Endoscopic submucosal dissection for removal of superficial gastrointestinal neoplasms: A technical review

Endoscopic submucosal dissection (ESD) is now the most common endoscopic treatment in Japan for intramucosal gastrointestinal neoplasms (non-metastatic). ESD is an invasive endoscopic surgical procedure, requiring extensive knowledge, skill, and specialized equipment. ESD starts with evaluation of the lesion, as accurate assessment of the depth and margin of the lesion is essential. The devices and strategies used in ESD vary, depending on the nature of the lesion. Prior to the procedure, the operator must be knowledgeable about the treatment strategy(ies), the device(s) to use, the electrocautery machine settings, the substances to inject, and other aspects. In addition, the operator must be able to manage complications, should they arise, including immediate recognition of the complication(s) and its treatment. Finally, in case the ESD treatment is not successful, the operator should be prepared to apply alternative treatments. Thus, adequate knowledge and training are essential to successfully perform ESD.

Prognostic factors associated with mortality in patients with gastric fundal variceal bleeding

AIM To determine the prognostic factors associated with mortality in patients with gastric fundal variceal (GFV) bleeding.METHODS In total, 42 patients were endoscopically diagnosed with GFV bleeding from January 2000 to March 2014. We retrospectively reviewed the patients' medical records and assessed their history, etiology of liver cirrhosis, disease conditions, treatment options for GFV bleeding, medications administered before and after onset of GFV bleeding, blood test results(hemoglobin, albumin, and bilirubin concentrations), and imaging results(including computed tomography and abdominal ultrasonography). We also assessed the prognostic factors associated with short-term mortality(up to 90 d) and long-term mortality in all patients.RESULTS Multivariate analysis showed that prophylactic administration of antibiotics was an independent prognostic factor associated with decreases in short-term mortality (OR = 0.08, 95%CI: 0.01-0.52) and longterm mortality (OR = 0.27, 95%CI: 0.08-0.91) in patients with GFV bleeding. In contrast, concurrent hepatocellular carcinoma (HCC) and regular use of proton pump inhibitors (PPI) were independent prognostic factors associated with increases in shortterm mortality(HCC: OR = 15.4, 95%CI: 2.08-114.75; PPI: OR = 12.76, 95%CI: 2.13-76.52) and long-term mortality (HCC: OR = 7.89, 95%CI: 1.98-31.58; PPI: OR = 10.91, 95%CI: 2.86-41.65) in patients with GFV bleeding. The long-term overall survival rate was significantly lower in patients who regularly used PPI than in those who did not use PPI(P = 0.0074).CONCLUSION Administration of antibiotics is associated with decreased short- and long-term mortality, while concurrent HCC and regular PPI administration are associated with increased short- and long-term mortality.

Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome

The pathogenesis of irritable bowel syndrome (IBS) is considered to be multifactorial and includes psychosocial factors, visceral hypersensitivity, infection, microbiota and immune activation. It is becoming increasingly clear that low-grade inflammation is present in IBS patients and a number of biomarkers have emerged. This review describes the evidence for low-grade inflammation in IBS and explores its mechanism with particular focus on gastrointestinal motor dysfunction. Understanding of the immunological basis of the altered gastrointestinal motor function in IBS may lead to new therapeutic stra- tegies for IBS.

Clinical outcomes of Clutch Cutter endoscopic submucosal dissection for older patients with early gastric cancer

AIM To evaluate the clinical outcome of endoscopic submucosal dissection using the Clutch Cutter(ESDCC) in older patients. METHODS We reviewed 232 consecutive patients with early gastric cancer who underwent ESDCC between June 2010 and February 2014 at Aso Iizuka Hospital. We divided patients into two groups according to age: Older patients(> 80 years, n = 64) and non-older patients(≤ 80 years, n = 168). We retrospectively compared the prevalence rates of pre-existing comorbidities, anticoagulant therapy, en bloc resection, mean duration of hospitalization, incidence of ESDCC-related complications, change in performance status(PS) before and after ESDCC, and financial cost of admission. RESULTS The older group comprised 64 patients with a mean age of 84.1 years, and the non-older group comprised 168 patients with a mean age of 69.5 years. Older patients had significantly more pre-existing comorbidities than did non-older patients, specifically heart disease(P < 0.05). The en bloc resection rate in non-older patients was significantly higher than that in older patients(100% vs 95.3%, P = 0.02). There were no significant differences between the older and non-older groups in the incidence of ESDCC-related complications(i.e., postoperative bleeding and perforation) and the post-ESDCC change in PS. There were also no significant differences between the older and non-older groups in the mean duration of hospitalization(11.4 and 10.7 d, respectively) and financial cost of admission(657040 JPY and 574890 JPY, respectively).CONCLUSION ESDCC has a good clinical outcome in older patients.

Cytokine-induced alterations of gastrointestinal motility in gastrointestinal disorders

Inflammation and immune activation in the gut are usually accompanied by alteration of gastrointestinal(GI) motility.In infection,changes in motor function have been linked to host defense by enhancing the expulsion of the infectious agents.In this review,we describe the evidence for inflammation and immune activation in GI infection,inflammatory bowel disease,ileus,achalasia,eosinophilic esophagitis,microscopic colitis,celiac disease,pseudo-obstruction and functional GI disorders. We also describe the possible mechanisms by which inflammation and immune activation in the gut affect GI motility.GI motility disorder is a broad spectrum disturbance of GI physiology.Although several systems including central nerves,enteric nerves,interstitial cells of Cajal and smooth muscles contribute to a coordinated regulation of GI motility,smooth muscle probably plays the most important role.Thus,we focus on the relationship between activation of cytokines induced by adaptive immune response and alteration of GI smooth muscle contractility.Accumulated evidence has shownthat Th1 and Th2 cytokines cause hypocontractility and hypercontractility of inflamed intestinal smooth muscle. Th1 cytokines downregulate CPI-17 and L-type Ca 2+ channels and upregulate regulators of G protein signaling 4,which contributes to hypocontractility of inflamed intestinal smooth muscle.Conversely,Th2 cytokines cause hypercontractilty via signal transducer and activator of transcription 6 or mitogen-activated protein kinase signaling pathways.Th1 and Th2 cytokines have opposing effects on intestinal smooth muscle contraction via 5-hydroxytryptamine signaling.Understanding the immunological basis of altered GI motor function could lead to new therapeutic strategies for GI functional and inflammatory disorders.

Mucosal-incision assisted biopsy for suspected gastric gastrointestinal stromal tumors

To evaluate the diagnostic yield of the procedure, mucosal-incision assisted biopsy (MIAB), for the histological diagnosis of gastric gastrointestinal stromal tumor (GIST), we performed a retrospective review of the 27 patients with suspected gastric GIST who underwent MIAB in our hospitals. Tissue samples obtained by MIAB were sufficient to make a histological diagnosis (diagnostic MIAB) in 23 out of the 27 patients, where the lesions had intraluminal growth patterns. Alternatively, the samples were insufficient (non-diagnosticMIAB) in remaining 4 patients, three of whom had gastric submucosal tumor with extraluminal growth patterns. Although endoscopic ultrasound and fine needle aspiration is the gold standard for obtaining tissue specimens for histological and cytological analysis of suspected gastric GISTs, MIAB can be used as an alternative method for obtaining biopsy specimens of lesions with an intraluminal growth pattern.

Endoscopic mucosal resection vs endoscopic submucosal dissection for superficial non-ampullary duodenal tumors

BACKGROUND The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors(SNADETs)is controversial.AIM To compare the efficacy and safety of endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)for SNADETs.METHODS We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs,which included eight hospitals in Fukuoka,Japan,between April 2001 and October 2017.A total of 142 patients with SNADETs treated with EMR or ESD were analyzed.Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups.We analyzed the treatment outcomes,including the rates of en bloc/complete resection,procedure time,adverse event rate,hospital stay,and local or metastatic recurrence.RESULTS Twenty-eight pairs of patients were created.The characteristics of patients between the two groups were similar after matching.The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group[median procedure time(interquartile range):6(3-10.75)min vs 87.5(68.5-136.5)min,P<0.001,hospital stay:8(6-10.75)d vs 11(8.25-14.75)d,P=0.006].Other outcomes were not significantly different between the two groups(en bloc resection rate:82.1%vs 92.9%,P=0.42;complete resection rate:71.4%vs 89.3%,P=0.18;and adverse event rate:3.6%vs 17.9%,P=0.19,local recurrence rate:3.6%vs 0%,P=1;metastatic recurrence rate:0%in both).Only one patient in the ESD group underwent emergency surgery owing to intraoperative perforation.CONCLUSION EMR has significantly shorter procedure time and hospital stay than ESD,and provides acceptable curability and safety compared to ESD.Accordingly,EMR for SNADETs is associated with lower medical costs.

Improved techniques for double-balloon-enteroscopy-assisted endoscopic retrograde cholangiopancreatography

AIM: To investigate the clinical outcome of double balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (DB-ERCP) in patients with altered gastrointestinal anatomy. METHODS: Between September 2006 and April 2011, 47 procedures of DB-ERCP were performed in 28 patients with a Roux-en-Y total gastrectomy (n = 11), Billroth Ⅱ gastrectomy (n = 15), or Roux-en-Y anastomosis with hepaticojejunostomy (n = 2). DB-ERCP was performed using a short-type DBE combined with several technical innovations such as using an endoscope attachment, marking by submucosal tattooing,selectively applying contrast medium, and CO2 insufflations. RESULTS: The papilla of Vater or hepaticojejunostomy site was reached in its entirety with a 96% success rate (45/47 procedures). There were no significant differences in the success rate of reaching the blind end with a DBE among Roux-en-Y total gastrectomy (96%), Billroth Ⅱ reconstruction (94%), or pancreatoduodenectomy (100%), respectively (P = 0.91). The total successful rate of cannulation and contrast enhancement of the target bile duct in patients whom the blind end was reached with a DBE was 40/45 procedures (89%). Again, there were no significant differences in the success rate of cannulation and contrast enhancement of the target bile duct with a DBE among Roux-en-Y total gastrectomy (88 %), Billroth Ⅱ reconstruction (89%), or pancreatoduodenectomy (100%), respectively (P = 0.67). Treatment was achieved in all 40 procedures (100%) in patients whom the contrast enhancement of the bile duct was successful. Common endoscopic treatments were endoscopic biliary drainage (24 procedures) and extraction of stones (14 procedures). Biliary drainage was done by placement of plastic stents. Stones extraction was done by lithotomy with the mechanical lithotripter followed by extraction with a basket or by the balloon pull-through method. Endoscopic sphincterotomy was performed in 14 procedures with a needle precutting knife using a guidewire. The mean total duration of the procedure was 93.6 ± 6.8 min and the mean time required to reach the papilla was 30.5 ± 3.7 min. The mean time required to reach the papilla tended to be shorter in Billroth Ⅱ reconstruction (20.9 ± 5.8 min) than that in Roux-en-Y total gastrectomy (37.1 ± 4.9 min) but there was no significant difference (P = 0.09). A major complication occurred in one patient (3.5%); perforation of the long limb in a patient with Billroth Ⅱ anastomosis.CONCLUSION: Short-type DBE combined with several technical innovations enabled us to perform ERCP in most patients with altered gastrointestinal anatomy.

Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms

AIM To compare the outcomes of endoscopic submucosal dissection(ESD) for gastric neoplasms using Clutch Cutter(ESD-C) or other knives(ESD-O).METHODS This was a single-center retrospective study. Gastric neoplasms treated by ESD between April 2016 and October 2017 at Kitakyushu Municipal Medical Center were reviewed. Multivariate analyses and propensity score matching were used to reduce biases. Covariates included factors that might affect outcomes of ESD, including age, sex, underlying disease, anti-thrombotic drugs use, tumor location, tumor position, tumor size, tumor depth, tumor morphology, tumor histology, ulcer(scar), and operator skill. The treatment outcomes were compared among two groups. The primary outcome was ESD procedure time. Secondary outcomes were en bloc, complete, and curative resection rates, and adverse events rates including perforation and delayed bleeding.RESULTS A total of 155 patients were included in this study; 44 pairs were created by propensity score matching. Background characteristics were quite similar among two groups after matching. Procedure time was significantly shorter for ESD-C(median; 49 min) than for ESD-O(median; 88.5 min)(P < 0.01). However, there was no significant difference in treatment outcomes between ESD-C and ESD-O including en bloc resection rate(100% in both groups), complete resection rate(100% in both groups), curative resection rate(86.4% vs 88.6%, P = 0.730), delayed bleeding(2.3% vs 6.8%, P = 0.62) and perforation(0% in both groups).CONCLUSION ESD-C achieved shorter procedure time without an increase in complication risk. Therefore, ESD-C could become an effective ESD option for gastric neoplasms.

Assistant skill in gastric endoscopic submucosal dissection using a clutch cutter

BACKGROUND A clutch cutter is a scissor-type knife used in endoscopic submucosal dissection(ESD)for gastrointestinal tract tumors.The assistant during the ESD using a clutch cutter(ESD-C)needs to rotate the device and grasp the target tissue appropriately;therefore,the assistant’s skill may affect the technical outcomes of ESD-C.AIM To determine how assistant skill level affected the technical outcomes of gastric ESD-C using an ex vivo porcine training model.METHODS In this pilot study,mock lesions of 15-30 mm in diameter were created in the middle or lower third of the porcine stomach.A total of 32 ESD-C procedures were performed by 16 trainees.Each trainee operator performed two ESD-C procedures;one ESD-C was assisted by an expert(ESD-C-E),and the other was assisted by a non-expert(ESD-C-NE).The total procedure time of the ESD was set as the primary outcome,and en bloc resection rate,complete procedure rate,perforation rate,and each procedure time/speed for mucosal incision or submucosal dissection were set as the secondary outcomes.In addition,we investigated factors associated with the difficulty of ESD including incompletion of ESD procedure,a long procedure time(≥20 min)or intraoperative perforation.RESULTS The median total procedure time of the ESD-C-E was significantly shorter than that of the ESD-C-NE(12.9 min vs 21.9 min,P=0.001).The en bloc resection rate was 100%in both groups.Complete resection rates of the ESD-C-E and ESD-C-NE groups were 100%and 93.8%,respectively.No intraoperative perforation was observed in both groups.In the multivariate analysis,assistant skill was significantly associated with the difficulty of ESD,with the highest odds ratio of 16.5.CONCLUSION Assistance by an expert is an important factor when trainees perform ESD-C procedures.

MAPKs represent novel therapeutic targets for gastrointestinal motility disorders

The number of patients suffering from symptoms associated with gastrointestinal(GI) motility disorders is on the rise. GI motility disorders are accompanied by alteration of gastrointestinal smooth muscle functions. Currently available drugs,which can directly affect gastrointestinal smooth muscle and restore altered smooth muscle contractility to normal,are not satisfactory for treating patients with GI motility disorders. We have recently shown that ERK1/2 and p38MAPK signaling pathways play an important role in the contractile response not only of normal intestinal smooth muscle but also of inflamed intestinal smooth muscle. Here we discuss the possibility that ERK1/2 and p38MAPK signaling pathways represent ideal targets for generation of novel therapeutics for patients with GI motility disorders.

Efficacy of hybrid endoscopic submucosal dissection with SOUTEN in gastric lesions:An ex vivo porcine model basic study

BACKGROUND Hybrid endoscopic submucosal dissection(ESD)that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner,has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD.Although the superiority of hybrid ESD with SOUTEN,a single multifunctional device,over conventional ESD has been indicated,the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group,but not to the conventional ESD group,due to ethical issue in clinical practice.AIM To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an ex vivo porcine model basic study.METHODS Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University,performing 32 procedures each for hybrid ESD and conventional ESD.Mock lesions(10-15 mm,diameter)were created in the porcine stomach.The primary outcome was total procedure time and secondary outcomes were en bloc or complete resection,perforation,procedure time/speed for both,mucosal incision,and submucosal dissection.Factors associated with difficulty in ESD including longer procedure time,incomplete resection,and perforation,were also investigated.Categorical and continuous data were analyzed using the chi-square test or Fisher’s exact test and the Mann-Whitney U test,respectively.RESULTS The median total procedure time of hybrid ESD was significantly shorter than that of conventional ESD(median:8.3 min vs 16.2 min,P<0.001).Time,speed,and the amount of hyaluronic acid during submucosal dissection were more favorable in hybrid ESD than conventional ESD(time,5.2 min vs 10.4 min,P<0.001;speed,43.7 mm^(2)/min vs 23.8 mm^(2)/min,P<0.00;injection volume,1.5 mL vs 3.0 mL,P<0.001),although no significant differences in those factors were observed between both groups during mucosal incision.There was also no significant difference between both groups in the en bloc/complete resection rate and perforation rate(complete resection,93.8%vs 87.5%,P=0.67;perforation,0% vs 3.1%,P=1).Selection of conventional ESD as the treatment method was significantly associated with difficulties during ESD(odds ratio=10.2;highest among factors).CONCLUSION Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions.It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive.

Endoscopic submucosal dissection of gastric adenomas using the clutch cutter

To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) using the clutch cutter (CC) (ESD-CC) for gastric adenoma (GA). METHODSFrom June 2007 to August 2015, 122 consecutive patients with histological diagnoses of GA from specimens resected by ESD-CC were enrolled in this prospective study. The CC was used for all ESD steps (marking, mucosal incision, submucosal dissection, and hemostatic treatment), and its therapeutic efficacy and safety were assessed. RESULTSBoth the en-bloc resection rate and the R0 resection rate were 100% (122/122). The mean surgical time was 77.4 min, but the time varied significantly according to tumor size and location. No patients suffered perforation. Post-ESD-CC bleeding occurred in six cases (4.9%) that were successfully resolved by endoscopic hemostatic treatment. CONCLUSIONESD-CC is a technically efficient, safe, and easy method for resecting GA.