AIM: To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver transplantation.METHODS: We retrospectively reviewed 200 patients of our newly est...AIM: To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver transplantation.METHODS: We retrospectively reviewed 200 patients of our newly established liver transplantation(LT) program, who received full size liver graft. Biliary reconstruction was performed by side-to-side(SS), end-to-end(EE) anastomosis or hepeaticojejunostomy(HJ). Biliary complications(BC), anastomotic stenosis, bile leak, papillary stenosis, biliary drain complication, ischemic type biliary lesion(ITBL) were evaluated by studying patient records, corresponding radiologic imaging and reports of interventional procedures [e.g., endoscopic retrograde cholangiopancreatography(ERCP)]. Laboratory results included alanine aminotransferase(ALT), gammaglutamyltransferase and direct/indirect bilirubin with focus on the first and fifth postoperative day, six weeks after LT. The routinely employed external bile drain was examined by a routine cholangiography on the fifth postoperative day and six weeks after transplantation as a standard procedure, but also whenever clinically indicated. If necessary, interventional(e.g., ERCP) or surgical therapy was performed. In case of biliary complication, patients were selected, assigned to different complication-groups and subsequently reviewed in detail. To evaluate the patients outcome, we focussed on appearance of postoperative/post-interventional cholangitis, need for rehospitalisation, retransplantation, ITBL or death caused by BC.RESULTS: A total of 200 patients [age: 56(19-72), alcoholic cirrhosis: n = 64(32%), hepatocellular carcinoma: n = 40(20%), acute liver failure: n = 23(11.5%), cryptogenic cirrhosis: n = 22(11%), hepatitis B virus /hepatitis C virus cirrhosis: n = 13(6.5%), primary sclerosing cholangitis: n = 13(6.5%), others: n = 25(12.5%) were included. The median follow-up was 27 mo until June 2015. The overall biliary complication rate was 37.5%(n = 75) with anastomotic strictures(AS): n = 38(19%), bile leak(BL): n = 12(6%), biliary drain complication: n = 12(6%); papillary stenosis(PS): n = 7(3.5%), ITBL: n = 6(3%). Clinically relevant were only 19%(n = 38). We established a comprehensive classification for AS with four grades according to clinical relevance. The reconstruction techniques [SS: n = 164, EE: n = 18, HJ: n = 18] showed no significant impact on the development of BCs in general(all n < 0.05), whereas in the HJ group significantly less AS were found(P = 0.031). The length of donor intensive care unit stay over 6 d had a significant influence on BC development(P = 0.007, HR = 2.85; 95%CI: 1.33-6.08) in the binary logistic regression model, whereas other reviewed variables had not [warm ischemic time > 45 min(P = 0.543), cold ischemic time > 10 h(P = 0.114), ALT init > 1500 U/L(P = 0.631), bilirubin init > 5 mg/d L(P = 0.595), donor age > 65(P = 0.244), donor sex(P = 0.068), rescue organ(P = 0.971)]. 13%(n = 10) of BCs had no therapeutic consequences, 36%(n = 27) resulted in repeated lab control, 40%(n = 30) received ERCP and 11%(n = 8) surgical therapy. Fifteen(7.5%) patients developed cholangitis [AS(n = 6), ITBL(n = 5), PS(n = 3), biliary lesion BL(n = 1)]. One patient developed ITBL twelve months after LT and subsequently needed retransplantation. Rehospitalisation rate was 10.5 %(n = 21) [AS(n = 11), ITBL(n = 5), PS(n = 3), BL(n = 1)] with intervention or reinterventional therapy as main reasons. Retransplantation was performed in 5(2.5%) patients [ITBL(n = 1), acute liver injury(ALI) by organ rejection(n = 3), ALI by occlusion of hepatic artery(n = 1)]. In total 21(10.5%) patients died within the follow-up period. Out of these, one patient with AS developed severe fatal chologenic sepsis after ERCP.CONCLUSION: In our data biliary reconstruction technique and ischemic times seem to have little impact on the development of BCs.展开更多
AIM： Recently it has been reported that granulocyte colony stimulating factor （G-CSF） can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a ...AIM： Recently it has been reported that granulocyte colony stimulating factor （G-CSF） can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model. METHODS： A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk. RESULTS： Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals. CONCLUSION： G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications .展开更多
<div style="text-align:justify;"> <strong>Introduction: </strong>Liver transplantation (LT) in children has undergone significant changes over the last years. Especially the use of split an...<div style="text-align:justify;"> <strong>Introduction: </strong>Liver transplantation (LT) in children has undergone significant changes over the last years. Especially the use of split and living donor transplants even for infants has led to new challenges in pre- and post-operative care. Systemic inflammatory response syndromes (SIRS, sepsis) as well-known complications after LT have not yet been systematically examined in the pediatric population. <strong>Methods:</strong> We analyzed clinical data of 39 pediatric liver transplant recipients regarding potential risk factors for post-transplant SIRS and sepsis. Secondly, the prognostic impact of SIRS and sepsis on post-transplant clinical course, patient and transplant-survival has been analyzed. <strong>Results:</strong> 64% of patients developed either SIRS (n = 16, 41%) or sepsis (n = 9, 23%) within 30 days after transplantation. No pre-transplant risk factors for increased susceptibility for SIRS or sepsis could be identified. Secondary closure of the abdomen (p = 0.045) and secondary biliary reconstruction (p = 0.043) were associated with a higher incidence of sepsis and were associated with significantly prolonged mechanical ventilation times in the presence of sepsis (p = 0.001). Patients with sepsis, but not SIRS, stayed significantly longer on PICU (p = 0.021) and suffered from higher mortality (n = 3 versus 0;p = 0.0006). All deaths within 30 days of transplantation were due to septic multiorgan failure. Neither early SIRS nor sepsis were associated with loss of transplant function. <strong>Conclusions:</strong> SIRS and sepsis are frequent events after pediatric liver transplantation. Sepsis increased length of PICU-stay and mortality significantly and prolonged duration of mechanical ventilation. Secondary biliary reconstruction and closure of the abdomen could be identified as potential risk factors for sepsis. </div>展开更多
Background:Successful liver resection in oncologic surgery depends on safety,precision,and efficacy,all of which require a thorough understanding of liver anatomy.Contrast-enhanced computed tomography(CT)-generated th...Background:Successful liver resection in oncologic surgery depends on safety,precision,and efficacy,all of which require a thorough understanding of liver anatomy.Contrast-enhanced computed tomography(CT)-generated three-dimensional(3D)models have been proposed as a valuable tool to enhance this understanding.However,a systematic comparison of different display modalities across professional groups has not yet been performed.Methods:In this prospective,monocentric randomized trial,we compared high-resolution twodimensional(2D)CT images of liver malignancies with their corresponding standardized,non-colored 3D virtual and printed models in facilitating anatomical and spatial understanding as well as surgical decision-making.A total of 91 participants,including 40 surgeons,10 radiologists,and 41 students,evaluated six clinical cases(three centrally and three peripherally located liver malignancies).Each participant assessed one central and one peripheral case per display modality,presented in a random order.Results:Compared to 2D CT images,both 3D virtual and printed models significantly improved the identification of tumor location(P<0.001),enhanced the comprehension of spatial relationships with adjacent liver and portal veins(P<0.001 and P=0.019,respectively),and facilitated clinical decisionmaking(P<0.001).No significant difference was observed between virtual and printed models in terms of effectiveness.Within the different groups,surgeons and students,but not radiologists,more accurately identified tumor location and spatial relationships with adjacent liver and portal veins using 3D models.Subjectively,most surgeons and students preferred 3D printed models over virtual models and 2D CT images.Conclusions:This study demonstrated that standardized,non-colored 3D virtual and printed models equally help preoperative anatomical understanding and decision-making,particularly for surgeons and students.By isolating the influence of display modality,our findings clarify prior inconsistent results and support the integration of cost-effective 3D visualization by applying virtual models into surgical planning and education.Preference for printed models despite comparable efficacy highlights the importance of user-centered implementation strategies.展开更多
AIM: To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuva...AIM: To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen.METHODS: Formalin fixed, paraffin embedded pre-therapeutical tumor biopsies (n = 22) and post-therapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage Ⅱ/Ⅲ) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan real-time PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system.RESULTS: Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a low Ki67 index in the pre-therapeutical tumor biopsies (corr. coef. = 0.46; P < 0.01) as well as in the post-therapeutical resection specimens (corr. coef. = 0.40; P < 0.05). No significant association was found between p53 and TS mRNA expression or tumor regression.CONCLUSION: Ki67 has, like TS, predictive value in rectal cancer patients after neoadjuvant 5-FU based chemoradiotherapy. The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.展开更多
Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible o...Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography （ERC） showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right Iobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.展开更多
AIM To characterize major determinants of 20-year survival after liver transplantation(LT).METHODS This longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. ...AIM To characterize major determinants of 20-year survival after liver transplantation(LT).METHODS This longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease(labM ELD)-score and the Eurotransplant Donor Risk Index(ET-DRI) to unravel their impact on 20-year survival after LT.RESULTS Twenty-year survivors were significantly younger(44 vs 50 years, P = 0.001), more likely to be female(49% vs 36%, P = 0.03) and less likely to be obese at the time of LT(19% vs 32%, P = 0.011). Mean labM ELD-score(P = 0.156), rate of high-urgency LT(P = 0.210), coldischemia time(P = 0.994), rate of retransplantation(P = 0.12) and average donor age(28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors(P = 0.007). ET-DRI > 1.4(P = 0.020) and donor age ≥ 30 years(P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labM ELD-score categories(P = 0.263).CONCLUSION LT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor-recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs.展开更多
Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive ca...Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a signifi cant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.展开更多
Metastatic disease from cutaneous melanoma can af-fect all organs of the body, and varies in its biological behavior and clinical presentation. We present the case of a 58-year-old man who arrived at our clinic with a...Metastatic disease from cutaneous melanoma can af-fect all organs of the body, and varies in its biological behavior and clinical presentation. We present the case of a 58-year-old man who arrived at our clinic with acute abdominal pain, which, after investigation, was diagnosed as acute cholecystitis. The patient under-went laparotomy and cholecystectomy. Two years ago, he underwent surgical removal of a primary cutaneous melanoma on his right upper back. Pathological exami-nation revealed the presence of malignant melanoma with a metastatic lesion of the gallbladder.展开更多
BackgroundOriginally, cava reconstruction (CR) in liver transplantation meant complete resection and reinsertion of the donor cava. Alternatively, preservation of the recipients inferior vena cava (IVC) with side-to-s...BackgroundOriginally, cava reconstruction (CR) in liver transplantation meant complete resection and reinsertion of the donor cava. Alternatively, preservation of the recipients inferior vena cava (IVC) with side-to-side anastomosis (known as “piggyback”) can be performed. Here, partial clamping maintains blood flow of the IVC, which may improve cardiovascular stability, reduce blood loss and stabilize kidney function. The aim of this study was to compare both techniques with particular focus on kidney function.MethodsA series of 414 patients who had had adult liver transplantations (2006-2009) were included. Among them, 176 (42.5%) patients had piggyback and 238 had classical CR operation, 112 (27.1%) of the patients underwent CR accompanied with veno-venous bypass (CR-B) and 126 (30.4%) without a bypass. The choice of either technique was based on the surgeons' individual preference. Kidney function [serum creatinine, calculated glomerular filtration rate (GFR), RIFLE stages] was assessed over 14 days.ResultsLab-MELD scores were significantly higher in CR-B (22.5±11.0) than in CR (17.3±9.0) and piggyback (18.8±10.0) (P=0.008). Unexpectedly, the incidences of arterial stenoses (P=0.045) and biliary leaks (P=0.042) were significantly increased in piggyback. Preoperative serum creatinine levels were the highest in CR-B [1.45±1.17 vs 1.25±0.85 (piggyback) and 1.13±0.60 mg/dL (CR); P=0.033]. Although a worsening of postoperative kidney function was observed among all groups, this was most pronounced in CR-B [creatinine day 14: 1.67±1.40 vs 1.35±0.96 (piggyback) and 1.45±1.03 mg/dL (CR); P=0.102]. Accordingly, the proportion of patients displaying RIFLE stages ≥2 was the highest in CR/CR-B (26%/19%) when compared to piggyback (18%).ConclusionsPiggyback revealed a shorter warm ischemic time, a reduced blood loss, and a decreased risk of acute kidney failure. Thus, piggyback is a useful technique, which should be applied in standard procedures. When piggyback is unfeasible, cava replacement, which displayed a lower incidence of vascular and biliary complications in our study, remains as a safe alternative.展开更多
BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of t...BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically significant.CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.展开更多
Hirschsprung＇s disease （HD） is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowe...Hirschsprung＇s disease （HD） is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel, However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of lid in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient＇s bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify lid patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage. 2005 The WJG Press and Elsevier Inc. All rights reserved展开更多
AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation o...AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels. CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.展开更多
A 17-year-old girl with colicky abdominal pain andchronic anemia presented to the gastrointestinal serviceof the University Hospital of Essen. In the routineworkup, there were no pathological findings despitethe anemi...A 17-year-old girl with colicky abdominal pain andchronic anemia presented to the gastrointestinal serviceof the University Hospital of Essen. In the routineworkup, there were no pathological findings despitethe anemia. Because of the fluctuation of symptomswith a climax at the time of menstruation, consecutiveultrasound studies were performed revealing a visiblemass inside the gallbladder. This finding was confirmedby a magnetic resonance imaging (MRI) study performedat the same time. Because of the severe anemia by thattime, a cholecystectomy was performed, and histologyreconfirmed the diagnosis of isolated gallbladderendometriosis. The patient recovered well and has hadno recurrence of the disease to date.展开更多
Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a di...Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy.展开更多
Background:Malnutrition is recognised as a preoperative risk factor for patients undergoing hepatic resection.It is important to identify malnourished patients and take preventive therapeutic action before surgery.How...Background:Malnutrition is recognised as a preoperative risk factor for patients undergoing hepatic resection.It is important to identify malnourished patients and take preventive therapeutic action before surgery.However,there is no evidence regarding which existing nutritional assessment score(NAS)is best suited to predict outcomes of liver surgery.Methods:All patients scheduled for elective liver resection at the surgical department of the University Hospital of Heidelberg and the Municipal Hospital of Karlsruhe were screened for eligibility.Twelve NASs were calculated before operation,and patients were categorised according to each score as being either at risk or not at risk for malnutrition.The association of malnutrition according to each score and occurrence of at least one major complication was the primary endpoint,which was achieved using a multivariate logistic regression analysis including established risk factors in liver surgery as covariates.Results:The population consisted of 182 patients.The percentage of patients deemed malnourished by the NAS varied among the different scores,with the lowest being 2.20%(Mini Nutritional Assessment)and the highest 52.20%(Nutritional Risk Classification).Forty patients(22.0%)had a major complication.None of the scores were significantly associated with major complications.Conclusions:None of the twelve investigated NAS defined a state of malnutrition that was independently associated with postoperative complications.Other means of measuring malnutrition in liver surgery should be investigated prospectively.展开更多
Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to a...Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas(PDAC)- since the approval of gemcitabine in 1997- more effective cytotoxic substances(nab-paclitaxel) and combinations(FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging(stroma depletion, immunotherapy, antiinflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of "borderline resectability". Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future.展开更多
This retrospective single centre report of 36 patients with resectable pancreatic cancer who had neoadjuvant systemic chemotherapy,found that only 25(69%)of patients could undergo resection with a median overall survi...This retrospective single centre report of 36 patients with resectable pancreatic cancer who had neoadjuvant systemic chemotherapy,found that only 25(69%)of patients could undergo resection with a median overall survival of 34.4 months(1).They concluded that a short course of neoadjuvant chemotherapy without chemoradiation may improve patient selection prior to surgical resection(1).Whilst the notion that effective neoadjuvant therapy does not require chemoradiation is interesting this study demonstrates the weaknesses of retrospective studies.Progress in the treatment of pancreatic cancer has only taken place through well designed prospective randomized controlled trials.展开更多
文摘AIM: To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver transplantation.METHODS: We retrospectively reviewed 200 patients of our newly established liver transplantation(LT) program, who received full size liver graft. Biliary reconstruction was performed by side-to-side(SS), end-to-end(EE) anastomosis or hepeaticojejunostomy(HJ). Biliary complications(BC), anastomotic stenosis, bile leak, papillary stenosis, biliary drain complication, ischemic type biliary lesion(ITBL) were evaluated by studying patient records, corresponding radiologic imaging and reports of interventional procedures [e.g., endoscopic retrograde cholangiopancreatography(ERCP)]. Laboratory results included alanine aminotransferase(ALT), gammaglutamyltransferase and direct/indirect bilirubin with focus on the first and fifth postoperative day, six weeks after LT. The routinely employed external bile drain was examined by a routine cholangiography on the fifth postoperative day and six weeks after transplantation as a standard procedure, but also whenever clinically indicated. If necessary, interventional(e.g., ERCP) or surgical therapy was performed. In case of biliary complication, patients were selected, assigned to different complication-groups and subsequently reviewed in detail. To evaluate the patients outcome, we focussed on appearance of postoperative/post-interventional cholangitis, need for rehospitalisation, retransplantation, ITBL or death caused by BC.RESULTS: A total of 200 patients [age: 56(19-72), alcoholic cirrhosis: n = 64(32%), hepatocellular carcinoma: n = 40(20%), acute liver failure: n = 23(11.5%), cryptogenic cirrhosis: n = 22(11%), hepatitis B virus /hepatitis C virus cirrhosis: n = 13(6.5%), primary sclerosing cholangitis: n = 13(6.5%), others: n = 25(12.5%) were included. The median follow-up was 27 mo until June 2015. The overall biliary complication rate was 37.5%(n = 75) with anastomotic strictures(AS): n = 38(19%), bile leak(BL): n = 12(6%), biliary drain complication: n = 12(6%); papillary stenosis(PS): n = 7(3.5%), ITBL: n = 6(3%). Clinically relevant were only 19%(n = 38). We established a comprehensive classification for AS with four grades according to clinical relevance. The reconstruction techniques [SS: n = 164, EE: n = 18, HJ: n = 18] showed no significant impact on the development of BCs in general(all n < 0.05), whereas in the HJ group significantly less AS were found(P = 0.031). The length of donor intensive care unit stay over 6 d had a significant influence on BC development(P = 0.007, HR = 2.85; 95%CI: 1.33-6.08) in the binary logistic regression model, whereas other reviewed variables had not [warm ischemic time > 45 min(P = 0.543), cold ischemic time > 10 h(P = 0.114), ALT init > 1500 U/L(P = 0.631), bilirubin init > 5 mg/d L(P = 0.595), donor age > 65(P = 0.244), donor sex(P = 0.068), rescue organ(P = 0.971)]. 13%(n = 10) of BCs had no therapeutic consequences, 36%(n = 27) resulted in repeated lab control, 40%(n = 30) received ERCP and 11%(n = 8) surgical therapy. Fifteen(7.5%) patients developed cholangitis [AS(n = 6), ITBL(n = 5), PS(n = 3), biliary lesion BL(n = 1)]. One patient developed ITBL twelve months after LT and subsequently needed retransplantation. Rehospitalisation rate was 10.5 %(n = 21) [AS(n = 11), ITBL(n = 5), PS(n = 3), BL(n = 1)] with intervention or reinterventional therapy as main reasons. Retransplantation was performed in 5(2.5%) patients [ITBL(n = 1), acute liver injury(ALI) by organ rejection(n = 3), ALI by occlusion of hepatic artery(n = 1)]. In total 21(10.5%) patients died within the follow-up period. Out of these, one patient with AS developed severe fatal chologenic sepsis after ERCP.CONCLUSION: In our data biliary reconstruction technique and ischemic times seem to have little impact on the development of BCs.
基金Supported by the Deutsche Forschungsgemeinschaft (KFO 117/1) and the IFORES Research Program, University Hospital Essen
文摘AIM： Recently it has been reported that granulocyte colony stimulating factor （G-CSF） can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model. METHODS： A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk. RESULTS： Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals. CONCLUSION： G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications .
文摘<div style="text-align:justify;"> <strong>Introduction: </strong>Liver transplantation (LT) in children has undergone significant changes over the last years. Especially the use of split and living donor transplants even for infants has led to new challenges in pre- and post-operative care. Systemic inflammatory response syndromes (SIRS, sepsis) as well-known complications after LT have not yet been systematically examined in the pediatric population. <strong>Methods:</strong> We analyzed clinical data of 39 pediatric liver transplant recipients regarding potential risk factors for post-transplant SIRS and sepsis. Secondly, the prognostic impact of SIRS and sepsis on post-transplant clinical course, patient and transplant-survival has been analyzed. <strong>Results:</strong> 64% of patients developed either SIRS (n = 16, 41%) or sepsis (n = 9, 23%) within 30 days after transplantation. No pre-transplant risk factors for increased susceptibility for SIRS or sepsis could be identified. Secondary closure of the abdomen (p = 0.045) and secondary biliary reconstruction (p = 0.043) were associated with a higher incidence of sepsis and were associated with significantly prolonged mechanical ventilation times in the presence of sepsis (p = 0.001). Patients with sepsis, but not SIRS, stayed significantly longer on PICU (p = 0.021) and suffered from higher mortality (n = 3 versus 0;p = 0.0006). All deaths within 30 days of transplantation were due to septic multiorgan failure. Neither early SIRS nor sepsis were associated with loss of transplant function. <strong>Conclusions:</strong> SIRS and sepsis are frequent events after pediatric liver transplantation. Sepsis increased length of PICU-stay and mortality significantly and prolonged duration of mechanical ventilation. Secondary biliary reconstruction and closure of the abdomen could be identified as potential risk factors for sepsis. </div>
文摘Background:Successful liver resection in oncologic surgery depends on safety,precision,and efficacy,all of which require a thorough understanding of liver anatomy.Contrast-enhanced computed tomography(CT)-generated three-dimensional(3D)models have been proposed as a valuable tool to enhance this understanding.However,a systematic comparison of different display modalities across professional groups has not yet been performed.Methods:In this prospective,monocentric randomized trial,we compared high-resolution twodimensional(2D)CT images of liver malignancies with their corresponding standardized,non-colored 3D virtual and printed models in facilitating anatomical and spatial understanding as well as surgical decision-making.A total of 91 participants,including 40 surgeons,10 radiologists,and 41 students,evaluated six clinical cases(three centrally and three peripherally located liver malignancies).Each participant assessed one central and one peripheral case per display modality,presented in a random order.Results:Compared to 2D CT images,both 3D virtual and printed models significantly improved the identification of tumor location(P<0.001),enhanced the comprehension of spatial relationships with adjacent liver and portal veins(P<0.001 and P=0.019,respectively),and facilitated clinical decisionmaking(P<0.001).No significant difference was observed between virtual and printed models in terms of effectiveness.Within the different groups,surgeons and students,but not radiologists,more accurately identified tumor location and spatial relationships with adjacent liver and portal veins using 3D models.Subjectively,most surgeons and students preferred 3D printed models over virtual models and 2D CT images.Conclusions:This study demonstrated that standardized,non-colored 3D virtual and printed models equally help preoperative anatomical understanding and decision-making,particularly for surgeons and students.By isolating the influence of display modality,our findings clarify prior inconsistent results and support the integration of cost-effective 3D visualization by applying virtual models into surgical planning and education.Preference for printed models despite comparable efficacy highlights the importance of user-centered implementation strategies.
文摘AIM: To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen.METHODS: Formalin fixed, paraffin embedded pre-therapeutical tumor biopsies (n = 22) and post-therapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage Ⅱ/Ⅲ) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan real-time PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system.RESULTS: Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a low Ki67 index in the pre-therapeutical tumor biopsies (corr. coef. = 0.46; P < 0.01) as well as in the post-therapeutical resection specimens (corr. coef. = 0.40; P < 0.05). No significant association was found between p53 and TS mRNA expression or tumor regression.CONCLUSION: Ki67 has, like TS, predictive value in rectal cancer patients after neoadjuvant 5-FU based chemoradiotherapy. The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.
文摘Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography （ERC） showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right Iobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.
文摘AIM To characterize major determinants of 20-year survival after liver transplantation(LT).METHODS This longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease(labM ELD)-score and the Eurotransplant Donor Risk Index(ET-DRI) to unravel their impact on 20-year survival after LT.RESULTS Twenty-year survivors were significantly younger(44 vs 50 years, P = 0.001), more likely to be female(49% vs 36%, P = 0.03) and less likely to be obese at the time of LT(19% vs 32%, P = 0.011). Mean labM ELD-score(P = 0.156), rate of high-urgency LT(P = 0.210), coldischemia time(P = 0.994), rate of retransplantation(P = 0.12) and average donor age(28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors(P = 0.007). ET-DRI > 1.4(P = 0.020) and donor age ≥ 30 years(P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labM ELD-score categories(P = 0.263).CONCLUSION LT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor-recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs.
文摘Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a signifi cant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.
文摘Metastatic disease from cutaneous melanoma can af-fect all organs of the body, and varies in its biological behavior and clinical presentation. We present the case of a 58-year-old man who arrived at our clinic with acute abdominal pain, which, after investigation, was diagnosed as acute cholecystitis. The patient under-went laparotomy and cholecystectomy. Two years ago, he underwent surgical removal of a primary cutaneous melanoma on his right upper back. Pathological exami-nation revealed the presence of malignant melanoma with a metastatic lesion of the gallbladder.
文摘BackgroundOriginally, cava reconstruction (CR) in liver transplantation meant complete resection and reinsertion of the donor cava. Alternatively, preservation of the recipients inferior vena cava (IVC) with side-to-side anastomosis (known as “piggyback”) can be performed. Here, partial clamping maintains blood flow of the IVC, which may improve cardiovascular stability, reduce blood loss and stabilize kidney function. The aim of this study was to compare both techniques with particular focus on kidney function.MethodsA series of 414 patients who had had adult liver transplantations (2006-2009) were included. Among them, 176 (42.5%) patients had piggyback and 238 had classical CR operation, 112 (27.1%) of the patients underwent CR accompanied with veno-venous bypass (CR-B) and 126 (30.4%) without a bypass. The choice of either technique was based on the surgeons' individual preference. Kidney function [serum creatinine, calculated glomerular filtration rate (GFR), RIFLE stages] was assessed over 14 days.ResultsLab-MELD scores were significantly higher in CR-B (22.5±11.0) than in CR (17.3±9.0) and piggyback (18.8±10.0) (P=0.008). Unexpectedly, the incidences of arterial stenoses (P=0.045) and biliary leaks (P=0.042) were significantly increased in piggyback. Preoperative serum creatinine levels were the highest in CR-B [1.45±1.17 vs 1.25±0.85 (piggyback) and 1.13±0.60 mg/dL (CR); P=0.033]. Although a worsening of postoperative kidney function was observed among all groups, this was most pronounced in CR-B [creatinine day 14: 1.67±1.40 vs 1.35±0.96 (piggyback) and 1.45±1.03 mg/dL (CR); P=0.102]. Accordingly, the proportion of patients displaying RIFLE stages ≥2 was the highest in CR/CR-B (26%/19%) when compared to piggyback (18%).ConclusionsPiggyback revealed a shorter warm ischemic time, a reduced blood loss, and a decreased risk of acute kidney failure. Thus, piggyback is a useful technique, which should be applied in standard procedures. When piggyback is unfeasible, cava replacement, which displayed a lower incidence of vascular and biliary complications in our study, remains as a safe alternative.
文摘BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically significant.CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.
文摘Hirschsprung＇s disease （HD） is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel, However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of lid in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient＇s bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify lid patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage. 2005 The WJG Press and Elsevier Inc. All rights reserved
基金Supported by (in part) Novartis Pharma GmbH,Germany,BU Transplantation and Immunology (to Lehner F)the Lower Saxony Ministry of Culture and Sciences and the Volk-swagen foundation,Germany,Grant No.25A.5-7251-99-3/00
文摘AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels. CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.
文摘A 17-year-old girl with colicky abdominal pain andchronic anemia presented to the gastrointestinal serviceof the University Hospital of Essen. In the routineworkup, there were no pathological findings despitethe anemia. Because of the fluctuation of symptomswith a climax at the time of menstruation, consecutiveultrasound studies were performed revealing a visiblemass inside the gallbladder. This finding was confirmedby a magnetic resonance imaging (MRI) study performedat the same time. Because of the severe anemia by thattime, a cholecystectomy was performed, and histologyreconfirmed the diagnosis of isolated gallbladderendometriosis. The patient recovered well and has hadno recurrence of the disease to date.
文摘Cholangiocarcinoma(CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells. A recent study by Boulter et al implicates the Wnt signaling cascade in cholangiocarcinogenesis. Wnt ligands Wnt7 B and Wnt10 A were found to be highly overexpressed in human CCA tissue. Wnt7 B protein was present throughout the tumor stroma, and often co-localized with a subset of CD68+ macrophages. To address in a direct manner whether Wnt signaling is engaged in development of CCA, Boulter et al explored the Wnt signaling pathway in an experimental model that recapitulates the multi-stage progression of human CCA.Wnt ligands found to be elevated in human CCA were also upregulated during the course of CCA development following thioacetamide treatment. Wnt10 a increased during the(pre-cancerous) regenerative phase, while Wnt7 b induction paralleled tumor growth. Along with upregulation of target genes, the findings demonstrate that the canonical Wnt pathway is progressively activated during cholangio-carcinogenesis. Macrophage depletion,eliminating a major source of Wnt7 b, prevented activation of the canonical Wnt cascade, and resulted in reduced number and volume of tumors in this model. Moreover,specific inhibitors of the canonical Wnt pathway(ICG-001 and C-59) caused reduction of tumor area and number,in xenograft and thioacetamide models of CCA. The aggregated findings show that experimental, and presumably human CCA, is a Wnt-driven tumor. Modulation of Wnt signaling, alone or in combination with surgicalor chemotherapy approaches, holds promise in the management of this fatal malignancy.
基金We acknowledge financial support by Deutsche Forschungsgemeinschaft within the funding programme Open Access Publishingthe Baden-Württemberg Ministry of Science,Research and the ArtsRuprecht-Karls-Universität Heidelberg.
文摘Background:Malnutrition is recognised as a preoperative risk factor for patients undergoing hepatic resection.It is important to identify malnourished patients and take preventive therapeutic action before surgery.However,there is no evidence regarding which existing nutritional assessment score(NAS)is best suited to predict outcomes of liver surgery.Methods:All patients scheduled for elective liver resection at the surgical department of the University Hospital of Heidelberg and the Municipal Hospital of Karlsruhe were screened for eligibility.Twelve NASs were calculated before operation,and patients were categorised according to each score as being either at risk or not at risk for malnutrition.The association of malnutrition according to each score and occurrence of at least one major complication was the primary endpoint,which was achieved using a multivariate logistic regression analysis including established risk factors in liver surgery as covariates.Results:The population consisted of 182 patients.The percentage of patients deemed malnourished by the NAS varied among the different scores,with the lowest being 2.20%(Mini Nutritional Assessment)and the highest 52.20%(Nutritional Risk Classification).Forty patients(22.0%)had a major complication.None of the scores were significantly associated with major complications.Conclusions:None of the twelve investigated NAS defined a state of malnutrition that was independently associated with postoperative complications.Other means of measuring malnutrition in liver surgery should be investigated prospectively.
文摘Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas(PDAC)- since the approval of gemcitabine in 1997- more effective cytotoxic substances(nab-paclitaxel) and combinations(FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging(stroma depletion, immunotherapy, antiinflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of "borderline resectability". Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future.
文摘This retrospective single centre report of 36 patients with resectable pancreatic cancer who had neoadjuvant systemic chemotherapy,found that only 25(69%)of patients could undergo resection with a median overall survival of 34.4 months(1).They concluded that a short course of neoadjuvant chemotherapy without chemoradiation may improve patient selection prior to surgical resection(1).Whilst the notion that effective neoadjuvant therapy does not require chemoradiation is interesting this study demonstrates the weaknesses of retrospective studies.Progress in the treatment of pancreatic cancer has only taken place through well designed prospective randomized controlled trials.
