Postoperative mortality commonly is defined as death occurring within 30 days of surgery or durin... more Postoperative mortality commonly is defined as death occurring within 30 days of surgery or during hospitalization. After resection for liver malignancies, this definition may result in underreporting, because mortality caused by postoperative complications can be delayed as the result of improved critical care. The aim of this study was to estimate statistically the acute postoperative period (APP) after partial hepatectomy and to compare mortality within this phase to standard timestamps. From a prospective database, 784 patients undergoing resection for primary and secondary hepatic malignancies between 2003 and 2013 were reviewed. For estimation of APP, a novel statistical method applying tests for a constant postoperative hazard was implemented. Multivariable mortality analysis was performed. The APP was determined to last for 80 postoperative days (95% confidence interval 40-100 days). Within this period, 55 patients died (7.0%; 80-day mortality). In comparison, 30-day mortali...
World journal of gastroenterology : WJG, Jan 21, 2015
To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer... more To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer. All the patients with rectosigmoid carcinoma who underwent laparoscopic radical surgical resection in the Shanghai Minimally Invasive Surgical Center at Ruijin Hospital affiliated to Shanghai Jiao-Tong University between October 2009 and October 2013 were included in this study. Twenty-six cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected. Symptoms, endoscopic findings and clinicopathological characteristics were evaluated retrospectively. There were no significant differences between patients with and without schistosomiasis in gender, age, CEA, CA19-9, preoperative biopsy findings or postoperative pathology. Patients with rectosigmoid schistosomiasis had a significantly higher CA-125 level and a larger proportion of these patients were at an early tumor stage (P = 0.003). Various morphologi...
Inter-cellular communication with stromal cells is vital for cancer cells. Molecules involved in ... more Inter-cellular communication with stromal cells is vital for cancer cells. Molecules involved in the communication are potential drug targets. To identify them systematically, we applied a systems level analysis that combined reverse network engineering with causal effect estimation. Using only observational transcriptome profiles we searched for paracrine factors sending messages from activated hepatic stellate cells (HSC) to hepatocellular carcinoma (HCC) cells. We condensed these messages to predict ten proteins that, acting in concert, cause the majority of the gene expression changes observed in HCC cells. Among the 10 paracrine factors were both known and unknown cancer promoting stromal factors, the former including Placental Growth Factor (PGF) and Periostin (POSTN), while Pregnancy-Associated Plasma Protein A (PAPPA) was among the latter. Further support for the predicted effect of PAPPA on HCC cells came from both in vitro studies that showed PAPPA to contribute to the act...
This is a report of a workshop held on the establishment of human research tissue banking which w... more This is a report of a workshop held on the establishment of human research tissue banking which was held in Levi, Finland 21-24 March 2002. There were 21 participants from 7 European countries. This meeting was attended by representatives from academia, research tissue banks and from the Biotech and Pharmaceutical Industries. The principal aim of the workshop was to find a way to progress the recommendations from ECVAM workshop 44 (ATLA 29, 125-134, 2001) and ECVAM workshop 32 (ATLA 26, 763-777, 1998). The workshop represented the first unofficial meeting of the European Network of Research Tissue Banks (ENRTB) steering group. It is expected that in the period preceding the next workshop the ENRTB steering group will co-ordinate the ethical, legislative and organisational aspects of research tissue banking. Key issues dealt with by the Levi workshop included the practical aspects of sharing expertise and experiences across the different European members. Such collaboration between r...
Tissue engineering using human cells and tissue has one of the greatest scientific and economical... more Tissue engineering using human cells and tissue has one of the greatest scientific and economical potential in the coming years. There are public concerns during the ongoing discussion about future trends in life sciences and if ethic boundaries might be respected sufficiently in the course of striving for industrial profit and scientific knowledge. Until now, the legal situation of using human tissue material for research is not clear. Accordingly, transparency of action and patients' information are a central component when handling patient material inside and outside of the patient-specific treatment. Whereas in the field of therapeutic use of tissue (e.g. transplantation) there is an emergency situation by the shortage of organs with the risk of the premature death of the potential recipient, this cannot be claimed for tissue donation for research. The basis of every surgical operation is the treatment contract, which places the doctor under obligation to the careful exercis...
Bone morphogenetic protein 6 (BMP6) has been identified as crucial regulator of iron homeostasis.... more Bone morphogenetic protein 6 (BMP6) has been identified as crucial regulator of iron homeostasis. However, its further role in liver pathology including non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH) is elusive. The aim of this study was to investigate the expression and function of BMP6 in chronic liver disease. BMP6 was analysed in hepatic samples from murine models of chronic liver injury and patients with chronic liver diseases. Furthermore, a tissue microarray comprising 110 human liver tissues with different degree of steatosis and inflammation was assessed. BMP6-deficient (BMP6(-/-)) and wild-type mice were compared in two dietary NASH-models, that is, methionine choline-deficient (MCD) and high-fat (HF) diets. BMP6 was solely upregulated in NAFLD but not in other murine liver injury models or diseased human livers. In NAFLD, BMP6 expression correlated with hepatic steatosis but not with inflammation or hepatocellular dama...
Objective: Liver regeneration is mainly based on cellular self-renewal including progenitor cells... more Objective: Liver regeneration is mainly based on cellular self-renewal including progenitor cells. Efforts have been made to harness this potential for cell transplantation, but shortage of hepatocytes and premature differentiated progenitor cells from extra-hepatic organs are limiting factors. Histological studies implied that resident cells in adult liver can proliferate, have bipotential character and may be a suitable source for cell
Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be prot... more Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be protective against oxidative stress-induced cell death. Hepatic ischemia-reperfusion (I/R) injury is triggered by reactive oxygen species. Here, we tested the hypothesis that ALR attenuates hepatic I/R injury in vivo. C57BL6 mice were subjected to warm hepatic ischemia for 90 min. Either recombinant ALR (100 μg/kg) or vehicle were administered to mice prior ischemia. During reperfusion, neutrophil and CD4+ T cell migration and sinusoidal perfusion were analyzed using intravital microscopy. Alanine aminotransferase-aspartate aminotransferase (plasma) and caspase-3 (tissue) activities were determined as markers of hepatocellular necrotic and apoptotic injury. Hepatic I/R led to dramatic enhancement of neutrophil and CD4+ T cell recruitment in hepatic microvessels, sinusoidal perfusion failure, and strong elevation of aspartate aminotransferase-alanine aminotransferase and caspase-3 activities. During early reperfusion (60 min), the pretreatment with ALR improved postischemic perfusion failure (P < 0.05) and attenuated liver enzyme activities. Recruitment of CD4+ T cells, but not of neutrophils was attenuated. After 240 min of reperfusion, the protective effect of ALR was stronger, since the liver enzyme activity, perfusion failure, and leukocyte influx were significantly attenuated. As shown by the measurement of caspase-3 activity, postischemic apoptosis was reduced in the ALR-treated group. Our in vivo data show that ALR has a therapeutic potential against postischemic liver injury. As a mechanism, we suggest a direct protective effect of ALR on apoptotic and necrotic death of hepatocytes and an attenuation of inflammatory cell influx into the postischemic tissue.
P-cadherin is a major contributor to cell-cell adhesion in epithelial tissues, playing pivotal ro... more P-cadherin is a major contributor to cell-cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes and in maintaining tissue integrity and homeostasis. Alterations of P-cadherin expression have been observed during the progression of several carcinomas where it appears to act as tumor suppressive or oncogenic in a context-dependent manner. Here, we found a significant downregulation of P-cadherin in hepatocellular carcinoma (HCC) cell lines and tissues compared to primary human hepatocytes and non-malignant liver tissues. Combined immunohistochemical analysis of a tissue microarray containing matched pairs of HCC tissue and corresponding non-tumorous liver tissue of 69 patients confirmed reduced P-cadherin expression in more than half of the cases. In 35 human HCC tissues, the P-cadherin immunosignal was completely lost which correlated with tumor staging and proliferation. Also in vitro, P-cadherin suppression in HCC cells via siRNA induced proliferation compared to cells transfected with control-siRNA. In summary, downregulation of P-cadherin expression appears to induce tumorigenicity in HCC. Therefore, P-cadherin expression may serve as a prognostic marker and therapeutic target of this highly aggressive tumor.
Major liver resection is a routine surgical treatment, but hemodynamic and pulmonary complication... more Major liver resection is a routine surgical treatment, but hemodynamic and pulmonary complications are common. We investigated the effects of hepatic resection on hemodynamics and pulmonary and liver function. Twelve patients who underwent major liver resection due to primary liver tumor, liver metastasis, or hemangioma were investigated prospectively and consecutively. Six patients who underwent gastrectomy due to gastric cancer served as a control group. Hemodynamic parameters (cardiac index, intrathoracic blood volume, mean arterial blood pressure), extravascular lung water, and indocyanine green clearance were measured after the induction of general anesthesia, during the preparation period, during total hilar clamping ("Pringle's maneuver"), at the end of surgery, and 24 and 72 h after surgery. In contrast to gastrectomy, patients who underwent liver resection developed a hyperdynamic circulatory state (cardiac index 72 h postoperatively: 4.6+/-1.2 l/m(2) vs. 3.6+/-0.6 l/m(2)). Simultaneously we observed a significant increase in extravascular lung water in the liver resection group, indicating a moderate pulmonary edema. Indocyanine green clearance did not deteriorate following liver resection. After liver resection the physiological response resulted in elevated cardiac output and moderate pulmonary edema. Dynamic liver function was elevated within 24 h due to an increase in perfusion and regeneration activity of the remaining parenchyma.
Postoperative mortality commonly is defined as death occurring within 30 days of surgery or durin... more Postoperative mortality commonly is defined as death occurring within 30 days of surgery or during hospitalization. After resection for liver malignancies, this definition may result in underreporting, because mortality caused by postoperative complications can be delayed as the result of improved critical care. The aim of this study was to estimate statistically the acute postoperative period (APP) after partial hepatectomy and to compare mortality within this phase to standard timestamps. From a prospective database, 784 patients undergoing resection for primary and secondary hepatic malignancies between 2003 and 2013 were reviewed. For estimation of APP, a novel statistical method applying tests for a constant postoperative hazard was implemented. Multivariable mortality analysis was performed. The APP was determined to last for 80 postoperative days (95% confidence interval 40-100 days). Within this period, 55 patients died (7.0%; 80-day mortality). In comparison, 30-day mortali...
World journal of gastroenterology : WJG, Jan 21, 2015
To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer... more To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer. All the patients with rectosigmoid carcinoma who underwent laparoscopic radical surgical resection in the Shanghai Minimally Invasive Surgical Center at Ruijin Hospital affiliated to Shanghai Jiao-Tong University between October 2009 and October 2013 were included in this study. Twenty-six cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected. Symptoms, endoscopic findings and clinicopathological characteristics were evaluated retrospectively. There were no significant differences between patients with and without schistosomiasis in gender, age, CEA, CA19-9, preoperative biopsy findings or postoperative pathology. Patients with rectosigmoid schistosomiasis had a significantly higher CA-125 level and a larger proportion of these patients were at an early tumor stage (P = 0.003). Various morphologi...
Inter-cellular communication with stromal cells is vital for cancer cells. Molecules involved in ... more Inter-cellular communication with stromal cells is vital for cancer cells. Molecules involved in the communication are potential drug targets. To identify them systematically, we applied a systems level analysis that combined reverse network engineering with causal effect estimation. Using only observational transcriptome profiles we searched for paracrine factors sending messages from activated hepatic stellate cells (HSC) to hepatocellular carcinoma (HCC) cells. We condensed these messages to predict ten proteins that, acting in concert, cause the majority of the gene expression changes observed in HCC cells. Among the 10 paracrine factors were both known and unknown cancer promoting stromal factors, the former including Placental Growth Factor (PGF) and Periostin (POSTN), while Pregnancy-Associated Plasma Protein A (PAPPA) was among the latter. Further support for the predicted effect of PAPPA on HCC cells came from both in vitro studies that showed PAPPA to contribute to the act...
This is a report of a workshop held on the establishment of human research tissue banking which w... more This is a report of a workshop held on the establishment of human research tissue banking which was held in Levi, Finland 21-24 March 2002. There were 21 participants from 7 European countries. This meeting was attended by representatives from academia, research tissue banks and from the Biotech and Pharmaceutical Industries. The principal aim of the workshop was to find a way to progress the recommendations from ECVAM workshop 44 (ATLA 29, 125-134, 2001) and ECVAM workshop 32 (ATLA 26, 763-777, 1998). The workshop represented the first unofficial meeting of the European Network of Research Tissue Banks (ENRTB) steering group. It is expected that in the period preceding the next workshop the ENRTB steering group will co-ordinate the ethical, legislative and organisational aspects of research tissue banking. Key issues dealt with by the Levi workshop included the practical aspects of sharing expertise and experiences across the different European members. Such collaboration between r...
Tissue engineering using human cells and tissue has one of the greatest scientific and economical... more Tissue engineering using human cells and tissue has one of the greatest scientific and economical potential in the coming years. There are public concerns during the ongoing discussion about future trends in life sciences and if ethic boundaries might be respected sufficiently in the course of striving for industrial profit and scientific knowledge. Until now, the legal situation of using human tissue material for research is not clear. Accordingly, transparency of action and patients' information are a central component when handling patient material inside and outside of the patient-specific treatment. Whereas in the field of therapeutic use of tissue (e.g. transplantation) there is an emergency situation by the shortage of organs with the risk of the premature death of the potential recipient, this cannot be claimed for tissue donation for research. The basis of every surgical operation is the treatment contract, which places the doctor under obligation to the careful exercis...
Bone morphogenetic protein 6 (BMP6) has been identified as crucial regulator of iron homeostasis.... more Bone morphogenetic protein 6 (BMP6) has been identified as crucial regulator of iron homeostasis. However, its further role in liver pathology including non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH) is elusive. The aim of this study was to investigate the expression and function of BMP6 in chronic liver disease. BMP6 was analysed in hepatic samples from murine models of chronic liver injury and patients with chronic liver diseases. Furthermore, a tissue microarray comprising 110 human liver tissues with different degree of steatosis and inflammation was assessed. BMP6-deficient (BMP6(-/-)) and wild-type mice were compared in two dietary NASH-models, that is, methionine choline-deficient (MCD) and high-fat (HF) diets. BMP6 was solely upregulated in NAFLD but not in other murine liver injury models or diseased human livers. In NAFLD, BMP6 expression correlated with hepatic steatosis but not with inflammation or hepatocellular dama...
Objective: Liver regeneration is mainly based on cellular self-renewal including progenitor cells... more Objective: Liver regeneration is mainly based on cellular self-renewal including progenitor cells. Efforts have been made to harness this potential for cell transplantation, but shortage of hepatocytes and premature differentiated progenitor cells from extra-hepatic organs are limiting factors. Histological studies implied that resident cells in adult liver can proliferate, have bipotential character and may be a suitable source for cell
Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be prot... more Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be protective against oxidative stress-induced cell death. Hepatic ischemia-reperfusion (I/R) injury is triggered by reactive oxygen species. Here, we tested the hypothesis that ALR attenuates hepatic I/R injury in vivo. C57BL6 mice were subjected to warm hepatic ischemia for 90 min. Either recombinant ALR (100 μg/kg) or vehicle were administered to mice prior ischemia. During reperfusion, neutrophil and CD4+ T cell migration and sinusoidal perfusion were analyzed using intravital microscopy. Alanine aminotransferase-aspartate aminotransferase (plasma) and caspase-3 (tissue) activities were determined as markers of hepatocellular necrotic and apoptotic injury. Hepatic I/R led to dramatic enhancement of neutrophil and CD4+ T cell recruitment in hepatic microvessels, sinusoidal perfusion failure, and strong elevation of aspartate aminotransferase-alanine aminotransferase and caspase-3 activities. During early reperfusion (60 min), the pretreatment with ALR improved postischemic perfusion failure (P < 0.05) and attenuated liver enzyme activities. Recruitment of CD4+ T cells, but not of neutrophils was attenuated. After 240 min of reperfusion, the protective effect of ALR was stronger, since the liver enzyme activity, perfusion failure, and leukocyte influx were significantly attenuated. As shown by the measurement of caspase-3 activity, postischemic apoptosis was reduced in the ALR-treated group. Our in vivo data show that ALR has a therapeutic potential against postischemic liver injury. As a mechanism, we suggest a direct protective effect of ALR on apoptotic and necrotic death of hepatocytes and an attenuation of inflammatory cell influx into the postischemic tissue.
P-cadherin is a major contributor to cell-cell adhesion in epithelial tissues, playing pivotal ro... more P-cadherin is a major contributor to cell-cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes and in maintaining tissue integrity and homeostasis. Alterations of P-cadherin expression have been observed during the progression of several carcinomas where it appears to act as tumor suppressive or oncogenic in a context-dependent manner. Here, we found a significant downregulation of P-cadherin in hepatocellular carcinoma (HCC) cell lines and tissues compared to primary human hepatocytes and non-malignant liver tissues. Combined immunohistochemical analysis of a tissue microarray containing matched pairs of HCC tissue and corresponding non-tumorous liver tissue of 69 patients confirmed reduced P-cadherin expression in more than half of the cases. In 35 human HCC tissues, the P-cadherin immunosignal was completely lost which correlated with tumor staging and proliferation. Also in vitro, P-cadherin suppression in HCC cells via siRNA induced proliferation compared to cells transfected with control-siRNA. In summary, downregulation of P-cadherin expression appears to induce tumorigenicity in HCC. Therefore, P-cadherin expression may serve as a prognostic marker and therapeutic target of this highly aggressive tumor.
Major liver resection is a routine surgical treatment, but hemodynamic and pulmonary complication... more Major liver resection is a routine surgical treatment, but hemodynamic and pulmonary complications are common. We investigated the effects of hepatic resection on hemodynamics and pulmonary and liver function. Twelve patients who underwent major liver resection due to primary liver tumor, liver metastasis, or hemangioma were investigated prospectively and consecutively. Six patients who underwent gastrectomy due to gastric cancer served as a control group. Hemodynamic parameters (cardiac index, intrathoracic blood volume, mean arterial blood pressure), extravascular lung water, and indocyanine green clearance were measured after the induction of general anesthesia, during the preparation period, during total hilar clamping ("Pringle's maneuver"), at the end of surgery, and 24 and 72 h after surgery. In contrast to gastrectomy, patients who underwent liver resection developed a hyperdynamic circulatory state (cardiac index 72 h postoperatively: 4.6+/-1.2 l/m(2) vs. 3.6+/-0.6 l/m(2)). Simultaneously we observed a significant increase in extravascular lung water in the liver resection group, indicating a moderate pulmonary edema. Indocyanine green clearance did not deteriorate following liver resection. After liver resection the physiological response resulted in elevated cardiac output and moderate pulmonary edema. Dynamic liver function was elevated within 24 h due to an increase in perfusion and regeneration activity of the remaining parenchyma.
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Papers by Wolfgang Thasler