of immunosuppression should be considered.

Modulation of endothelial cell migration by extracellular nucleotides: involvement of focal adhesion kinase and phosphatidylinositol 3-kinase-mediated pathways.

Extracellular nucleotides bind to type-2 purinergic/pyrimidinergic (P2) receptors that mediate various responses, such as cell activation, proliferation and apoptosis, implicated in inflammatory processes. The role of P2 receptors and their associated signal transduction pathways in endothelial cell responses has not been fully investigated. Here, it is shown that stimulation of human umbilical vein endothelial cells (HUVEC) with extracellular ATP or UTP increased intracellular free calcium ion concentrations ([Ca(2+)](i)), induced phosphorylation of focal adhesion kinase (FAK), p130(cas) and paxillin, and caused cytoskeletal rearrangements with consequent cell migration. Furthermore, UTP increased migration of HUVEC in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner. BAPTA or thapsigargin inhibited the extracellular nucleotide-induced increase in [Ca(2+)](i), a response crucial for both FAK phosphorylation and cell migration. Furthermore, long-term exposure of HUVEC to ATP and UTP, agonists of the G protein-coupled P2Y2 and P2Y4 receptor subtypes, caused upregulation of alpha(v) integrin expression, a cell adhesion molecule known to directly interact with P2Y2 receptors. Our results suggest that extracellular nucleotides modulate signaling pathways in HUVEC influencing cell functions, such as cytoskeletal changes, cellular adhesion and motility, typically associated with integrin-activation and the action of growth factors. We propose that P2Y2 and possibly P2Y4 receptors mediate those responses that are important in vascular inflammation, atherosclerosis and angiogenesis.

Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up.

BACKGROUND: Recurrence of hepatitis C (HCV) infection after orthotopic liver transplantation (OLT) in HCV-positive patients is almost universal. Severity of graft hepatitis increases during the long-term follow-up, and up to 30% of patients develop severe graft hepatitis and cirrhosis. However, there are still no clear predictors for severe recurrence. The aim of this study was to examine the 10-year outcome and risk factors for graft failure caused by HCV recurrence. METHODS: In a prospective analysis, 234 OLTs in 209 HCV-positive patients with a median age of 53 years were analyzed. Immunosuppression was based on cyclosporine A or tacrolimus in different protocols. Predictors for outcome were genotype, viremia, donor variables, recipient demographics, postoperative immunosuppression, and human leukocyte antigen (HLA) compatibilities. RESULTS: Actuarial 5-, and 10-year patient survival was 75.8% and 68.8%. Eighteen of 209 (8.7%) patients died because of HCV recurrence, which was responsible for 35.9% of the total 53 deaths. Significant risk factors for HCV-related graft failure in an univariate analysis were multiple steroid pulses, use of OKT3, and donor age greater than 40. However, in a multivariate analysis, multiple rejection treatments with steroids and OKT3 treatment proved to be significantly associated with HCV-related graft loss. CONCLUSIONS: The analysis of causes leading to graft failure in patients with HCV showed that HCV recurrence is responsible for one of three deaths in HCV-positive patients. Rejection treatment contributed significantly to an enhanced risk for HCV-related graft loss. New antiviral treatments, as well as adapted immunosuppressive protocols, will be necessary to further improve the outcome of HCV-positive patients after liver transplantation.

Impact of human leukocyte antigen matching in liver transplantation.

BACKGROUND: Human leukocyte antigen (HLA) compatibilities are beneficial in the setting of kidney transplantation but have demonstrated inconclusive results after liver transplantation. On the basis of recent controversial reports, the authors analyzed the impact of HLA matching in their patients after liver transplantation under modern immunosuppressive drug regimens and new HLA typing techniques with respect to outcome and adverse immunologic events. METHODS: Data from 924 transplants with complete donor-recipient HLA typing were retrospectively analyzed. Immunosuppression was commenced as either cyclosporine A- or tacrolimus-based therapy in different protocols. The follow-up period ranged from 1 to 144.8 months (median, 66 months). RESULTS: The actuarial graft survival was 88% after 1 year and 78.7% after 5 years and was similar in tacrolimus- and cyclosporine A-treated patients. However, cyclosporine A-treated patients underwent significantly more rejection episodes. The number of HLA compatibilities had no influence on graft survival, whereas the number of acute rejections was significantly less in transplants with more HLA compatibilities (P<0.05). Graft survival tended to be improved in patients with chronic hepatitis B and more HLA compatibilities (P=0.05). In contrast, graft survival in transplants for primary sclerosing cholangitis was significantly impaired in the presence of one or two HLA-DR compatibilities (P<0.05). In addition, in autoimmune hepatitis, survival tended to be lower in the presence of more HLA compatibilities (P=0.1). Overall graft survival or frequency of adverse immunologic events was not influenced by any specific donor-recipient HLA allele. CONCLUSION: This study demonstrated fewer acute rejections in transplants with more HLA compatibilities. However, in liver transplantation, a more specific investigation of HLA typing may be necessary, because in some indications HLA antigens play a role in the nature of the disease. Therefore, recurrence of autoimmune disease may be more severe in patients sharing HLA antigens.

Quality control of the European Liver Transplant Registry: results of audit visits to the contributing centers.

BACKGROUND: The number of registries is increasing, but few of them perform reliability audits by comparing the data contained in the database with data contained in hospital charts. METHODS: The European Liver Transplant Registry (ELTR) cocoordinating committee appointed an independent team to check the reliability of data contained in ELTR. Centers were selected at random. Ten percent of each center's files were selected at random, and 25 items per file were checked during the site visits. The rates of completeness and inconsistencies and the agreement between ELTR and charts were established. We also assessed the correlation between the quality of data and the visited centers' activity. RESULTS: Seven hundred thirty-four files from 21 centers have been audited between June 1998 and June 2001. The rate of ELTR completeness was 95%, and the rate of consistency between charts and ELTR was 98%. The agreement between the ELTR and charts review was very good for all conditions (kappa value < or =0.81). However, comparisons of rates between items indicated that specific items, mostly cause of death or graft failure and patient outcome, should be targeted for improvement. No significant correlation was found between the quality of data and the experience of visited centers. The mean (min-max) and median cost per audited file were EUR 60 (8-150) and EUR 44, respectively. CONCLUSION: The results of audit visits indicate that ELTR data are reliable, and the scientific results of ELTR can be considered credible and representative of liver transplantation in Europe. The method could serve as a model for auditing a registry.

Localization of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and NTPDase2 in pancreas and salivary gland.

Ectonucleoside triphosphate diphosphohydrolases (NTPDases) are membrane-bound ectoenzymes that hydrolyze extracellular nucleotides. We investigated the distribution of NTPDase1 and NTPDase2 in murine salivary gland and pancreas. Histochemistry and immunostaining (by both light and electron microscopy), combined with functional assays, were used to describe the localization patterns and enzyme activities in the organs of wild-type and NTPDase1/cd39-null mice. Pancreatic acinar cells and salivary gland acinar/myoepithelial cells were positive for NTPDase1 and NTPDase2. Ecto-ATPase activity was slightly higher in salivary glands. Ductal epithelial cells expressed ecto-ATPase activity but NTPDase1 and NTPDase2 expression were weak at best. ATPase activity was found in blood vessels of both tissues and its localization pattern overlapped with NTPDase1 staining. In these structures, NTPDase2 antibodies stained the basolateral aspect of endothelial cells and the supporting cells. Biochemical assays and histochemical staining showed relatively high levels of ATPase activity in both glands of cd39(-/-) mice. Our data therefore support a physiological role for NTPDase2 and other ectonucleotidases in the pancreas and salivary glands. Because NTPDase1 is expressed in non-vascular cell types, this finding suggests that NTPDase1 may have functions in the gastrointestinal tract that differ from those demonstrated in the vascular system.

Beneficial effects of CD39/ecto-nucleoside triphosphate diphosphohydrolase-1 in murine intestinal ischemia-reperfusion injury.

CD39 (ecto-nucleoside triphosphate diphosphohydrolase-1; E-NTPDase-1), is highly expressed on quiescent vascular endothelial cells and efficiently hydrolyzes extracellular ATP and ADP to AMP and ultimately adenosine. This action blocks extracellular nucleotide-dependent platelet aggregation and abrogates endothelial cell activation. However, CD39 enzymatic activity is rapidly lost following exposure to oxidant stress. Modulation of extracellular nucleotide levels may therefore play an important role in the pathogenesis of vascular injury. Acute ischemic injury of the bowel is a serious medical condition characterized by high mortality rates with limited therapeutic options. Here we evaluate the effects of cd39-deletion in mutant mice and the use of supplemental NTPDase or adenosine in influencing the outcomes of intestinal ischemia-reperfusion. Wild-type, cd39-null, or hemizygous cd39-deficient mice were subjected to intestinal ischemia. In selected animals, 0.2 U/g apyrase (soluble NTPDase) was administered prior to re-establishment of blood-flow. In parallel experiments adenosine/amrinone was infused over 60 min during reperfusion periods. Survival rates were determined, serum and tissue samples were taken. Intravital videomicroscopy and studies of vascular permeability were used to study platelet-endothelial cell interactions and determine capillary leakage. In wild-type animals, ischemia reperfusion injury resulted in 60% mortality within 48 hours. In mutant mice null or deficient for cd39, ischemia reperfusion-related death occurred in 80% of animals. Apyrase supplementation protected all wild-type animals from death due to intestinal ischemia but did not fully protect cd39-null and cd39-hemizygote mice. Adenosine/amrinone treatment failed to improve survival figures. In wild type mice, platelet adherence to postcapillary venules was significantly decreased and vascular integrity was well preserved following apyrase administration. In cd39-null mice, ischemia-reperfusion induced marked albumin leakage indicative of heightened vascular permaeability when compared to wild-type animals (p=0.04). Treatment with NTPDase or adenosine supplementation abrogated the increased vascular permeability in ischemic jejunal specimens of both wild-type mice and cd39-null. CD39 activity modulates platelet activation and vascular leak during intestinal ischemia reperfusion injury in vivo. The potential of NTPDases to maintain vascular integrity suggests potential pharmacological benefit of these agents in mesenteric ischemic injury.

Prognostic factors for long-term survival in patients with ampullary carcinoma: the results of a 15-year observation period after pancreaticoduodenectomy.

Introduction. Although ampullary carcinoma has the best prognosis among all periampullary carcinomas, its long-term survival remains low. Prognostic factors are only available for a period of 10 years after pancreaticoduodenectomy. The aim of this retrospective study was to identify factors that influence the long-term patient survival over a 15-year observation period. Methods. From 1992 to 2007, 143 patients with ampullary carcinoma underwent pancreatic resection. 86 patients underwent pylorus-preserving pancreaticoduodenectomy (60%) and 57 patients underwent standard Kausch-Whipple pancreaticoduodenectomy (40%). Results. The overall 1-, 5-, 10-, and 15-year survival rates were 79%, 40%, 24%, and 10%, respectively. Within a mean observation period of 30 (0-205) months, 100 (69%) patients died. Survival analysis showed that positive lymph node involvement (P = 0.001), lymphatic vessel invasion (P = 0.0001), intraoperative administration of packed red blood cells (P = 0.03), an elevated CA 19-9 (P = 0.03), jaundice (P = 0.04), and an impaired patient condition (P = 0.01) are strong negative predictors for a reduced patient survival. Conclusions. Patients with ampullary carcinoma have distinctly better long-term survival than patients with pancreatic adenocarcinoma. Long-term survival depends strongly on lymphatic nodal and vessel involvement. Moreover, a preoperative elevated CA 19-9 proved to be a significant prognostic factor. Adjuvant therapy may be essential in patients with this risk constellation.

The impact of elevated serum IgG4 levels in patients with primary sclerosing cholangitis.

BACKGROUND: Elevated IgG4 levels have been reported among patients with primary sclerosing cholangitis. Epidemiological data has only been provided from tertiary centres. AIMS: To investigate the prevalence of elevated IgG4 levels and to compare prognosis between patients with and without elevated IgG4 levels in serum in two European cohorts of patients with primary sclerosing cholangitis. METHODS: Serum IgG4-levels were measured in a consecutive series of patients from Berlin, and retrospectively collected in a population-based cohort from Sweden (total N=345). Cox's proportional hazard analysis was used to calculate relative risks for liver-related death or liver transplantation and cholangiocarcinoma. RESULTS: Elevated IgG4 values were demonstrated in 10% of patients. A previous history of pancreatitis, combined intra- and extrahepatic biliary involvement and jaundice were independently associated with elevated IgG4 in multivariate analysis. IgG4 status was not associated with an increased risk for the combined endpoint liver-related death or liver transplantation or cholangiocarcinoma. CONCLUSION: The prevalence of elevated IgG4 values among European patients with primary sclerosing cholangitis is similar to what previously has been reported from the United States. Elevated IgG4 was not associated with an increased risk of liver transplantation or liver-related death or cholangiocarcinoma.

Incidence, risk factors and management of incisional hernia in a high volume liver transplant center.

BACKGROUND: Incisional hernia after liver transplantation is a common complication with an incidence between 5% and 34%. This prospective study analyzed risk factors, surgical management and long-term results after hernia repair. MATERIAL AND METHODS: From February 2002 until August 2009, 810 liver transplantations were performed. 77 patients (9.5%) underwent incisional hernia repair after a median time of 21.1 months (4.6-76.7) following transplant. These patients were compared to patients without hernia (n=733). RESULTS: No statistically significant differences between the groups were observed with respect to gender, underlying liver disease, Child-Pugh classification, MELD-Score and preoperative renal failure (p=NS). Multivariate analysis revealed advanced age (p=0.014), body mass index (p=0.016), and re-laparotomies (p<0.001) as independent risk factors for incisional hernias. Pre-existing diabetes mellitus and immunosuppression with mycophenolate mofetil reached significance only in the univariate analysis (p<0.001). Recurrent hernia was observed in 12 of 77 patients (15.6%) at a median time of 7.9 months (4.8-46.8) after primary surgical repair. The recurrence rate after intraperitoneal onlay mesh implantation was lower compared to other mesh techniques (7.7% vs. 21.4%). CONCLUSIONS: The risk factors for the development of incisional hernias in liver transplant patients are similar to patients with prior abdominal surgery for other reasons. Intraperitoneal onlay mesh implantation may lead to a decrease of hernia recurrences. The role of immunosuppression in the genesis of incisional hernias requires further elucidation.

Survival without biliary complications after liver transplant for primary sclerosing cholangitis.

OBJECTIVES: Patients who have a liver transplant for primary sclerosing cholangitis may develop recurrent disease and biliary complications, organ loss necessitating revision liver transplant, or death. We evaluated long-term outcomes in patients who had liver transplant for primary sclerosing cholangitis. MATERIALS AND METHODS: In 71 patients who had a liver transplant for end-stage liver disease because of primary sclerosing cholangitis, a retrospective review was done to evaluate biliary complication-free survival, transplanted organ survival, and death. Human leukocyte antigen typing and matching were reviewed. RESULTS: There were 39 patients (55%) who had biliary complications, loss of the liver transplant, or death at a mean 12.1 years after transplant. The 5- and 10-year event-free survival reached 74.6% and 45% (53 patients after 5 years, and 32 patients after 10 years). Male sex of transplant recipients was a significant risk factor for biliary complications, revision liver transplant, or death. Most patients had inflammatory bowel disease, primarily ulcerative colitis. The human leukocyte antigen profile or number of mismatches had no effect on complication-free survival. CONCLUSIONS: Biliary complications, revision liver transplant, and death are a useful combined primary endpoint for recurrent primary sclerosing cholangitis after liver transplant.