7A). On the contrary, we found that SVIGF-I-treated rats exhibited significant up-regulation of HNF4α, a hepatocyte nuclear factor that stimulates the expression of genes characterizing the mature hepatocyte phenotype (Fig. 7B).20 It seems possible that this effect

might contribute to the improvement of liver function observed in IGF-I-treated cirrhotic rats. We also assessed the safety of SVIGF-I in normal rats. To this aim, control healthy rats, rats Selleck PF-6463922 injected with SVIGF-I or with SVLuc were sacrificed 8 weeks after vector administration. IGF-I, IGFBP3, and HGF were up-regulated in the liver of rats given SVIGF-I but histopathological analysis of several organs and evaluation of different serum biochemical parameters showed no significant differences between the groups (Supporting Fig. 4 and data not shown). To evaluate the robustness of IGF-I therapy we tested SVIGF-I in a different model of liver cirrhosis more difficult to revert. To this aim, Selleck Enzalutamide we administered saline or recombinant SV40 vectors encoding SVLuc or IGF-I (SVIGF-I) to rats in which cirrhosis had been previously induced by TAA administration for 7 weeks. All animals and healthy controls were evaluated 8 weeks after vector administration. Similar to what was observed in the

CCl4 model, SVIGF-I vector was able to express functional IGF-I protein in the TAA cirrhotic liver. Thus, both IGF-I and IGF-IBP3 mRNAs were increased in IGF-I-treated animals compared to controls (Fig. 8A). This was accompanied by improved liver biochemistry, being the levels medchemexpress of serum ALP and serum bilirubin significantly lower than in cirrhotic controls and similar to values found in healthy animals (Fig. 8B). Also, the liver of IGF-I-treated animals exhibited less nodularity macroscopically (data not shown) and on histological

examination showed a marked decrease of liver fibrosis and less ductular proliferation in portal tracts compared to cirrhotic controls (Fig. 8C,D). Reduced fibrosis correlated with a strong decrease of activated HSCs as detected by immunohistochemistry and quantification of αSMA mRNA (Fig. 8C,E). In parallel to findings in the CCl4 model, rats with TAA-induced cirrhosis treated with SVIGF-I showed in liver tissue up-regulation of HGF accompanied by increased expression of MMPs and decreased levels of TIMP-1 (Fig. 8A, Supporting Fig. 5). Because liver transplantation can be offered to only a limited number of cirrhotic patients, alternative therapies for advanced liver cirrhosis are urgently needed. In keeping with the fact that IGF-I deficiency is a key feature of liver cirrhosis, a previous work by our group showed that daily administration of recombinant IGF-I to cirrhotic patients induces a significant amelioration of liver function.4 However, the amount of recombinant protein needed to accomplish hormone replacement therapy is high and a prolonged treatment would be exceedingly costly.

, Inc, Ajinomoto Co., Inc, Bayer Japan The following people have nothing to disclose: Kai Takegoshi, Masao Honda, Hikari Okada, Hajime Sunagozaka, Naoto Matsuzawa, Toshinari Takamura, Takuji Tanaka

CD248 is a stromal cell marker expressed on fibroblasts and pericytes. We hypothesised that CD248 expression may be upregulated in liver fibrosis and thatCD248 knockout (ko) mice will develop less fibrosis than equivalent wild-type (WT) mice. Methods: CD248 expression was studied by immunostaining and quantitative PCR in both normal and diseased human/murine liver tissue and isolated hepatic stellate cells (HSC). Chronic liver injury was induced in CD248 ko and wild-type (WT) controls by bi-weekly injections of carbon tetrachlo-ride (CCl4) for CH5424802 mw 8 or 12 weeks. Liver fibrosis was quantified by picrosirius red staining (PSR) and qPCR for Collagen I and a-smooth muscle actin (α-SMA). Expression of platelet derived growth factor receptor (PDGFR) on hepatic stellate cells and their response to PDGF stimulation was studied by CyQUANT proliferation assay and c-fos analysis. Results: CD248 expression was seen in normal human and mouse liver but was

significantly increased in liver injury on both immunostaining and gene expression. CD248 was found to be co-expressed with a range of fibroblast/HSC markers Selleck PLX3397 including desmin, vimentin, αSMA and GFAP in murine and human liver sections. CD248 expression was restricted to isolated murine and human HSC (co-stained with GFAP, desmin and αSMA) and was not seen on isolated hepatocytes, biliary endothelial cells or sinusoidal endothelial cells. PSR staining of liver tissue after chronic CCl4 injury revealed less fibrosis in CD248ko mice compared to wt mice as assessed by digital morphometric analysis

of PSR stained sections (56.4 & 51.1% less; p<0.001 and p<0.05 at 8 & 12 weeks respectively) and qPCR for Collagen I (65.3 & 64.0% less; p<0.05 at 8 & 12 weeks respectively) & αSMA (62.5 & 86.1% less; MCE公司 p=0.01 and p<0.05 at 8 & 12 weeks respectively). Isolated HSC from WT and CD248ko mice expressed PDGFR α and β at similar levels. As expected PDGF-BB induced proliferation of WT HSC (80.5% proliferation), whereas CD248ko HSC did not demonstrate a proliferative response to PDGF-BB (10.3%). Abrogated PDGF signalling in CD248ko HSC was confirmed by significantly reduced c-fos expression compared to WT HSC at gene level (0.03+/-0.01 vs 0.22+/-0.06, p<0.05). Conclusion Our data indicate that CD248 is upregulated in liver fibrosis and its expression is restricted to stellate cells and myofibroblasts in both murine and human settings. We demonstrate that genetic knockout of CD248 reduces susceptibility to liver fibrosis by reducing PDGF-BB mediated proliferation of HSC. These data highlight CD248 as a potential novel therapeutic target in fibrotic liver disease. Disclosures: Philip N. Newsome – Grant/Research Support: Novo Nordisk The following people have nothing to disclose: Victoria Aldridge, Annika Wilhelm, Abhilok Garg, Amy J.

, Inc, Ajinomoto Co., Inc, Bayer Japan The following people have nothing to disclose: Kai Takegoshi, Masao Honda, Hikari Okada, Hajime Sunagozaka, Naoto Matsuzawa, Toshinari Takamura, Takuji Tanaka

CD248 is a stromal cell marker expressed on fibroblasts and pericytes. We hypothesised that CD248 expression may be upregulated in liver fibrosis and thatCD248 knockout (ko) mice will develop less fibrosis than equivalent wild-type (WT) mice. Methods: CD248 expression was studied by immunostaining and quantitative PCR in both normal and diseased human/murine liver tissue and isolated hepatic stellate cells (HSC). Chronic liver injury was induced in CD248 ko and wild-type (WT) controls by bi-weekly injections of carbon tetrachlo-ride (CCl4) for Ivacaftor solubility dmso 8 or 12 weeks. Liver fibrosis was quantified by picrosirius red staining (PSR) and qPCR for Collagen I and a-smooth muscle actin (α-SMA). Expression of platelet derived growth factor receptor (PDGFR) on hepatic stellate cells and their response to PDGF stimulation was studied by CyQUANT proliferation assay and c-fos analysis. Results: CD248 expression was seen in normal human and mouse liver but was

significantly increased in liver injury on both immunostaining and gene expression. CD248 was found to be co-expressed with a range of fibroblast/HSC markers this website including desmin, vimentin, αSMA and GFAP in murine and human liver sections. CD248 expression was restricted to isolated murine and human HSC (co-stained with GFAP, desmin and αSMA) and was not seen on isolated hepatocytes, biliary endothelial cells or sinusoidal endothelial cells. PSR staining of liver tissue after chronic CCl4 injury revealed less fibrosis in CD248ko mice compared to wt mice as assessed by digital morphometric analysis

of PSR stained sections (56.4 & 51.1% less; p<0.001 and p<0.05 at 8 & 12 weeks respectively) and qPCR for Collagen I (65.3 & 64.0% less; p<0.05 at 8 & 12 weeks respectively) & αSMA (62.5 & 86.1% less; MCE公司 p=0.01 and p<0.05 at 8 & 12 weeks respectively). Isolated HSC from WT and CD248ko mice expressed PDGFR α and β at similar levels. As expected PDGF-BB induced proliferation of WT HSC (80.5% proliferation), whereas CD248ko HSC did not demonstrate a proliferative response to PDGF-BB (10.3%). Abrogated PDGF signalling in CD248ko HSC was confirmed by significantly reduced c-fos expression compared to WT HSC at gene level (0.03+/-0.01 vs 0.22+/-0.06, p<0.05). Conclusion Our data indicate that CD248 is upregulated in liver fibrosis and its expression is restricted to stellate cells and myofibroblasts in both murine and human settings. We demonstrate that genetic knockout of CD248 reduces susceptibility to liver fibrosis by reducing PDGF-BB mediated proliferation of HSC. These data highlight CD248 as a potential novel therapeutic target in fibrotic liver disease. Disclosures: Philip N. Newsome – Grant/Research Support: Novo Nordisk The following people have nothing to disclose: Victoria Aldridge, Annika Wilhelm, Abhilok Garg, Amy J.

The celiac artery (CA), gastroduodenal artery (GDA) and right gastroepiploic artery (RGEA) are also shown. Sirolimus molecular weight During the surgical procedure of pancreaticoduodenectomy, the IPDA is usually ligated and cut. However, with the above anatomy, we were concerned about the possibility of significant hepatic ischemia. Because of this, the operation was planned with a view to preserve the IPDA. At laparotomy, intraoperative ultrasound was used to confirm that the LHA and IPDA were not closely applied to the pancreatic tumor. After dividing the pancreas above the portal vein, the LHA and IPDA were taped and clamped and the pancreas was transected along the vessels without cutting the pancreas tumor.

The GDA and small arterial branches were ligated after which clamps on the IPDA and LHA were released (Figure 2). She was discharged from hospital 2-weeks after surgery without any complication. When operating on tumors in the head of the pancreas, it is important to recognize aberrant hepatic arteries. Relatively common anomalies are an hepatic artery or RHA that arises from the SMA. These anomalous arteries usually run laterally to the portal vein behind the head of the pancreas and enter the right side of the hepatoduodenal ligament, Selleck Target Selective Inhibitor Library posterolateral to the common bile duct. In the above patient, there was not only an anomalous RHA but also a LHA

that arose from the IPDA within the pancreatic parenchyma. This may be the first report of successful pancreatoduodenectomy without injury to these arteries. Pre-operative 3-dimensional CT arteriography is helpful in demonstrating aberrant blood vessels that may alter operative procedures and perhaps reduce operative morbidity and mortality. Contributed by “
“To the Editor: We read with great interest the article recently published in this 上海皓元 journal by Dr. Guy et al.1 The authors show a direct correlation between liver damage and deregulated Hedgehog (HH)-pathway in liver biopsies from a

cohort of 90 nonalcoholic fatty liver disease (NAFLD) patients. They demonstrate the association between HH-producing/responsive target cells and fibrosis stage. Shh and Gli2-expressing cells have been positively correlated with portal inflammation, ballooning, and fibrosis stage. Furthermore, they reported a pivotal role of the HH-pathway in both hepatic and extrahepatic tissue, highlighted by the colocalization of Gli2 with vimentin or α-smooth muscle actin. Guy et al. hypothesize the possibility to control the HH signaling pathway through specific inhibitors as a useful tool to hamper the progression of NAFLD. In this regard we wish to report our preliminary data. We treated Huh7.5.1 cells with a combination of fatty acids (FAs), palmitic and oleic acid (1 mM), for 14 hours to mimic the intrahepatic fat accumulation typical of NAFLD.

The celiac artery (CA), gastroduodenal artery (GDA) and right gastroepiploic artery (RGEA) are also shown. selleck kinase inhibitor During the surgical procedure of pancreaticoduodenectomy, the IPDA is usually ligated and cut. However, with the above anatomy, we were concerned about the possibility of significant hepatic ischemia. Because of this, the operation was planned with a view to preserve the IPDA. At laparotomy, intraoperative ultrasound was used to confirm that the LHA and IPDA were not closely applied to the pancreatic tumor. After dividing the pancreas above the portal vein, the LHA and IPDA were taped and clamped and the pancreas was transected along the vessels without cutting the pancreas tumor.

The GDA and small arterial branches were ligated after which clamps on the IPDA and LHA were released (Figure 2). She was discharged from hospital 2-weeks after surgery without any complication. When operating on tumors in the head of the pancreas, it is important to recognize aberrant hepatic arteries. Relatively common anomalies are an hepatic artery or RHA that arises from the SMA. These anomalous arteries usually run laterally to the portal vein behind the head of the pancreas and enter the right side of the hepatoduodenal ligament, 5-Fluoracil purchase posterolateral to the common bile duct. In the above patient, there was not only an anomalous RHA but also a LHA

that arose from the IPDA within the pancreatic parenchyma. This may be the first report of successful pancreatoduodenectomy without injury to these arteries. Pre-operative 3-dimensional CT arteriography is helpful in demonstrating aberrant blood vessels that may alter operative procedures and perhaps reduce operative morbidity and mortality. Contributed by “
“To the Editor: We read with great interest the article recently published in this 上海皓元 journal by Dr. Guy et al.1 The authors show a direct correlation between liver damage and deregulated Hedgehog (HH)-pathway in liver biopsies from a

cohort of 90 nonalcoholic fatty liver disease (NAFLD) patients. They demonstrate the association between HH-producing/responsive target cells and fibrosis stage. Shh and Gli2-expressing cells have been positively correlated with portal inflammation, ballooning, and fibrosis stage. Furthermore, they reported a pivotal role of the HH-pathway in both hepatic and extrahepatic tissue, highlighted by the colocalization of Gli2 with vimentin or α-smooth muscle actin. Guy et al. hypothesize the possibility to control the HH signaling pathway through specific inhibitors as a useful tool to hamper the progression of NAFLD. In this regard we wish to report our preliminary data. We treated Huh7.5.1 cells with a combination of fatty acids (FAs), palmitic and oleic acid (1 mM), for 14 hours to mimic the intrahepatic fat accumulation typical of NAFLD.

For the first time in history, Selleckchem LY2606368 the majority of the human population resides within urban areas, with over 3 billion people living in cities across the world (UNFPA, 2007; Gehrt, 2010). Gehrt (2010) defines ‘urban’ as an area of human residence, activity and associated land area developed for those purposes, usually defined by a threshold human density. These large groupings of people and associated structures comprise at least one town or city (Gehrt, 2010) and include a wide range of anthropogenic disturbances, including buildings and associated infrastructure, for example, gardens, roads, waste ground and parkland (Baker & Harris, 2007). However, the definition of what is classified

as ‘urban’ varies greatly depending on geographic location, which, in part, may reflect population density present in the country. Furthermore, while city centres may represent the extreme of anthropogenically altered environments, city suburbs, villages and small towns or even rural farmland also represent challenges in terms of altered landscapes (Fig. 1). With the spread of urban environments (e.g. McKinney, 2002; Radeloff et al., 2005), many terrestrial species have withdrawn into FDA approved Drug Library high throughput reduced ranges; this response is particularly noticeable in mammalian carnivores (Woodroffe & Ginsberg, 1998; Woodroffe, 2000; Cardillo et al., MCE 2004). Many carnivore

species actively avoid urban areas, rapidly disappearing from encroaching urban spread (‘urbanophobes’, sensu Witte, Diesing & Godde, 1985, ‘urban avoiders’, sensu McKinney, 2006). A number of other species, however, can be described as truly urban dwellers, maintaining varying levels of intimacy with humans, residing within cities and built-up areas across the globe, despite the significantly artificial environment. For some, cities have grown up around their preferred habitat; their presence close to human societies therefore represents continuation of a somewhat altered lifestyle (e.g. Radeloff et al., 2005), and they usually do not make extensive use of anthropogenic

resources, largely still relying on natural resources (‘urban adapters’, sensu McKinney, 2006). By contrast, fully synanthropic species (‘urban exploiters’, sensu McKinney, 2006) may actively invade city environments, make use of anthropogenic food and shelter, and often attain population densities far above those found for rural habitats. In this paper, we have reviewed available information on carnivores dwelling in urban environments (either as ‘urban adapters’ or ‘urban exploiters’) and compare these with species that have not successfully adapted to the urban environment (‘urban avoiders’). Why review the biology and ecology of urban carnivores? Firstly, as cities grow, we are removing alternative habitat for these animals.

For the first time in history, buy Gemcitabine the majority of the human population resides within urban areas, with over 3 billion people living in cities across the world (UNFPA, 2007; Gehrt, 2010). Gehrt (2010) defines ‘urban’ as an area of human residence, activity and associated land area developed for those purposes, usually defined by a threshold human density. These large groupings of people and associated structures comprise at least one town or city (Gehrt, 2010) and include a wide range of anthropogenic disturbances, including buildings and associated infrastructure, for example, gardens, roads, waste ground and parkland (Baker & Harris, 2007). However, the definition of what is classified

as ‘urban’ varies greatly depending on geographic location, which, in part, may reflect population density present in the country. Furthermore, while city centres may represent the extreme of anthropogenically altered environments, city suburbs, villages and small towns or even rural farmland also represent challenges in terms of altered landscapes (Fig. 1). With the spread of urban environments (e.g. McKinney, 2002; Radeloff et al., 2005), many terrestrial species have withdrawn into this website reduced ranges; this response is particularly noticeable in mammalian carnivores (Woodroffe & Ginsberg, 1998; Woodroffe, 2000; Cardillo et al., MCE 2004). Many carnivore

species actively avoid urban areas, rapidly disappearing from encroaching urban spread (‘urbanophobes’, sensu Witte, Diesing & Godde, 1985, ‘urban avoiders’, sensu McKinney, 2006). A number of other species, however, can be described as truly urban dwellers, maintaining varying levels of intimacy with humans, residing within cities and built-up areas across the globe, despite the significantly artificial environment. For some, cities have grown up around their preferred habitat; their presence close to human societies therefore represents continuation of a somewhat altered lifestyle (e.g. Radeloff et al., 2005), and they usually do not make extensive use of anthropogenic

resources, largely still relying on natural resources (‘urban adapters’, sensu McKinney, 2006). By contrast, fully synanthropic species (‘urban exploiters’, sensu McKinney, 2006) may actively invade city environments, make use of anthropogenic food and shelter, and often attain population densities far above those found for rural habitats. In this paper, we have reviewed available information on carnivores dwelling in urban environments (either as ‘urban adapters’ or ‘urban exploiters’) and compare these with species that have not successfully adapted to the urban environment (‘urban avoiders’). Why review the biology and ecology of urban carnivores? Firstly, as cities grow, we are removing alternative habitat for these animals.

Second, InsP3R function was inhibited by see more treating hepatocytes with the InsP3R inhibitor xestospongin C.32 This resulted in an 83% reduction in canalicular fluorescence

of CGamF relative to controls (Fig. 4A,B). Most InsP3Rs in hepatocytes are type II,21 so InsP3R2 expression was reduced by 70% (Fig. 5A) using an isoform-specific siRNA validated previously.22 This resulted in a 53% reduction in canalicular CGamF fluorescence relative to controls (Fig. 5C,D), similar to what was observed in matched preparations treated with BAPTA-AM (Fig. 5C,D). Interestingly, in InsP3R2-depleted cells there was a 40% decrease in Bsep expression (Fig. 5A). Finally, the importance of InsP3R2′s pericanalicular localization was examined. Cells were treated with mβCD to disrupt lipid rafts, which had no effect on the amount of InsP3R2 or Bsep that was expressed (Fig. 6A), but redistributed InsP3R2 and Bsep so that they were less concentrated in the canalicular region (Fig. 6B,C). This reduced canalicular CGamF fluorescence by 67% relative to controls, similar to what was observed in BAPTA-treated preparations (Fig. 6D,E). Together,

these findings provide evidence that Bsep activity is Ca2+-dependent, check details and in particular depends on expression and pericanalicular localization of InsP3R2. In rats treated with either LPS or estrogen, InsP3R2 expression was significantly decreased (Fig. 7A,B). Moreover, InsP3R2 labeling in proximity to the canalicular membrane was decreased, and

InsP3R2 labeling was seen in a punctate pattern in the pericanalicular region (Fig. 7C). Quantification of InsP3R2 labeling confirmed that the receptor is distributed more diffusely 上海皓元医药股份有限公司 throughout the canalicular region in LPS- or estrogen-treated animals (Fig. 7D). Together, these findings raise the possibility that the mistargeting of canalicular transporters such as Bsep observed in canalicular cholestasis33, 34 may be related to decreased expression and/or mislocalization of InsP3R2. InsP3R2 is the major intracellular Ca2+ release channel in hepatocytes.16 Ca2+ release from pericanalicular InsP3R2 promotes the activity of Mrp2, in part by increasing Mrp2 insertion into the plasma membrane.22 The present study demonstrates that InsP3R2 also promotes the activity of Bsep. Pericanalicular Ca2+ signaling likely promotes Bsep activity by enhancing exocytic insertion, as with Mrp2. Vesicle fusion depends on a localized Ca2+ increase, which must be in the range of ∼10 μM for the form of exocytosis that governs transporter insertion.35 Apical clusters of InsP3R in other polarized cells are capable of producing such large amplitude, focal Ca2+ transients to regulate secretion.36 In Wif-B9 cells,37 Bsep constitutively recycles between a subapical endosomal pool and the canalicular membrane. Therefore, it would be predicted that Bsep would accumulate intracellularly and bile secretion would decrease without InsP3R2.

Questions were carried out before and after surgery. Results: i) Between April 2012 and May 2013, 13 patients received preoperative simulation on the “Liversim”. This system enables us to demonstrate the real-time deformation and resection of the liver. The portal and hepatic veins are easily detectable on the resection line. There was no obvious discrepancy during the resection process; i. e., emergence of branches Erlotinib mw of the portal vein or hepatic vein, depth and direction of the resection line; between our simulation and the real surgery. ii) 1. Scores about usefulness of the “Liversim” were 9.67±0.71 for the student group (n = 9) and 9.56±0.73 for the surgeon group (n = 9). All respondents

thought that this system was valuable, with no significant differences between the two groups.2. The scores about the portal vein were 7.88±2.7 for the students (n = 8) and 8.67±0.58 for the surgeons (n = 3). The scores about the hepatic vein were 8.0±2.62 for the students (n = 8), and 8.33±0.58

for the surgeons (n = 3). The scores for the surgeons about the portal and hepatic vein were significantly higher than those for the students. It was revealed that students felt difficulty in recognizing the anatomy of the portal and hepatic vein. Conclusion: This novel system may be useful for realizing the hepatic anatomy and operative procedure to young surgeons and students. Disclosures: The following people have nothing to disclose: Yukio Oshiro, Tyoichi Miyamoto, Ken Nakayama, Jun Mitani, Nobuhiro Ohkohchi “
“Appendectomy protects http://www.selleckchem.com/products/Maraviroc.html against the development of ulcerative colitis (UC). However, the relationship between appendectomy and the clinical course of UC is complex, and could be impacted by a number of variables. Data on 2648 UC patients were retrieved from the Inflammatory Bowel Disease registry at Asan Medical Center. This retrospective

cohort study compared the clinical course of UC in 68 patients who received an appendectomy before their UC diagnosis and 2544 patients who did not receive this 上海皓元医药股份有限公司 procedure. A nested case-control study was also conducted to compare the disease course before and after appendectomy in 36 patients who received this surgery after UC diagnosis. To control for potential confounders, 144 matched controls were retrieved from among 2544 non-appendectomized patients In the retrospective cohort study, an appendectomy before UC diagnosis demonstrated no influence on disease extent at diagnosis, rates of medication use, proximal disease extension, or colectomy. The 10- and 20-year probabilities of receiving a colectomy were 12.7% and 20.6%, respectively, in appendectomized patients, in comparison with 8.9% and 16.4%, respectively, in non-appendectomized patients (p = 0.81). According to the nested case-control study, an appendectomy after UC diagnosis did not change the subsequent disease course in terms of medication use, proximal disease extension, or hospital admission rate.

In conclusion, constitutive activation of ERBB3-dependent signaling driven by an NRG1/ERBB3 autocrine mechanism is strongly associated with microscopic vascular invasion, early recurrence, and poor prognosis of HCC. ERBB3-dependent signaling plays a crucial role in the regulation of tumor invasion and metastasis of HCC rather than tumor CP 868596 initiation and growth. ERBB3 is a marker indicating microscopic vascular

invasion and a predictor for the early recurrence of HCC. ERBB3-dependent signaling is a candidate target for the treatment of microscopic intrahepatic invasion and for the prevention of HCC recurrence. The authors are grateful to Professor Yun-Fan Liaw for his comments on this study and to Miss Shao-Jung Erlotinib chemical structure Lo for her technique assistance. They also thank the Taiwan Liver Cancer Network

for providing some of the clinical samples for this study and the National RNAi Core of Taiwan for providing the lentivirus-based shRNA clones. Additional Supporting Information may be found in the online version of this article. “
“Background and Aims:  The change of therapeutic strategy for large colorectal tumors after the introduction of endoscopic submucosal dissection (ESD) has not yet been clarified. The aim of this study was to estimate the impact of ESD as an initial treatment strategy. Methods:  A questionnaire was administered to nine expert panelists in colorectal ESD. The questionnaire used retrospective data from consecutive case series. Forty-seven cases of early colorectal tumors (≥ 20 mm) were included. Endoscopic growth types were 25 laterally-spreading tumors (LST) of granular type (G), 15 LST of non-granular types (NG), and seven protruded types. Pathological diagnoses included 15 adenomas (Ad), 18 intramucosal cancers (M), three submucosally-shallow invasive

cancers (< 1000 µm) (SMs), and 11 submucosally-deep invasive cancers (≥ 1000 µm) (SMd). The expert panelists completed questionnaires about recommended initial treatment under suppositions of before and after the introduction of ESD. Over-surgery was defined as surgery for Ad, M, and SMs. Non-curative endoscopic resection (ER) MCE was defined as ER for SMd. Results:  After the introduction of ESD, the reduction in the over-surgery rate was estimated at 10.8% for Ad, M, and SMs, and the increase in the non-curative ER rate was estimated at 27.2% for SMd. By endoscopic growth type, the reduction of over-surgery rates for LST–NG, LST–G, and protruded type was 15.5%, 10.5%, and 2.2%, respectively. Conclusions:  The endoscopists changed their therapeutic strategy for large colorectal tumors to reduce over-surgery, especially in LST–NG, demonstrating the impact of ESD.