Impact of formal training in endoscopic submucosal dissection for early gastrointestinal cancer: A systematic review and a meta-analysis

AIM: To summarize the clinical impact of a formal training for the effectiveness and safety of endoscopic submucosal dissection for gastrointestinal cancer.METHODS: We searched databases including PubM ed, EMBASE and the Cochrane Library and Science citation Index updated to August 2014 to include eligible articles. In the Meta-analysis, the main outcome measurements were en bloc resection rate, local recurrence rate(R0) and the incidence of procedure-related complications(perforation, bleeding). RESULTS: En bloc resection was high for both, dissecting stomach tumors with an overall percentage of 93.2%(95%CI: 90.5-95.8) and dissecting colorectal tumors with an overall percentage of 89.4%(95%CI: 85.1-93.7). Although the number of studies reporting R0 resection(the dissected specimen was revealed free of tumor in both vertical and lateral margins) was small, the overall estimates for R0 resection were 81.4%(95%CI: 72-90.8) for stomach and 85.9%(95%CI: 77.5-95.5) for colorectal tumors, respectively. The analysis showed that the percentage of immediate perforation and bleeding were very low; 4.96(95%CI: 3.6-6.3) and 1.4%(95%CI: 0.8-1.9) for colorectal tumors and 3.1%(95%CI: 2.0-4.1) and 4.8%(95%CI: 2.8-6.7) for stomach tumors, respectively. CONCLUSION: In order to obtain the same rate of success of the analyzed studies it is a necessity to create training centers in the western countries during the "several years" of gastroenterology residence first only to teach EGC diagnose and second only to train endoscopic submucosal dissection.

The opening of maitotoxin-sensitive calcium channels induces the acrosome reaction in human spermatozoa： differences from the zona pellucida

The acrosome reaction （AR）, an absolute requirement for spermatozoa and egg fusion, requires the influx of Ca2＋ into the spermatozoa through voltage-dependent Ca2＋ channels and store-operated channels. Maitotoxin （MTx）, a Ca2＋-mobilizing agent, has been shown to be a potent inducer of the mouse sperm AR, with a pharmacology similar to that of the zona pellucida （ZP）, possibly suggesting a common pathway for both inducers. Using recombinant human ZP3 （rhZP3）, mouse ZP and two MTx channel blockers （U73122 and U73343）, we investigated and compared the MTx- and ZP-induced ARs in human and mouse spermatozoa. Herein, we report that MTx induced AR and elevated intracellular Ca2＋ （[Ca2＋]~） in human spermatozoa, both of which were blocked by U73122 and U73343. These two compounds also inhibited the MTx-induced AR in mouse spermatozoa. In disagreement with our previous proposal, the AR triggered by rhZP3 or mouse ZP was not blocked by U73343, indicating that in human and mouse spermatozoa, the AR induction by the physiological ligands or by MTx occurred through distinct pathways. U73122, but not U73343 （inactive analogue）, can block phospholipase C （PLC）. Another PLC inhibitor, edelfosine, also blocked the rhZP3- and ZP-induced ARs. These findings confirmed the participation of a PLC-dependent signalling pathway in human and mouse zona protein-induced AR. Notably, edelfosine also inhibited the MTx-induced mouse sperm AR but not that of the human, suggesting that toxin-induced AR is PLC-dependent in mice and PLC-independent in humans.

Pancreatic cancer,autoimmune or chronic pancreatitis,beyond tissue diagnosis:Collateral imaging and clinical characteristics may differentiate them

Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal malignancies and is developing into the 2nd leading cause of cancer-related death.Often,the clinical and radiological presentation of PDAC may be mirrored by other inflammatory pancreatic masses,such as autoimmune pancreatitis(AIP)and massforming chronic pancreatitis(MFCP),making its diagnosis challenging.Differentiating AIP and MFCP from PDAC is vital due to significant therapeutic and prognostic implications.Current diagnostic criteria and tools allow the precise differentiation of benign from malignant masses;however,the diagnostic accuracy is imperfect.Major pancreatic resections have been performed in AIP cases under initial suspicion of PDAC after a diagnostic approach failed to provide an accurate diagnosis.It is not unusual that after a thorough diagnostic evaluation,the clinician is confronted with a pancreatic mass with uncertain diagnosis.In those cases,a re-evaluation must be entertained,preferably by an experienced multispecialty team including radiologists,pathologists,gastroenterologists,and surgeons,looking for disease-specific clinical,imaging,and histological hallmarks or collateral evidence that could favor a specific diagnosis.Our aim is to describe current diagnostic limitations that hinder our ability to reach an accurate diagnosis among AIP,PDAC,and MFCP and to highlight those disease-specific clinical,radiological,serological,and histological characteristics that could support the presence of any of these three disorders when facing a pancreatic mass with uncertain diagnosis after an initial diagnostic approach has been unsuccessful.

Endoscopic submucosal dissection in dogs in a World Gastroenterology Organisation training center

AIM: To evaluate if canine models are appropriate for teaching endoscopy fellows the techniques of endoscopic submucosal dissection (ESD). METHODS: ESD was performed in 10 canine models under general anesthesia, on artificial lesions of the esophagus or stomach marked with coagulation points. After ESD, each canine model was euthanized and surgical resection of the esophagus or stomach was carried out according to "The Principles of Humane Experimental Technique, Russel and Burch". The ESD specimens were fixed with needles on cork submerged in a formol solution with the esophagus or stomach, and delivered to the pathology department to be analyzed. RESULTS: ESD was completed without complications using the Hook-knife in five esophageal areas, with a procedural duration of 124 ± 19 min, a length of 27.4 ± 2.6 mm and a width of 21 ± 2.4 mm. ESD was also completed without complications using the IT-knife2 in five gastric areas, with a procedural duration of 92.6 ± 19 min, a length of 32 ± 2.5 mm and a width of 18 ± 3.7 mm. CONCLUSION: ESD is feasible in the normal esopha- gus and stomach of canine models, which are appropriate for teaching this technique.

Gene transcription profiting of astheno-and normo-zoospermic sperm subpopulations

Spermatozoa contain a repertoire of RNAs considered to be potential functional fertility biomarkers.In this study,the gene expression of human sperm subpopulations with high(F1)and low(F2)motility from healthy normozoospermic(N)and asthenozoospermic(A)individuals was evaluated using RNA microarray followed by functional genomic analysis of differentially expressed genes.Results from A-F1 versus N-F1,A-F2 versus N-F2,N-F1 versus N-F2,and A-F1 versus A-F2 comparisons showed a considerably larger set of downregulated genes in tests versus controls.Gene ontology(GO)analysis of A-F1 versus N-F1 identified 507 overrepresented biological processes(BPs),several of which are associated with sperm physiology.In addition,gene set enrichment analysis of the same contrast showed 110 BPs,36 cellular comp on ents,and 31 molecular functions,several of which are involved in sperm motility.A leadi ng・edge analysis of selected GO terms resulted in several down regulated genes encoding to dyn eins and kin esins,both related to sperm physiology.Furthermore,the predicted activation state of asthenozoospermia was increased,while fertility,cell movement of sperm,and gametogenesis were decreased.Interestingly,several downregulated genes characteristic of the canonical pathway protein ubiquitination were involved in asthenozoospermia activation.Conversely,GO analysis of A-F2 versus N-F2 did not identify overrepresented BPs,although the gene set enrichment analysis detected six enriched BPs,one cellular component,and two molecular functions.Overall,the results show differences in gene transcription between sperm subpopulations from asthenozoospermic and normozoospermic semen samples and allowed the identification of gene sets relevant to sperm physiology and reproduction.

Steroid-responsive pancreatitides

Autoimmune pancreatitis has received considerable attention,especially due to the marked effect of corticosteroid therapy on its clinical course.Knowledge,especially regarding type 1 autoimmune pancreatitis,has significantly increased over the last decades,and despite significant differences in pathophysiology and outcomes,both type 1 and 2 autoimmune pancreatitis are still considered different types of the same disease.Some have proposed a different nomenclature reflecting these differences.Although the term steroid-responsive pancreatitides may be interpreted as synonymous to type 1 and 2 autoimmune pancreatitis,these are not the only pancreatic conditions that show a response to steroid therapy.Acute pancreatitis caused by vasculitis and connective tissue diseases and acute pancreatitis secondary to checkpoint inhibitors or programmed cell death receptor antibody-mediated blockage cancer therapy may also benefit from steroid treatment.This review presents current concepts on these disorders,aiming to increase awareness,analyze similarities and differences,and propose a new nomenclature that reflects their specific particularities,clustering them under the term"steroid-responsive pancreatitides".