While flexible endoscopy is essential for macroscopic evaluation,confocal laser endomicroscopy(CLE)has recently emerged as an endoscopic method enabling visualization at a cellular level.Two systems are currently avai...While flexible endoscopy is essential for macroscopic evaluation,confocal laser endomicroscopy(CLE)has recently emerged as an endoscopic method enabling visualization at a cellular level.Two systems are currently available,one based on miniprobes that can be inserted via a conventional endoscope or via a needle guided by endoscopic ultrasound.The second system has a confocal microscope integrated into the distal part of an endoscope.By adding molecular probes like fluorescein conjugated antibodies or fluorescent peptides to this procedure(either topically or systemically administered during on-going endoscopy),a novel world of molecular evaluation opens up.The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas,subsequently resulting in immediate individualization of treatment regimens,but also for improving the diagnostic accuracy of endoscopic procedures by identifying otherwise invisible mucosal lesions.Furthermore,studies have shown that fluorescein labelled drugs can be used to estimate the affinity of the drug to a target organ,which probably can be correlated to the efficacy of the drug.However,several of the studies in this research field have been conducted in animal facilities or in vitro,while only a limited number of trials have actually been carried out in vivo.Therefore,safety issues still needs further evaluations.This review will present an overview of the implications and pitfalls,as well as future challenges of molecular CLE in gastrointestinal diseases.展开更多
In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failu...In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitatingthe hepatorenal syndrome.Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation.As a bridge to this treatment,knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs,antibiotics,drugs with specific effects on fibrogenesis and inflammation,and drugs that target specific receptors.展开更多
AIM To develop a scale of domains associated with the health-related quality-of-life(HRQOL) in patients with cirrhosis-related ascites.METHODS We initially undertook literature searches and a qualitative study in orde...AIM To develop a scale of domains associated with the health-related quality-of-life(HRQOL) in patients with cirrhosis-related ascites.METHODS We initially undertook literature searches and a qualitative study in order to design a cirrhosis-associated ascites symptom(CAS) scale describing symptoms with a potential detrimental impact on health related quality of life(HRQL)(the higher the score, the worse the symptoms). Discriminatory validity was assessed in a validation cohort including cirrhotic patients with(1) tense/severe;(2) moderate/mild; or(3) no ascites(controls). Patients also completed chronic liver disease questionnaire(CLDQ) and the Euro QoL 5-Dimensions 5-Level(EQ-5D-5L) questionnaire evaluating HRQL. The relation between scale scores was analysed using Spearman correlations. RESULTS The final CAS scale included 14 items. The equivalent reliability was high(Chronbach's alpha 0.88). The validation cohort included 103 patients(72% men, mean age 62.4 years). The mean scores for each question in the CAS scale were higher for patients with severe/tense ascites than for mild/moderate ascites and controls. Compared with controls(mean = 9.9 points), the total CAS scale score was higher for severe/tense ascites(mean = 23.8 points) as well as moderate/mild ascites(mean = 18.6 points)(P < 0.001 both groups). We found a strong correlation between the total CAS and CLDQ score(rho = 0.82, P < 0.001) and a moderate correlation between the CAS and the EQ-5D-5L score(0.67, P < 0.001). CONCLUSION The CAS is a valid tool, which reflects HRQOL in patients with ascites.展开更多
BACKGROUND Infected walled-off necrosis is a potentially life-threatening complication of necrotizing pancreatitis.While some patients can be treated by drainage alone,many patients also need evacuation of the infecte...BACKGROUND Infected walled-off necrosis is a potentially life-threatening complication of necrotizing pancreatitis.While some patients can be treated by drainage alone,many patients also need evacuation of the infected debris.Central necroses in relation to the pancreatic bed are easily reached via an endoscopic transluminal approach,whereas necroses that involve the paracolic gutters and the pelvis are most efficiently treated via a percutaneous approach.Large and complex necroses may need a combination of the two methods.CASE SUMMARY Transluminal and percutaneous drainage followed by simultaneous endoscopic and modified video-assisted retroperitoneal debridement was carried out in two patients with very large(32-38 cm),infected walled-off necroses using a laparoscopic access platform.After 34 d and 86 d and a total of 9 and 14 procedures,respectively,complete regression of the walled-off necroses was achieved.The laparoscopic access platform improved both access to the cavities as well as the overview.Simultaneous transluminal and percutaneous necrosectomy are feasible with the laparoscopic access platform serving as a useful adjunctive.CONCLUSION This approach may be necessary to control infection and achieve regression in some patients with complex collections.展开更多
BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A grow...BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.展开更多
Pancreatic cysts are increasingly diagnosed due to expanding use of cross-sectional imaging,but current diagnostic modalities have limited diagnostic accuracy.Recently,a novel through-the-needle microbiopsy forceps ha...Pancreatic cysts are increasingly diagnosed due to expanding use of cross-sectional imaging,but current diagnostic modalities have limited diagnostic accuracy.Recently,a novel through-the-needle microbiopsy forceps has become available,offering the possibility of obtaining cyst-wall biopsies.We present a case of 41-year-old male with chronic pancreatitis and a 2-cm pancreatic cyst,initially considered a pseudocyst.Subsequently,endoscopic ultrasou-nd guided microbiopsies were successfully obtained,which surprisingly revealed an intraductal papillary mucinous neoplasm of mixed subtype with low grade dysplasia.In conclusion,obtaining biopsies from the wall of the pancreatic cystic lesions with this novel instrument is feasible and,as demonstrated in this case,can possibly alter the clinical outcome.Microbiopsies offered enough cellular material,allowing supplemental gene mutation analysis,which combined with other modalities could lead to a more individual approach when treating pancreatic cysts.However,prospective studies are warranted before routine clinical implementation.展开更多
Hereditary hemochromatosis is a condition characterized by iron overload, which is both treatable and preventable. It’s mainly related to hepcidin deficiency related to mutations in genes involved in hepcidin regulat...Hereditary hemochromatosis is a condition characterized by iron overload, which is both treatable and preventable. It’s mainly related to hepcidin deficiency related to mutations in genes involved in hepcidin regulation. Iron overload increases the risk of disease such as liver cirrhosis, heart disease and diabetes. Two HFE genotypes have been commonly described in cases of iron overload, C282Y homozygosity and C282Y/H63D compound heterozygoty. The diagnosis of this rare disease now can be explored by biological and imaging tools. We report a case of compound heterozygous C282Y/H63D discovered by family screening for elevated serum ferritin.展开更多
IPEX (immune-dysregulation, polyendocrinopathy, enteropathy, X-linked) syndr ome is an autoimmune disorder with an often lethal outcome in spite of immunosup pressive therapy. We report the successful use of sirolimus...IPEX (immune-dysregulation, polyendocrinopathy, enteropathy, X-linked) syndr ome is an autoimmune disorder with an often lethal outcome in spite of immunosup pressive therapy. We report the successful use of sirolimus in 3 patients with I PEX. The efficacy of sirolimus is probably due to its different mode of action c ompared to calcineurin-dependent agents.展开更多
基金Supported by ERC-like nr.7/2012 "Real-time Evaluation of Treatment Effects in Advanced Colorectal Carcinoma (REACT)",project ID PNII-CT-ERC-2012-1financed by the Executive Agency for Higher Education,Research,Development and Innovation Funding (CNCS-UEFISCDI)+2 种基金Romanian National Authority for Scientific Research,Ministry of National Education,ROMANIAEstablishment of confocal laser endomicroscopy in Copenhagen was possible due to the generous contributions of A.P.Moller and Chastine McKinney Mollers Foundation,Foundation Jochum,The Toyota Foundation and the Foundation of Aase and Ejnar DanielsenThe Foundation of Arvid Nilsson and The Lundbeck Foundation supported the activity of JGK and AS,respectively
文摘While flexible endoscopy is essential for macroscopic evaluation,confocal laser endomicroscopy(CLE)has recently emerged as an endoscopic method enabling visualization at a cellular level.Two systems are currently available,one based on miniprobes that can be inserted via a conventional endoscope or via a needle guided by endoscopic ultrasound.The second system has a confocal microscope integrated into the distal part of an endoscope.By adding molecular probes like fluorescein conjugated antibodies or fluorescent peptides to this procedure(either topically or systemically administered during on-going endoscopy),a novel world of molecular evaluation opens up.The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas,subsequently resulting in immediate individualization of treatment regimens,but also for improving the diagnostic accuracy of endoscopic procedures by identifying otherwise invisible mucosal lesions.Furthermore,studies have shown that fluorescein labelled drugs can be used to estimate the affinity of the drug to a target organ,which probably can be correlated to the efficacy of the drug.However,several of the studies in this research field have been conducted in animal facilities or in vitro,while only a limited number of trials have actually been carried out in vivo.Therefore,safety issues still needs further evaluations.This review will present an overview of the implications and pitfalls,as well as future challenges of molecular CLE in gastrointestinal diseases.
基金Supported by Novo Nordisk Foundation and the University of Copenhagen
文摘In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitatingthe hepatorenal syndrome.Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation.As a bridge to this treatment,knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs,antibiotics,drugs with specific effects on fibrogenesis and inflammation,and drugs that target specific receptors.
文摘AIM To develop a scale of domains associated with the health-related quality-of-life(HRQOL) in patients with cirrhosis-related ascites.METHODS We initially undertook literature searches and a qualitative study in order to design a cirrhosis-associated ascites symptom(CAS) scale describing symptoms with a potential detrimental impact on health related quality of life(HRQL)(the higher the score, the worse the symptoms). Discriminatory validity was assessed in a validation cohort including cirrhotic patients with(1) tense/severe;(2) moderate/mild; or(3) no ascites(controls). Patients also completed chronic liver disease questionnaire(CLDQ) and the Euro QoL 5-Dimensions 5-Level(EQ-5D-5L) questionnaire evaluating HRQL. The relation between scale scores was analysed using Spearman correlations. RESULTS The final CAS scale included 14 items. The equivalent reliability was high(Chronbach's alpha 0.88). The validation cohort included 103 patients(72% men, mean age 62.4 years). The mean scores for each question in the CAS scale were higher for patients with severe/tense ascites than for mild/moderate ascites and controls. Compared with controls(mean = 9.9 points), the total CAS scale score was higher for severe/tense ascites(mean = 23.8 points) as well as moderate/mild ascites(mean = 18.6 points)(P < 0.001 both groups). We found a strong correlation between the total CAS and CLDQ score(rho = 0.82, P < 0.001) and a moderate correlation between the CAS and the EQ-5D-5L score(0.67, P < 0.001). CONCLUSION The CAS is a valid tool, which reflects HRQOL in patients with ascites.
文摘BACKGROUND Infected walled-off necrosis is a potentially life-threatening complication of necrotizing pancreatitis.While some patients can be treated by drainage alone,many patients also need evacuation of the infected debris.Central necroses in relation to the pancreatic bed are easily reached via an endoscopic transluminal approach,whereas necroses that involve the paracolic gutters and the pelvis are most efficiently treated via a percutaneous approach.Large and complex necroses may need a combination of the two methods.CASE SUMMARY Transluminal and percutaneous drainage followed by simultaneous endoscopic and modified video-assisted retroperitoneal debridement was carried out in two patients with very large(32-38 cm),infected walled-off necroses using a laparoscopic access platform.After 34 d and 86 d and a total of 9 and 14 procedures,respectively,complete regression of the walled-off necroses was achieved.The laparoscopic access platform improved both access to the cavities as well as the overview.Simultaneous transluminal and percutaneous necrosectomy are feasible with the laparoscopic access platform serving as a useful adjunctive.CONCLUSION This approach may be necessary to control infection and achieve regression in some patients with complex collections.
文摘BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.
文摘Pancreatic cysts are increasingly diagnosed due to expanding use of cross-sectional imaging,but current diagnostic modalities have limited diagnostic accuracy.Recently,a novel through-the-needle microbiopsy forceps has become available,offering the possibility of obtaining cyst-wall biopsies.We present a case of 41-year-old male with chronic pancreatitis and a 2-cm pancreatic cyst,initially considered a pseudocyst.Subsequently,endoscopic ultrasou-nd guided microbiopsies were successfully obtained,which surprisingly revealed an intraductal papillary mucinous neoplasm of mixed subtype with low grade dysplasia.In conclusion,obtaining biopsies from the wall of the pancreatic cystic lesions with this novel instrument is feasible and,as demonstrated in this case,can possibly alter the clinical outcome.Microbiopsies offered enough cellular material,allowing supplemental gene mutation analysis,which combined with other modalities could lead to a more individual approach when treating pancreatic cysts.However,prospective studies are warranted before routine clinical implementation.
文摘Hereditary hemochromatosis is a condition characterized by iron overload, which is both treatable and preventable. It’s mainly related to hepcidin deficiency related to mutations in genes involved in hepcidin regulation. Iron overload increases the risk of disease such as liver cirrhosis, heart disease and diabetes. Two HFE genotypes have been commonly described in cases of iron overload, C282Y homozygosity and C282Y/H63D compound heterozygoty. The diagnosis of this rare disease now can be explored by biological and imaging tools. We report a case of compound heterozygous C282Y/H63D discovered by family screening for elevated serum ferritin.
文摘IPEX (immune-dysregulation, polyendocrinopathy, enteropathy, X-linked) syndr ome is an autoimmune disorder with an often lethal outcome in spite of immunosup pressive therapy. We report the successful use of sirolimus in 3 patients with I PEX. The efficacy of sirolimus is probably due to its different mode of action c ompared to calcineurin-dependent agents.
