Is Helicobacter pylori infection protective against esophageal cancer?

Helicobacter pylori(H.pylori)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric cancer.Recent studies have found an inverse relationship between H.pylori infection and eso-phageal cancer(EC),suggesting a protective role against EC.This editorial focuses on the possible mechanisms underlying the role of H.pylori infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of H.pylori eradication.EC has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk factors.Gut microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin production.H.pylori infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell apoptosis.Though H.pylori infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in H.pylori-infected in-dividuals.There are concerns regarding a plausible increase in EC after H.pylori eradication treatments.However,H.pylori eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

Confocal laser endomicroscopy for gastric neoplasm

Confocal laser endomicroscopy(CLE)is a novel endoscopic modality that provides real-time histological information via high-resolution magnified view of the mucosa.CLE has a higher sensitivity,specificity,and diagnostic accuracy in detecting atrophic gastritis as compared to chromoendoscopy and narrow-band imaging.It can even predict low-grade and high-grade intraepithelial neoplasia by analyzing gastric pit patterns.CLE may have some advantages over the standard biopsy protocol,such as higher diagnostic yield and fewer biopsy requirements.Its diagnostic accuracy in detecting superficial gastric cancer is higher than that of white-light endoscopy.Inherent limitations,such as a narrow field of vision,can be surpassed by technological advancements and integration with other detection methods.Artificial intelligence holds promise in automated analysis of histopathological images.Thus,CLE can be helpful in screening for early gastric cancer and may help reduce the risk of complications from repeated biopsies,such as mucosal damage,bleeding,and infection.

Capsule endoscopy:Current practice and future directions

Capsule endoscopy (CE) has transformed investigation of the small bowel providing a non-invasive, well tolerated means of accurately visualising the distal duodenum, jejunum and ileum. Since the introduction of small bowel CE thirteen years ago a high volume of literature on indications, diagnostic yields and safety profile has been presented. Inclusion in national and international guidelines has placed small bowel capsule endoscopy at the forefront of investigation into suspected diseases of the small bowel. Most commonly, small bowel CE is used in patients with suspected bleeding or to identify evidence of active Crohn’s disease (CD) (in patients with or without a prior history of CD). Typically, CE is undertaken after upper and lower gastrointestinal flexible endoscopy has failed to identify a diagnosis. Small bowel radiology or a patency capsule test should be considered prior to CE in those at high risk of strictures (such as patients known to have CD or presenting with obstructive symptoms) to reduce the risk of capsule retention. CE also has a role in patients with coeliac disease, suspected small bowel tumours and other small bowel disorders. Since the advent of small bowel CE, dedicated oesophageal and colon capsule endoscopes have expanded the fields of application to include the investigation of upper and lower gastrointestinal disorders. Oesophageal CE may be used to diagnose oesophagitis, Barrett’s oesophagus and varices but reliability in identifying gastroduodenal pathology is unknown and it does not have biopsy capability. Colon CE provides an alternative to conventional colonoscopy for symptomatic patients, while a possible role in colorectal cancer screening is a fascinating prospect. Current research is already addressing the possibility of controlling capsule movement and developing capsules which allow tissue sampling and the administration of therapy.

Upper gastrointestinal tract capsule endoscopy using a nurse-led protocol: First reported experience

AIM To test the feasibility and performance of a novel upper gastrointestinal(GI) capsule endoscope using a nurse-led protocol. METHODS We conducted a prospective cohort analysis of patients who declined gastroscopy(oesophagogastroduodenoscopy, OGD) but who consented to upper GI capsule endoscopy. Patients swallowed the upper GI capsule following ingestion of 1 liter of water(containing simethicone). A series of positional changes were used to exploit the effects of water flow and move the upper GI capsule from one gravity-dependent area to another using a nurse-led protocol. Capsule transit time, video reading time, mucosal visualisation, pathology detection and patient tolerance was evaluated.RESULTS Fifty patients were included in the study. The mean capsule transit times in the oesophagus and stomach were 28 s and 68 min respectively. Visualisation of the following major anatomical landmarks was achieved(graded 1-5: Poor to excellent): Oesophagus, 4.8(± 0.5); gastro-oesophageal junction(GOJ), 4.8(± 0.8); cardia, 4.8(± 0.8); fundus, 3.8(± 1.2); body, 4.5(± 1); antrum, 4.5(± 1); pylorus, 4.7(± 0.8); duodenal bulb, 4.7(± 0.7); second part of the duodenum(D2), 4.7(± 1). The upper GI capsule reached D2 in 64% of patients. The mean video reading time was 48 min with standard playback mode and 20 min using Quickview(P = 0.0001). No pathology was missed using Quickview. Procedural tolerance was excellent. No complications were seen with the upper GI capsule. CONCLUSION The upper GI capsule achieved excellent views of the upper GI tract. Future studies should compare the diagnostic accuracy between upper GI capsule and OGD.

Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.

Natural history of hepatic metastases from colorectal cancer-pathobiological pathways with clinical significance

Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process.This process starts with a series of mutations in colonic epithelial cells,continues with their detachment from the large intestine,dissemination through the blood and/or lymphatic circulation,attachment to the hepatic sinusoids and interactions with the sinusoidal cells,such as sinusoidal endothelial cells,Kupffer cells,stellate cells and pit cells.The metastatic sequence terminates with colorectal cancer cell invasion,adaptation and colonisation of the hepatic parenchyma.All these events,termed the colorectal cancer invasion-metastasis cascade,include multiple molecular pathways,intercellular interactions and expression of a plethora of chemokines and growth factors,and adhesion molecules,such as the selectins,the integrins or the cadherins,as well as enzymes including matrix metalloproteinases.This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

Tissue engineering in urethral reconstruction--an update

The field of tissue engineering is rapidly progressing. Much work has gone into developing a tissue engineered urethral graft. Current grafts, when long, can create initial donor site morbidity. In this article, we evaluate the progress made in finding a tissue engineered substitute for the human urethra. Researchers have investigated cell-free and cell-seeded grafts. We discuss different approaches to developing these grafts and review their reported successes in human studies. With further work, tissue engineered grafts may facilitate the management of lengthy urethral strictures requiring oral mucosa substitution urethroplasty.

Underactive bladder:Pathophysiology and clinical significance

Underactive bladder(UAB)is a voiding disorder which generates disabling lower urinary tract symptoms(LUTS)due to the inability to produce an effective voiding contraction sufficient to empty the bladder.The underlying abnormality,that is usually appreciated when performing urodynamic studies,has been defined by the International Continence Society(ICS)as detrusor underactivity(DUA).DUA is a common yet under-researched bladder dysfunction.The prevalence of DUA in different patient groups suggests that multiple aetiologies are implicated.Currently there is no effective therapeutic approach to treat this condition.An improved understanding of the underlying mechanisms is needed to facilitate the development of new advances in treatment.The purpose of this review is to discuss the epidemiology,pathophysiology,common causes and risk factors potentially leading to DUA;to aid in the appropriate diagnosis of DUA to potentially improve treatment outcomes.

Endoscopic ultrasound sedation in the United Kingdom: Is life without propofol tolerable?

There is compelling evidence to support the quality,cost effectiveness and safety profile of non-anesthesiologist-administered propofol for endoscopic ultrasound (EUS). However in the United Kingdom, it is recommended that the administration and monitoring of propofol sedation for endoscopic procedures should be the responsibility of a dedicated and appropriately trained anaesthetist only. The majority of United Kingdom EUS procedures are performed with opiate and benzodiazepine sedation rather than anaesthetist led propofol lists due to anaesthetist resource availability. We sought to prospectively determine the tolerability and safety of EUS with benzodiazepine and opiate sedation in single United Kingdom centre. Two hundred consecutive patients undergoing either EUS or oesophago-gastroduodenoscopy (OGD) with conscious sedation were prospectively recruited with a 1:1 enrolment ratio. Patients completed questionnaires pre and post procedure detailing anticipated and actual pain experienced on a 1-10 visual analogue scale. Demographics, procedure duration, sedation doses and willingness to repeat the procedure were also recorded. EUS procedures lasted significantly longer than OGDs(15 min vs 6 min, P < 0.0001), however, there was no difference in anticipated pain scores between the groups(EUS 3.37/10 vs OGD 3.47/10, P = 0.46). Pain scores indicated EUS was better tolerated than OGD(1.16/10 vs 1.88/10, P = 0.03) although higher doses of sedation were used for EUS procedures. There were no complications identified in either group. We feel our study demonstrates that the tolerability of EUS with opiate and benzodiazepine sedation is acceptable.

Current trends in urethral stricture management

The recent International Consultation on Urological Disease(ICUD)panel 2010 confirmed that a urethral stricture is defined as a narrowing of the urethra consequent upon ischaemic spongiofibrosis,as distinct from sphincter stenoses and a urethral disruption injury.Whenever possible,an anastomotic urethroplasty should be performed because of the higher success rate as compared to augmentation urethroplasty.There is some debate currently regarding the critical stricture length at which an anastomotic procedure can be used,but clearly the extent of the spongiofibrosis and individual anatomical factors(the length of the penis and urethra)are important,the limitation for this being extension of dissection beyond the peno-scrotal junction and the subsequent production of chordee.More recently,there has been interest in whether to excise and anastomose or to carry out a stricturotomy and reanastomosis using a Heineke-Miculicz technique.Augmentation urethroplasty has evolved towards the more extensive use of oral mucosa grafts as compared to penile skin flaps,as both flaps and grafts have similar efficacy and certainly the use of either dorsal or ventral positioning seems to provide comparable results.It is important that the reconstructive surgeon is well versed in the full range of available repair techniques,as no single method is suitable for all cases and will enable the management of any unexpected anatomical findings discovered intra-operatively.

The treatment of complex female urethral pathology

Lower urinary tract symptoms(LUTS)in women produce significant bother.Common conditions causing LUTS in women include urinary tract infections,overactive bladder,and stress incontinence.Urethral diverticulae and female urethral strictures are rare pathologies.They can cause symptoms,which can mimic commoner conditions,leading to delay in diagnosis and unnecessary delay in treatment.In this article,we discuss in detail the definition,symptoms,epidemiology,pathogenesis,diagnosis,and treatment option for these two conditions.Further understanding of these conditions will aid in the proper diagnosis and prevent delay in management.

Miniature gastrointestinal endoscopy: Now and the future

Since its original application,gastrointestinal(GI)endoscopy has undergone many innovative transformations aimed at expanding the scope,safety,accuracy,acceptability and cost-effectiveness of this area of clinical practice.One method of achieving this has been to reduce the caliber of endoscopic devices.We propose the collective term“Miniature GI Endoscopy”.In this Opinion Review,the innovations in this field are explored and discussed.The progress and clinical use of the three main areas of miniature GI endoscopy(ultrathin endoscopy,wireless endoscopy and scanning fiber endoscopy)are described.The opportunities presented by these technologies are set out in a clinical context,as are their current limitations.Many of the positive aspects of miniature endoscopy are clear,in that smaller devices provide access to potentially all of the alimentary canal,while conferring high patient acceptability.This must be balanced with the costs of new technologies and recognition of device specific challenges.Perspectives on future application are also considered and the efforts being made to bring new innovations to a clinical platform are outlined.Current devices demonstrate that miniature GI endoscopy has a valuable place in investigation of symptoms,therapeutic intervention and screening.Newer technologies give promise that the potential for enhancing the investigation and management of GI complaints is significant.

Gastric sarcoidosis mimicking irritable bowel syndrome-Cause not association?

Sarcoidosis is a systemic disease of unknown aetiology that may affect any organ in the body. The gastrointestinal tract however is only rarely affected outside the liver. Symptoms may be non-specific. Irritable bowel syndrome （IBS） is a common diagnosis. The recognition of IBS is aided by the use of the Rome Ⅱ criteria-in the absence of organic disease. We describe the first case of a patient with gastric sarcoidosis who presented with IBS symptoms but subsequently responded to immunosuppressive therapy.

The choice of surgical approach in the treatment of vesico-vaginal fistulae

Vesico-vaginal fistula is a global healthcare problem that has a high prevalence in sub-Saharan Africa,where obstetric complications lead to the development of this condition.Despite this,comparatively few fistula repairs are performed in well-resourced countries,where iatrogenic injury is the leading aetiological factor.As a consequence,much of our knowledge results from the experience of relatively few fistula surgeons in areas of high prevalence borne out of large case series or retrospective cohorts rather than high level evidence.At present,debate surrounds the exact timing of repair and the most appropriate surgical approach for this condition.Certain fistulae can be selected for conservative management,while those that do not demonstrate factors associated with spontaneous closure can be selected for surgery.Fistula surgeons should be aware of several potential repair options and the principles of contemporary fistula surgery,as the first attempt at repair is likely to be the best opportunity to achieve a successful outcome.We review the available literature and provide evidence on the optimal timing of repair,the appropriate surgical approach and the use of tissue interpositioning in fistula surgery.

Dengue:epidemiology,prevention and pressing need for vaccine development

Dengue fever is a mosquito born viral infection,and the complicated form of dengue is dengue hemorrhagic fever(DHF).In the recent decades incidence and distribution of dengue has increased dramatically.Dengue viruses belong to family flaviviridae with four serotypes and are transmitted mainly by mosquito Aedes aegypti.Today almost two-fifth of world’s population (2.5 million) is at risk of dengue and no specific antiviral drug or vaccine is available against it.Uncontrolled population growth in Africa and South East Asia has increased number of susceptible hosts in urban and semi urban areas.About 40%of world population resides in the high risk area for dengue transmission.According to latest estimates by WHO,yearly 50 to 100 million infections occur globally,this includes around 500 000 DHF and 22 000 deaths,mostly among children.Only symptomatic treatment in the form of analgesic,antipyretics and body fluid management is provided to the patient.Prevention strategies mainly focus on two approaches, firsdy on activities to control vector and secondly on activities to protect human from mosquito bite but there is always concerns regarding their sustainably and effectiveness.Theoretically development of an effective dengue vaccine is feasible and production of an effective and affordable vaccine could be a viable option to save humans from this dreadful disease. Conceptually vaccine production is possible,but it has to be tetravalent,providing immunity against all serotypes.Few candidate vaccines are in advance stage of their development:however international cooperation is needed to make these vaccines available on cheaper rates to the poor and vulnerable countries.Objective of this review is to discuss various aspects related to dengue,its epidemiology,available preventive methods,need for vaccine and challenges in its development.

Overcoming scarring in the urethra: Challenges for tissue engineering

Urethral stricture disease is increasingly common occurring in about 1%of males over the age of 55.The stricture tissue is rich in myofibroblasts and multi-nucleated giant cells which are thought to be related to stricture formation and collagen synthesis.An increase in collagen is associated with the loss of the normal vasculature of the normal urethra.The actual incidence differs based on worldwide populations,geography,and income.The stricture aetiology,location,length and patient’s age and comorbidity are important in deciding the course of treatment.In this review we aim to summarise the existing knowledge of the aetiology of urethral strictures,review current treatment regimens,and present the challenges of using tissue-engineered buccal mucosa(TEBM)to repair scarring of the urethra.In asking this question we are also mindful that recurrent fibrosis occurs in other tissuesdhow can we learn from these other pathologies?

心脏MRI诊断肺动脉高压:回归模型的推导与验证

目的通过推导和测试多参数心脏MRI肺动脉高压(PH)诊断模型。材料与方法回顾性连续收集2012—2016年期间疑为PH病人的心脏MRI及右心导管术(RHC)检查的图像及病人相关数据。

Update summarising the conclusions of the international consultation on male lower urinary tract symptoms

The International Consultation on Urological Disease have recently published comprehensive conclusions, based on evidence reviewed by eight committees, on aspects of male lower urinary tract symptoms(LUTS). In this review, we summarise the conclusions from fourof the committees, namely, the evidence regarding the epidemiology of male LUTS, patient assessment, nocturia and medical management. It is indisputable that with an expanding and ageing global population the prevalence of male LUTS is likely to increase. Therefore symptom prevention and preservation of quality of life(Qo L) feature highly in the guidelines. There are now a number of different medical options, proven to lead to significant improvements in symptom scores, flow rate and Qo L available to men with LUTS. Metaanalyses have shown the benefits for alpha blockers, antimuscarinics, 5-α reductase and phosphodiesterase-5 inhibitors. High level evidence also exists for combinations of all of the above with alpha blockers and so men with concomitant storage symptoms, prostate volume > 30 mL, PSA > 1.4 or erectile dysfunction may be considered for combination treatment of an alpha blocker with an antimuscarinic, 5-α reductase inhibitor or phosphodiesterase-5 inhibitor respectively. In an era of personalised medicine, appropriate patient selection is likely to provide the key to the most effective clinical management strategy.

Magnetic resonance angiography for the primary diagnosis of pulmonary embolism: A review from the international workshop for pulmonary functional imaging

Pulmonary contrast enhanced magnetic resonance angiography(CE-MRA) is useful for the primary diagnosis of pulmonary embolism(PE). Many sites have chosen not to use CE-MRA as a first line of diagnostic tool for PE because of the speed and higher efficacy of computerized tomographic angiography(CTA). In this review, we discuss the strengths and weaknesses of CEMRA and the appropriate imaging scenarios for the primary diagnosis of PE derived from our unique multiinstitutional experience in this area. The optimal patient for this test has a low to intermediate suspicion for PE based on clinical decision rules. Patients in extremis are not candidates for this test. Younger women(< 35 years of age) and patients with iodinated contrast allergies are best served by using this modality We discuss the history of the use of this test, recent technical innovations, artifacts, direct and indirect findings for PE, ancillary findings, and the effectiveness(patient outcomes) of CE-MRA for the exclusion of PE. Current outcomes data shows that CE-MRA and NM V/Q scans are effective alternative tests to CTA for the primary diagnosis of PE.

Khat(Catha Edulis) as a possible cause of autoimmune hepatitis

AIM:To investigate the potential role of khat in triggering auto immune hepatitis.METHODS:Patients with a history of khat use and acute hepatitis were identified using the computer database in the hepatology department at the Royal Hallamshire Hospital.They were then assessed for probability of having autoimmune hepatitis using the revised autoimmune hepatitis scoring criteria.RESULTS:Six patients were identified.All of them had presented with acute hepatitis on a background of khat.All were male and five of these patients were of Somali origin,while one patient was from Yemen.The patients were given points on the modified autoimmune hepatitis score which is based on their liver enzymes,autoimmune screen,exclusion of viral hepatitis alcohol and drugs,immunoglobulin levels and liver histology.The patients were given a score of-4 for khat use due to its potential to cause drug induced liver injury.Five of these patients scored between 10 and 15 points,placing them in the probable group for having autoimmune hepatitis.All of these patients were treated with prednisolone and demonstrated a good response to immunosuppression.CONCLUSION:One possibile cause of hepatotoxicity with khat could be via triggering of autoimmune hepatitis in a genetically susceptible individual.Further studies are needed for confirmation.