Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health

The complex gut microbial flora harbored by individuals(microbiota) has long been proposed to contribute tointestinal health as well as disease. Pre-and probioticproducts aimed at improving health by modifyingmicrobiota composition have already become widelyavailable and acceptance of these products appearsto be on the rise. However, although required forthe development of effective microbiota basedinterventions, our basic understanding of microbiotavariation on a population level and its dynamics withinindividuals is still rudimentary. Powerful new parallelsequence technologies combined with other efficientmolecular microbiota analysis methods now allow forcomprehensive analysis of microbiota composition inlarge human populations. Recent fi ndings in the fi eldstrongly suggest that microbiota contributes to thedevelopment of obesity, atopic diseases, inflammatorybowel diseases and intestinal cancers. Through theongoing National Institutes of Health Roadmap 'HumanMicrobiome Project' and similar projects in other partsof the world, a large coordinated effort is currentlyunderway to study how microbiota can impact humanhealth. Translating findings from these studies intoeffective interventions that can improve health,possibly personalized based on an individuals existingmicrobiota, will be the task for the next decade(s).

Evaluation and management of patients with refractory ascites

Some patients with ascites due to liver cirrhosis become no longer responsive to diuretics. Once other causes of ascites such as portal vein thrombosis, malignancy or infection and non-compliance with medications and low sodium diet have been excluded, the diagnosis of refractory ascites can be made based on strict criteria. Patients with refractory ascites have very poor prognosis and therefore referral for consideration for liver transplantation should be initiated. Search for reversible components of the underlying liver pathology should be undertaken and targeted therapy, when available, should be considered. Currently, serial large volume paracentesis (LVP) and transjugular intrahepatic portasystemic stent-shunt (TIPS) are the two mainstay treatment options for refractory ascites. Other treatment options are available but not widely used either because they carry high morbidity and mortality (most surgical options) rates, or are new interventions that have shown promise but still need further evaluation. In this comprehensive review, we describe the evaluation and management of patients with refractory ascites from the prospective of the practicing physician.

Endoscopic management of biliary strictures after liver transplantation

Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Biliary strictures are classifi ed as anastomotic or non-anastomotic strictures according to location and are defi ned by distinct clinical behaviors. Anastomotic strictures are localized and short. The outcome of endoscopic treatment for anastomotic strictures is excellent. Nonanastomotic strictures often result from ischemic and immunological events, occur earlier and are usually multiple and longer. They are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and need for retransplantation. Living donor OLT patients present a unique set of challenges arising from technical factors, and stricture risk for both recipients and donors. Endoscopic treatment of living donor OLT patients is less promising. Current endoscopic strategies for biliary strictures after OLT include repeated balloon dilations and placement of multiple side-by-side plastic stents. Lifelong surveillance is required in all types of strictures. Despite improvements in incidence and long term outcomes with endoscopic management, and a reduced need for surgical treatment, the impact of strictures on patients after OLT is signifi cant. Future considerations include new endoscopic technologies and improved stents, which could potentially allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. This review focuses on the role of endoscopy in biliary strictures, one of the most common biliary complications after OLT.

Colorectal cancer surveillance in inflammatory bowel disease: The search continues

Patients with infl ammatory bowel disease (IBD) are at increased risk for colorectal cancer (CRC). Risk factors for the development of CRC in the setting of IBD include disease duration, anatomic extent of disease, age at time of diagnosis, severity of inflammation, family history of colon cancer, and concomitant primary sclerosing cholangitis. The current surveillance strategy of surveillance colonoscopy with multiple random biopsies most likely reduces morbidity and mortality associated with IBD-related CRC. Unfortunately, surveillance colonoscopy also has severe limitations including high cost, sampling error at time of biopsy, and interobserver disagreement in histologically grading dysplasia. Furthermore, once dysplasia is detected there is disagreement about its management. Advances in endoscopic imaging techniques are already underway, and may potentially aid in dysplasia detection and improve overall surveillance outcomes. Management of dysplasia depends predominantly on the degree and focality of dysplasia, with the mainstay of management involving either proctocolectomy or continued colonoscopic surveillance. Lastly, continued research into additional chemopreventive agents may increase our arsenal in attempting to reduce the incidence of IBD-associated CRC.

Air embolism complicating gastrointestinal endoscopy: A systematic review

Gastrointestinal endoscopy has become an important modality for the diagnosis and treatment of various gastrointestinal disorders. One of its major advantages is that it is minimally invasive and has an excellent safety record. Nevertheless, some complications do occur, and endoscopists are well aware and prepared to deal with the commonly recognized ones including bleeding, perforation, infection, and adverse effects from the sedative medications. Air embolism is a very rare endoscopic complication but possesses the poten-tial to be severe and fatal. It can present with cardio-pulmonary instability and neurologic symptoms. The diagnosis may be difficult because of its clinical presen-tation, which can overlap with sedation-related cardio-pulmonary problems or neurologic symptoms possibly attributed to an ischemic or hemorrhagic central nervous system event. Increased awareness is essential for prompt recognition of the air embolism, which can allow potentially life-saving therapy to be provided.Therefore, we wanted to review the risk factors, the clinical presentation, and the therapy of an air embolism from the perspective of the practicing endoscopist.

Early successes and late failures in the prevention of post endoscopic retrograde cholangiopancreatography

Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The only way to prevent this complication is to avoid an ERCP all together. Because of the risks involved, a careful consideration should be given to the indication for ERCP and the potential risk/benefit ratio of the test. Once a decision to perform an ERCP is made, the procedure should be carried out with meticulous care by an experienced endoscopist, and with a minimum of pancreatic duct opacification. Several pharmacologic agents have been tested, but to date the most important method of reducing post ERCP pancreatitis is the placement of pancreatic stent. Pancreatic stents should be placed in all patients at high risk of this complication such as those undergoing pancreatic sphincterotomy, pancreatic duct manipulation and intervention, and patients with suspected sphincter of Oddi dysfunction. Pancreatic stents should be also considered in patients requiring precut sphincterotomy to gain biliary access.

Role of observation of live cases done by Japanese experts in the acquisition of ESD skills by a western endoscopist

AIM:To evaluate the role of observation of experts performing endoscopic submucosal dissection(ESD)in the acquisition of ESD skills.METHODS:This prospective study is documenting the learning curve of one Western endoscopist.The study consisted of three periods.In the first period(preobservation),the trainee performed ESDs in animal models in his home institution in the United States.The second period(observation)consisted of visit to Japan and observation of live ESD cases done by experts.The observation of cases occurred over a 5-wk period.During the third period(post-observation),the trainee performed ESD in animal models in a similar fashion as in the first period.Three animal models were used:live40-50 kg Yorkshire pig,explanted pig stomach model,and explanted pig rectum model.The outcomes from the ESDs done in the animal models before and after observation of live human cases(main study intervention)were compared.Statistical analysis of the data included:Fisher’s exact test to compare distributions of a categorical variable,Wilcoxon rank sum test to compare distributions of a continuous variable between the two groups(pre-observation and post-observation),and Kruskal-Wallis test to evaluate the impact of lesion location and type of model(ex-vivo vs live pig)on lesion removal time.RESULTS:The trainee performed 38 ESDs in animal model(29 pre-observation/9 post-observation).The removal times post-observation were significantly shorter than those pre-observation(32.7±15.0 min vs 63.5±9.8 min,P<0.001).To minimize the impact of improving physician skill,the 9 lesions post-observation were compared to the last 9 lesions pre-observation and the removal times remained significantly shorter(32.7±15.0 min vs 61.0±7.4 min,P=0.0011).Regression analysis showed that ESD observation significantly reduced removal time when controlling for the sequence of lesion removal(P=0.025).Furthermore,it was also noted a trend towards decrease in failure to remove lesions and decrease in complications after the period of observation.This study did not find a significant difference in the time needed to remove lesions in different animal models.This finding could have important implications in designing training programs due to the substantial difference in cost between live animal and explanted organ models.The main limitation of this study is that it reflects the experience of a single endoscopist.CONCLUSION:Observation of experts performing ESD over short period of time can significantly contribute to the acquisition of ESD skills.

Advances in the management of cholangiocarcinoma

Cholangiocarcinoma(CCA)is a primary malignancy of the bile ducts with three anatomically and molecularly distinct entities:Intrahepatic CCA(iCCA),perihilar CCA(pCCA),and distal CCA.As a result of phenotypic and anatomic differences they differ significantly with respect to management.For each type of CCA there have been significant changes in management over the last several years which will be discussed in this review.Although resection remains the standard of care for all types of CCA,liver transplantation has been established as curative treatment for selected patients with pCCA and is being evaluated for iCCA with early success.With respect to systemic therapy capecitabine is now first line adjuvant therapy for all biliary tract malignancies after curative intent resection.Progress in exploiting the pathologic mutations and molecular abnormalities has also yielded regulatory approval of targeted therapy for CCA in patients with acquired alterations in the fibroblast growth factor receptor.There is also increased consensus in managing malignant biliary obstruction associated with CCA where pre-operative biliary stenting is not beneficial while self-expanding metal stents have been shown to be superior to plastic stents in patients who are not surgical candidates.

Gastroparesis: Current diagnostic challenges and management considerations

Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most common symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to affect 4% of the population and symptomatology may range from little effect on daily activity to severe disability and frequent hospitalizations. The gold standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal and includes dietary modification, prokinetic and anti-emetic medications, and surgical interventions. New advances in drug therapy, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. In this comprehensive review, we discuss gastroparesis with emphasis on the latest developments; from the perspective of the practicing clinician.

Pancreatic pseudocyst

Pancreatic pseudocysts are complications of acute or chronic pancreatitis. Initial diagnosis is accomplished most often by cross-sectional imaging. Endoscopic ultrasound with fine needle aspiration has become the preferred test to help distinguish pseudocyst from other cystic lesions of the pancreas. Most pseudocysts resolve spontaneously with supportive care. The size of the pseudocyst and the length of time the cyst has been present are poor predictors for the potential of pseudocyst resolution or complications, but in general, larger cysts are more likely to be symptomatic or cause complications. The main two indications for some type of invasive drainage procedure are persistent patient symptoms or the presence of complications (infection, gastric outlet or biliary obstruction, bleeding). Three different strategies for pancreatic pseudocysts drainage are available: endoscopic (transpapillary or transmural) drainage, percutaneous catheter drainage, or open surgery. To date, no prospective controlled studies have compared directly these approaches. As a result, the management varies based on local expertise, but in general, endoscopic drainage is becoming the preferred approach because it is less invasive than surgery, avoids the need for external drain, and has a high long-term success rate. A tailored therapeutic approach taking into consideration patient preferences and involving multidisciplinary team of therapeutic endoscopist, interventional radiologist and pancreatic surgeon should be considered in all cases.

Colonoscopic polypectomy and associated techniques

Polypectomy of colonic polyps has been shown to reduce the risk of colon cancer development and is considered a fundamental skill for all endoscopists who perform colonoscopy.A variety of polypectomy techniques and devices are available,and their use can vary greatly based on local availability and preferences.In general,cold forceps and cold snare have been the polypectomy methods of choice for smaller polyps,and hot snare has been the method of choice for larger polyps.The use of hot forceps has mostly fallen out of favor.Polypectomy for difficult to remove polyps may require the use of special devices and advanced techniques and has continued to evolve.As a result,the vast majority of polyps today can be removed endoscopically.Since electrocautery is frequently used for polypectomy,endoscopists should be thoroughly familiar with the basic principles of electrosurgery as it pertains to polypectomy.Tattooing of a polypectomy site is an important adjunct to polypectomy and can greatly facilitate future surgery or endoscopic surveillance.The two most common post-polypectomy complications are bleeding and perforation.Their incidence can be decreased with the use of meticulous polypectomy techniques and the application of some prophylactic maneuvers.This review will examine the technique of polypectomy and its complications from the perspective of the practicing gastroenterologist.

Treatment of malignant gastric outlet obstruction with endoscopically placed self-expandable metal stents

Malignant gastroduodenal obstruction can occur in up to 20%of patients with primary pancreatic,gastric or duodenal carcinomas.Presenting symptoms include nausea,vomiting,abdominal distention,pain and decreased oral intake which can lead to dehydration, malnutrition,and poor quality of life.Endoscopic stent placement has become the primary therapeutic modality because it is safe,minimally invasive,and a cost-effective option for palliation.Stents can be successfully deployed in the majority of patients. Stent placement appears to lead to a shorter time to symptomatic improvement,shorter time to resumption of an oral diet,and shorter hospital stays as compared with surgical options.Recurrence of the obstructive symptoms resulting from stent occlusion,due to tumor ingrowth or overgrowth,can be successfully treated with repeat endoscopic stent placement in the majority of the cases.Both endoscopic stenting and surgical bypass are considered palliative treatments and,to date,no improvement in survival with either modality has been demonstrated.A tailored therapeutic approach,taking into consideration patient preferences and involving a multidisciplinary team including the therapeutic endoscopist,surgeon,medical oncologist, radiation therapist,and interventional radiologist, should be considered in all cases.

Intraductal biliary and pancreatic endoscopy: An expanding scope of possibility

Intraductal endoscopy describes the use of an endoscope to directly visualize the biliary and pancreatic ducts. For many years, technological challenges have made performing these procedures difficult. The "mother-baby" system and other various miniscopes have been developed, but routine use has been hampered due to complex setup, scope fragility and the time consuming, technically demanding nature of the procedure. Recently, the SpyGlass peroral cholangiopancreatoscopy system has shown early success at providing diagnostic information and therapeutic options. The clinical utility of intraductal endoscopy is broad. It allows better differentiation between benign and malignant processes by allowing direct visualization and targeted sampling of tissue. Therapeutic interventions, such as electrohydraulic lithotripsy (EHL), laser lithotripsy, photodynamic therapy, and argon plasma coagulation (APC), may also be performed as part of intraductal endoscopy. Intraductal endoscopy significantly increases the diagnostic and therapeutic yield of standard endoscopic retrograde cholangiography (ERCP), and as technology progresses, it is likely that its utilization will only increase. In this review of intraductal endoscopy, we describe in detail the various endoscopic platforms and their diagnostic and clinical applications.

Endoscopic ultrasound-guided biliary drainage

Endoscopic ultrasound(EUS)-guided biliary drainage has emerged as a minimally invasive alternative to percutaneous and surgical interventions for patients with biliary obstruction who had failed endoscopic retrograde cholangiopancreatography(ERCP).EUSguided biliary drainage has become feasible due to the development of large channel curvilinear therapeutic echo-endoscopes and the use of real-time ultrasound and fluoroscopy imaging in addition to standard ERCP devices and techniques.EUS-guided biliary drainage is an attractive option because of its minimally invasive,single step procedure which provides internal biliary decompression.Multiple investigators have reported high success and low complication rates.Unfortunately,high quality prospective data are still lacking.We provide detailed review of the use of EUS for biliary drainage from the perspective of practicing endoscopists with specific focus on the technical aspects of the procedure.

Endoscopic therapy of benign biliary strictures

Benign biliary strictures are being increasingly treated with endoscopic techniques. The benign nature of the stricture should be first confirmed in order to ensure appropriate therapy. Surgery has been the traditional treatment, but there is increasing desire for minimally invasive endoscopic therapy. At present, endoscopy has become the first line approach for the therapy of post- liver transplant anastomotic strictures and distal (Bismuth Ⅰand Ⅱ) post-operative strictures. Strictures related to chronic pancreatitis have proven more difficult to treat, and endoscopic therapy is reserved for patients who are not surgical candidates. The preferred endoscopic approach is aggressive treatment with gradual dilation of the stricture and insertion of multiple plastic stents. The use of uncovered self expandable metal stents should be discouraged due to poor long-term results. Treatment with covered metal stents or bioabsorbable stents warrants further evaluation. This area of therapeutic endoscopy provides an ongoing opportunity for fresh research and innovation.

Training in endoscopic submucosal dissection

Endoscopic submucosal dissection (ESD) represents an important advancement in the therapy of early neoplastic gastrointestinal lesions by providing higher en-bloc curative resection rate with lower recurrence compared to endoscopic mucosal resection (EMR) and by sparing the involved organ and protecting patient' s quality of life. Despite these advantages ESD is associated with long procedure times and a higher rate of complications, making ESD a challenging procedure which requires advanced endoscopic skills. Thus, there has been a recognized need for structured training system for ESD to enhance trainee experience and, to reduce the risks of complications and inadequate treatment. ESD has a very flat learning curve. However, we do not have uniformly accepted benchmarks for competency. Nevertheless, it appears that, in Japan, more than 30 supervised gastric ESD procedures are required to achieve technical proficiency and minimize complications. A number of training algorithms have been pro-posed in Japan with the aim to standardize ESD training. These algorithms cannot be directly applied in the West due to substantial differences including the availability of highly qualified mentors, the type of pathology seen, choice of devices, and trainee's background. We propose a training algorithm for Western physicians which integrates both hands-on training courses, animal model work as well as visits to expert centers. No specific preceptor training programs have been yet developed but there is a consensus that these programs are important for permeation of ESD worldwide.

Endoscopic ultrasonography guided celiac plexus neurolysis and celiac plexus block in the management of pain due to pancreatic cancer and chronic pancreatitis

Pain is a common symptom of pancreatic disease and is frequently difficult to manage. Pain relief provided by narcotics is often suboptimal and is associated with significant side effects. An alternative approach to pain management in pancreatic disease is the use of celiac plexus block (CPB) or neurolysis (CPN). Originally performed by anesthesiologists and radiologists via a posterior approach,recent advances in endoscopic ultrasonography (EUS) have made this technique an attractive alternative. EUS guided celiac plexus block/ neurolysis is simple to perform and avoids serious complications such as paraplegia or pneumothorax that are associated with the posterior approach. EUS guided CPN should be considered first line therapy in patients with pain due to pancreatic cancer. It provides superior pain control compared to traditional management with narcotics. A trend for improved survival in pancreatic cancer patients treated with CPN has been reported,but larger studies are needed to confirm this finding. At this time,the use of EUS guided CPB cannot be recommended as routine therapy for pain in chronic pancreatitis since only one-half of the patients experience pain reduction and the beneficial effect tends to be short lived. EUS guided CPB and CPN should be used as part of a multidisciplinary team approach for pain management.

Effect of prophylactic clip placement following endoscopic mucosal resection of large colorectal lesions on delayed polypectomy bleeding: A meta-analysis

BACKGROUND The role of prophylactic clipping for the prevention of delayed polypectomy bleeding(DPB) remains unclear and conclusions from prior meta-analyses are limited due to the inclusion of variety of resection techniques and polyp sizes.AIM To conduct a meta-analysis on the effect of clipping on DPB following endoscopic mucosal resection(EMR) of colorectal lesions ≥ 20 mm.METHODS We performed a search of PubMed and the Cochrane library for studies comparing the effect of clipping vs no clipping on DPB following endoscopic resection. The Cochran Q test and I^2 were used to test for heterogeneity. Pooling was conducted using a random-effects model.RESULTS Thirteen studies with a total of 7794 polyps were identified, of which data was available on 1701 cases of EMR of lesions ≥ 20 mm. Prophylactic clipping was associated with a lower rate of DPB(1.4%) when compared to no clipping(5.2%)(pooled OR: 0.24, 95%CI: 0.12-0.50, P < 0.001) following EMR of lesions ≥ 20 mm.There was no significant heterogeneity among the studies(I^2 = 0%, P = 0.67).CONLUSION Prophylactic clipping may reduce DPB following EMR of large colorectal lesions.Future trials are needed to further identify risk factors and stratify high risk cases in order to implement a cost-effective preventive strategy.

Squamous cell cancer of the rectum

Squamous cell carcinoma of the rectum is a rare malignancy.It appears to be associated with chronic inflammatory conditions and infections.The clear association seen between Human Papilloma Virus and various squamous cancers has not been firmly established for the squamous cell cancer of the rectum. The presentation is nonspecific and patients tend to present with advanced stage disease.Diagnosis relies on endoscopic examination with biopsy of the lesion.Distinction from squamous cell cancer of the anus can be difficult,but can be facilitated by immunohistochemical staining for cytokeratins.Staging of the cancer with endoscopic ultrasound and computed tomography provides essential information on prognosis and can guide therapy.At present,surgery remains the main therapeutic option;however recent advances have made chemoradiation a valuable therapeutic addition. Squamous cell carcinoma of the rectum is a distinct entity and it is of crucial importance for the practicing Gastroenterologist to be thoroughly familiar with this disease.Compared to adenocarcinoma of the rectum and squamous cell cancer of the anal canal,squamous cell carcinoma of the rectum has different epidemiology, etiology,pathogenesis,and prognosis but,most importantly,requires a different therapeutic approach. This review will examine and summarize the available information regarding this disease from the perspective of the practicing gastroenterologist.

ampullary 腺瘤的诊断和管理: 内视镜检查法的膨胀角色

Ampullary adenoma is a pre-cancerous lesion arising from the duodenal papilla that is often asymptomatic.It is important to distinguish whether the adenoma is sporadic or arises in the setting of familial adenomatous polyposis as this has important implications with respect to management and surveillance.Multiple modalities are available for staging of these lesions to help guide the most appropriate therapy.Those that are used most commonly include computed tomography,endoscopic ultrasound,and endoscopic retrograde cholangiopancreatography.In recent years,endoscopy has become the primary modality for therapeutic management of the majority of ampullary adenomas.Surgery remains the standard curative procedure for confirmed or suspected adenocarcinoma.This review will provide the framework for the diagnosis and management of ampullary adenomas from the perspective of the practicing gastroenterologist.