Role of copper in central nervous system physiology and pathology

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

Poke And Delayed Drink Intertemporal Choice Task(POKE-ADDICT):An open-source behavioral apparatus for intertemporal choice testing in rodents

Advancements in neuroscience research present opportunities and challenges,requiring substantial resources and funding.To address this,we describe here“Poke And Delayed Drink Intertemporal Choice Task(POKE-ADDICT)”,an open-source,versatile,and cost-effective apparatus for intertemporal choice testing in rodents.This allows quantification of delay discounting(DD),a cross-species phenomenon observed in decision making which provides valuable insights into higher-order cognitive functioning.In DD,the subjective value of a delayed reward is reduced as a function of the delay for its receipt.Using our apparatus,we implemented an effective intertemporal choice paradigm for the quantification of DD based on an adjusting delayed amount(ADA)algorithm using mango juice as a reward.Our paradigm requires limited training,a few 3D-printed parts and inexpensive electrical components,including a Raspberry Pi control unit.Furthermore,it is compatible with several in vivo procedures and the use of nose pokes instead of levers allows for faster task learning.Besides the main application described here,the apparatus can be further extended to implement other behavioral tests and protocols,including standard operant conditioning.In conclusion,we describe a versatile and cost-effective design based on Raspberry Pi that can support research in animal behavior,decision making and,more specifically,delay discounting.

Double-face urethroplasty in patients with obliterative bulbar strictures post-transurethral resection of the prostate mid-term outcomes in high-volume referral center

Objective Incidences of post-transurethral resection of the prostate(post-TURP)strictures are between 2.2%and 9.8%.Stricture commonly occurs within the first 6 months.Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty.Methods This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020.We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention.We have excluded patients with bladder neck contracture.Primary outcome was treatment success,defined as the no need for further treatments.Secondary outcome was post-urethroplasty continent rate.Results Seventeen patients were included in the study with median age of 66(interquartile range 40-77)years;median time of follow-up was 24(interquartile range 12-84)months;median stricture length was 4(interquartile range 2-6)cm.Of the 17 patients,15(88.2%)were successful.All patients were continent after urethroplasty.Conclusion With mid-term follow-up,treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure.Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.

Paradoxical association between dyspepsia and autoimmune chronic atrophic gastritis:Insights into mechanisms,pathophysiology,and treatment options

BACKGROUND Autoimmune gastritis(AIG)is a progressive,chronic,immune-mediated inflammatory disease characterized by the destruction of gastric parietal cells leading to hypo/anacidity and loss of intrinsic factor.Gastrointestinal symptoms such as dyspepsia and early satiety are very common,being second in terms of frequency only to anemia,which is the most typical feature of AIG.AIM To address both well-established and more innovative information and knowledge about this challenging disorder.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 10 years.RESULTS A total of 125 records were reviewed and 80 were defined as fulfilling the criteria.CONCLUSION AIG can cause a range of clinical manifestations,including dyspepsia.The pathophysiology of dyspepsia in AIG is complex and involves changes in acid secretion,gastric motility,hormone signaling,and gut microbiota,among other factors.Managing dyspeptic symptoms of AIG is challenging and there are no specific therapies targeting dyspepsia in AIG.While proton pump inhibitors are commonly used to treat dyspepsia and gastroesophageal reflux disease,they may not be appropriate for AIG.Prokinetic agents,antidepressant drugs,and non-pharmacological treatments may be of help,even if not adequately evidence-based supported.A multidisciplinary approach for the management of dyspepsia in AIG is recommended,and further research is needed to develop and validate more effective therapies for dyspepsia.

Gastric cancer in 2022:Is there still a role for endoscopic ultrasound?

Gastric cancer(GC)represents the fourth leading cause of cancer death worldwide and many factors can influence its development(diet,geographic area,genetic,Helicobacter pylori or Epstein-Barr virus infections).High quality endoscopy represents the modality of choice for GC diagnosis.The correct morphologic classification during a high-resolution endoscopy is fundamental for oncologic diagnosis,staging and therapeutic decisions.Since its initial introduction in clinical practice the endoscopic ultrasound(EUS)has been considered a valuable tool for tumor(T-)and lymph nodes(N-)staging also in GC,in order to establish the best therapeutic strategy for the patient(e.g.,upfront surgery vs neoadjuvant treatments).EUS tools as elastography,Doppler and contrast administration can improve diagnosis mainly in case of malignant lymph node evaluation.EUS has a marginal role in disease staging but has a fundamental role in case of a pre-endoscopic resection management and in the new era of endoscopic mucosal resection or submucosal dissection as minimally invasive surgery.Diagnosis and locoregional staging of GC with EUS are a method of inarguable value for the assessment of gastric wall involvement and presence of infiltrated paragastric lymph nodes.EUS can also have a role in disease restaging in those patients who have undergone neoadjuvant treatment.EUS can also have a role in the advanced phases of the disease,in facilitating palliative,minimallyinvasive treatments,such as gastroenterostomy or biliary drainages.This review intends to discuss the modern role of EUS in GC topic.

Congenital Absence of Pericardium:The Largest Systematic Review in the Field on 247 Worldwide Cases(1977-Now)

Background:Congenital absence of pericardium(CAP),also known as pericardial agenesis,represents an uncommon cardiac abnormality and mostly incidental finding.It can be subdivided into complete and partial(left or right-sided)forms.Because of its infrequency,just case reports and a few case series have been released so far.This paper represents the largest systematic review in the field.Nine features(age at diagnosis,type,gender,clinical presentation,electrocardiography,imaging(ultrasounds,CT/MRI),concomitant cardiac defects,and outcome)were analysed.Methods:The electronic database PubMed was investigated from its establishment up to July 15th,2023.Just case reports and case series were included.Animal studies,papers that were not in English,Spanish,and Italian,and those manuscripts not reporting at least seven of the nine analysed features.were ruled out.The analysed data were reported mostly in terms of percentage.Results:One hundred eighty studies were included encompassing 247 patients.More than half of reviewed CAP cases were in males(63.2%).The mean age at diagnosis was 31.8±19.3 years;a range of 32 weeks of gestation-81 years).23.5%of the patients did not report any symptoms.The most common clinical presentations were chest pain(35.2%)and dyspnoea(29.2%).The most commonly seen ECG changes were right axis deviation(28.7%)and right bundle branch block(23.9%).CAP was suspected or diagnosed by echocardiography in 20.1%of cases.The diagnosis was made by CT and/or MRI in 61.9%of cases.CAP was left-sided in 71.2%,complete in 23.1%,and right-sided in 5.7%.A concomitant congenital heart defect was found in 22.7%,especially in the form of atrial septal defect(6.5%)and patency of ductus arteriosus(2.8%).The pericardial repair was required in 12.9% of the incomplete forms of the disease.Never did the complete form require surgical correction.The outcome appeared favourable in the vast majority of cases,with just 18 deaths(7.3%).Discussion:The main limitation of this systematic review is that it is based just on case reports and case series,due to the lack of large studies on CAP.However,it represents the largest analysis in the field.Due to the rarity of CAP establishing an International Registry is recommended.

Heart Rate Variability as an Indicator of Stress in Students’ Athletes

Introduction: The wellbeing of student’s athletes has a paramount importance, a prolonged period of cognitive and physical performance that characterizes the life of student’s athletes often leads to fatigue, and a psychobiological state that increases the risk of injury and accidents. The use of Heart rate variability (HRV) has become increasingly popular as a non-invasive methodology that provides an indirect insight into the autonomic nervous system. HRV can be utilized as a diagnostic tool in detection of autonomic nervous system impairment and sympatho-vagal imbalance. HRV technology is employed to monitor the internal response of athletes to workload and identify athletes’s psychophysical stress to predict and therefore prevent injuries. Objective: The objective of the investigation is to establish whether the use of Polar H10 sensor heart rate monitors worn by athletes in a sitting position (inclination 60 degrees) during periods characterized by stress can provide a valid and non-invasive method to assess the psychophysiological state during sports competition and school exams. Method and Statistics: In the study, the HRV of 12 basketball students athletes and 4 students non-athletes was analyzed as a control group. The autonomic nervous system activity was assessed based on heart variability parameters (HRV): SDNN, rMSSD, LF, HF, and LF/HF. The measurements were made after establishing the baseline at rest, during the training phase (CT), competition phase (CC) and during the acute phase of stressors due to school exams coinciding with the competitive season (CC + E). Results: Compared to the respective values prior to the stress of the competitions and exams, a significant decrease in HRV indices was found: SDNN (P Conclusions: The analysis and examination of the data on the sample of the student population also showed a statistically significant correlation between decreased cardiac variability and injuries or indisposition to physical exertion.

Peri-operative score for elderly patients with resectable hepatocellular carcinoma

BACKGROUND Liver resection is the mainstay for a curative treatment for patients with resectable hepatocellular carcinoma(HCC),also in elderly population.Despite this,the evaluation of patient condition,liver function and extent of disease remains a demanding process with the aim to reduce postoperative morbidity and mortality.AIM To identify new perioperative risk factors that could be associated with higher 90-and 180-d mortality in elderly patients eligible for liver resection for HCC considering traditional perioperative risk scores and to develop a risk score.METHODS A multicentric,retrospective study was performed by reviewing the medical records of patients aged 70 years or older who electively underwent liver resection for HCC;several independent variables correlated with death from all causes at 90 and 180 d were studied.The coefficients of Cox regression proportional-hazards model for sixmonth mortality were rounded to the nearest integer to assign risk factors'weights and derive the scoring algorithm.RESULTS Multivariate analysis found variables(American Society of Anesthesiology score,high rate of comorbidities,Mayo end stage liver disease score and size of biggest lesion)that had independent correlations with increased 90-and 180-d mortality.A clinical risk score was developed with survival profiles.CONCLUSION This score can aid in stratifying this population in order to assess who can benefit from surgical treatment in terms of postoperative mortality.

胰肾联合移植治疗1型糖尿病并尿毒症22例

对22例合并尿毒症的1型糖尿病患者实施胰肾联合移植术(SPKT),采用肠—肠内引流(ED)术式;术后给予他克莫司、环孢霉素、霉酚酸酯及皮质激素预防排斥反应,同时常规抗菌、抗真菌、抗病毒和抗凝治疗。22例手术均获成功,2例并发血管栓塞(1例药物治疗好转,1例再次手术切除移植物),3例出现排斥反应(抗排斥治疗好转),1例原发性移植胰腺无功能再次手术切除,2例消化道出血(1例药物治疗好转,1例手术止血),所有患者均存活。认为SPKT治疗糖尿病并尿毒症是可行的,但围手术期并发症发生率较高,防止并发症的发生是手术成功的技术关键。

Acute recurrent pancreatitis:Etiopathogenesis, diagnosis and treatment

Acute recurrent pancreatitis(ARP)refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion.Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland,however,an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up.The aetiology of ARP can be identified in the majority of patients.Most common causes include common bile duct stones or sludge and bile crystals;sphincter of oddi dysfunction;anatomical ductal variants interfering with pancreatic juice outflow;obstruction of the main pancreatic duct or pancreatico-biliary junction;genetic mutations;alcohol consumption.However,despite diagnostic technologies,the aetiology of ARP still remains unknown in up to 30%of cases:in these cases the term"idiopathic"is used.Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases,cholecystectomy,and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases.Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80%of patients.Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge.In uncertain cases toxinbotulin injection may help in identifying some sphincter of oddi dysfunction,but this treatment is not widely used.In the last twenty years,pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction,independently from the cause of obstruction,and has been widely used instead of more aggressive approaches.

A randomized double-blind trial on perioperative administration of probiotics in colorectal cancer patients

AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for cancer.Patients were allocated to receive either a placebo(group A,n=10),or a dose of 10 7 of a mixture of Bifidobacterium longum(BB536) and Lactobacillus johnsonii(La1)(group B,n=11),or the same mixture at a concentration of 10 9 (group C,n=10).Probiotics,or a placebo,were given orally 2 doses/d for 3 d before operation.The same treatment continued postoperatively from day two to day four. Stools were collected before treatment,during surgery (day 0)and 5 d after operation.During the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells(DCs)and lymphocyte subsets by surface antigen expression(flow cytometry).The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS:The three groups were balanced for baseline and surgical parameters.BB536 was never found at any time-points studied.At day 0,La1 was present in 6/10(60%)patients in either stools or by biopsy in group C,in 3/11(27.2%)in group B,and none in the placebo group(P=0.02,C vs A).There was a linear correlation between dose given and number of adher- ent La1(P=0.01).The rate of mucosal colonization by enterobacteriacae was 30%(3/10)in C,81.8%(9/11) in B and 70%(7/10)in A(P=0.03,C vs B).The Enterobacteriacae count in stools was 2.4(log10 scale) in C,4.6 in B,and 4.5 in A(P=0.07,C vs A and B). The same trend was observed for colonizing enterococ- ci.La1 was not found at day+5.We observed greater expression of CD3,CD4,CD8,and naive and memory lymphocyte subsets in group C than in group A with a dose response trend(C>B>A).Treatment didnot affect DC phenotype or activation,but after ex vivo stimulation with lipopolysaccharides,groups C and B had a lower proliferation rate compared to group A (P=0.04).Moreover,dendritic phenotypes CD83-123, CD83-HLADR,and CD83-11c(markers of activation) were significantly less expressed in patients colonized with La1(P=0.03 vs not colonized). CONCLUSION:La1,but not BB536,adheres to the colonic mucosa,and affects intestinal microbiota byreducing the concentration of pathogens and modulates local immunity.

High-definition colonoscopy with i-Scan:Better diagnosis for small polyps and flat adenomas

AIM:To investigate if high-definition (HD) colonoscope with i-Scan gave a higher detection rate of mucosal lesions vs standard white-light instruments. METHODS:Data were collected from the computerized database of the endoscopy unit of our tertiary referral center. We retrospectively analyzed 1101 consecutive colonoscopies that were performed over 1 year with standard white-light (n = 849) or HD+ with i-Scan (n = 252) instruments by four endoscopists, in an outpatient setting. Colonoscopy records included patients' main details and family history for colorectal cancer, indication for colonoscopy (screening, diagnostic or surveillance), type of instrument used (standard white-light or HD+ plus i-Scan), name of endoscopist and bowel preparation. Records for each procedure included whether the cecum was reached or not and the reason for failure, complications during or immediately after the procedure, and number, size, location and characteristics of the lesions. Polyps or protrudinglesions were defined as sessile or pedunculated, and nonprotruding lesions were defined according to Paris classification. For each lesion, histological diagnosis was recorded. RESULTS:Eight hundred and forty-nine colonoscopies were carried with the standard white-light video colonoscope and 252 with the HD+ plus i-Scan video colonoscope. The four endoscopists did 264, 300, 276 and 261 procedures, respectively; 21.6%, 24.0%, 21.7% and 24.1% of them with the HD+ plus i-Scan technique. There were no significant differences between the four endoscopists in either the number of procedures done or the proportions of each imaging technique used. Both techniques detected one or more mucosal lesions in 522/1101 procedures (47.4%). The overall number of lesions recognized was 1266; 645 in the right colon and 621 in the left. A significantly higher number of colonoscopies recognized lesions in the HD+ plus i-Scan mode (171/252 = 67.9%) than with the standard white-light technique (408/849 = 48.1%) (P < 0.0001). HD+ with i-Scan colonoscopies identified more lesions than standard white-light imaging (459/252 and 807/849, P < 0.0001), in the right or left colon (mean ± SD, 1.62 ± 1.36 vs 1.33 ± 0.73, P < 0.003 and 1.55 ± 0.98 vs 1.17 ± 0.93, P = 0.033), more lesions < 10 mm (P < 0.0001) or nonprotruding (P < 0.022), and flat polyps (P = 0.04). The cumulative mean number of lesions per procedure detected by the four endoscopists was significantly higher with HD+ with i-Scan than with standard white-light imaging (1.82 ± 2.89vs 0.95 ± 1.35,P < 0.0001). CONCLUSION:HD imaging with i-Scan during the withdrawal phase of colonoscopy significantly increased the detection of colonic mucosal lesions, particularly small and nonprotruding polyps.

国际糖尿病足工作组:糖尿病足溃疡减压指南——《国际糖尿病足工作组:糖尿病足防治国际指南(2019)》的一部分

1999年,国际糖尿病足工作组(IWGDF)根据循证医学证据发表了采用减压治疗促进糖尿病足溃疡愈合的预防和管理指南,这一版指南是在此基础上的更新。我们遵循GRADE方法学,采用患者-干预-比较-结果(PICO)模式设计临床问题和关键的重要结局,对医学科学文献进行系统评价分析后撰写了建议并阐述其理由。这些建议是基于系统评价、专家意见(尚无有效证据时)的基础上建立,并在患者依从性、可行性、实用性以及干预的成本等方面进行了利弊权衡。针对糖尿病患者前足或中足底的溃疡愈合,我们建议不可拆卸齐膝高减压装置作为减压治疗的首选。若出现禁忌或患者不耐受不可拆卸减压装置,则可拆卸齐膝高和齐踝高减压装置可作为二线或三线减压治疗方法。合适的鞋袜结合泡沫毡垫可被视为四线减压治疗选择。如果非外科手术减压失败,我们建议通过外科减压干预以促进跖骨头和足趾溃疡愈合。我们还增加了采用减压治疗促进合并感染、缺血的复杂足溃疡和足跟溃疡愈合的新的推荐意见。减压是促进糖尿病神经性足底溃疡愈合诸多干预措施中最重要的手段。遵循这些建议将帮助医务人员和团队,为那些具有感染、住院和截肢风险的糖尿病足溃疡患者提供更好的治疗。

Optical coherence tomography in detection of dysplasia and cancer of the gastrointestinal tract and bilio-pancreatic ductal system

Optical coherence tomography(OCT) is an optical imaging modality that performs high-resolution,cross-sectional,subsurface tomographic imaging of the microstructure of tissues.The physical principle of OCT is similar to that of B-mode ultrasound imaging,except that it uses infrared light waves rather than acoustic waves.The in vivo resolution is 10-25 times better(about 10 μm) than with high-frequency ultrasound imaging,but the depth of penetration is limited to 1-3 mm,depending upon tissue structure,depth of focus of the probe used,and pressure applied to the tissue surface.In the last decade,OCT technology has evolved from an experimental laboratory tool to a new diagnostic imaging modality with a wide spectrum of clinical applications in medical practice,including the gastrointestinal(GI) tract and pancreatic-biliary ductal system.OCT imaging from the GI tract can be done in humans by using narrow-diameter,catheter-based probes that can be inserted through the accessory channel of either a conventional front-view endoscope,for investigating the epithelial structure of the GI tract,or a side-view endoscope,inside a standard transparent ERCP catheter,for investigating the pancreatico-biliary ductal system.Esophagus and the esophago-gastric junction has been the most widely investigated organ so far;more recently,also duodenum,colon and pancreatico-biliary ductal system have been extensively investigated.OCT imaging of the gastro-intestinal wall structure is characterized by a multiple-layer architecture that permits an accurate evaluation of the mucosa,lamina propria,muscularis mucosae,andpart of the submucosa.The technique may be,therefore,used to identify pre-neoplastic conditions of the GI tract,such as Barrett's epithelium and dysplasia,and evaluate the depth of penetration of early-stage neoplastic lesions.OCT imaging of the pancreatic and biliary ductal system could improve the diagnostic accuracy for ductal epithelial changes and the differential diagnosis between neoplastic and non-neoplastic lesions.

Laparoscopic surgery for rectal cancer:The state of the art

At present time,there is evidence from randomized controlled studies of the success of laparoscopic resection for the treatment of colon cancer with reported smaller incisions,lower morbidity rate and earlier recovery compared to open surgery.Technical limitations and a steep learning curve have limited the wide application of miniinvasive surgery for rectal cancer.The present article discusses the current status of laparoscopic resection for rectal cancer.A review of the more recent retrospective,prospective and randomized controlled trial(RCT) data on laparoscopic resection of rectal cancer including the role of trans-anal endoscopic microsurgery and robotics was performed.A particular emphasis was dedicated to mid and low rectal cancers.Few prospective and RCT trials specif ically addressing laparoscopic rectal cancer resection are currently available in the literature.Improved short-term outcomes in term of lesser intraoperative blood loss,reduced analgesic requirements and a shorter hospital stay have been demonstrated.Concerns have recently been raised in the largest RCT trial of the oncological adequacy of laparoscopy in terms of increased rate of circumferential margin.This data however was not conf irmed by other prospective comparative studies.Moreover,a similar local recurrence rate has been reported in RCT and comparative series.Similar f indings of overall and disease free survival have been reported but the follow-up time period is too short in all these studies and the few RCT trials currently available do not draw any def initive conclusions.On the basis of available data in the literature,the mini-invasive approach to rectal cancer surgery has some short-term advantages and does not seem to confer any disadvantage in term of local recurrence.With respect to longterm survival,a definitive answer cannot be given at present time as the results of RCT trials focused on long-term survival currently ongoing are still to fully clarify this issue.

Long-term outcomes after laparoscopic colectomy

AIM:To evaluate long-term outcomes in a large series of patients who randomly received laparoscopic or open colorectal resection.METHODS:From February 2000 to December 2004,six hundred sixty-two patients with colorectal disease were randomly assigned to laparoscopic(LPS,n = 330) or open(n = 332) colorectal resection.All patients were analyzed on an intention-to-treat basis.Long-term follow-up was carried out every 6 mo by office visits.In 526 cancer patients five-year overall and disease-free survival were evaluated.Median oncologic follow-up was 96 mo.RESULTS:Eight(4.2%) LPS group patients needed conversion to open surgery.Overall long-term morbidity rate was 7.6%(25/330) in the LPS vs 11.1%(37/332) in the open group(P = 0.17).In cancer patients,fiveyear overall survival was 68.6% in the LPS group and 64.0% in the Open group(P = 0.27).Excluding stage Ⅳ patients,five-year local and distant recurrence rates were 32.5% in the LPS group and 36.8% in the Open group(P = 0.36).Further,no difference in recurrence rate was found when patients were stratified according to cancer stage.CONCLUSION:LPS colorectal resection was associated with a slightly lower incidence of long-term complications than open surgery.No difference between groups was found in overall and disease-free survival rates.

Sedation and analgesia in gastrointestinal endoscopy: What’s new?

Various types of sedation and analgesia technique have been used during gastrointestinal endoscopy procedures.The best methods for analgesia and sedation during gastrointestinal endoscopy are still debated.Providing an adequate regimen of sedation/analgesia might be considered an art,influencing several aspects of endoscopic procedures: the quality of the examination,the patient’s cooperation and the patient’s and physician’s satisfaction with the sedation.The properties of a model sedative agent for endoscopy would include rapid onset and offset of action,analgesic and anxiolytic effects,ease of titration to desired level of sedation,rapid recovery and an excellent safety prof ile.Therefore there is an impulse for development of new approaches to endoscopic sedation.This article provides an update on the methods of sedation today available and future directions in endoscopic sedation.

Apparent diffusion coefficient by diffusion-weighted magnetic resonance imaging as a sole biomarker for staging and prognosis of gastric cancer

Objective： To investigate the role of apparent diffusion coefficient （ADC） from diffusion-weighted magnetic resonance imaging （DW-MRI） when applied to the 7th TNM classification in the staging and prognosis of gastric cancer （GC）. Methods： Between October 2009 and May 2014, a total of 89 patients with non-metastatic, biopsy proven GC underwent 1.5T DW-MRI, and then treated with radical surgery. Tumor ADC was measured retrospectively and compared with final histology following the 7th TNM staging （local invasion, nodal involvement and according to the different groups -- stage Ⅰ, Ⅱ and Ⅲ）. Kaplan-Meier curves were also generated. The follow-up period is updated to May 2016. Results： Median follow-up period was 33 months and 45/89 （51%） deaths from GC were observed. ADC was significantly different both for local invasion and nodal involvement （P〈0.001）. Considering final histology as the reference standard, a preoperative ADC cut-offof 1.80×10-3 mm^2/s could distinguish between stages I and Ⅱ and an ADC value of ≤1.36-10-3 mm^2/s was associated with stage Ⅲ（P〈0.001）. Kaplan-Meier curves demonstrated that the survival rates for the three prognostic groups were significantly different according to final histology and ADC cut-offs （P〈0.001）. Conclusions： ADC is different according to local invasion, nodal involvement and the 7th TNM stage groups for GC, representing a potential, additional prognostic biomarker. The addition of DW-MRI could aid in the staging and risk stratification of GC.

Endoscopic ultrasonography for evaluating patients with recurrent pancreatitis

Acute recurrent pancreatitis (ARP) is still a complex diagnostic and therapeutic challenge in clinical practice. In up to 30% of cases of ARP, it is not possible to establish the etiology of the disease. In the other 70%, many factors play an etiological role in ARP: microlithiasis, sphincter of Oddi dysfunction (SOD), pancreas divisum, hereditary pancreatitis, cystic fibrosis, a choledochocele, annular pancreas, an anomalous pancreatobiliary junction, pancreatic tumors or chronic pancreatitis are diagnosed. EUS should be useful in ARP as it is sensitive for diagnosing bile duct stones, gallbladder sludge, pancreatic lesions, ductal abnormalities and chronic pancreatitis. Endoscopic ultrasound (EUS) appears to be diagnostic in the majority of patients with previously unexplained pancreatitis, and offers an alternative to endoscopic retrograde cholangiopancreatography (ERCP) as the initial diagnostic test in patients with ARP.

Oropharyngeal acid reflux and motility abnormalities of the proximal esophagus

AIM To investigate the relationship between pathological oropharyngeal(OP) acid exposure and esophageal motility in patients with extra-esophageal syndromes.METHODS In this prospective study we enrolled consecutive outpatients with extra-esophageal symptoms suspected to be related to gastroesophageal reflux disease(GERD). We enrolled only patients with a reflux symptom index(RSI) score-higher than 13 and with previous lung, allergy and ear, nose and throat evaluations excluding other specific diagnoses. All patients underwent 24-h OP pH-metry with the Dx probe and esophageal highresolution manometry(HRM). Patients were divided into two groups on the basis of a normal or pathological p H-metric finding(Ryan Score) and all manometric characteristics of the two groups were compared.RESULTS We examined 135 patients with chronic extra-esophageal syndromes. Fifty-one were considered eligible for the study. Of these, 42 decided to participate in the protocol. Patients were divided into two groups on the basis of normal or pathological OP acid exposure. All the HRM parameters were compared for the two groups. Significant differences were found in the median upper esophageal sphincter resting pressure(median 71 mmH g vs 126 mmH g, P = 0.004) and the median proximal contractile integral(median 215.5 cm·mmH g·s vs 313.5 cm·mmH g·s, P = 0.039), both being lower in the group with pathological OP acid exposure, and the number of contractions with small or large breaks, which were more frequent in the same group. This group also had a larger number of peristaltic contractions with breaks in the 20 mm Hg isobaric contour(38.7% vs 15.38%, P < 0.0001).CONCLUSION In patients with suspected GERD-related extraesophageal syndromes pathological OP acid exposure was associated with weaker proximal esophageal motility.