Covering the Cover

Abstract

How Sweet It Is: Carbonation and Brain ProcessingThe rising prevalence of obesity over the last several decades, and its associated increased risk of heart disease, type 2 diabetes, hypertension, liver disease, and osteoarthritis, among other conditions, has been widely reported. Less is known about the factors contributing to the obesity epidemic. Food preferences and dietary behavior are predominantly influenced by our sense of taste. The central nervous system processing of taste is thought to involve the anterior insula and frontal operculum, the opercular and orbitofrontal cortex, the amygdala, and the prefrontal cortex. Recently, in addition to the gustatory processing of the 5 basic tastes (sweet, salty, sour, bitter, and umami, characterized by the taste of monosodium glutamate), the taste of carbonation, its cellular and molecular substrates, and the modulation of CO2 of sweet perception, has been the focus of investigation. In this issue of Gastroenterology (accompanied by an editorial), Di Salle et al examine, using functional magnetic resonance imaging, the interference between CO2 and perception of sweetness and the differential effects of CO2 and sucrose and the artificial sweetener commonly used in diet beverages, aspartame–acesulfame (As-Ac). The presence of carbonation in sweet solutions, regardless of the sweetening agent, reduced neural activity in the anterior insula, orbitofrontal cortex, and the posterior pons. However, the effect of carbonation on sucrose was greater than on As-Ac perception. Independent of carbonation, As-Ac increased activity in the anterior insula and sucrose increased activity in the amygdala. This differential brain activity between sucrose and As-Ac was much more prominent in the absence of carbonation (Figure 1). These findings demonstrate that carbonation reduces the neural processing of sucrose more than of artificial sweeteners and suggest that the combination of CO2 and sucrose leads to increased consumption of sucrose.See page 537; editorial on page 500.Endoscopy vs Surgery for Pancreatic Pseudocyst DrainagePancreatic pseudocysts are pancreatic fluid collections not encased by a wall of epithelial cells. They commonly occur in the setting of acute or chronic pancreatitis secondary to pancreatic duct disruption or the inflammation itself. Many pseudocysts spontaneous spontaneously resolve, but active intervention is necessary when pseudocysts continue to grow, are associated with significant abdominal pain, or interfere with gastric, biliary, or pancreatic drainage. In such cases, the standard of care has been surgical drainage, which is often achieved with cystgastrostomy, which involves forming an internal fistula between the stomach and pancreatic pseudocyst. Advances in therapeutic endoscopy, however, have led to its increasing use for performing cystgastrostomies for pancreatic pseudocysts. In this setting, endoscopically placed stents are used to establish a fistula from within the stomach lumen to the pseudocyst cavity without the need to violate the abdominal wall.In this issue of Gastroenterology, Varadarajulu et al report on a randomized, controlled trial of 40 patients that compared endoscopic with surgical cystgastrostomy for the treatment of pancreatic pseudocysts. The primary endpoint used was the pseudocyst recurrence rate over a 24-month follow-up period. Secondary endpoints included treatment success or failure, complications, re-interventions, duration of hospital stay, physical and mental health scores, and total costs.Endoscopic cystgastrostomy was successful in 19 of 20 patients. A residual pseudocyst was present in 1 patient who was successfully treated with the placement of additional stents. Therapy was successful for all 20 surgical patients. For the primary endpoint, only 1 patient in the surgical group experienced a recurrent pseudocyst within 24 months, which was in the setting of continued alcohol consumption. The secondary endpoints of duration of hospital stay, physical and mental health scores, and total costs all exhibited statistically better outcomes with the endoscopic approach. The total mean cost was lower for endoscopy versus operative management ($7011 vs $15,052; P = .003). The results support endoscopic cystgastrostomy as a superior approach for the treatment of pancreatic pseudocysts. Chris Forsmark provides additional insights in an accompanying editorial.See page 583; editorial on page 511.Colorectal Cancer Stem Cells With Organ-Specific Metastasis PotentialColon cancer remains one of the most common causes of cancer-related death. In most cases, death is associated with the development of metastatic disease, which for colon cancer is most often the liver or lungs. Cancer-specific stem cells have been proposed as a likely source for metastasis. Thus, defining the characteristics of migrating cancer stem cells (MCSC) may provide prognostic value and insights into the underlying mechanisms of metastases.In this issue of Gastroenterology, Gao et al report on their success in isolating and characterizing MCSCs derived from the primary tumor as well as lung and liver metastases from a single patient. Harvested cells were orthotopically propagated in the cecal wall of immunodeficient NOG mice. Subsequent metastases to the liver and lung were again harvested followed by another cycle of propagation in another immunodeficient NOG mouse. The whole process was repeated for a total of 6 rounds, which resulted in cancer cells that spontaneously produced liver or lung metastases that was dependent on their origin. After the sixth round, cells derived from liver or lung metastases were also more likely to form oncospheres than nonmetastasizing cells derived from the primary tumor. Oncospheres are suspension cultures of cells that are enriched in cancer stem cells (also known as cancer initiation cells), and are able to produce tumors in nude mice. When the oncospheres were orthotopically implanted in nude mice, they exhibited a greater propensity to metastasize to their original tissue from which they were harvested. The authors conclude that such cells represent organ-specific MCSCs.Microarrays were utilized to determine the gene expression profile of oncospheres derived from either the primary tumor, lung, or liver for the purpose of identifying biomarkers for organ specific MCSCs. CD110 (myeloproliferative leukemia virus oncogene) was selected as a marker for liver and CDCP1 (CUB domain containing protein 1) for lung metastases. The 2 markers were then applied to 128 human colorectal carcinomas, 38 of which were without metastases on presentation. All cases of liver metastases expressed CD110 and 79.5% of lung metastases expressed CDCP1. The authors go on to propose that CD110 and CDCP1 also serve as stem cell markers considering that an established marker, CD133, is co-expressed. In addition, the subcutaneous injection of fewer CD110+ or CDCP1+ cells were required to establish tumors in mice, which is a known feature of enriched populations of cancer stem cells. Subsequent tumors also recapitulated features common to stem cells such as the propagation of multiple cell lineages.The authors subsequently show that expression of CD110 or CDCP1 in primary tumors carries prognostic value for metastasis and survival in the murine xenograft model. In addition to serving as biomarkers, additional studies also supported a biologic role for CD110 and CDCP1 in promoting metastases (Figure 2).Figure 2Propensity for organ-specific metastasis of oncospheres derived from nonmetastasizing tumor (CRC108), or metastasis from the liver (CRC108-LM) or lung (CRC108-PM).View Large Image Figure ViewerDownload Hi-res image Download (PPT)See page 636.Targeting Prostaglandin Synthases in Experimental HCV InfectionThe development of in vitro systems that support the replication of hepatitis C virus (HCV) has significantly advanced our understanding of the molecular mechanisms involved in the life cycle of this virus. Metabolites of the arachidonic acid cascade, or prostanoids, including prostaglandin (PG)E2, PGD2, PGI2, and PGF2, and thromboxane (TX)A2, have been shown to be involved in multiple physiologic functions in the liver, such as liver regeneration. However, their role, if any, in viral replication in hepatocytes is unclear. In this issue of Gastroenterology, Abe et al examine the role of prostanoids in HCV replication using in vitro model systems, including a 3-dimensional culture system for immortalized human hepatocytes and the JFH1 RNA-transfected cell culture system, as well as in vivo using HCV-infected chimeric mice transplanted with human hepatocytes. Consistent with a functional role of prostanoids in human liver, expression of the arachidonic acid cascade enzymes, cyclooxygenase 1, PGD2 synthase, and TX2 synthase, was increased in human hepatocytes cultured under 3-dimensional conditions; PGE2 and PGI2 expression was, instead, decreased. The addition of a COX1 inhibitor to JFH1 RNA-transfected cell cultures resulted in a dose-dependent decrease in HCV infectivity, although HCV replication or release from infected cells was unaffected. Similarly, inhibition of TXA2 synthase decreased infectious HCV production and this effect was independent of the TXA2 receptor. Of note, inhibition of TXA synthase-mediated signaling affected HCV infectivity by altering the physicochemical properties of HCV. These in vitro findings were confirmed in vivo with the demonstration that the anti-HCV drug, ONO1301, which is both a TXA2 synthase inhibitor and PGI2 agonist, the PGI2 agonist, beraprost, and the TXA2 synthase inhibitor, ozagrel, all inhibited HCV proliferation in HCV-infected chimeric mice (Figure 3). These findings demonstrate the role of the arachidonic acid cascade in the HCV life cycle and suggest this signaling pathway may be a potential target for novel anti-HCV therapy.Figure 3Effects of ONO1301, Beraprost, Ozagrel, and Telaprevir on the expansion of bbHCV-infected urokinase plasminogen activator/severe combined immunodeficiency mice bearing human hepatocytes. Data are presented as means ± SD for 6 (control, diamonds), 4 (ONO1301, squares; Ozagrel, crosses; Telaprevir, asterisk), and 3 (Beraprost, triangles) samples. *Differs from control, P < .05.View Large Image Figure ViewerDownload Hi-res image Download (PPT)See page 658. How Sweet It Is: Carbonation and Brain ProcessingThe rising prevalence of obesity over the last several decades, and its associated increased risk of heart disease, type 2 diabetes, hypertension, liver disease, and osteoarthritis, among other conditions, has been widely reported. Less is known about the factors contributing to the obesity epidemic. Food preferences and dietary behavior are predominantly influenced by our sense of taste. The central nervous system processing of taste is thought to involve the anterior insula and frontal operculum, the opercular and orbitofrontal cortex, the amygdala, and the prefrontal cortex. Recently, in addition to the gustatory processing of the 5 basic tastes (sweet, salty, sour, bitter, and umami, characterized by the taste of monosodium glutamate), the taste of carbonation, its cellular and molecular substrates, and the modulation of CO2 of sweet perception, has been the focus of investigation. In this issue of Gastroenterology (accompanied by an editorial), Di Salle et al examine, using functional magnetic resonance imaging, the interference between CO2 and perception of sweetness and the differential effects of CO2 and sucrose and the artificial sweetener commonly used in diet beverages, aspartame–acesulfame (As-Ac). The presence of carbonation in sweet solutions, regardless of the sweetening agent, reduced neural activity in the anterior insula, orbitofrontal cortex, and the posterior pons. However, the effect of carbonation on sucrose was greater than on As-Ac perception. Independent of carbonation, As-Ac increased activity in the anterior insula and sucrose increased activity in the amygdala. This differential brain activity between sucrose and As-Ac was much more prominent in the absence of carbonation (Figure 1). These findings demonstrate that carbonation reduces the neural processing of sucrose more than of artificial sweeteners and suggest that the combination of CO2 and sucrose leads to increased consumption of sucrose.See page 537; editorial on page 500. The rising prevalence of obesity over the last several decades, and its associated increased risk of heart disease, type 2 diabetes, hypertension, liver disease, and osteoarthritis, among other conditions, has been widely reported. Less is known about the factors contributing to the obesity epidemic. Food preferences and dietary behavior are predominantly influenced by our sense of taste. The central nervous system processing of taste is thought to involve the anterior insula and frontal operculum, the opercular and orbitofrontal cortex, the amygdala, and the prefrontal cortex. Recently, in addition to the gustatory processing of the 5 basic tastes (sweet, salty, sour, bitter, and umami, characterized by the taste of monosodium glutamate), the taste of carbonation, its cellular and molecular substrates, and the modulation of CO2 of sweet perception, has been the focus of investigation. In this issue of Gastroenterology (accompanied by an editorial), Di Salle et al examine, using functional magnetic resonance imaging, the interference between CO2 and perception of sweetness and the differential effects of CO2 and sucrose and the artificial sweetener commonly used in diet beverages, aspartame–acesulfame (As-Ac). The presence of carbonation in sweet solutions, regardless of the sweetening agent, reduced neural activity in the anterior insula, orbitofrontal cortex, and the posterior pons. However, the effect of carbonation on sucrose was greater than on As-Ac perception. Independent of carbonation, As-Ac increased activity in the anterior insula and sucrose increased activity in the amygdala. This differential brain activity between sucrose and As-Ac was much more prominent in the absence of carbonation (Figure 1). These findings demonstrate that carbonation reduces the neural processing of sucrose more than of artificial sweeteners and suggest that the combination of CO2 and sucrose leads to increased consumption of sucrose. See page 537; editorial on page 500. Endoscopy vs Surgery for Pancreatic Pseudocyst DrainagePancreatic pseudocysts are pancreatic fluid collections not encased by a wall of epithelial cells. They commonly occur in the setting of acute or chronic pancreatitis secondary to pancreatic duct disruption or the inflammation itself. Many pseudocysts spontaneous spontaneously resolve, but active intervention is necessary when pseudocysts continue to grow, are associated with significant abdominal pain, or interfere with gastric, biliary, or pancreatic drainage. In such cases, the standard of care has been surgical drainage, which is often achieved with cystgastrostomy, which involves forming an internal fistula between the stomach and pancreatic pseudocyst. Advances in therapeutic endoscopy, however, have led to its increasing use for performing cystgastrostomies for pancreatic pseudocysts. In this setting, endoscopically placed stents are used to establish a fistula from within the stomach lumen to the pseudocyst cavity without the need to violate the abdominal wall.In this issue of Gastroenterology, Varadarajulu et al report on a randomized, controlled trial of 40 patients that compared endoscopic with surgical cystgastrostomy for the treatment of pancreatic pseudocysts. The primary endpoint used was the pseudocyst recurrence rate over a 24-month follow-up period. Secondary endpoints included treatment success or failure, complications, re-interventions, duration of hospital stay, physical and mental health scores, and total costs.Endoscopic cystgastrostomy was successful in 19 of 20 patients. A residual pseudocyst was present in 1 patient who was successfully treated with the placement of additional stents. Therapy was successful for all 20 surgical patients. For the primary endpoint, only 1 patient in the surgical group experienced a recurrent pseudocyst within 24 months, which was in the setting of continued alcohol consumption. The secondary endpoints of duration of hospital stay, physical and mental health scores, and total costs all exhibited statistically better outcomes with the endoscopic approach. The total mean cost was lower for endoscopy versus operative management ($7011 vs $15,052; P = .003). The results support endoscopic cystgastrostomy as a superior approach for the treatment of pancreatic pseudocysts. Chris Forsmark provides additional insights in an accompanying editorial.See page 583; editorial on page 511. Pancreatic pseudocysts are pancreatic fluid collections not encased by a wall of epithelial cells. They commonly occur in the setting of acute or chronic pancreatitis secondary to pancreatic duct disruption or the inflammation itself. Many pseudocysts spontaneous spontaneously resolve, but active intervention is necessary when pseudocysts continue to grow, are associated with significant abdominal pain, or interfere with gastric, biliary, or pancreatic drainage. In such cases, the standard of care has been surgical drainage, which is often achieved with cystgastrostomy, which involves forming an internal fistula between the stomach and pancreatic pseudocyst. Advances in therapeutic endoscopy, however, have led to its increasing use for performing cystgastrostomies for pancreatic pseudocysts. In this setting, endoscopically placed stents are used to establish a fistula from within the stomach lumen to the pseudocyst cavity without the need to violate the abdominal wall. In this issue of Gastroenterology, Varadarajulu et al report on a randomized, controlled trial of 40 patients that compared endoscopic with surgical cystgastrostomy for the treatment of pancreatic pseudocysts. The primary endpoint used was the pseudocyst recurrence rate over a 24-month follow-up period. Secondary endpoints included treatment success or failure, complications, re-interventions, duration of hospital stay, physical and mental health scores, and total costs. Endoscopic cystgastrostomy was successful in 19 of 20 patients. A residual pseudocyst was present in 1 patient who was successfully treated with the placement of additional stents. Therapy was successful for all 20 surgical patients. For the primary endpoint, only 1 patient in the surgical group experienced a recurrent pseudocyst within 24 months, which was in the setting of continued alcohol consumption. The secondary endpoints of duration of hospital stay, physical and mental health scores, and total costs all exhibited statistically better outcomes with the endoscopic approach. The total mean cost was lower for endoscopy versus operative management ($7011 vs $15,052; P = .003). The results support endoscopic cystgastrostomy as a superior approach for the treatment of pancreatic pseudocysts. Chris Forsmark provides additional insights in an accompanying editorial. See page 583; editorial on page 511. Colorectal Cancer Stem Cells With Organ-Specific Metastasis PotentialColon cancer remains one of the most common causes of cancer-related death. In most cases, death is associated with the development of metastatic disease, which for colon cancer is most often the liver or lungs. Cancer-specific stem cells have been proposed as a likely source for metastasis. Thus, defining the characteristics of migrating cancer stem cells (MCSC) may provide prognostic value and insights into the underlying mechanisms of metastases.In this issue of Gastroenterology, Gao et al report on their success in isolating and characterizing MCSCs derived from the primary tumor as well as lung and liver metastases from a single patient. Harvested cells were orthotopically propagated in the cecal wall of immunodeficient NOG mice. Subsequent metastases to the liver and lung were again harvested followed by another cycle of propagation in another immunodeficient NOG mouse. The whole process was repeated for a total of 6 rounds, which resulted in cancer cells that spontaneously produced liver or lung metastases that was dependent on their origin. After the sixth round, cells derived from liver or lung metastases were also more likely to form oncospheres than nonmetastasizing cells derived from the primary tumor. Oncospheres are suspension cultures of cells that are enriched in cancer stem cells (also known as cancer initiation cells), and are able to produce tumors in nude mice. When the oncospheres were orthotopically implanted in nude mice, they exhibited a greater propensity to metastasize to their original tissue from which they were harvested. The authors conclude that such cells represent organ-specific MCSCs.Microarrays were utilized to determine the gene expression profile of oncospheres derived from either the primary tumor, lung, or liver for the purpose of identifying biomarkers for organ specific MCSCs. CD110 (myeloproliferative leukemia virus oncogene) was selected as a marker for liver and CDCP1 (CUB domain containing protein 1) for lung metastases. The 2 markers were then applied to 128 human colorectal carcinomas, 38 of which were without metastases on presentation. All cases of liver metastases expressed CD110 and 79.5% of lung metastases expressed CDCP1. The authors go on to propose that CD110 and CDCP1 also serve as stem cell markers considering that an established marker, CD133, is co-expressed. In addition, the subcutaneous injection of fewer CD110+ or CDCP1+ cells were required to establish tumors in mice, which is a known feature of enriched populations of cancer stem cells. Subsequent tumors also recapitulated features common to stem cells such as the propagation of multiple cell lineages.The authors subsequently show that expression of CD110 or CDCP1 in primary tumors carries prognostic value for metastasis and survival in the murine xenograft model. In addition to serving as biomarkers, additional studies also supported a biologic role for CD110 and CDCP1 in promoting metastases (Figure 2).See page 636. Colon cancer remains one of the most common causes of cancer-related death. In most cases, death is associated with the development of metastatic disease, which for colon cancer is most often the liver or lungs. Cancer-specific stem cells have been proposed as a likely source for metastasis. Thus, defining the characteristics of migrating cancer stem cells (MCSC) may provide prognostic value and insights into the underlying mechanisms of metastases. In this issue of Gastroenterology, Gao et al report on their success in isolating and characterizing MCSCs derived from the primary tumor as well as lung and liver metastases from a single patient. Harvested cells were orthotopically propagated in the cecal wall of immunodeficient NOG mice. Subsequent metastases to the liver and lung were again harvested followed by another cycle of propagation in another immunodeficient NOG mouse. The whole process was repeated for a total of 6 rounds, which resulted in cancer cells that spontaneously produced liver or lung metastases that was dependent on their origin. After the sixth round, cells derived from liver or lung metastases were also more likely to form oncospheres than nonmetastasizing cells derived from the primary tumor. Oncospheres are suspension cultures of cells that are enriched in cancer stem cells (also known as cancer initiation cells), and are able to produce tumors in nude mice. When the oncospheres were orthotopically implanted in nude mice, they exhibited a greater propensity to metastasize to their original tissue from which they were harvested. The authors conclude that such cells represent organ-specific MCSCs. Microarrays were utilized to determine the gene expression profile of oncospheres derived from either the primary tumor, lung, or liver for the purpose of identifying biomarkers for organ specific MCSCs. CD110 (myeloproliferative leukemia virus oncogene) was selected as a marker for liver and CDCP1 (CUB domain containing protein 1) for lung metastases. The 2 markers were then applied to 128 human colorectal carcinomas, 38 of which were without metastases on presentation. All cases of liver metastases expressed CD110 and 79.5% of lung metastases expressed CDCP1. The authors go on to propose that CD110 and CDCP1 also serve as stem cell markers considering that an established marker, CD133, is co-expressed. In addition, the subcutaneous injection of fewer CD110+ or CDCP1+ cells were required to establish tumors in mice, which is a known feature of enriched populations of cancer stem cells. Subsequent tumors also recapitulated features common to stem cells such as the propagation of multiple cell lineages. The authors subsequently show that expression of CD110 or CDCP1 in primary tumors carries prognostic value for metastasis and survival in the murine xenograft model. In addition to serving as biomarkers, additional studies also supported a biologic role for CD110 and CDCP1 in promoting metastases (Figure 2). See page 636. Targeting Prostaglandin Synthases in Experimental HCV InfectionThe development of in vitro systems that support the replication of hepatitis C virus (HCV) has significantly advanced our understanding of the molecular mechanisms involved in the life cycle of this virus. Metabolites of the arachidonic acid cascade, or prostanoids, including prostaglandin (PG)E2, PGD2, PGI2, and PGF2, and thromboxane (TX)A2, have been shown to be involved in multiple physiologic functions in the liver, such as liver regeneration. However, their role, if any, in viral replication in hepatocytes is unclear. In this issue of Gastroenterology, Abe et al examine the role of prostanoids in HCV replication using in vitro model systems, including a 3-dimensional culture system for immortalized human hepatocytes and the JFH1 RNA-transfected cell culture system, as well as in vivo using HCV-infected chimeric mice transplanted with human hepatocytes. Consistent with a functional role of prostanoids in human liver, expression of the arachidonic acid cascade enzymes, cyclooxygenase 1, PGD2 synthase, and TX2 synthase, was increased in human hepatocytes cultured under 3-dimensional conditions; PGE2 and PGI2 expression was, instead, decreased. The addition of a COX1 inhibitor to JFH1 RNA-transfected cell cultures resulted in a dose-dependent decrease in HCV infectivity, although HCV replication or release from infected cells was unaffected. Similarly, inhibition of TXA2 synthase decreased infectious HCV production and this effect was independent of the TXA2 receptor. Of note, inhibition of TXA synthase-mediated signaling affected HCV infectivity by altering the physicochemical properties of HCV. These in vitro findings were confirmed in vivo with the demonstration that the anti-HCV drug, ONO1301, which is both a TXA2 synthase inhibitor and PGI2 agonist, the PGI2 agonist, beraprost, and the TXA2 synthase inhibitor, ozagrel, all inhibited HCV proliferation in HCV-infected chimeric mice (Figure 3). These findings demonstrate the role of the arachidonic acid cascade in the HCV life cycle and suggest this signaling pathway may be a potential target for novel anti-HCV therapy.See page 658. The development of in vitro systems that support the replication of hepatitis C virus (HCV) has significantly advanced our understanding of the molecular mechanisms involved in the life cycle of this virus. Metabolites of the arachidonic acid cascade, or prostanoids, including prostaglandin (PG)E2, PGD2, PGI2, and PGF2, and thromboxane (TX)A2, have been shown to be involved in multiple physiologic functions in the liver, such as liver regeneration. However, their role, if any, in viral replication in hepatocytes is unclear. In this issue of Gastroenterology, Abe et al examine the role of prostanoids in HCV replication using in vitro model systems, including a 3-dimensional culture system for immortalized human hepatocytes and the JFH1 RNA-transfected cell culture system, as well as in vivo using HCV-infected chimeric mice transplanted with human hepatocytes. Consistent with a functional role of prostanoids in human liver, expression of the arachidonic acid cascade enzymes, cyclooxygenase 1, PGD2 synthase, and TX2 synthase, was increased in human hepatocytes cultured under 3-dimensional conditions; PGE2 and PGI2 expression was, instead, decreased. The addition of a COX1 inhibitor to JFH1 RNA-transfected cell cultures resulted in a dose-dependent decrease in HCV infectivity, although HCV replication or release from infected cells was unaffected. Similarly, inhibition of TXA2 synthase decreased infectious HCV production and this effect was independent of the TXA2 receptor. Of note, inhibition of TXA synthase-mediated signaling affected HCV infectivity by altering the physicochemical properties of HCV. These in vitro findings were confirmed in vivo with the demonstration that the anti-HCV drug, ONO1301, which is both a TXA2 synthase inhibitor and PGI2 agonist, the PGI2 agonist, beraprost, and the TXA2 synthase inhibitor, ozagrel, all inhibited HCV proliferation in HCV-infected chimeric mice (Figure 3). These findings demonstrate the role of the arachidonic acid cascade in the HCV life cycle and suggest this signaling pathway may be a potential target for novel anti-HCV therapy. See page 658. Isolation and Phenotypic Characterization of Colorectal Cancer Stem Cells With Organ-Specific Metastatic PotentialGastroenterologyVol. 145Issue 3PreviewMigrating cancer stem cells (MCSCs) are believed to form metastases. We sought to identify markers of MCSCs from human colorectal cancers (CRCs) and determine their roles in organ-specific metastasis. Full-Text PDF Effect of Carbonation on Brain Processing of Sweet Stimuli in HumansGastroenterologyVol. 145Issue 3PreviewLittle is known about how CO2 affects neural processing of taste. We used functional magnetic resonance imaging to investigate the effects of carbonation on brain processing of sweet stimuli, which has relevance to studies of food selection and satiety. The presence of carbonation produced an overall decrease in the neural processing of sweetness-related signals, especially from sucrose. CO2 reduced the neural processing of sucrose more than that of artificial sweeteners. These findings might be relevant to dietary interventions that include noncaloric beverages, whereas the combination of CO2 and sucrose might increase consumption of sucrose. Full-Text PDF Equal Efficacy of Endoscopic and Surgical Cystogastrostomy for Pancreatic Pseudocyst Drainage in a Randomized TrialGastroenterologyVol. 145Issue 3PreviewAlthough surgery is the standard technique for drainage of pancreatic pseudocysts, use of endoscopic methods is increasing. We performed a single-center, open-label, randomized trial to compare endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage. Full-Text PDF Thromboxane A2 Synthase Inhibitors Prevent Production of Infectious Hepatitis C Virus in Mice With Humanized LiversGastroenterologyVol. 145Issue 3PreviewA 3-dimensional (3D) culture system for immortalized human hepatocytes (HuS-E/2 cells) recently was shown to support the lifecycle of blood-borne hepatitis C virus (HCV). We used this system to identify proteins that are active during the HCV lifecycle under 3D culture conditions. Full-Text PDF Evidence-Based Treatment of Pancreatic PseudocystsGastroenterologyVol. 145Issue 3PreviewThe evaluation and management of pancreatic pseudocysts has changed dramatically. This change has largely been driven by better natural history data and by an increasing focus on minimally invasive approaches, but has occurred in the absence of high-quality comparative effectiveness data. Open surgical drainage (to the stomach or a jejunal Roux limb), the primary therapy in the past with a wealth of data supporting its effectiveness and safety, has been largely replaced by laparoscopic and endoscopic drainage techniques. Full-Text PDF In Search of a Role for Carbonation: Is This a Good or Bad Taste?GastroenterologyVol. 145Issue 3PreviewSince the discovery in the 1800s that the addition of carbon dioxide to water makes it effervescent and pleasant, carbonation has gained popularity for its enjoyable taste and has become an important ingredient of sparkling drinks such as sodas. In recent years, there has been an exponential rise in the consumption of sweetened, carbonated drinks, which has been linked to increasing rates of obesity and increasing prevalence of metabolic diseases.1 Surprisingly, the consumption of diet sodas, which have reduced or zero calories because of the noncaloric sweeteners, is also linked to the risk of obesity and poor health outcomes. Full-Text PDF