Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common ...Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.展开更多
Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-mo...Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall phenotype.Clinically,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses inexorably.New biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).展开更多
BACKGROUND Detailed information on metastatic patterns in of patients with esophageal and gastric cancer is limited.Early recognition of metastases is important to avoid futile locoregional treatments.Furthermore,know...BACKGROUND Detailed information on metastatic patterns in of patients with esophageal and gastric cancer is limited.Early recognition of metastases is important to avoid futile locoregional treatments.Furthermore,knowledge on metastatic patterns is necessary for further development of personalized treatment modalities.AIM To gain insight into the metastatic pattern of gastroesophageal cancer.METHODS A nationwide retrospective autopsy study of 3876 patients with adenocarcinoma(AC)or squamous cell carcinoma(SCC)of the esophagus or stomach between 1990 and 2017 was performed.Only patient with metastases were included for analysis.The metastatic pattern was analyzed according to the primary tumor location and histological subtype.RESULTS Metastatic disease was found in 268 esophageal and 331 gastric cancer patients.In esophageal cancer,the most common metastatic locations were liver(56%),distant lymph nodes(53%)and lung(50%).Esophageal AC showed more frequently metastases to the peritoneum and bone compared with esophageal SCC.In gastric cancer,the most common metastatic locations were distant lymph nodes(56%),liver(53%)and peritoneum(51%).Intestinal-type AC of the stomach showed metastases to the liver more frequently,whereas metastases to the bone,female reproductive organs and colorectum were observed more frequently in diffuse-type gastric AC.CONCLUSION This study showed differences in metastatic patterns of patients with esophageal and gastric cancer according to the primary tumor location and histological subtype.展开更多
Stress urinary incontinence is not a deadly disease,but for the large population of women suffering from it,it is a very important issue.Especially in the continuously aging population all over the world,there is more...Stress urinary incontinence is not a deadly disease,but for the large population of women suffering from it,it is a very important issue.Especially in the continuously aging population all over the world,there is more and more need for treatment of this serious medical condition.Treatment of female stress urinary incontinence exists already for ages.In the 20th century invasive treatments like Burch colposuspension and pubovaginal slings were the mainstay of surgical treatments.The introduction of the midurethral sling made the procedure less invasive and accessible for more caregivers.Luckily there are many options available and the field is developing quickly.In recent years many new medical devices have been developed,that increase the number of treatment options available and make it possible to find a suitable solution for the individual patient based on subjective and objective results and the chances of complications.This manuscript provides an introduction to the therapeutical options that are available nowadays for female stress urinary incontinence.展开更多
AIM:To determine the possible modulating effect of the COX-2 polymorphisms,-765G→C and-1195A→G, on the risk of colorectal cancer(CRC)in a Dutch population. METHODS:This case-control study includes 326 patients with ...AIM:To determine the possible modulating effect of the COX-2 polymorphisms,-765G→C and-1195A→G, on the risk of colorectal cancer(CRC)in a Dutch population. METHODS:This case-control study includes 326 patients with CRC and 369 age-and gender-matched controls.Genotypes of the COX-2 polymorphisms -765G→C and-1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism.COX-2 genotypes and haplotypes were analyzed and odds ratios with 95%confi- dence intervals were estimated by logistic regression. RESULTS:The-765GG genotype was associated with an increased risk of developing CRC(OR,1.45; 95%CI,1.03-2.04).No significant difference was observed in the genotype distribution of the-1195A→ G polymorphism between patients and controls.The GG/AC haplotype was present significantly less often in patients than in controls(OR 0.44;95%CI,0.22-0.85). When the AC,AG and GG haplotypes were investigated separately,the AC haplotype showed a tendency to be less frequent in patients than in controls(OR(AG/AC)0.78; 95%CI,0.57-1.06). CONCLUSION:The-765GG genotype is associatedwith an increased risk of developing CRC and the GG/ AC haplotype seems to protect against CRC.These findings suggest a modulating role for the COX-2 polymorphisms-765G→C and-1195A→G in the development of CRC in a Dutch population.展开更多
Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain inclu...Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.展开更多
The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances pe...The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration;however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of preexisting vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.展开更多
Many upper gastrointestinal(GI) endoscopies worldwide are performed for inappropriate indications. This overuse of healthcare negatively affects healthcare quality and puts pressure on endoscopy services. Dyspepsia is...Many upper gastrointestinal(GI) endoscopies worldwide are performed for inappropriate indications. This overuse of healthcare negatively affects healthcare quality and puts pressure on endoscopy services. Dyspepsia is one of the most common inappropriate indications for upper GI endoscopy as diagnostic yield is low. Reasons for untimely referral are: unfamiliarity with dyspepsia guidelines,uncertainty about etiology of symptoms, and therapy failure. Unfiltered openaccess referrals feed upper GI endoscopy overuse. This review highlights strategies applied to diminish use of upper GI endoscopies for dyspepsia. First,we describe the impact of active guideline implementation. We found improved guideline adherence, but resistance was encountered in the process. Secondly, we show several forms of clinical assessment. While algorithm use reduced upper GI endoscopy volume, effects of referral assessment of individual patients were minor. A third strategy proposed Helicobacter pylori test and treat for all dyspeptic patients. Many upper GI endoscopies can be avoided using this strategy, but outcomes may be prevalence dependent. Lastly, empirical treatment with Proton pump inhibitors achieved symptom relief for dyspepsia and avoided upper GI endoscopies in about two thirds of patients. Changing referral behavior is complex as contributing factors are manifold. A collaboration of multiple strategies is most likely to succeed.展开更多
BACKGROUND An increasing number of older patients is undergoing curative,surgical treatment of esophageal cancer.Previous meta-analyses have shown that older patients suffered from more postoperative morbidity and mor...BACKGROUND An increasing number of older patients is undergoing curative,surgical treatment of esophageal cancer.Previous meta-analyses have shown that older patients suffered from more postoperative morbidity and mortality compared to younger patients,which may lead to patient selection based on age.However,only studies including patients that underwent open esophagectomy were included.Therefore,it remains unknown whether there is an association between age and outcome in patients undergoing minimally invasive esophagectomy.AIM To perform a systematic review on age and postoperative outcome in esophageal cancer patients undergoing esophagectomy.METHODS Studies comparing older with younger patients with primary esophageal cancer undergoing curative esophagectomy were included.Meta-analysis of studies using a 75-year age threshold are presented in the manuscript,studies using other age thresholds in the Supplementary material.MEDLINE,Embase and the Cochrane Library were searched for articles published between 1995 and 2020.Risk of bias was assessed with the Newcastle-Ottawa Scale.Primary outcomes were anastomotic leak,pulmonary and cardiac complications,delirium,30-and 90-d,and in-hospital mortality.Secondary outcomes included pneumonia and 5-year overall survival.RESULTS Seven studies(4847 patients)using an age threshold of 75 years were included for meta-analysis with 755 older and 4092 younger patients.Older patients(9.05%)had higher rates of 90-d mortality compared with younger patients(3.92%),(confidence interval=1.10-5.56).In addition,older patients(9.45%)had higher rates of in-hospital mortality compared with younger patients(3.68%),(confidence interval=1.01-5.91).In the subgroup of 2 studies with minimally invasive esophagectomy,older and younger patients had comparable 30-d,90-d and in-hospital mortality rates.CONCLUSION Older patients undergoing curative esophagectomy for esophageal cancer have a higher postoperative mortality risk.Minimally invasive esophagectomy may be important for minimizing mortality in older patients.展开更多
AIM:To determine whether-1195 A→G and/or-765 G→C polymorphisms in Cyclooxygenase-2(COX-2 ) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population.METHODS:Two stud...AIM:To determine whether-1195 A→G and/or-765 G→C polymorphisms in Cyclooxygenase-2(COX-2 ) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population.METHODS:Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area.DNA was isolated from whole blood and used for genotyping.PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis.Odds ratios(OR) and 95% confldence intervals(CI) were estimated.RESULTS:The distribution of the-1195 A→G polymorphism was signif icantly different in esophageal cancer patients compared to controls.The-1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma(OR = 3.85, 95% CI:1.45-10.3) compared with the-1195 AA genotype as a reference.The-765 G→C genotype distribution was not different between the two groups.The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls(OR = 3.45, 95% CI:1.24-9.58;with AG/AG as a reference).The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical signif icance.CONCLUSION:Presence of the COX-2-1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.展开更多
AIM To study the effect of different techniques of cystic duct closure on bile leakage after laparoscopic cholecystectomy(LC) for biliary disease.METHODS A systematic search of MEDLINE, Cochrane and EMBASE was perform...AIM To study the effect of different techniques of cystic duct closure on bile leakage after laparoscopic cholecystectomy(LC) for biliary disease.METHODS A systematic search of MEDLINE, Cochrane and EMBASE was performed. Rate of cystic duct leakage(CDL) was the primary outcome. Risk of bias was evaluated. Odds ratios were analyzed for comparison of techniques and pooled event rates for non-comparative analyses. Pooled event rates were compared for each of included techniques.RESULTS Out of 1491 articles, 38 studies were included. A total of 47491 patients were included, of which 38683(81.5%)underwent cystic duct closure with non-locking(metal)clips. All studies were of low-moderate methodological quality. Only two studies reported separate data on uncomplicated and complicated gallbladder disease. For overall CDL, an odds ratio of 0.4(95%CI: 0.06-2.48)was found for harmonic energy vs clip closure and an odds ratio of 0.17(95%CI: 0.03-0.93) for locking vs non-locking clips. Pooled CDL rate was around 1% for harmonic energy and metal clips, and 0% for locking clips and ligatures. CONCLUSION Based on available evidence it is not possible to either recommend or discourage any of the techniques for cystic duct closure during LC with respects to CDL,although data point out a slight preference for locking clips and ligatures vs other techniques. No separate recommendation can be made for complicated gallbladder disease.展开更多
Surgical innovation and pioneering are important for improving patient outcome, but can be associated with learning curves. Although learning curves in surgery are a recognized problem, the impact of surgical learning...Surgical innovation and pioneering are important for improving patient outcome, but can be associated with learning curves. Although learning curves in surgery are a recognized problem, the impact of surgical learning curves is increasing, due to increasing complexity of innovative surgical procedures, the rapid rate at which new interventions are implemented and a decrease in relative effectiveness of new interventions compared to old interventions. For minimally invasive esophagectomy(MIE), there is now robust evidence that implementation can lead to significant learning associated morbidity(morbidity during a learning curve, that could have been avoided if patients were operated by surgeons that have completed the learning curve). This article provides an overview of the evidence of the impact of learning curves after implementation of MIE. In addition, caveats for implementation and available evidence regarding factors that are important for safe implementation and safe pioneering of MIE are discussed.展开更多
AIM:To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.METHODS:We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltrans...AIM:To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.METHODS:We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase(UGT)and the cytosomal glutathione S-transferase(GST)in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer.Biopsies were taken from the mucosa during colonoscopies which were done for clinical(diagnostic)reasons.After storage,the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol(UGT)and 1-chloro 2,4-dinitrobenzene(GST)as substrates.RESULTS:About 48 patients were included of which28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology.Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT.Analysis of variance(F-test)indicated that both enzymes were more widely distributed in adenoma than in cancer patients.The means±SD were smaller for cancer patients:GST for adenomas 268±152 vs 241±69 for carcinomas and UGT for adenomas 197±200 vs 150±86 for carcinomas.CONCLUSION:Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range.展开更多
Liver cysts are common,affecting 5%-10% of the population.Most are asymptomatic,however 5% of patients develop symptoms,sometimes due to complications and will require intervention.There is no consensus on their manag...Liver cysts are common,affecting 5%-10% of the population.Most are asymptomatic,however 5% of patients develop symptoms,sometimes due to complications and will require intervention.There is no consensus on their management because complications are so uncommon.The aim of this study was to perform a collected review of how a series of complications were managed at our institutions.Six different patients presenting with rare complications of liver cysts were obtained from Hepatobiliary Units in the United Kingdom and The Netherlands.History and radiological imaging were obtained from case notes and computerised radiology.As a result,1 patient admitted with inferior vena cava obstruction was managed by cyst aspiration and lanreotide;1 patient with common bile duct obstruction was first managed by endoscopic retrograde cholangiopancreatography and stenting,followed by open fenestration;1 patient with ruptured cysts and significant medical co-morbidities was managed by percutaneous drainage;1 patient with portal vein occlusion and varices was managed by open liver resection;1 patient with infected cysts was treated with intravenous antibiotics and is awaiting liver transplantation.The final patient with a simple liver cyst mimicking a hydatid was managed by open liver resection.In conclusion,complications of cystic liver disease are rare,and we have demonstrated in this series that both operative and non-operative strategies have defined roles in management.The mainstays of treatment are either aspiration/sclerotherapy or,alternatively laparoscopic fenestration.Medical management with somatostatin analogues is a potentially new and exciting treatment option but requires further study.展开更多
The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the ...The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the role of adipose-derived stem cells,and the indications of adipose tissue grafting in peripheral nerve surgery.Adipose tissue is easily accessible through the lower abdomen and inner thighs.Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress,resulting in variable survival of adipocytes within the first 24 hours.Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts.Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization,and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue.In clinical studies,the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results.Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new,more studies are needed to explore safety and long-term effects on peripheral nerve regeneration.The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated,enzyme-free,and used in the same surgical procedure,e.g.adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction.Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival.Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.展开更多
文摘Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.
文摘Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall phenotype.Clinically,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses inexorably.New biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).
文摘BACKGROUND Detailed information on metastatic patterns in of patients with esophageal and gastric cancer is limited.Early recognition of metastases is important to avoid futile locoregional treatments.Furthermore,knowledge on metastatic patterns is necessary for further development of personalized treatment modalities.AIM To gain insight into the metastatic pattern of gastroesophageal cancer.METHODS A nationwide retrospective autopsy study of 3876 patients with adenocarcinoma(AC)or squamous cell carcinoma(SCC)of the esophagus or stomach between 1990 and 2017 was performed.Only patient with metastases were included for analysis.The metastatic pattern was analyzed according to the primary tumor location and histological subtype.RESULTS Metastatic disease was found in 268 esophageal and 331 gastric cancer patients.In esophageal cancer,the most common metastatic locations were liver(56%),distant lymph nodes(53%)and lung(50%).Esophageal AC showed more frequently metastases to the peritoneum and bone compared with esophageal SCC.In gastric cancer,the most common metastatic locations were distant lymph nodes(56%),liver(53%)and peritoneum(51%).Intestinal-type AC of the stomach showed metastases to the liver more frequently,whereas metastases to the bone,female reproductive organs and colorectum were observed more frequently in diffuse-type gastric AC.CONCLUSION This study showed differences in metastatic patterns of patients with esophageal and gastric cancer according to the primary tumor location and histological subtype.
基金supported by an unrestricted grant from Urogyn BV,Nijmegen,The Netherlands.
文摘Stress urinary incontinence is not a deadly disease,but for the large population of women suffering from it,it is a very important issue.Especially in the continuously aging population all over the world,there is more and more need for treatment of this serious medical condition.Treatment of female stress urinary incontinence exists already for ages.In the 20th century invasive treatments like Burch colposuspension and pubovaginal slings were the mainstay of surgical treatments.The introduction of the midurethral sling made the procedure less invasive and accessible for more caregivers.Luckily there are many options available and the field is developing quickly.In recent years many new medical devices have been developed,that increase the number of treatment options available and make it possible to find a suitable solution for the individual patient based on subjective and objective results and the chances of complications.This manuscript provides an introduction to the therapeutical options that are available nowadays for female stress urinary incontinence.
文摘AIM:To determine the possible modulating effect of the COX-2 polymorphisms,-765G→C and-1195A→G, on the risk of colorectal cancer(CRC)in a Dutch population. METHODS:This case-control study includes 326 patients with CRC and 369 age-and gender-matched controls.Genotypes of the COX-2 polymorphisms -765G→C and-1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism.COX-2 genotypes and haplotypes were analyzed and odds ratios with 95%confi- dence intervals were estimated by logistic regression. RESULTS:The-765GG genotype was associated with an increased risk of developing CRC(OR,1.45; 95%CI,1.03-2.04).No significant difference was observed in the genotype distribution of the-1195A→ G polymorphism between patients and controls.The GG/AC haplotype was present significantly less often in patients than in controls(OR 0.44;95%CI,0.22-0.85). When the AC,AG and GG haplotypes were investigated separately,the AC haplotype showed a tendency to be less frequent in patients than in controls(OR(AG/AC)0.78; 95%CI,0.57-1.06). CONCLUSION:The-765GG genotype is associatedwith an increased risk of developing CRC and the GG/ AC haplotype seems to protect against CRC.These findings suggest a modulating role for the COX-2 polymorphisms-765G→C and-1195A→G in the development of CRC in a Dutch population.
文摘Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.
文摘The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration;however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of preexisting vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.
文摘Many upper gastrointestinal(GI) endoscopies worldwide are performed for inappropriate indications. This overuse of healthcare negatively affects healthcare quality and puts pressure on endoscopy services. Dyspepsia is one of the most common inappropriate indications for upper GI endoscopy as diagnostic yield is low. Reasons for untimely referral are: unfamiliarity with dyspepsia guidelines,uncertainty about etiology of symptoms, and therapy failure. Unfiltered openaccess referrals feed upper GI endoscopy overuse. This review highlights strategies applied to diminish use of upper GI endoscopies for dyspepsia. First,we describe the impact of active guideline implementation. We found improved guideline adherence, but resistance was encountered in the process. Secondly, we show several forms of clinical assessment. While algorithm use reduced upper GI endoscopy volume, effects of referral assessment of individual patients were minor. A third strategy proposed Helicobacter pylori test and treat for all dyspeptic patients. Many upper GI endoscopies can be avoided using this strategy, but outcomes may be prevalence dependent. Lastly, empirical treatment with Proton pump inhibitors achieved symptom relief for dyspepsia and avoided upper GI endoscopies in about two thirds of patients. Changing referral behavior is complex as contributing factors are manifold. A collaboration of multiple strategies is most likely to succeed.
文摘BACKGROUND An increasing number of older patients is undergoing curative,surgical treatment of esophageal cancer.Previous meta-analyses have shown that older patients suffered from more postoperative morbidity and mortality compared to younger patients,which may lead to patient selection based on age.However,only studies including patients that underwent open esophagectomy were included.Therefore,it remains unknown whether there is an association between age and outcome in patients undergoing minimally invasive esophagectomy.AIM To perform a systematic review on age and postoperative outcome in esophageal cancer patients undergoing esophagectomy.METHODS Studies comparing older with younger patients with primary esophageal cancer undergoing curative esophagectomy were included.Meta-analysis of studies using a 75-year age threshold are presented in the manuscript,studies using other age thresholds in the Supplementary material.MEDLINE,Embase and the Cochrane Library were searched for articles published between 1995 and 2020.Risk of bias was assessed with the Newcastle-Ottawa Scale.Primary outcomes were anastomotic leak,pulmonary and cardiac complications,delirium,30-and 90-d,and in-hospital mortality.Secondary outcomes included pneumonia and 5-year overall survival.RESULTS Seven studies(4847 patients)using an age threshold of 75 years were included for meta-analysis with 755 older and 4092 younger patients.Older patients(9.05%)had higher rates of 90-d mortality compared with younger patients(3.92%),(confidence interval=1.10-5.56).In addition,older patients(9.45%)had higher rates of in-hospital mortality compared with younger patients(3.68%),(confidence interval=1.01-5.91).In the subgroup of 2 studies with minimally invasive esophagectomy,older and younger patients had comparable 30-d,90-d and in-hospital mortality rates.CONCLUSION Older patients undergoing curative esophagectomy for esophageal cancer have a higher postoperative mortality risk.Minimally invasive esophagectomy may be important for minimizing mortality in older patients.
文摘AIM:To determine whether-1195 A→G and/or-765 G→C polymorphisms in Cyclooxygenase-2(COX-2 ) may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population.METHODS:Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area.DNA was isolated from whole blood and used for genotyping.PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis.Odds ratios(OR) and 95% confldence intervals(CI) were estimated.RESULTS:The distribution of the-1195 A→G polymorphism was signif icantly different in esophageal cancer patients compared to controls.The-1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma(OR = 3.85, 95% CI:1.45-10.3) compared with the-1195 AA genotype as a reference.The-765 G→C genotype distribution was not different between the two groups.The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls(OR = 3.45, 95% CI:1.24-9.58;with AG/AG as a reference).The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical signif icance.CONCLUSION:Presence of the COX-2-1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.
文摘AIM To study the effect of different techniques of cystic duct closure on bile leakage after laparoscopic cholecystectomy(LC) for biliary disease.METHODS A systematic search of MEDLINE, Cochrane and EMBASE was performed. Rate of cystic duct leakage(CDL) was the primary outcome. Risk of bias was evaluated. Odds ratios were analyzed for comparison of techniques and pooled event rates for non-comparative analyses. Pooled event rates were compared for each of included techniques.RESULTS Out of 1491 articles, 38 studies were included. A total of 47491 patients were included, of which 38683(81.5%)underwent cystic duct closure with non-locking(metal)clips. All studies were of low-moderate methodological quality. Only two studies reported separate data on uncomplicated and complicated gallbladder disease. For overall CDL, an odds ratio of 0.4(95%CI: 0.06-2.48)was found for harmonic energy vs clip closure and an odds ratio of 0.17(95%CI: 0.03-0.93) for locking vs non-locking clips. Pooled CDL rate was around 1% for harmonic energy and metal clips, and 0% for locking clips and ligatures. CONCLUSION Based on available evidence it is not possible to either recommend or discourage any of the techniques for cystic duct closure during LC with respects to CDL,although data point out a slight preference for locking clips and ligatures vs other techniques. No separate recommendation can be made for complicated gallbladder disease.
文摘Surgical innovation and pioneering are important for improving patient outcome, but can be associated with learning curves. Although learning curves in surgery are a recognized problem, the impact of surgical learning curves is increasing, due to increasing complexity of innovative surgical procedures, the rapid rate at which new interventions are implemented and a decrease in relative effectiveness of new interventions compared to old interventions. For minimally invasive esophagectomy(MIE), there is now robust evidence that implementation can lead to significant learning associated morbidity(morbidity during a learning curve, that could have been avoided if patients were operated by surgeons that have completed the learning curve). This article provides an overview of the evidence of the impact of learning curves after implementation of MIE. In addition, caveats for implementation and available evidence regarding factors that are important for safe implementation and safe pioneering of MIE are discussed.
基金Supported by The Technical University of Dresden/Germany
文摘AIM:To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds.METHODS:We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase(UGT)and the cytosomal glutathione S-transferase(GST)in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer.Biopsies were taken from the mucosa during colonoscopies which were done for clinical(diagnostic)reasons.After storage,the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol(UGT)and 1-chloro 2,4-dinitrobenzene(GST)as substrates.RESULTS:About 48 patients were included of which28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology.Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT.Analysis of variance(F-test)indicated that both enzymes were more widely distributed in adenoma than in cancer patients.The means±SD were smaller for cancer patients:GST for adenomas 268±152 vs 241±69 for carcinomas and UGT for adenomas 197±200 vs 150±86 for carcinomas.CONCLUSION:Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range.
文摘Liver cysts are common,affecting 5%-10% of the population.Most are asymptomatic,however 5% of patients develop symptoms,sometimes due to complications and will require intervention.There is no consensus on their management because complications are so uncommon.The aim of this study was to perform a collected review of how a series of complications were managed at our institutions.Six different patients presenting with rare complications of liver cysts were obtained from Hepatobiliary Units in the United Kingdom and The Netherlands.History and radiological imaging were obtained from case notes and computerised radiology.As a result,1 patient admitted with inferior vena cava obstruction was managed by cyst aspiration and lanreotide;1 patient with common bile duct obstruction was first managed by endoscopic retrograde cholangiopancreatography and stenting,followed by open fenestration;1 patient with ruptured cysts and significant medical co-morbidities was managed by percutaneous drainage;1 patient with portal vein occlusion and varices was managed by open liver resection;1 patient with infected cysts was treated with intravenous antibiotics and is awaiting liver transplantation.The final patient with a simple liver cyst mimicking a hydatid was managed by open liver resection.In conclusion,complications of cystic liver disease are rare,and we have demonstrated in this series that both operative and non-operative strategies have defined roles in management.The mainstays of treatment are either aspiration/sclerotherapy or,alternatively laparoscopic fenestration.Medical management with somatostatin analogues is a potentially new and exciting treatment option but requires further study.
文摘The application of autologous fat grafting in reconstructive surgery is commonly used to improve functional form.This review aims to provide an overview of the scientific evidence on the biology of adipose tissue,the role of adipose-derived stem cells,and the indications of adipose tissue grafting in peripheral nerve surgery.Adipose tissue is easily accessible through the lower abdomen and inner thighs.Non-vascularized adipose tissue grafting does not support oxidative and ischemic stress,resulting in variable survival of adipocytes within the first 24 hours.Enrichment of adipose tissue with a stromal vascular fraction is purported to increase the number of adipose-derived stem cells and is postulated to augment the long-term stability of adipose tissue grafts.Basic science nerve research suggests an increase in nerve regeneration and nerve revascularization,and a decrease in nerve fibrosis after the addition of adipose-derived stem cells or adipose tissue.In clinical studies,the use of autologous lipofilling is mostly applied to secondary carpal tunnel release revisions with promising results.Since the use of adipose-derived stem cells in peripheral nerve reconstruction is relatively new,more studies are needed to explore safety and long-term effects on peripheral nerve regeneration.The Food and Drug Administration stipulates that adipose-derived stem cell transplantation should be minimally manipulated,enzyme-free,and used in the same surgical procedure,e.g.adipose tissue grafts that contain native adipose-derived stem cells or stromal vascular fraction.Future research may be shifted towards the use of tissue-engineered adipose tissue to create a supportive microenvironment for autologous graft survival.Shelf-ready alternatives could be enhanced with adipose-derived stem cells or growth factors and eliminate the need for adipose tissue harvest.