Colorectal cancer(CRC) represents one of the most commonly diagnosed cancers worldwide.It is the second leading cause of cancer death in Western Countries.In the last decade the survival of patients with metastatic CR...Colorectal cancer(CRC) represents one of the most commonly diagnosed cancers worldwide.It is the second leading cause of cancer death in Western Countries.In the last decade the survival of patients with metastatic CRC has improved dramatically.Due to the advent of new drugs(irinotecan and oxaliplatin) and target therapies(i.e.,bevacizumab,cetuximab and panitumab),the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently.Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy.Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings,and a greater emphasis on early detection,the outlook still remains poor for most patients.Molecular analyses have shown that the natural history of all CRCs is not the same.Individual patients with same stage tumours may have different long term prognosis and response to therapy.In addition,some prognostic variables are likely to be more important than others.Here we review the role of prognostic factors and predictive factors according to the recently published English literature.展开更多
Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing i...Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn’s disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.展开更多
Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spe...Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.展开更多
Colorectal cancer is the most prevalent among digestive system cancers.Carcinogenesis relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and apoptosis....Colorectal cancer is the most prevalent among digestive system cancers.Carcinogenesis relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and apoptosis.Cell,tissue,organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery.Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis,and altered expression of clock genes has been found in cancer patients.Epidemiological studies have shown that circadian disruption,that is,alteration of bodily temporal organization,is a cancer risk factor,and an increased incidence of colorectal neoplastic disease is reported in shift workers.In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.展开更多
In recent years,self-expandable metal stents(SEMSs)have been employed to treat benign gastrointestinal strictures secondary to several conditions:Acute diverticulitis,radiation colitis,inflammatory bowel disease(IBD),...In recent years,self-expandable metal stents(SEMSs)have been employed to treat benign gastrointestinal strictures secondary to several conditions:Acute diverticulitis,radiation colitis,inflammatory bowel disease(IBD),and postanastomotic leakages and stenosis.Other applications include endometriosis and fistulas of the lower gastrointestinal tract.Although it may be technically feasible to proceed to stenting in the aforementioned benign diseases of the lower gastrointestinal tract,the outcome has been reported to be poor.In fact,in some settings(such as complicated diverticulitis and postsurgical anastomotic strictures),stenting seems to have a limited evidence-based benefit as a bridge to surgery,while in other settings(such as endometriosis,IBD,radiation colitis,etc.),even society guidelines are not able to guide the endoscopist through decisional algorithms for SEMS placement.The aim of this narrative paper is to review the scientific evidence regarding the use of SEMSs in nonmalignant diseases of the lower gastrointestinal tract,both in adult and pediatric settings.展开更多
AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis.METHODS: Nineteen consecutive patients with histologi...AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis.METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test.RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction(PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant(χ2 = 9.55, P = 0.002).CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.展开更多
The red palm weevil(RPW; Rhynchophorus ferrugineus) is spreading worldwide and severely harming many palm species. However, most studies on RPW focused on insect biology, and little information is available about th...The red palm weevil(RPW; Rhynchophorus ferrugineus) is spreading worldwide and severely harming many palm species. However, most studies on RPW focused on insect biology, and little information is available about the plant response to the attack. In the present experiment, we used metabolomics to study the alteration of the leaf metabolome of Phoenix canariensis at initial(1^(st) stage) or advanced(2^(nd) stage)attack by RPW compared with healthy(unattacked) plants.The leaf metabolome significantly varied among treatments. At the 1^(st) stage of attack, plants showed a reprogramming of carbohydrate and organic acid metabolism; in contrast, peptides and lipid metabolic pathways underwent more changes during the 2^(nd) than 1^(st) stage of attack. Enrichment metabolomics analysis indicated that RPW attack mostly affected a particular group of compounds rather than rearranging plant metabolic pathways. Some compounds selectively affected during the 1^(st) rather than 2^(nd) stage(e.g. phenylalanine; tryptophan; cellobiose;xylose; quinate; xylonite; idonate; and iso-threonate; cellobiotol and arbutine) are upstream events in the phenylpropanoid,terpenoid and alkaloid biosynthesis. These compounds could be designated as potential markers of initial RPW attack. However,further investigation is needed to determine efficient early screening methods of RPW attack based on the concentrations of these molecules.展开更多
文摘Colorectal cancer(CRC) represents one of the most commonly diagnosed cancers worldwide.It is the second leading cause of cancer death in Western Countries.In the last decade the survival of patients with metastatic CRC has improved dramatically.Due to the advent of new drugs(irinotecan and oxaliplatin) and target therapies(i.e.,bevacizumab,cetuximab and panitumab),the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently.Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy.Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings,and a greater emphasis on early detection,the outlook still remains poor for most patients.Molecular analyses have shown that the natural history of all CRCs is not the same.Individual patients with same stage tumours may have different long term prognosis and response to therapy.In addition,some prognostic variables are likely to be more important than others.Here we review the role of prognostic factors and predictive factors according to the recently published English literature.
文摘Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. The CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset and progression of this pathology. Moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the promotion of colonic health. The gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. In utero, the intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota is acquired by ingesting maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. The development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). The healthy human gut harbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in health and in the progression of diseases such as IBD and CRC. In healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. The microbiota exerts diverse physiological functions to include: growth inhibition of pathogenic microorganisms, synthesis of compounds useful for the trophism of colonic mucosa, regulation of intestinal lymphoid tissue and synthesis of amino acids. Furthermore, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. Changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolites associated with carcinogenesis and induces dysregulation of the immune response which promotes and sustains inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. The associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn’s disease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet fully known. However, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.
文摘Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.
基金Supported by The"5x1000"voluntary contribution and by a grant to GM from the Italian Ministry of Health through Department of Medical Sciences,Division of Internal Medicine and Chronobiology Unit,IRCCS Scientific Institute and Regional General Hospital"Casa Sollievo della Sofferenza",Opera di Padre Pio da Pietrelcina,San Giovanni Rotondo(FG),Italy,Nos.RC1203ME46 and RC1302ME31by a grant to AP from the Italian Ministry of Health through Department of Medical Sciences,Division of Gastroenterology and Research Laboratory,Nos.RC1203GA55 and RC1203GA56by a grant to MV from AIRC,No.MFAG-AIRC2012-13419
文摘Colorectal cancer is the most prevalent among digestive system cancers.Carcinogenesis relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and apoptosis.Cell,tissue,organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery.Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis,and altered expression of clock genes has been found in cancer patients.Epidemiological studies have shown that circadian disruption,that is,alteration of bodily temporal organization,is a cancer risk factor,and an increased incidence of colorectal neoplastic disease is reported in shift workers.In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.
文摘In recent years,self-expandable metal stents(SEMSs)have been employed to treat benign gastrointestinal strictures secondary to several conditions:Acute diverticulitis,radiation colitis,inflammatory bowel disease(IBD),and postanastomotic leakages and stenosis.Other applications include endometriosis and fistulas of the lower gastrointestinal tract.Although it may be technically feasible to proceed to stenting in the aforementioned benign diseases of the lower gastrointestinal tract,the outcome has been reported to be poor.In fact,in some settings(such as complicated diverticulitis and postsurgical anastomotic strictures),stenting seems to have a limited evidence-based benefit as a bridge to surgery,while in other settings(such as endometriosis,IBD,radiation colitis,etc.),even society guidelines are not able to guide the endoscopist through decisional algorithms for SEMS placement.The aim of this narrative paper is to review the scientific evidence regarding the use of SEMSs in nonmalignant diseases of the lower gastrointestinal tract,both in adult and pediatric settings.
文摘AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis.METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test.RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction(PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant(χ2 = 9.55, P = 0.002).CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.
基金funded by the Project PROPALMA(D.M.25618/7301/11)by the Italian Ministry of Agricultural,Food and Forestry Policies(Mi PAAF)
文摘The red palm weevil(RPW; Rhynchophorus ferrugineus) is spreading worldwide and severely harming many palm species. However, most studies on RPW focused on insect biology, and little information is available about the plant response to the attack. In the present experiment, we used metabolomics to study the alteration of the leaf metabolome of Phoenix canariensis at initial(1^(st) stage) or advanced(2^(nd) stage)attack by RPW compared with healthy(unattacked) plants.The leaf metabolome significantly varied among treatments. At the 1^(st) stage of attack, plants showed a reprogramming of carbohydrate and organic acid metabolism; in contrast, peptides and lipid metabolic pathways underwent more changes during the 2^(nd) than 1^(st) stage of attack. Enrichment metabolomics analysis indicated that RPW attack mostly affected a particular group of compounds rather than rearranging plant metabolic pathways. Some compounds selectively affected during the 1^(st) rather than 2^(nd) stage(e.g. phenylalanine; tryptophan; cellobiose;xylose; quinate; xylonite; idonate; and iso-threonate; cellobiotol and arbutine) are upstream events in the phenylpropanoid,terpenoid and alkaloid biosynthesis. These compounds could be designated as potential markers of initial RPW attack. However,further investigation is needed to determine efficient early screening methods of RPW attack based on the concentrations of these molecules.