Role of nutrition in liver transplantation for end-stage chronic liver disease

Patients with end-stage liver disease often reveal significant protein-energy malnutrition, which may deteriorate after listing for transplantation. Since malnutrition affects post-transplant survival, precise assessment must be an integral part of pre- and post-surgical management. While there is wide agreement that aggressive treatment of nutritional deficiencies is required, strong scientific evidence supporting nutritional therapy is sparse. In practice, oral nutritional supplements are preferred over parenteral nutrition, but enteral tube feeding may be necessary to maintain adequate calorie intake. Protein restriction should be avoided and administration of branched-chain amino acids may help yield a sufficient protein supply. Specific problems such as micronutrient deficiency, fluid balance, cholestasis, encephalopathy, and comorbid conditions need attention in order to optimize patient outcom

Validation of the Estimation of Physiologic Ability and Surgical Stress (E-PASS) Score in Liver Surgery

Background: The estimation of physiologic ability and surgical stress (E-PASS) has been used to produce a numerical estimate of expected mortality and morbidity after elective gastrointestinal surgery. The aim of this study was to validate E-PASS in a selected cohort of patients requiring liver resections (LR). Methods: In this retrospective study, E-PASS predictor equations for morbidity and mortality were applied to the prospective data from 243 patients requiring LR. The observed rates were compared with predicted rates using Fisher's exact test. The discriminative capability of E-PASS was evaluated using receiver-operating characteristic (ROC) curve analysis. Results: The observed and predicted overall mortality rates were both 3.3% and the morbidity rates were 31.3 and 26.9%, respectively. There was a significant difference in the comprehensive risk scores for deceased and surviving patients (p=0.043). However, the scores for patients with or without complications were not significantly different (p=0.120). Subsequent ROC curve analysis revealed a poor predictive accuracy for morbidity. Conclusions: The E-PASS score seems to effectively predict mortality in this specific group of patients but is a poor predictor of complications. A new modified logistic regression might be required for LR in order to better predict the postoperative outcom

Long-Term Quality of Life After Hepatic Resection: Health Is not Simply the Absence of Disease

Background: Due to advances in operative methods and perioperative care, mortality and morbidity following major hepatic resection have decreased substantially, making long-term quality of life (QoL) an increasingly prominent issue. We evaluated whether postoperative diagnosis was associated with long-term QoL and health in patients requiring hepatic surgery for benign or malignant disease. Methods: QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and the liver-specific QLQ-LMC21 module. Results: Between 2002 and 2006, 249 patients underwent hepatic surgery for malignant (76%) and benign (24%) conditions. One hundred thirty-five patients were available for QoL analysis after a mean of 26.5months. There was no statistical difference in global QoL scores between patients with malignant and benign diseases (p=0.367). Neither the extent of the resection (≥2 segments vs. <2 segments; p=0.975; OR=0.988; 95% CI=0.461-2.119) nor patient age had a significant influence on overall QoL (p=0.092). Conclusions: These results indicate that long-term QoL for patients who underwent liver resection for malignant disease is quite good and that a poor clinical prognosis does not seem to correlate with a poor Qo

Functional comparison of bone marrow-derived liver stem cells: Selection strategy for cell-based therapy

Several distinct subpopulations of bone marrow-derived liver progenitor cells were recently described. However, there is inadequate information comparing these subpopulations from a liver-function point of view. This study was undertaken to compare two subpopulations of liver progenitors: β2-microglobulin (β2m)-negative/Thy-1-positive cells, and liver progenitors obtained from the non-adherent cell fraction after a panning procedure. The cells were cultured under several conditions including high- and lowdose hepatocyte growth factor, various cellular densities, and different media. Growth characteristics, liver-specific metabolic capacity, and liver regeneration-associated gene expression were studied. Both isolation procedures yielded cells that produced albumin and metabolized ammonia into urea. The study demonstrated that the β2m-negative/Thy-1-positive cell fraction metabolized ammonia into urea more efficiently and produced a superior amount of albumin compared with the panned cell fraction. The β2m-negative/Thy-1-positive cell fraction could be optimal for the development of novel cell-based treatment strategies for congenital or acquired liver disease

Strengthening Cooperation and Enhancing Activation in Problem-Based Learning through Concrete External Representations

In this pilot study, an effort was made to strengthen cooperation and enhance activation in medical problem-based learning. We compared traditional problem-based learning sessions with learning sessions of smaller groups that used a concrete external representation tool. Our experience shows that the use of icons for representing problems and solutions has important advantages for collaborative learning and the way problems are positioned and connected to prior knowledge. Other advantages of this approach seem to be an increase of individual participation and a decreasing need for tutor supervision. The results of this pilot study encourage the investigation of this promising educational method on a larger scale.In dieser Pilotstudie wurde untersucht, wie im medizinischen Problem-Based Learning die Kooperation zwischen Studierenden gestärkt und ihre Aktivität erhöht werden kann. Wir verglichen traditionelle Seminare mit Sitzungen kleinerer Gruppen, die Gegenstände für konkrete externe Repräsentationen benutzten. Wir fanden heraus, dass die bildliche Darstellung von Problemen und Lösungen die Zusammenarbeit stärkt, da Probleme besser erkundet und mit Vorwissen verknüpft werden. Des Weiteren beteiligten sich die Studierenden deutlich häufiger und hatten weniger Bedarf an Unterstützung durch Tutoren. Die Ergebnisse dieser Pilotstudie regen zur weiteren Erkundung dieser vielversprechenden Ausbildungsmethode an

Interleukin-3 induces hepatocyte-specific metabolic activity in bone marrow-derived liver stem cells

Bone marrow-derived adult liver stem cells (BALSC) are a promising target for the development of future cell-based therapies for a variety of liver disorders. However, the ability of stem cells to fully function, as hepatocytes, is limited and differentiation is time dependent. Therefore, it will be conducive to find a growth factor that is able to enhance liver-specific metabolic activity in freshly isolated liver stem cells. Recently, a subpopulation of BALSC was isolated and characterized (β2-microglobulin-negative/ Thy-1-positive cells). We hypothesized that using interleukin-3 (IL-3), a hematopoietic differentiation growth factor, we may be able to enhance liver-specific metabolic activity in freshly isolated BALSC. Rat BALSC from normal and injured livers (bile duct ligated) were isolated and stimulated with IL-3 in culture. Cells were co-cultured with or without hepatocytes, separated by a semipermeable membrane. We measured the effect of IL-3 on BALSC to metabolize ammonia into urea (a liver-specific metabolic activity). IL-3 increased the ability of BALSC, purified from normal animals, to metabolize ammonia into urea by several folds. Interestingly, no such effect was found in cell cultures from bile ductligated animals. Additionally, co-cultures of BALSC with hepatocytes induced higher rate of ammonia metabolism, which was further enhanced by IL-3. Our study indicates that IL-3 may be used as an agent to enhance differentiation of BALSC, both qualitatively and quantitatively. It is conceivable that stem cells may undergo IL-3 priming before their clinical application in cell transplantation or bioartificial liver system

Stent grafting of acute hepatic artery bleeding following pancreatic head resection

The purpose of this study was to report the potential of hepatic artery stent grafting in cases of acute hemorrhage of the gastroduodenal artery stump following pancreatic head resection. Five consecutive male patients were treated because of acute, life-threatening massive bleeding. Instead of re-operation, emergency angiography, with the potential of endovascular treatment, was performed. Because of bleeding from the hepatic artery, a stent graft (with the over-the-wire or monorail technique) was implanted to control the hemmorhage by preserving patency of the artery. The outcome was evaluated. In all cases, the hepatic artery stent grafting was successfully performed, and the bleeding was immediately stopped. Clinically, immediately after the procedure, there was an obvious improvement in the general patient condition. There were no immediate procedure-related complications. Completion angiography (n=5) demonstrated control of the hemorrhage and patency of the hepatic artery and the stent graft. Although all patients recovered hemodynamically, three individuals died 2 to 10days after the procedure. The remaining two patients survived, without the need for re-operation. Transluminal stent graft placement in the hepatic artery is a safe and technically feasible solution to control life-threatening bleeding of the gastroduodenal artery stum

How to Counter the Problem of R1 Resection in Duodenopancreatectomy for Pancreatic Cancer?

Objective: Although duodenopancreatectomy has been standardized for many years, the pathological examination of the specimen was re-described in the last years. In methodical pathological studies up to 85% had an R1 margin.1,2 These mainly involved the posterior und medial resection margin.3 As a consequence we need to optimize and standardize the pathological workup of the specimen and to extend the surgical resection, where possible without risk for the patient. Method and Result: In an instructive video we show the technique of duodenopancreatectomy with emphasis on the dorsal and medial resection margin. Furthermore we show the standardized pathological workup of the specimen, involving the reporting of all the resection margins. Conclusion: To accurately determine R1 status at the posterior and medial resection margin, a close collaboration between pathologist and surgeon is crucial. Pathologists do a standardized workup of the resected specimen with staining of the surfaces and systematic analysis of all the resection margins. Surgeons need to extend the resection of the pancreatic head to the superior mesenteric artery by dorsal dissectio

Indocyanine Green Plasma Disappearance Rate During the Anhepatic Phase of Orthotopic Liver Transplantation

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI] = 0.8-2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into accoun

The homeobox gene HLXB9 is upregulated in a morphological subset of poorly differentiated hepatocellular carcinoma

The prognostic outcome for hepatocellular carcinoma (HCC) remains poor. Disease progression is accompanied by dedifferentiation of the carcinoma, a process that is not well understood. The aim of this study was to get more insight into the molecular characteristics of dedifferentiated carcinomas using high throughput techniques. Microarray-based global gene expression analysis was performed on five poorly differentiated HCC cell lines compared with non-neoplastic hepatic controls and a set of three cholangiolar carcinoma (CC) cell lines. The gene with the highest upregulation was HLXB9. HLXB9 is a gene of the homeobox genfamily important for the development of the pancreas. RT-PCR confirmed the upregulation of HLXB9 in surgical specimens of carcinoma tissue, suggesting its biological significance. Interestingly, HLXB9 upregulation was primary observed in poorly differentiated HCC with a pseudoglandular pattern compared with a solid pattern HCC or in moderate or well-differentiated HCC. Additional the expression of translated HLXB9, the protein HB9 (NCBI: NP_001158727), was analyzed by western blotting. Expression of HB9 was only detected in the cytoplasm but not in the nuclei of the HCC cells. For validation CC were also investigated. Again, we found an upregulation of HLXB9 in CC cells accompanied by an expression of HB9 in the cytoplasms of these tumor cells, respectively. In conclusion, homeobox HLXB9 is upregulated in poorly differentiated HCC with a pseudoglandular pattern. The translated HB9 protein is found in the cytoplasm of these HCC and CC. We therefore assume HLXB9 as a possible link in the understanding of the development of HCC and CC, respectivel