Environmental pollution is one of the major problems for human health. Toxic heavy metals are normally present as soil constituents or can also be spread out in the environment by human activity and agricultural techn...Environmental pollution is one of the major problems for human health. Toxic heavy metals are normally present as soil constituents or can also be spread out in the environment by human activity and agricultural techniques. Soil contamination by heavy metals as cadmium, highlights two main aspects: on one side they interfere with the life cycle of plants and therefore reduce crop yields, and on the other hand, once adsorbed and accumulated into the plant tissues, they enter the food chain poisoning animals and humans. Considering this point of view, understanding the mechanism by which plants handle heavy metal exposure, in particular cadmium stress, is a primary goal of plant-biotechnology research or plant breeders whose aim is to create plants that are able to recover high amounts of heavy metals, which can be used for phytoremediation, or identify crop varieties that do not accumulate toxic metal in grains or fruits. In this review we focus on the main symptoms of cadmium toxicity both on root apparatus and shoots. We elucidate the mechanisms that plants activate to prevent absorption or to detoxify toxic metal ions, such as synthesis of phytochelatins, metallothioneins and enzymes involved in stress response. Finally we consider new plant-biotechnology applications that can be applied for phytoremediation.展开更多
Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with live...Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.展开更多
Every colorectal surgeon during his or her career is faced with anastomotic leakage(AL); one of the most dreaded complications following any type of gastrointestinal anastomosis due to increased risk of morbidity, mor...Every colorectal surgeon during his or her career is faced with anastomotic leakage(AL); one of the most dreaded complications following any type of gastrointestinal anastomosis due to increased risk of morbidity, mortality, overall impact on functional and oncologic outcome and drainage on hospital resources. In order to understand and give an overview of the AL risk factors in laparoscopic colorectal surgery, we carried out a careful review of the existing literature on this topic and found several different definitions of AL which leads us to believe that the lack of a consensual, standard definition can partly explain the considerable variations in reported rates of AL in clinical studies. Colorectal leak rates have been found to vary depending on the anatomic location of the anastomosis with reported incidence rates ranging from 0 to 20%, while the laparoscopic approach to colorectal resections has not yet been associated with a significant reduction in AL incidence. As well, numerous risk factors, though identified, lack unanimous recognition amongst researchers. For example, the majority of papers describe the risk factors for left-sided anastomosis, the principal risk being male sex and lower anastomosis, while little data exists defining AL risk factors in a right colectomy. Also, gut microbioma is gaining an emerging role as potential risk factor for leakage.展开更多
AIM:To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation...AIM:To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS:A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrastenhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m2,infused over 30 min using a peristaltic pump,and followed by Lipiodol and Gelfoam embolization. RESULTS:Patients characteristics were:mean age,62 years; male/female 117/45; Child-Pugh score 6.2 ± 1.1; MELD 8.7 ± 2.3; mean HCC size,3.6 (range 1.0-12.0) cm. HCC size class was ≤ 2.0 cm,n = 51; 2.1-3.0 cm,n = 35; 3.1-4.0 cm,n = 29; 4.1-5.0 cm,n = 22; 5.1-6.0 cm,n = 11; and > 6.0 cm,n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 ± 1.7). Complete tumor necrosis was obtained in 94 patients (58%),massive (90%-99%) necrosis in 16 patients (10%),partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was:69%,69%,52%,68%,50% and,13% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. Kaplan-Mayer survival at 24-mo was 88%,68%,59%,59%,45%,and 53% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. CONCLUSION:Our study showed that in cirrhotic patients with single HCC smaller than 6.0 cm,TAE/TACE produces complete local control of tumor in a significant proportion of patients. TAE/TACE is an effective therapeutic option in patients with single HCC not suitable for surgical resection or percutaneous ablation therapies. Further studies should investigate if the new available embolization agents or drug eluting beads m展开更多
The rate of choledocholithiasis in patients with symptomatic cholelithiasis is estimated to be approximately 10%-33%,depending on the patient's age.Development of Endoscopic Retrograde Cholangiopancreatography and...The rate of choledocholithiasis in patients with symptomatic cholelithiasis is estimated to be approximately 10%-33%,depending on the patient's age.Development of Endoscopic Retrograde Cholangiopancreatography and Laparoscopic Surgery and improvement of diagnostic procedures have influenced new approaches to the management of common bile duct stones in association with gallstones.At present available minimally-invasive treatments of cholecysto-choledocal lithiasis include:single-stage laparoscopic treatment,perioperative endoscopic treatment and endoscopic treatment alone.Published data evidence that,associated endoscopic-laparoscopic approach necessitates increased number of procedures per patient while single-stage laparoscopic treatment is associated with a shorter hospital stay.However,current data does not suggest clear superiority of any one approach with regard to success,mortality,morbidity and cost-effectiveness.Considering the variety of therapeutic options available for management,a critical appraisal and decision-making is required.endoscopic retrograde cholangiopancreatography/EST should be adopted on a selective basis,i.e.,in patients with acute obstructive suppurative cholangitis,severe biliary pancreatitis,ampullary stone impaction or severe comorbidity.In a setting where all facilities are available,decision in the selection of the therapeutic option depends on the patients,the number and size of choledocholithiasis stones,the anatomy of the cystic duct and common bile duct,the surgical history of patients and local expertise.展开更多
Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of Met...Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of MetS, as they share the pathophysiologic basis of insulin resistance. It is also recognized that NAFLD is the hepatic manifestation of MetS. To define MetS, the presence of at least three of the proposed criteria is required, and sometimes it is sufficient to have only one laboratory value, modified by diet or drugs, for the classification of MetS. Ultrasonographically-detected NAFLD (US-NAFLD) is more stable, only changing during the middleto long-term. Although controversies over MetS continue, and considering that abdominal ultrasonography for diagnosing NAFLD has high specificity and guidelines to modify the natural course of NAFLD by diet composition or lifestyle have not yet been established, why should we not introduce US-NAFLD as a new criterion to define MetS?展开更多
Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in s...Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelialand endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic proc-ess, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.展开更多
The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur after both surgic...The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur after both surgical and medical treatment.The recurrence rate involves 2 phases:an early phase and a late phase.The early phase usually occurs within 2 years after resection;it is mainly related to local invasion and intrahepatic metastases and,therefore,to the intrinsic biology of the tumor.On the other hand,the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment.Since recent studies have reported that early and late recurrences may have different risk factors,it is clinically important to recognize these factors in the individual patient as soon as possible.The aim of this review was,therefore,to identify predicting factors for the recurrence of hepatocellularcarcinoma,by means of invasive and non-invasive methods,according to the different therapeutic strategies available.In particular the role of emerging techniques(e.g.,transient elastography)and biological features of hepatocellular carcinoma in predicting recurrence have been discussed.In particular,invasive methods were differentiated from non-invasive ones for research purposes,taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.展开更多
H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to Hpylori infection and therefore can be treated with antibio...H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to Hpylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (darithromycin and amoxicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When Hpylori eradication is striclly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonsbated that Hpylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.展开更多
D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucos...D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials(RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council(MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recur-rence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.展开更多
The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-4...The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.展开更多
Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries.Insulin resistance is a key factor in the pathogenesis of NAFLD,the latter being considered...Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries.Insulin resistance is a key factor in the pathogenesis of NAFLD,the latter being considered as the hepatic component of insulin resistance or obesity.Adiponectin is the most abundant adipose-specific adipokine.There is evidence that adiponectin decreases hepatic and systematic insulin resistance,and attenuates liver inflammation and fibrosis.Adiponectin generally predicts steatosis grade and the severity of NAFLD;however,to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed.Although there is no proven pharmacotherapy for the treatment of NAFLD,recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications.In this adiponectin-focused review,the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.展开更多
AIM: To identify risk factors related to pancreatic fistula in patients undergoing distal pancreatectomy (DP) and to determine the effectiveness of using a stapled and a sutured closed of pancreatic stump. METHODS: Si...AIM: To identify risk factors related to pancreatic fistula in patients undergoing distal pancreatectomy (DP) and to determine the effectiveness of using a stapled and a sutured closed of pancreatic stump. METHODS: Sixty-four patients underwent DP during a 10-year period. Information regarding diagnosis, operative details, and perioperative morbidity or mortality was collected. Eight risk factors were examined. RESULTS: Indications for DP included primary pancreatic disease (n = 38, 59%) and non-pancreatic malignancy (n = 26, 41%). Postoperative mortality and morbidity rates were 1.5% and 37% respectively; one patient died due to sepsis and two patients required a reoperation due to postoperative bleeding. Pancreatic fistula was developed in 14 patients (22%); 4 of fistulas were classified as Grade A, 9 as Grade B and only 1 as Grade C. Incidence of pancreatic fistula rate was significantly associated with four risk factors: pathology, use of prophylactic octreotide therapy, concomitant splenectomy, and texture of pancreatic parenchyma. The role that technique (either stapler or suture) of pancreatic stump closure plays in the development of pancreatic leak remains unclear. CONCLUSION: The pancreatic fistula rate after DP is 22%. This is reduced for patients with non-pancreatic malignancy, fibrotic pancreatic tissue, postoperative prophylactic octreotide therapy and concomitant splenectomy.展开更多
Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenc...Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.展开更多
Chronic inflammation is thought to be the leading cause of many human cancers including colorectal cancer(CRC).Accordingly,epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and C...Chronic inflammation is thought to be the leading cause of many human cancers including colorectal cancer(CRC).Accordingly,epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease,the two major forms of inflammatory bowel disease,have an increased risk of developing CRC.In recent years,the role of immune cells and their products have been shown to be pivotal in initiation and progression of colitis-associated CRC.On the other hand,activation of the immune system has been shown to cause dysplastic cell elimination and cancer suppression in other settings.Clinical and experimental data herein reviewed,while confirming chronic inflammation as a risk factor for colon carcinogenesis,do not completely rule out the possibility that under certain conditions the chronic activation of the mucosal immune system might protect from colonic dysplasia.展开更多
Inflammatory bowel diseases (IBD) can be really considered to be systemic diseases since they are often associated with extraintestinal manifestations,complications, and other autoimmune disorders. Indeed,physicians w...Inflammatory bowel diseases (IBD) can be really considered to be systemic diseases since they are often associated with extraintestinal manifestations,complications, and other autoimmune disorders. Indeed,physicians who care for patients with ulcerative colitis and Crohn's disease, the two major forms of IBD, face a new clinical challenge every day, worsened by the very frequent rate of extraintestinal complications. The goal of this review is to provide an overview and an update on the extraintestinal complications occurring in IBD.Indeed, this paper highlights how virtually almost every organ system can be involved, principally eyes, skin,joints, kidneys, liver and biliary tracts, and vasculature (or vascular system) are the most common sites of systemic IBD and their involvement is dependent on different mechanisms.展开更多
Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty...Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.展开更多
文摘Environmental pollution is one of the major problems for human health. Toxic heavy metals are normally present as soil constituents or can also be spread out in the environment by human activity and agricultural techniques. Soil contamination by heavy metals as cadmium, highlights two main aspects: on one side they interfere with the life cycle of plants and therefore reduce crop yields, and on the other hand, once adsorbed and accumulated into the plant tissues, they enter the food chain poisoning animals and humans. Considering this point of view, understanding the mechanism by which plants handle heavy metal exposure, in particular cadmium stress, is a primary goal of plant-biotechnology research or plant breeders whose aim is to create plants that are able to recover high amounts of heavy metals, which can be used for phytoremediation, or identify crop varieties that do not accumulate toxic metal in grains or fruits. In this review we focus on the main symptoms of cadmium toxicity both on root apparatus and shoots. We elucidate the mechanisms that plants activate to prevent absorption or to detoxify toxic metal ions, such as synthesis of phytochelatins, metallothioneins and enzymes involved in stress response. Finally we consider new plant-biotechnology applications that can be applied for phytoremediation.
基金Supported by(in part)the Southampton National Institute for Health Research Biomedical Research Centre(Byrne CD)grants from the School of Medicine of the Verona University(Targher GT)
文摘Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.
文摘Every colorectal surgeon during his or her career is faced with anastomotic leakage(AL); one of the most dreaded complications following any type of gastrointestinal anastomosis due to increased risk of morbidity, mortality, overall impact on functional and oncologic outcome and drainage on hospital resources. In order to understand and give an overview of the AL risk factors in laparoscopic colorectal surgery, we carried out a careful review of the existing literature on this topic and found several different definitions of AL which leads us to believe that the lack of a consensual, standard definition can partly explain the considerable variations in reported rates of AL in clinical studies. Colorectal leak rates have been found to vary depending on the anatomic location of the anastomosis with reported incidence rates ranging from 0 to 20%, while the laparoscopic approach to colorectal resections has not yet been associated with a significant reduction in AL incidence. As well, numerous risk factors, though identified, lack unanimous recognition amongst researchers. For example, the majority of papers describe the risk factors for left-sided anastomosis, the principal risk being male sex and lower anastomosis, while little data exists defining AL risk factors in a right colectomy. Also, gut microbioma is gaining an emerging role as potential risk factor for leakage.
文摘AIM:To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS:A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrastenhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m2,infused over 30 min using a peristaltic pump,and followed by Lipiodol and Gelfoam embolization. RESULTS:Patients characteristics were:mean age,62 years; male/female 117/45; Child-Pugh score 6.2 ± 1.1; MELD 8.7 ± 2.3; mean HCC size,3.6 (range 1.0-12.0) cm. HCC size class was ≤ 2.0 cm,n = 51; 2.1-3.0 cm,n = 35; 3.1-4.0 cm,n = 29; 4.1-5.0 cm,n = 22; 5.1-6.0 cm,n = 11; and > 6.0 cm,n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 ± 1.7). Complete tumor necrosis was obtained in 94 patients (58%),massive (90%-99%) necrosis in 16 patients (10%),partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was:69%,69%,52%,68%,50% and,13% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. Kaplan-Mayer survival at 24-mo was 88%,68%,59%,59%,45%,and 53% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. CONCLUSION:Our study showed that in cirrhotic patients with single HCC smaller than 6.0 cm,TAE/TACE produces complete local control of tumor in a significant proportion of patients. TAE/TACE is an effective therapeutic option in patients with single HCC not suitable for surgical resection or percutaneous ablation therapies. Further studies should investigate if the new available embolization agents or drug eluting beads m
基金This work was supported by the British Heart Foundation, Heart Research UK, Biotechnology and Biological Sciences Research Council, Medical Research Council, Wellcome Trust, KC Wong/China Scholarship Council, and EU COST ACTION B35.
文摘The rate of choledocholithiasis in patients with symptomatic cholelithiasis is estimated to be approximately 10%-33%,depending on the patient's age.Development of Endoscopic Retrograde Cholangiopancreatography and Laparoscopic Surgery and improvement of diagnostic procedures have influenced new approaches to the management of common bile duct stones in association with gallstones.At present available minimally-invasive treatments of cholecysto-choledocal lithiasis include:single-stage laparoscopic treatment,perioperative endoscopic treatment and endoscopic treatment alone.Published data evidence that,associated endoscopic-laparoscopic approach necessitates increased number of procedures per patient while single-stage laparoscopic treatment is associated with a shorter hospital stay.However,current data does not suggest clear superiority of any one approach with regard to success,mortality,morbidity and cost-effectiveness.Considering the variety of therapeutic options available for management,a critical appraisal and decision-making is required.endoscopic retrograde cholangiopancreatography/EST should be adopted on a selective basis,i.e.,in patients with acute obstructive suppurative cholangitis,severe biliary pancreatitis,ampullary stone impaction or severe comorbidity.In a setting where all facilities are available,decision in the selection of the therapeutic option depends on the patients,the number and size of choledocholithiasis stones,the anatomy of the cystic duct and common bile duct,the surgical history of patients and local expertise.
文摘Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of MetS, as they share the pathophysiologic basis of insulin resistance. It is also recognized that NAFLD is the hepatic manifestation of MetS. To define MetS, the presence of at least three of the proposed criteria is required, and sometimes it is sufficient to have only one laboratory value, modified by diet or drugs, for the classification of MetS. Ultrasonographically-detected NAFLD (US-NAFLD) is more stable, only changing during the middleto long-term. Although controversies over MetS continue, and considering that abdominal ultrasonography for diagnosing NAFLD has high specificity and guidelines to modify the natural course of NAFLD by diet composition or lifestyle have not yet been established, why should we not introduce US-NAFLD as a new criterion to define MetS?
文摘Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelialand endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic proc-ess, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.
文摘The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur after both surgical and medical treatment.The recurrence rate involves 2 phases:an early phase and a late phase.The early phase usually occurs within 2 years after resection;it is mainly related to local invasion and intrahepatic metastases and,therefore,to the intrinsic biology of the tumor.On the other hand,the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment.Since recent studies have reported that early and late recurrences may have different risk factors,it is clinically important to recognize these factors in the individual patient as soon as possible.The aim of this review was,therefore,to identify predicting factors for the recurrence of hepatocellularcarcinoma,by means of invasive and non-invasive methods,according to the different therapeutic strategies available.In particular the role of emerging techniques(e.g.,transient elastography)and biological features of hepatocellular carcinoma in predicting recurrence have been discussed.In particular,invasive methods were differentiated from non-invasive ones for research purposes,taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.
文摘H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to Hpylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (darithromycin and amoxicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When Hpylori eradication is striclly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonsbated that Hpylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.
文摘D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials(RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council(MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recur-rence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.
文摘The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.
文摘Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries.Insulin resistance is a key factor in the pathogenesis of NAFLD,the latter being considered as the hepatic component of insulin resistance or obesity.Adiponectin is the most abundant adipose-specific adipokine.There is evidence that adiponectin decreases hepatic and systematic insulin resistance,and attenuates liver inflammation and fibrosis.Adiponectin generally predicts steatosis grade and the severity of NAFLD;however,to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed.Although there is no proven pharmacotherapy for the treatment of NAFLD,recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications.In this adiponectin-focused review,the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.
文摘AIM: To identify risk factors related to pancreatic fistula in patients undergoing distal pancreatectomy (DP) and to determine the effectiveness of using a stapled and a sutured closed of pancreatic stump. METHODS: Sixty-four patients underwent DP during a 10-year period. Information regarding diagnosis, operative details, and perioperative morbidity or mortality was collected. Eight risk factors were examined. RESULTS: Indications for DP included primary pancreatic disease (n = 38, 59%) and non-pancreatic malignancy (n = 26, 41%). Postoperative mortality and morbidity rates were 1.5% and 37% respectively; one patient died due to sepsis and two patients required a reoperation due to postoperative bleeding. Pancreatic fistula was developed in 14 patients (22%); 4 of fistulas were classified as Grade A, 9 as Grade B and only 1 as Grade C. Incidence of pancreatic fistula rate was significantly associated with four risk factors: pathology, use of prophylactic octreotide therapy, concomitant splenectomy, and texture of pancreatic parenchyma. The role that technique (either stapler or suture) of pancreatic stump closure plays in the development of pancreatic leak remains unclear. CONCLUSION: The pancreatic fistula rate after DP is 22%. This is reduced for patients with non-pancreatic malignancy, fibrotic pancreatic tissue, postoperative prophylactic octreotide therapy and concomitant splenectomy.
文摘Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.
基金Supported by"Associazione Italiana perla Ricerca sul Cancro",AIRC,MFAG-9353 and"Fondazione Umberto di Mario",Rome
文摘Chronic inflammation is thought to be the leading cause of many human cancers including colorectal cancer(CRC).Accordingly,epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease,the two major forms of inflammatory bowel disease,have an increased risk of developing CRC.In recent years,the role of immune cells and their products have been shown to be pivotal in initiation and progression of colitis-associated CRC.On the other hand,activation of the immune system has been shown to cause dysplastic cell elimination and cancer suppression in other settings.Clinical and experimental data herein reviewed,while confirming chronic inflammation as a risk factor for colon carcinogenesis,do not completely rule out the possibility that under certain conditions the chronic activation of the mucosal immune system might protect from colonic dysplasia.
基金Supported by an unrestricted grant from Fondazione Ricerca in Medicina
文摘Inflammatory bowel diseases (IBD) can be really considered to be systemic diseases since they are often associated with extraintestinal manifestations,complications, and other autoimmune disorders. Indeed,physicians who care for patients with ulcerative colitis and Crohn's disease, the two major forms of IBD, face a new clinical challenge every day, worsened by the very frequent rate of extraintestinal complications. The goal of this review is to provide an overview and an update on the extraintestinal complications occurring in IBD.Indeed, this paper highlights how virtually almost every organ system can be involved, principally eyes, skin,joints, kidneys, liver and biliary tracts, and vasculature (or vascular system) are the most common sites of systemic IBD and their involvement is dependent on different mechanisms.
文摘Non-alcoholic fatty liver disease (NAFLD), a further expression of metabolic syndrome, strictly linked to obesity and diabetes mellitus, is characterized by insulin resistance (IR), elevated serum levels of free fatty acids and fatty infi ltration of the liver, which is known as hepatic steatosis. Hepatocyte apoptosis is a key feature of this disease and correlates with its severity. Free-fatty-acidinduced toxicity represents one of mechanisms for the pathogenesis of NAFLD and hormones, growth factors and adipokines influence also play a key role. This review highlights the various pathways that contribute to the development of hepatic steatosis. Circulating concentrations of inflammatory cytokines are reckoned to be the most important factor in causing and maintaining IR. Low-grade chronic inflammation is fundamental in the progression of NAFLD toward higher risk cirrhotic states.