The presence of a continuously renewing squamous cell epithelium that covers the esophagus demons... more The presence of a continuously renewing squamous cell epithelium that covers the esophagus demonstrates the crucial role of a pluripotent stem cell population that regulates esophageal homeostasis and pathogenesis of the most esophageal diseases. Esophageal development and maintenance of adult esophageal homeostasis share common mechanisms, as transformation of early columnar esophageal epithelium into mature squamous epithelial cells is based on molecular regulators such as SOX2, p63, Notch, and NANOG, which are also present in fetal esophageal development. In addition, esophageal cancer seems to be associated with the cancer stem cell hypothesis, which refers to mutated pluripotent stem cell populations that give rise to cancerous cell accumulations. These mutations have been related to stem cell markers like aldehyde dehydrogenase-1 (ALDH1), Lgr5, Wnt/β-catenin, Notch, CD44, and CD177. Dietary habits, like alcohol consumption, and caustic injury of the esophagus have been correlated to such mutations and consequent carcinogenesis. Moreover, Barrett’s esophagus due to gastroesophageal reflux disease (GERD), which is a precancerous lesion that leads to esophageal adenocarcinoma, rises from either a native squamous esophageal stem cell population that turns into intestinal epithelial cell (transdifferentiation) or an intestinal esophageal stem cell population derived from the esophagus, stomach, or circulation (transcommitment), which turns immortal due to mutations in the stem cell markers Sox9, Sox2, p63, Cdx1, Cdx2, and Foxa2. Nevertheless, esophageal cancer stem cell-regulating molecules could be ideal pharmaceutic targets for future therapeutic attempts against esophageal cancer. Furthermore, stem cell technology could enhance tissue-engineering esophageal scaffolds in order to replace damaged esophageal segments with transplanted artificial segments, after radical surgical operations due to esophageal cancer, massive esophageal caustic injury, endoscopic esophageal dissection due to Barrett’s esophagus, ionizing radiation, and pediatric diseases, such as esophageal atresia or tracheoesophageal fistula.
BACKGROUND Remote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce card... more BACKGROUND Remote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce cardiac injury and inflammation in patients undergoing diverse cardiac invasive and; surgical procedures. However, it is unclear whether RIPC has protective effects in patients; undergoing the transfemoral transcatheter aortic valve implantation (TF-TAVΙ) procedure. METHODS Between September 2013 and September 2015, 55 consecutive patients were prospectively randomly assigned to receive SHAM preconditioning (SHAM, 22 patients) or Remote Ischemic Preconditioning (RIPC) (4 cycles of 5 min intermittent leg ischemia and 5 min reperfusion, 33 patients) prior TF-TAVI. The primary endpoint was to determine the serum levels of: hs-cTn-I (necrosis), CK-18 (apoptosis) and IL-1b (inflammation). Quantification was performed using commercially available ELISA kits. Patients were sampled 1-day pre TF-TAVΙ and 24-hours post TF-TAVΙ. Secondary endpoints included: total mortality, incidence of periprocedural clinical acute myocardial infarction (AMI), acute kidney injury (AKI) and stroke. RESULTS 22 SHAM patients and 33 RIPC patients were finally analyzed. Our data revealed no significant differences in serum levels of hs-cTn-I and CK-18 among groups. However, in the RIPC group the IL1b level increase was significantly lower 24h post TF-TAVΙ, (p<0.01). There were no significant differences between groups in the secondary endpoints at the follow-up interval of 1 month. No RIPC-related adverse events were observed. CONCLUSIONS Our data suggest that RIPC did not exhibit significant cardiac or kidney protective effects regarding necrosis and apoptosis in patients undergoing TF-TAVΙ. However, an important anti-inflammatory effect was detected in RIPC group.
Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite a... more Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite advances in diagnostic modalities and treatment options, five-year survival rates are below 20%. Esophagectomy with extended lymph node dissection is the mainstay of treatment. More than 50% of patients experience recurrence within 1-3 years postoperatively. Recurrent disease may present locoregionally at the site of anastomosis or as recurrence through lymphatic spread in lymph node basins, as hematogenic metastasis, or as a combination of these. The standard treatment of recurrence is currently predicated on systemic chemotherapy and/or radiotherapy. Recent evidence suggests that surgical treatment of metachronous oligometastatic disease may be prognostically advantageous over medical management alone. Given the considerably low response rates to chemoradiotherapy, many institutions have adopted surgical treatment strategies for oligo-recurrent disease on a case-by-case basis. The aim of this article is to review the current evidence on the role of surgical treatment for metachronous oligometastases from esophageal cancer.
Inflammation and coagulation pathways are implicated in circulatory disease, but their interactio... more Inflammation and coagulation pathways are implicated in circulatory disease, but their interaction has not been completely deciphered yet. In this study, we investigated the association of coagulation and inflammation indices (activated clotting time [ACT], C-reactive protein, neutrophils) in hospitalized patients. Blood samples were drawn from consecutive patients at admission and at 48 hours for the assessment of the aforementioned parameters (n = 63). Healthy controls matched for sex and age were also examined (n = 39). Activated clotting time positively correlated with CRP on admission ( r = 0.354, P = .005), while the correlation was more robust on the second day ( r = 0.775, P < .001). Activated clotting time was significantly more prolonged in patients with abnormal CRP or abnormal absolute neutrophil count compared to patients with normal inflammatory markers ( U = 55.0, P < .001 and U = 310.5, P = .035, respectively). At 48 hours, a positive relationship was observed ...
Journal of investigative surgery : the official journal of the Academy of Surgical Research, Jan 30, 2018
To investigate the expression of toll-like receptors (TLRs) in the liver of septic mouse model. F... more To investigate the expression of toll-like receptors (TLRs) in the liver of septic mouse model. For this study seventy-two C57BL/6J mice were utilized. Sepsis was induced by cecal ligation and puncture (CLP) in the mice of the three septic (S) groups (euthanized at 24 hours, 48 hours and 72 hours). Sham (laparotomy)- operated mice constituted the control (C) groups (euthanized at 24, 48 and 72 hours). Blood samples were drawn and liver tissues were extracted and examined histologically. The expression of TLRs 2, 3, 4 and 7 was assessed via immunohistochemistry (IHC) and qrt-PCR (quantitative- Polymerase Chain Reaction). Liver function tests were elevated in all S-groups in contrast to their time-equivalent control groups (S24 versus C24, S48 versus C48 and S72 versus C72) (p < 0.05). Liver histology displayed progressive deterioration in the septic groups. IHC and qrt-PCR both showed an increased expression of all TLRs in the septic mice in comparison to their analogous control o...
Journal of cardiovascular medicine (Hagerstown, Md.), 2015
The role of the novel adipokines, omentin-1 and chemerin, in coronary artery disease is still obs... more The role of the novel adipokines, omentin-1 and chemerin, in coronary artery disease is still obscure. The present study analyzed the serum levels of omentin-1 and chemerin in patients with acute myocardial infarction (AMI) as well as prospectively 6 months post-AMI. Seventy-eight patients (63 men and 15 women) with first AMI were enrolled. Thirty-two age-matched and sex-matched individuals without overt cardiovascular disease served as healthy controls. Serum levels of omentin-1, chemerin, interleukin-18 (IL-18), high-sensitivity C-reactive protein (hsCRP), glycemic and lipid profiles, blood pressure, BMI and ejection fraction were assayed. In AMI patients, blood samples were obtained at hospital admission and after 6 months, whereas coronary angiography was performed within 7 days after admission. At baseline, AMI group appeared with significantly lower ejection fraction, omentin-1 and high-density lipoprotein serum levels, whereas it had higher concentrations of white blood cells...
Apelin and ghrelin have emerged as novel adipokines, but their role in coronary artery disease (C... more Apelin and ghrelin have emerged as novel adipokines, but their role in coronary artery disease (CAD) remains obscure. In the present study, we analyzed their serum levels in patients with acute coronary syndromes (ACS) or established asymptomatic CAD. A total of 355 participants were enrolled. Among them were 80 patients with unstable angina (UA) and 115 patients with acute myocardial infarction (AMI) hospitalized in the coronary care unit. We also included 88 asymptomatic patients with established CAD (asymptomatic CAD) and 72 age-and sex-matched healthy controls (HCs). All groups with CAD underwent coronary angiography, and the Gensini score was determined. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), as well as apelin and ghrelin were assayed. Patients with ACS (UA or AMI) were sampled at hospital admission. All 3 groups with CAD (UA, AMI, or asymptomatic CAD) showed significantly higher levels of hsCRP, HOMA-IR, and white blood cells than controls (P &amp;amp;amp;amp;amp;amp;lt; 0.01). Conversely, apelin and ghrelin concentrations were considerably (P &amp;amp;amp;amp;amp;amp;lt; 0.05) lower in CAD patients with respect to the control group. Most importantly, UA (6.72 +/- 3.51 ng/mL) and AMI (6.02 +/- 4.07 ng/mL) groups had even lower apelin levels on admission compared with the asymptomatic CAD group (13.53 +/- 5.2 ng/mL) (P &amp;amp;amp;amp;amp;amp;lt; 0.05). Logistic regression analysis showed an independent association of low apelin and ghrelin levels with CAD presence. Besides this result, apelin showed an inverse relationship with ACS incidence and a Gensini score independent of other cardiovascular risk factors (P &amp;amp;amp;amp;amp;amp;lt; 0.05). In conclusion, CAD seemed to correlate with low serum apelin and ghrelin levels. Moreover, apelin concentrations inversely were associated with the severity and the acute phase of CAD, which suggests its involvement in the progression and destabilization of coronary atherosclerotic plaques.
Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. Th... more Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. The aim of the present study was to investigate the effects of atorvastatin and lifestyle modification on the above adipokines in hypercholesterolemic patients. One hundred four statin-free subjects with moderate cardiovascular risk (Framingham risk score of 10-20%) were randomly assigned to receive either atorvastatin 20mg per day (AT group, n=52) or lifestyle modification (LM, group, n=52). For comparison, age and gender-matched blood donors, without any chronic cardiovascular or metabolic disease served as healthy controls (HC group, n=40). Clinical and anthropometrical parameters, lipids, fasting glucose, serum vaspin, visfatin and insulin levels were obtained at the beginning and after 12 weeks. At the end of the study, intra-group and inter-group comparison revealed that atorvastatin administration considerably ameliorated most lipid parameters and downregulated hsCRP levels (p=0.002, p=0.041, respectively). Moreover, we observed a significant increase of vaspin concentrations after 12-week atorvastatin treatment (from 1.37±0.6ng/ml to 2.13±0.61ng/ml), as compared to baseline (p=0.007) and LM group (p=0.030). In standard multiple regression analysis, the atorvastatin-induced decrease of vaspin was independently associated with hsCRP reduction (p=0.015). On the other hand, within and between groups comparison revealed a non-significant (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05) reduction of visfatin serum levels. In our study, lifestyle modification had totally modest influence on clinical and biochemical variables (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). In hypercholesterolemic patients with moderate estimated cardiovascular risk, atorvastatin administration reduced hsCRP and increased serum vaspin levels compared to lifestyle modification. The relation of those pleiotropic, non-lipid-lowering effects of statins with their clinical outcomes remains to be proved.
The presence of a continuously renewing squamous cell epithelium that covers the esophagus demons... more The presence of a continuously renewing squamous cell epithelium that covers the esophagus demonstrates the crucial role of a pluripotent stem cell population that regulates esophageal homeostasis and pathogenesis of the most esophageal diseases. Esophageal development and maintenance of adult esophageal homeostasis share common mechanisms, as transformation of early columnar esophageal epithelium into mature squamous epithelial cells is based on molecular regulators such as SOX2, p63, Notch, and NANOG, which are also present in fetal esophageal development. In addition, esophageal cancer seems to be associated with the cancer stem cell hypothesis, which refers to mutated pluripotent stem cell populations that give rise to cancerous cell accumulations. These mutations have been related to stem cell markers like aldehyde dehydrogenase-1 (ALDH1), Lgr5, Wnt/β-catenin, Notch, CD44, and CD177. Dietary habits, like alcohol consumption, and caustic injury of the esophagus have been correlated to such mutations and consequent carcinogenesis. Moreover, Barrett’s esophagus due to gastroesophageal reflux disease (GERD), which is a precancerous lesion that leads to esophageal adenocarcinoma, rises from either a native squamous esophageal stem cell population that turns into intestinal epithelial cell (transdifferentiation) or an intestinal esophageal stem cell population derived from the esophagus, stomach, or circulation (transcommitment), which turns immortal due to mutations in the stem cell markers Sox9, Sox2, p63, Cdx1, Cdx2, and Foxa2. Nevertheless, esophageal cancer stem cell-regulating molecules could be ideal pharmaceutic targets for future therapeutic attempts against esophageal cancer. Furthermore, stem cell technology could enhance tissue-engineering esophageal scaffolds in order to replace damaged esophageal segments with transplanted artificial segments, after radical surgical operations due to esophageal cancer, massive esophageal caustic injury, endoscopic esophageal dissection due to Barrett’s esophagus, ionizing radiation, and pediatric diseases, such as esophageal atresia or tracheoesophageal fistula.
BACKGROUND Remote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce card... more BACKGROUND Remote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce cardiac injury and inflammation in patients undergoing diverse cardiac invasive and; surgical procedures. However, it is unclear whether RIPC has protective effects in patients; undergoing the transfemoral transcatheter aortic valve implantation (TF-TAVΙ) procedure. METHODS Between September 2013 and September 2015, 55 consecutive patients were prospectively randomly assigned to receive SHAM preconditioning (SHAM, 22 patients) or Remote Ischemic Preconditioning (RIPC) (4 cycles of 5 min intermittent leg ischemia and 5 min reperfusion, 33 patients) prior TF-TAVI. The primary endpoint was to determine the serum levels of: hs-cTn-I (necrosis), CK-18 (apoptosis) and IL-1b (inflammation). Quantification was performed using commercially available ELISA kits. Patients were sampled 1-day pre TF-TAVΙ and 24-hours post TF-TAVΙ. Secondary endpoints included: total mortality, incidence of periprocedural clinical acute myocardial infarction (AMI), acute kidney injury (AKI) and stroke. RESULTS 22 SHAM patients and 33 RIPC patients were finally analyzed. Our data revealed no significant differences in serum levels of hs-cTn-I and CK-18 among groups. However, in the RIPC group the IL1b level increase was significantly lower 24h post TF-TAVΙ, (p<0.01). There were no significant differences between groups in the secondary endpoints at the follow-up interval of 1 month. No RIPC-related adverse events were observed. CONCLUSIONS Our data suggest that RIPC did not exhibit significant cardiac or kidney protective effects regarding necrosis and apoptosis in patients undergoing TF-TAVΙ. However, an important anti-inflammatory effect was detected in RIPC group.
Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite a... more Esophageal cancer is the sixth most common cause of cancer-related mortality worldwide. Despite advances in diagnostic modalities and treatment options, five-year survival rates are below 20%. Esophagectomy with extended lymph node dissection is the mainstay of treatment. More than 50% of patients experience recurrence within 1-3 years postoperatively. Recurrent disease may present locoregionally at the site of anastomosis or as recurrence through lymphatic spread in lymph node basins, as hematogenic metastasis, or as a combination of these. The standard treatment of recurrence is currently predicated on systemic chemotherapy and/or radiotherapy. Recent evidence suggests that surgical treatment of metachronous oligometastatic disease may be prognostically advantageous over medical management alone. Given the considerably low response rates to chemoradiotherapy, many institutions have adopted surgical treatment strategies for oligo-recurrent disease on a case-by-case basis. The aim of this article is to review the current evidence on the role of surgical treatment for metachronous oligometastases from esophageal cancer.
Inflammation and coagulation pathways are implicated in circulatory disease, but their interactio... more Inflammation and coagulation pathways are implicated in circulatory disease, but their interaction has not been completely deciphered yet. In this study, we investigated the association of coagulation and inflammation indices (activated clotting time [ACT], C-reactive protein, neutrophils) in hospitalized patients. Blood samples were drawn from consecutive patients at admission and at 48 hours for the assessment of the aforementioned parameters (n = 63). Healthy controls matched for sex and age were also examined (n = 39). Activated clotting time positively correlated with CRP on admission ( r = 0.354, P = .005), while the correlation was more robust on the second day ( r = 0.775, P < .001). Activated clotting time was significantly more prolonged in patients with abnormal CRP or abnormal absolute neutrophil count compared to patients with normal inflammatory markers ( U = 55.0, P < .001 and U = 310.5, P = .035, respectively). At 48 hours, a positive relationship was observed ...
Journal of investigative surgery : the official journal of the Academy of Surgical Research, Jan 30, 2018
To investigate the expression of toll-like receptors (TLRs) in the liver of septic mouse model. F... more To investigate the expression of toll-like receptors (TLRs) in the liver of septic mouse model. For this study seventy-two C57BL/6J mice were utilized. Sepsis was induced by cecal ligation and puncture (CLP) in the mice of the three septic (S) groups (euthanized at 24 hours, 48 hours and 72 hours). Sham (laparotomy)- operated mice constituted the control (C) groups (euthanized at 24, 48 and 72 hours). Blood samples were drawn and liver tissues were extracted and examined histologically. The expression of TLRs 2, 3, 4 and 7 was assessed via immunohistochemistry (IHC) and qrt-PCR (quantitative- Polymerase Chain Reaction). Liver function tests were elevated in all S-groups in contrast to their time-equivalent control groups (S24 versus C24, S48 versus C48 and S72 versus C72) (p < 0.05). Liver histology displayed progressive deterioration in the septic groups. IHC and qrt-PCR both showed an increased expression of all TLRs in the septic mice in comparison to their analogous control o...
Journal of cardiovascular medicine (Hagerstown, Md.), 2015
The role of the novel adipokines, omentin-1 and chemerin, in coronary artery disease is still obs... more The role of the novel adipokines, omentin-1 and chemerin, in coronary artery disease is still obscure. The present study analyzed the serum levels of omentin-1 and chemerin in patients with acute myocardial infarction (AMI) as well as prospectively 6 months post-AMI. Seventy-eight patients (63 men and 15 women) with first AMI were enrolled. Thirty-two age-matched and sex-matched individuals without overt cardiovascular disease served as healthy controls. Serum levels of omentin-1, chemerin, interleukin-18 (IL-18), high-sensitivity C-reactive protein (hsCRP), glycemic and lipid profiles, blood pressure, BMI and ejection fraction were assayed. In AMI patients, blood samples were obtained at hospital admission and after 6 months, whereas coronary angiography was performed within 7 days after admission. At baseline, AMI group appeared with significantly lower ejection fraction, omentin-1 and high-density lipoprotein serum levels, whereas it had higher concentrations of white blood cells...
Apelin and ghrelin have emerged as novel adipokines, but their role in coronary artery disease (C... more Apelin and ghrelin have emerged as novel adipokines, but their role in coronary artery disease (CAD) remains obscure. In the present study, we analyzed their serum levels in patients with acute coronary syndromes (ACS) or established asymptomatic CAD. A total of 355 participants were enrolled. Among them were 80 patients with unstable angina (UA) and 115 patients with acute myocardial infarction (AMI) hospitalized in the coronary care unit. We also included 88 asymptomatic patients with established CAD (asymptomatic CAD) and 72 age-and sex-matched healthy controls (HCs). All groups with CAD underwent coronary angiography, and the Gensini score was determined. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), as well as apelin and ghrelin were assayed. Patients with ACS (UA or AMI) were sampled at hospital admission. All 3 groups with CAD (UA, AMI, or asymptomatic CAD) showed significantly higher levels of hsCRP, HOMA-IR, and white blood cells than controls (P &amp;amp;amp;amp;amp;amp;lt; 0.01). Conversely, apelin and ghrelin concentrations were considerably (P &amp;amp;amp;amp;amp;amp;lt; 0.05) lower in CAD patients with respect to the control group. Most importantly, UA (6.72 +/- 3.51 ng/mL) and AMI (6.02 +/- 4.07 ng/mL) groups had even lower apelin levels on admission compared with the asymptomatic CAD group (13.53 +/- 5.2 ng/mL) (P &amp;amp;amp;amp;amp;amp;lt; 0.05). Logistic regression analysis showed an independent association of low apelin and ghrelin levels with CAD presence. Besides this result, apelin showed an inverse relationship with ACS incidence and a Gensini score independent of other cardiovascular risk factors (P &amp;amp;amp;amp;amp;amp;lt; 0.05). In conclusion, CAD seemed to correlate with low serum apelin and ghrelin levels. Moreover, apelin concentrations inversely were associated with the severity and the acute phase of CAD, which suggests its involvement in the progression and destabilization of coronary atherosclerotic plaques.
Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. Th... more Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. The aim of the present study was to investigate the effects of atorvastatin and lifestyle modification on the above adipokines in hypercholesterolemic patients. One hundred four statin-free subjects with moderate cardiovascular risk (Framingham risk score of 10-20%) were randomly assigned to receive either atorvastatin 20mg per day (AT group, n=52) or lifestyle modification (LM, group, n=52). For comparison, age and gender-matched blood donors, without any chronic cardiovascular or metabolic disease served as healthy controls (HC group, n=40). Clinical and anthropometrical parameters, lipids, fasting glucose, serum vaspin, visfatin and insulin levels were obtained at the beginning and after 12 weeks. At the end of the study, intra-group and inter-group comparison revealed that atorvastatin administration considerably ameliorated most lipid parameters and downregulated hsCRP levels (p=0.002, p=0.041, respectively). Moreover, we observed a significant increase of vaspin concentrations after 12-week atorvastatin treatment (from 1.37±0.6ng/ml to 2.13±0.61ng/ml), as compared to baseline (p=0.007) and LM group (p=0.030). In standard multiple regression analysis, the atorvastatin-induced decrease of vaspin was independently associated with hsCRP reduction (p=0.015). On the other hand, within and between groups comparison revealed a non-significant (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05) reduction of visfatin serum levels. In our study, lifestyle modification had totally modest influence on clinical and biochemical variables (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.05). In hypercholesterolemic patients with moderate estimated cardiovascular risk, atorvastatin administration reduced hsCRP and increased serum vaspin levels compared to lifestyle modification. The relation of those pleiotropic, non-lipid-lowering effects of statins with their clinical outcomes remains to be proved.
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