Kasper Andersen - Academia.edu (original) (raw)

Papers by Kasper Andersen

Research paper thumbnail of Validation of a surgical model for posthepatectomy liver failure in rats

Animal models and experimental medicine, May 14, 2023

BackgroundThe upper limit for liver resections in rats is approximately 90%. In the early postope... more BackgroundThe upper limit for liver resections in rats is approximately 90%. In the early postoperative phase, mortality increases. The aim of the present study was to validate the rat model of 90% partial hepatectomy (PH) as a model of post‐hepatectomy liver failure (PHLF). Further, we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats.MethodsSixty‐eight rats were randomized to 90% PH, sham operation, or no surgery. Further, block randomization was performed based on time of euthanization: 12, 24, or 48 h after surgery. A general distress score (GDS) ≥10 during the day or ≥6 at midnight prompted early euthanization and classification as nonsurvivor. Animals euthanized as planned were classified as survivors. During euthanization, blood and liver tissue were collected, and liver‐specific biochemistry was evaluated.ResultsBased on the biochemical results, all animals subjected to 90% PH experienced PHLF. Seventeen rats were euthanized due to irreversible PHLF. The GDS increased for nonsurvivors within 12–18 h after surgery. The mean time for euthanization was 27 h after surgery.ConclusionBased on the GDS and liver‐specific biochemistry, we concluded that the model of 90% PH seems to be a proper model for investigating PHLF in rats. As a high GDS is associated with increased mortality, the GDS appears to be valuable in detecting lethal outcomes caused by PHLF in rats.

Research paper thumbnail of Postoperative but not preoperative treatment with sorafenib inhibits liver regeneration in rats

Journal of Surgical Research, Oct 1, 2014

Background: Sorafenib, a multikinase inhibitor, has been shown to halt the growth of hepatocellul... more Background: Sorafenib, a multikinase inhibitor, has been shown to halt the growth of hepatocellular carcinoma. The aim of the present study was to investigate the effect of Sorafenib on liver regeneration in healthy rats. Methods: In two substudies we examined the effect of pre-or post-operative treatment with Sorafenib (15 mg/kg/d). Wistar rats (n ¼ 120) received either Sorafenib (S) or placebo (P). After 70% partial hepatectomy, the rats were euthanized on postoperative days 2, 4, or 8. Body weight and liver weight were recorded and regeneration rate (RR) calculated. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using unbiased stereological methods. Results: Eleven animals (9%) died after surgery. In the preoperative substudy, lower body weight gains during the gavage period in the S group were found. No difference between groups S and P regarding liver weight gain, liver RRs, and hepatocyte proliferation on postoperative days 2 and 4 were found. In the postoperative substudy, significantly lower values of liver weight gain, liver RRs, and hepatocyte proliferation were found in the S group. Conclusions: In our rat model, Sorafenib did not increase posthepatectomy mortality. Postoperative treatment significantly impaired liver regeneration. Preoperative treatment impaired body weight during the gavage period, but was without effect on liver regeneration.

Research paper thumbnail of The natural history of liver regeneration in rats: Description of an animal model for liver regeneration studies

International Journal of Surgery, Nov 1, 2013

Research paper thumbnail of Gene expression in the liver remnant is significantly affected by the size of partial hepatectomy - an experimental rat study

Hpb, 2019

accuracy was calculated by measuring distances of anatomical landmarks between 3D model and in-si... more accuracy was calculated by measuring distances of anatomical landmarks between 3D model and in-situ liver (mm RMS). Results: Ten patients were recruited to the study. Ease of use, mental integration and accuracy were rated positively (8 each). Length of setup time was rated negatively (2). Objectively measured accuracy was 137AE39. A consensus was reached to integrate depth fogging, outlining and plane clipping as enhanced visualisation features into SmartLiver (video). Conclusion: The findings of this study demonstrate that SmartLiver is easy to use and capable of creating an AR environment that integrates well into the surgical workflow. Enhanced visualisation methods may improve the interpretation of AR data. An automatic registration method is needed to improve accuracy and setup time.

Research paper thumbnail of A new technique for accelerated liver regeneration. An experimental study in rats

Hpb, 2019

patterns between right-and left-sided colon cancer are emerging suggestive of a worse prognosis f... more patterns between right-and left-sided colon cancer are emerging suggestive of a worse prognosis for right-sided cancer. The aim of the study was to describe the liver metastatic patterns and survival as a function of site of primary tumour. Methods: Patients diagnosed with CRC during 2008 in the region of Stockholm, Sweden, were identified through the Swedish Colorectal Cancer Register and followed for 5 years. Additional information on liver metastatic pattern were retrieved from patient electronic charts. Factors influencing overall survival (OS) were examined using Cox proportional hazards model with 95 per cent confidence interval (c.i.) and OS was compared using log-rank test. Results: LM were more often diagnosed in hindgut cancer (28.4% versus 22.1%, p=0.029) but the number and segmental involvement of LM were less extensive compared to midgut cancer (p=0.001). 5-year OS were significantly worse in liver metastatic midgut cancer compared to hindgut cancer (6.5% vs. 21.6%, p<0.001), still significant in the multivariate analysis of patients with LM (HR=0.56, c.i. 0.39 to 0.79). Conclusion: Detailed population-based data on the metastatic pattern of CRC and survival could assist in more structured and individualized guidelines for follow-up. The results are in agreement with previous publications on the worse prognosis for right-sided cancers.

Research paper thumbnail of Kupffer cell targeted anti-inflammatory treatment by anti-CD163 dexamethasone has no effect on liver regeneration in rats

Hpb, Apr 1, 2016

To assess the intraoperative effects of somatostatin (SM) on splanchnic hemodynamic parameters in... more To assess the intraoperative effects of somatostatin (SM) on splanchnic hemodynamic parameters in two porcine models of extended hepatectomy. Methods: Twenty female pigs underwent surgery and were divided in 3 groups: 7 animals underwent 70% hepatectomy (H70 group), 7 underwent 90% (subtotal) hepatectomy (H90 group), and 6 underwent sham laparotomy (control group). The variations of splanchnic hemodynamic parameters (portal vein flow, PVF; hepatic artery flow, HAF; portal vein pressure, PVP; inferior vena cava pressure, IVCP; and hepatic venous pressure gradient, HVPG [defined as IVCP-PVP]) were assessed before and after infusion of SM. Flow values were normalized to the liver remnant weight. Results: The mean body and liver weights were 28,600 and 784 grams, respectively (liver-to-body ratio = 2.8%). The mean weights of the excised livers were 600 and 711 grams (71.3% and 88.6% of the whole liver), and the liver remantto-body ratios were 0.77% and 0.33% in the H70 and in the H90 groups, respectively. A significant increase in PVF was observed after both 70% and 90% hepatectomy (+67%, p = 0.031 and +278%, p = 0.016, respectively), while HVPG significantly increased only after 90% hepatectomy (from 5.5 to 13 mmHg, p = 0.004). After intraoperative infusion of SM, PVF decreased in all 3 groups (À13% in the control group, p = 0.062; À12% in the H70 group, p = 0.031; À17% in the H90 group, p = 0.016), while HVPG significantly decreased and returned to normal value in the H90 group only (from 14.3 to 7.7 mmHg, p = 0.047). No significant changes in HAF were observed after SM infusion. Conclusions: Somatostatin reduces portal inflow and restores a normal HVPG below critical values, without changes in HAF in a porcine model of small-for-size syndrome.

Research paper thumbnail of Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries: An experimental study in rats

Research paper thumbnail of Chronic stress does not impair liver regeneration in rats

Regenerative Medicine Research, Dec 1, 2015

Research paper thumbnail of Anti-inflammatory liposomes have no impact on liver regeneration in rats

Annals of medicine and surgery, Dec 1, 2015

h i g h l i g h t s Use of anti-CD163-dexamethasone is an attractive strategy for anti-inflammato... more h i g h l i g h t s Use of anti-CD163-dexamethasone is an attractive strategy for anti-inflammatory treatment. In the present study the impact of anti-CD163 dexamethasone on liver regeneration in rats was studied. We show that low dose anti-CD163 dexamethasone has no negative effect on liver regeneration after 70% hepatectomy in rats. Characters should then be down to 122.

Research paper thumbnail of Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver

Annals of medicine and surgery, Dec 1, 2015

Research paper thumbnail of Liver regeneration is dependent on the extent of hepatectomy

Journal of Surgical Research, Sep 1, 2016

Research paper thumbnail of Upregulation of ureagenesis may be pivotal for survival of post-hepatectomy liver failure in rats

HPB, 2020

Background: This study sought to evaluate the impact of the advancements in clinical care, obtain... more Background: This study sought to evaluate the impact of the advancements in clinical care, obtained over the last 20 years, for patients aged 70 and older undergoing liver resection for colorectal liver metastases (CRLM). Materials & Methods: 161 consecutive patients age 70 or older who underwent liver resection for CRLM at Aintree University Hospital (Liverpool, UK) between May 2008 and May 2015 were compared to a dataset of 178 consecutive patients, meeting the same criteria, between 1990 and 2007. An enhanced recovery programme after surgery (ERAS) combined with cardiopulmonary exercise testing (CPET) was introduced in January 2008. Results: The proportion of patients over 70 years undergoing liver resection for CRLM increased over the study period (6% in 1990, 16.3% in 2000, 26.5% in 2005 and 25.8% in 2007). The patients in the later group were more often treated with neoadjuvant chemotherapy (58 vs 34, p=0.006) and underwent parenchymal sparing surgery, resulting in fewer major hepatectomies (51 vs 110, p<0.001) and less perioperative morbidity (49 vs 70, p=0.043) and mortality (3 vs 9, p=0.229). Although there was shorter disease free survival (DFS) in the later group (DFS at 1, 3 and 5 years was 52.1%, 31.6%, 29% vs. 71.8%, 49.1%, 44.0%)(p<0.01), similar overall survival (OS) was achieved (OS at 1, 3 and 5 years was 85.4%, 51.6%, 32.8% vs. 81.7%, 42.1%, 27.3%)(p=0.21). Conclusions: This study demonstrates that, with modern management (ERAS, CPET, neoadjuvant chemotherapy and parenchymal sparing surgery), a greater number of patients with CRLM, over the age of seventy, can undergo liver resection, with improved perioperative outcomes.

Research paper thumbnail of Liver Regeneration Capacity after Partial Hepatectomy in Rats with Non-Alcoholic Steatohepatitis

Journal of Hepatology, 2016

Research paper thumbnail of Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis

World Journal of Hepatology, 2018

AIM To evaluate the liver regeneration capacity (LRC) after partial hepatectomy (PH) in experimen... more AIM To evaluate the liver regeneration capacity (LRC) after partial hepatectomy (PH) in experimental non-alcoholic steatohepatitis (NASH). METHODS Fifty-four female rats were fed a high-fat, high-cholesterol diet (HFCD, 65% fat, 1% cholesterol) or standard diet (STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d post-PH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe)

Research paper thumbnail of Proteomic characterization of biological features in the small for size future rat liver remnant

Research paper thumbnail of Adaptive growth changes in the liver remnant are affected by the size of hepatectomy in rats

International journal of experimental pathology, 2018

In this study we investigated the dynamics of hepatocyte hyperplasia and hypertrophy in rats subj... more In this study we investigated the dynamics of hepatocyte hyperplasia and hypertrophy in rats subjected to increasing sizes of partial hepatectomy (PH). A total of 104 rats were randomized according to the size of PH. On postoperative days (PODs) 1, 3 and 5, blood was drawn and the remnant liver removed for stereological analysis. Liver parameters and regeneration rate were significantly affected by size of PH. On POD 1, hepatocyte volumes had increased significantly in all PH groups. On POD 3, all groups showed hepatocyte volumes approximating baseline. On POD 5, hepatocyte volumes were significantly lower in PH (90) than in baseline, sham and PH (30) rats. Increasing hepatocyte proliferation was not observed following PH (30). Following PH (70), cell proliferation was significantly elevated on PODs 1 and 3, and following PH (90) on PODs 3 and 5. In conclusion, general hypertrophy of hepatocytes after different size of PH was followed by hepatocyte proliferation only in the liver re...

Research paper thumbnail of Gene Expression in the Liver Remnant Is Significantly Affected by the Size of Partial Hepatectomy: An Experimental Rat Study

Gene Expression, 2017

Extended hepatectomies may result in posthepatectomy liver failure, a condition with a high morta... more Extended hepatectomies may result in posthepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy (PH). Thirty Wistar rats were subjected to 30%, 70%, or 90% PH, sham operation, or no operation. Twenty-four hours following resection, liver tissue was harvested and genome-wide expression analysis was performed. Cluster analysis revealed two main groupings, one containing the PH(90%) and one containing the remaining groups [baseline, sham, PH(30%), and PH(70%)]. Categorization of specific affected molecular pathways in the PH(90%) group revealed a downregulation of cellular homeostatic function degradation and biosynthesis, whereas proliferation, cell growth, and cellular stress and injury were upregulated in the PH(90%) group. After PH(90%), the main upregulated pathways were mTOR and ILK. The main activated upstream regula...

Research paper thumbnail of Extended hepatectomy induces pronounced changes in protein expression levels

Research paper thumbnail of A new technique for accelerated liver regeneration: An experimental study in rats

Surgery, 2017

Background. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) i... more Background. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is used to accelerate growth of the future liver remnant. We investigated alternative methods for increasing the future liver remnant. Methods. A total of 152 rats were randomized as follows: (1) sham; (2) portal vein ligation; (3) portal vein ligation/surgical split (ALPPS); (4) portal vein ligation/split of the liver with a radiofrequency ablation needle; (5) portal vein ligation/radiofrequency ablation of the deportalized liver (portal vein ligation/ radiofrequency ablation necrosis in the deportalized liver); (6) portal vein ligation/radiofrequency ablation of the future liver remnant (portal vein ligation/radiofrequency ablation-future liver remnant); and (7) controls. Animals were evaluated on postoperative days 2 and 4. Bodyweight, liver parameters, hepatic regeneration rate, proinflammatory cytokines, hepatocyte proliferation, and gene expression were measured. Results. Hepatic regeneration rate indicated a steady increase in all intervention groups compared with sham rats (P < .001). At postoperative day 2, the hepatic regeneration rate was significantly higher in the portal vein ligation/radiofrequency ablation necrosis in the deportalized liver group than in the portal vein ligation group (P = .039). On postoperative day 4, we found significant differences between the portal vein ligation group and the ALPPS (P = .015), portal vein ligation/split of the liver with a radiofrequency ablation needle (P = .010), and portal vein ligation/radiofrequency ablation necrosis in the deportalized liver (P = .046) groups. Hepatocyte proliferation was significantly higher at all times compared with sham rats. On postoperative day 4, we found a significantly higher proliferation in groups 3, 4, 5, and 6 compared to portal vein ligation. Gene analysis revealed upregulation of genes involved in cellular proliferation and downregulation of genes involved in cellular homeostasis in all intervention groups. Between the intervention groups, gene expression was nearly identical. Biochemical markers and proinflammatory cytokines were comparable between groups. Conclusion. The surplus liver regeneration after ALPPS is probably mediated through parenchymal damage and subsequent release of growth stimulators, which again upregulates genes involved in cellular regeneration and downregulates genes involved in cellular homeostasis. We also demonstrate that growth of the future liver remnant, comparable to that seen after ALPPS, could be achieved by radiofrequency ablation treatment of the deportalized liver, that is, a procedure in which the initial step in humans can be performed percutaneously. (Surgery 2017;162:233-47.

Research paper thumbnail of Liver regeneration is dependent on the extent of hepatectomy

Journal of Surgical Research, 2016

Research paper thumbnail of Validation of a surgical model for posthepatectomy liver failure in rats

Animal models and experimental medicine, May 14, 2023

BackgroundThe upper limit for liver resections in rats is approximately 90%. In the early postope... more BackgroundThe upper limit for liver resections in rats is approximately 90%. In the early postoperative phase, mortality increases. The aim of the present study was to validate the rat model of 90% partial hepatectomy (PH) as a model of post‐hepatectomy liver failure (PHLF). Further, we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats.MethodsSixty‐eight rats were randomized to 90% PH, sham operation, or no surgery. Further, block randomization was performed based on time of euthanization: 12, 24, or 48 h after surgery. A general distress score (GDS) ≥10 during the day or ≥6 at midnight prompted early euthanization and classification as nonsurvivor. Animals euthanized as planned were classified as survivors. During euthanization, blood and liver tissue were collected, and liver‐specific biochemistry was evaluated.ResultsBased on the biochemical results, all animals subjected to 90% PH experienced PHLF. Seventeen rats were euthanized due to irreversible PHLF. The GDS increased for nonsurvivors within 12–18 h after surgery. The mean time for euthanization was 27 h after surgery.ConclusionBased on the GDS and liver‐specific biochemistry, we concluded that the model of 90% PH seems to be a proper model for investigating PHLF in rats. As a high GDS is associated with increased mortality, the GDS appears to be valuable in detecting lethal outcomes caused by PHLF in rats.

Research paper thumbnail of Postoperative but not preoperative treatment with sorafenib inhibits liver regeneration in rats

Journal of Surgical Research, Oct 1, 2014

Background: Sorafenib, a multikinase inhibitor, has been shown to halt the growth of hepatocellul... more Background: Sorafenib, a multikinase inhibitor, has been shown to halt the growth of hepatocellular carcinoma. The aim of the present study was to investigate the effect of Sorafenib on liver regeneration in healthy rats. Methods: In two substudies we examined the effect of pre-or post-operative treatment with Sorafenib (15 mg/kg/d). Wistar rats (n ¼ 120) received either Sorafenib (S) or placebo (P). After 70% partial hepatectomy, the rats were euthanized on postoperative days 2, 4, or 8. Body weight and liver weight were recorded and regeneration rate (RR) calculated. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using unbiased stereological methods. Results: Eleven animals (9%) died after surgery. In the preoperative substudy, lower body weight gains during the gavage period in the S group were found. No difference between groups S and P regarding liver weight gain, liver RRs, and hepatocyte proliferation on postoperative days 2 and 4 were found. In the postoperative substudy, significantly lower values of liver weight gain, liver RRs, and hepatocyte proliferation were found in the S group. Conclusions: In our rat model, Sorafenib did not increase posthepatectomy mortality. Postoperative treatment significantly impaired liver regeneration. Preoperative treatment impaired body weight during the gavage period, but was without effect on liver regeneration.

Research paper thumbnail of The natural history of liver regeneration in rats: Description of an animal model for liver regeneration studies

International Journal of Surgery, Nov 1, 2013

Research paper thumbnail of Gene expression in the liver remnant is significantly affected by the size of partial hepatectomy - an experimental rat study

Hpb, 2019

accuracy was calculated by measuring distances of anatomical landmarks between 3D model and in-si... more accuracy was calculated by measuring distances of anatomical landmarks between 3D model and in-situ liver (mm RMS). Results: Ten patients were recruited to the study. Ease of use, mental integration and accuracy were rated positively (8 each). Length of setup time was rated negatively (2). Objectively measured accuracy was 137AE39. A consensus was reached to integrate depth fogging, outlining and plane clipping as enhanced visualisation features into SmartLiver (video). Conclusion: The findings of this study demonstrate that SmartLiver is easy to use and capable of creating an AR environment that integrates well into the surgical workflow. Enhanced visualisation methods may improve the interpretation of AR data. An automatic registration method is needed to improve accuracy and setup time.

Research paper thumbnail of A new technique for accelerated liver regeneration. An experimental study in rats

Hpb, 2019

patterns between right-and left-sided colon cancer are emerging suggestive of a worse prognosis f... more patterns between right-and left-sided colon cancer are emerging suggestive of a worse prognosis for right-sided cancer. The aim of the study was to describe the liver metastatic patterns and survival as a function of site of primary tumour. Methods: Patients diagnosed with CRC during 2008 in the region of Stockholm, Sweden, were identified through the Swedish Colorectal Cancer Register and followed for 5 years. Additional information on liver metastatic pattern were retrieved from patient electronic charts. Factors influencing overall survival (OS) were examined using Cox proportional hazards model with 95 per cent confidence interval (c.i.) and OS was compared using log-rank test. Results: LM were more often diagnosed in hindgut cancer (28.4% versus 22.1%, p=0.029) but the number and segmental involvement of LM were less extensive compared to midgut cancer (p=0.001). 5-year OS were significantly worse in liver metastatic midgut cancer compared to hindgut cancer (6.5% vs. 21.6%, p<0.001), still significant in the multivariate analysis of patients with LM (HR=0.56, c.i. 0.39 to 0.79). Conclusion: Detailed population-based data on the metastatic pattern of CRC and survival could assist in more structured and individualized guidelines for follow-up. The results are in agreement with previous publications on the worse prognosis for right-sided cancers.

Research paper thumbnail of Kupffer cell targeted anti-inflammatory treatment by anti-CD163 dexamethasone has no effect on liver regeneration in rats

Hpb, Apr 1, 2016

To assess the intraoperative effects of somatostatin (SM) on splanchnic hemodynamic parameters in... more To assess the intraoperative effects of somatostatin (SM) on splanchnic hemodynamic parameters in two porcine models of extended hepatectomy. Methods: Twenty female pigs underwent surgery and were divided in 3 groups: 7 animals underwent 70% hepatectomy (H70 group), 7 underwent 90% (subtotal) hepatectomy (H90 group), and 6 underwent sham laparotomy (control group). The variations of splanchnic hemodynamic parameters (portal vein flow, PVF; hepatic artery flow, HAF; portal vein pressure, PVP; inferior vena cava pressure, IVCP; and hepatic venous pressure gradient, HVPG [defined as IVCP-PVP]) were assessed before and after infusion of SM. Flow values were normalized to the liver remnant weight. Results: The mean body and liver weights were 28,600 and 784 grams, respectively (liver-to-body ratio = 2.8%). The mean weights of the excised livers were 600 and 711 grams (71.3% and 88.6% of the whole liver), and the liver remantto-body ratios were 0.77% and 0.33% in the H70 and in the H90 groups, respectively. A significant increase in PVF was observed after both 70% and 90% hepatectomy (+67%, p = 0.031 and +278%, p = 0.016, respectively), while HVPG significantly increased only after 90% hepatectomy (from 5.5 to 13 mmHg, p = 0.004). After intraoperative infusion of SM, PVF decreased in all 3 groups (À13% in the control group, p = 0.062; À12% in the H70 group, p = 0.031; À17% in the H90 group, p = 0.016), while HVPG significantly decreased and returned to normal value in the H90 group only (from 14.3 to 7.7 mmHg, p = 0.047). No significant changes in HAF were observed after SM infusion. Conclusions: Somatostatin reduces portal inflow and restores a normal HVPG below critical values, without changes in HAF in a porcine model of small-for-size syndrome.

Research paper thumbnail of Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries: An experimental study in rats

Research paper thumbnail of Chronic stress does not impair liver regeneration in rats

Regenerative Medicine Research, Dec 1, 2015

Research paper thumbnail of Anti-inflammatory liposomes have no impact on liver regeneration in rats

Annals of medicine and surgery, Dec 1, 2015

h i g h l i g h t s Use of anti-CD163-dexamethasone is an attractive strategy for anti-inflammato... more h i g h l i g h t s Use of anti-CD163-dexamethasone is an attractive strategy for anti-inflammatory treatment. In the present study the impact of anti-CD163 dexamethasone on liver regeneration in rats was studied. We show that low dose anti-CD163 dexamethasone has no negative effect on liver regeneration after 70% hepatectomy in rats. Characters should then be down to 122.

Research paper thumbnail of Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver

Annals of medicine and surgery, Dec 1, 2015

Research paper thumbnail of Liver regeneration is dependent on the extent of hepatectomy

Journal of Surgical Research, Sep 1, 2016

Research paper thumbnail of Upregulation of ureagenesis may be pivotal for survival of post-hepatectomy liver failure in rats

HPB, 2020

Background: This study sought to evaluate the impact of the advancements in clinical care, obtain... more Background: This study sought to evaluate the impact of the advancements in clinical care, obtained over the last 20 years, for patients aged 70 and older undergoing liver resection for colorectal liver metastases (CRLM). Materials & Methods: 161 consecutive patients age 70 or older who underwent liver resection for CRLM at Aintree University Hospital (Liverpool, UK) between May 2008 and May 2015 were compared to a dataset of 178 consecutive patients, meeting the same criteria, between 1990 and 2007. An enhanced recovery programme after surgery (ERAS) combined with cardiopulmonary exercise testing (CPET) was introduced in January 2008. Results: The proportion of patients over 70 years undergoing liver resection for CRLM increased over the study period (6% in 1990, 16.3% in 2000, 26.5% in 2005 and 25.8% in 2007). The patients in the later group were more often treated with neoadjuvant chemotherapy (58 vs 34, p=0.006) and underwent parenchymal sparing surgery, resulting in fewer major hepatectomies (51 vs 110, p<0.001) and less perioperative morbidity (49 vs 70, p=0.043) and mortality (3 vs 9, p=0.229). Although there was shorter disease free survival (DFS) in the later group (DFS at 1, 3 and 5 years was 52.1%, 31.6%, 29% vs. 71.8%, 49.1%, 44.0%)(p<0.01), similar overall survival (OS) was achieved (OS at 1, 3 and 5 years was 85.4%, 51.6%, 32.8% vs. 81.7%, 42.1%, 27.3%)(p=0.21). Conclusions: This study demonstrates that, with modern management (ERAS, CPET, neoadjuvant chemotherapy and parenchymal sparing surgery), a greater number of patients with CRLM, over the age of seventy, can undergo liver resection, with improved perioperative outcomes.

Research paper thumbnail of Liver Regeneration Capacity after Partial Hepatectomy in Rats with Non-Alcoholic Steatohepatitis

Journal of Hepatology, 2016

Research paper thumbnail of Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis

World Journal of Hepatology, 2018

AIM To evaluate the liver regeneration capacity (LRC) after partial hepatectomy (PH) in experimen... more AIM To evaluate the liver regeneration capacity (LRC) after partial hepatectomy (PH) in experimental non-alcoholic steatohepatitis (NASH). METHODS Fifty-four female rats were fed a high-fat, high-cholesterol diet (HFCD, 65% fat, 1% cholesterol) or standard diet (STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d post-PH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe)

Research paper thumbnail of Proteomic characterization of biological features in the small for size future rat liver remnant

Research paper thumbnail of Adaptive growth changes in the liver remnant are affected by the size of hepatectomy in rats

International journal of experimental pathology, 2018

In this study we investigated the dynamics of hepatocyte hyperplasia and hypertrophy in rats subj... more In this study we investigated the dynamics of hepatocyte hyperplasia and hypertrophy in rats subjected to increasing sizes of partial hepatectomy (PH). A total of 104 rats were randomized according to the size of PH. On postoperative days (PODs) 1, 3 and 5, blood was drawn and the remnant liver removed for stereological analysis. Liver parameters and regeneration rate were significantly affected by size of PH. On POD 1, hepatocyte volumes had increased significantly in all PH groups. On POD 3, all groups showed hepatocyte volumes approximating baseline. On POD 5, hepatocyte volumes were significantly lower in PH (90) than in baseline, sham and PH (30) rats. Increasing hepatocyte proliferation was not observed following PH (30). Following PH (70), cell proliferation was significantly elevated on PODs 1 and 3, and following PH (90) on PODs 3 and 5. In conclusion, general hypertrophy of hepatocytes after different size of PH was followed by hepatocyte proliferation only in the liver re...

Research paper thumbnail of Gene Expression in the Liver Remnant Is Significantly Affected by the Size of Partial Hepatectomy: An Experimental Rat Study

Gene Expression, 2017

Extended hepatectomies may result in posthepatectomy liver failure, a condition with a high morta... more Extended hepatectomies may result in posthepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy (PH). Thirty Wistar rats were subjected to 30%, 70%, or 90% PH, sham operation, or no operation. Twenty-four hours following resection, liver tissue was harvested and genome-wide expression analysis was performed. Cluster analysis revealed two main groupings, one containing the PH(90%) and one containing the remaining groups [baseline, sham, PH(30%), and PH(70%)]. Categorization of specific affected molecular pathways in the PH(90%) group revealed a downregulation of cellular homeostatic function degradation and biosynthesis, whereas proliferation, cell growth, and cellular stress and injury were upregulated in the PH(90%) group. After PH(90%), the main upregulated pathways were mTOR and ILK. The main activated upstream regula...

Research paper thumbnail of Extended hepatectomy induces pronounced changes in protein expression levels

Research paper thumbnail of A new technique for accelerated liver regeneration: An experimental study in rats

Surgery, 2017

Background. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) i... more Background. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is used to accelerate growth of the future liver remnant. We investigated alternative methods for increasing the future liver remnant. Methods. A total of 152 rats were randomized as follows: (1) sham; (2) portal vein ligation; (3) portal vein ligation/surgical split (ALPPS); (4) portal vein ligation/split of the liver with a radiofrequency ablation needle; (5) portal vein ligation/radiofrequency ablation of the deportalized liver (portal vein ligation/ radiofrequency ablation necrosis in the deportalized liver); (6) portal vein ligation/radiofrequency ablation of the future liver remnant (portal vein ligation/radiofrequency ablation-future liver remnant); and (7) controls. Animals were evaluated on postoperative days 2 and 4. Bodyweight, liver parameters, hepatic regeneration rate, proinflammatory cytokines, hepatocyte proliferation, and gene expression were measured. Results. Hepatic regeneration rate indicated a steady increase in all intervention groups compared with sham rats (P < .001). At postoperative day 2, the hepatic regeneration rate was significantly higher in the portal vein ligation/radiofrequency ablation necrosis in the deportalized liver group than in the portal vein ligation group (P = .039). On postoperative day 4, we found significant differences between the portal vein ligation group and the ALPPS (P = .015), portal vein ligation/split of the liver with a radiofrequency ablation needle (P = .010), and portal vein ligation/radiofrequency ablation necrosis in the deportalized liver (P = .046) groups. Hepatocyte proliferation was significantly higher at all times compared with sham rats. On postoperative day 4, we found a significantly higher proliferation in groups 3, 4, 5, and 6 compared to portal vein ligation. Gene analysis revealed upregulation of genes involved in cellular proliferation and downregulation of genes involved in cellular homeostasis in all intervention groups. Between the intervention groups, gene expression was nearly identical. Biochemical markers and proinflammatory cytokines were comparable between groups. Conclusion. The surplus liver regeneration after ALPPS is probably mediated through parenchymal damage and subsequent release of growth stimulators, which again upregulates genes involved in cellular regeneration and downregulates genes involved in cellular homeostasis. We also demonstrate that growth of the future liver remnant, comparable to that seen after ALPPS, could be achieved by radiofrequency ablation treatment of the deportalized liver, that is, a procedure in which the initial step in humans can be performed percutaneously. (Surgery 2017;162:233-47.

Research paper thumbnail of Liver regeneration is dependent on the extent of hepatectomy

Journal of Surgical Research, 2016