Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers

AIM:To prospectively compare the healing rates of endoscopic submucosal dissection(ESD)-induced ulcers treated with either a proton-pump inhibitor(PPI)or rebamipide.METHODS:We examined 90 patients with early gastric cancer who had undergone ESD.All patients were administered an intravenous infusion of the PPI lansoprazole(20 mg)every 12 h for 2 d,followed by oral administration of lansoprazole(30 mg/d,5 d).After7-d treatment,the patients were randomly assigned to 2 groups and received either lansoprazole(30 mg/d orally,n=45;PPI group)or rebamipide(300 mg orally,three times a day;n=45;rebamipide group).At 4and 8 wk after ESD,the ulcer outcomes in the 2 groups were compared.RESULTS:No significant differences were noted in patient age,underlying disease,tumor location,Helicobacter pylori infection rate,or ESD-induced ulcersize between the 2 groups.At both 4 and 8 wk,the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients(4 wk:PPI,27.2%;rebamipide,33.3%;P=0.5341;8 wk:PPI,90.9%;rebamipide,93.3%;P=0.6710).At 8 wk,the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group(13.6%)than in the rebamipide-treated group(0.0%;P=0.0103).Ulcer-related symptoms were similar in the2 treatment groups at 8 wk.The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide.No ulcer bleeding or complications due to the drugs were observed in either treatment group.CONCLUSION:The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment;however,rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.

Removal of diminutive colorectal polyps: A prospective randomized clinical trial between cold snare polypectomy and hot forceps biopsy

AIMTo compare the efficacy and safety of cold snare polypectomy (CSP) and hot forceps biopsy (HFB) for diminutive colorectal polyps.METHODSThis prospective, randomized single-center clinical trial included consecutive patients ≥ 20 years of age with diminutive colorectal polyps 3-5 mm from December 2014 to October 2015. The primary outcome measures were en-bloc resection (endoscopic evaluation) and complete resection rates (pathological evaluation). The secondary outcome measures were the immediate bleeding or immediate perforation rate after polypectomy, delayed bleeding or delayed perforation rate after polypectomy, use of clipping for bleeding or perforation, and polyp retrieval rate. Prophylactic clipping after polyp removal wasn’t routinely performed.RESULTSTwo hundred eight patients were randomized into the CSP (102), HFB (106) and 283 polyps were evaluated (CSP: 148, HFB: 135). The en-bloc resection rate was significantly higher with CSP than with HFB [99.3% (147/148) vs 80.0% (108/135), P < 0.0001]. The complete resection rate was significantly higher with CSP than with HFB [80.4% (119/148) vs 47.4% (64/135), P < 0.0001]. The immediate bleeding rate was similar between the groups [8.6% (13/148) vs 8.1% (11/135), P = 1.000], and endoscopic hemostasis with hemoclips was successful in all cases. No cases of perforation or delayed bleeding occurred. The rate of severe tissue injury to the pathological specimen was higher HFB than CSP [52.6% (71/135) vs 1.3% (2/148), P < 0.0001]. Polyp retrieval failure was encountered CSP (7), HFB (2).CONCLUSIONCSP is more effective than HFB for resecting diminutive polyps. Further long-term follow-up study is required.

Endoscopic ultrasound-guided gallbladder drainage for acute cholecystitis: Long-term outcomes after removal of a self-expandable metal stent

AIM To assess the long-term outcomes of this procedure after removal of self-expandable metal stent(SEMS). The efficacy and safety of endoscopic ultrasoundguided gallbladder drainage(EUS-GBD) with SEMS were also assessed.METHODS Between January 2010 and April 2015, 12 patients with acute calculous cholecystitis, who were deemed unsuitable for cholecystectomy, underwent EUSGBD with a SEMS. EUS-GBD was performed under the guidance of EUS and fluoroscopy, by puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a SEMS. TheSEMS was removed and/or replaced with a 7-Fr plastic pigtail stent after cholecystitis improved. The technical and clinical success rates, adverse event rate, and recurrence rate were all measured.RESULTS The rates of technical success, clinical success, and adverse events were 100%, 100%, and 0%, respectively. After cholecystitis improved, the SEMS was removed without replacement in eight patients, whereas it was replaced with a 7-Fr pigtail stent in four patients. Recurrence was seen in one patient(8.3%) who did not receive a replacement pigtail stent. The median follow-up period after EUS-GBD was 304 d(78-1492).CONCLUSION EUS-GBD with a SEMS is a possible alternative treatment for acute cholecystitis. Long-term outcomes after removal of the SEMS were excellent. Removal of the SEMS at 4-wk after SEMS placement and improvement of symptoms might avoid migration of the stent and recurrence of cholecystitis due to food impaction.

Risk factors for local recurrence and appropriate surveillance interval after endoscopic resection

BACKGROUND Risk factors for local recurrence after polypectomy, endoscopic mucosal resection(EMR), and endoscopic submucosal dissection(ESD) have not been identified.Additionally, the appropriate interval for endoscopic surveillance of colorectal tumors at high-risk of local recurrence has not been established.AIM To clarify the clinicopathological characteristics of recurrent lesions after endoscopic colorectal tumor resection and determine the appropriate interval.METHODS Three hundred and sixty patients(1412 colorectal tumors) who underwent polypectomy, EMR, or ESD and received endoscopic surveillance subsequently for more than one year to detect local recurrence were enrolled in this study. The clinicopathological factors associated with local recurrence were determined via univariate and multivariate analyses.RESULTS Local recurrence was observed in 31 of 360(8.6%) patients [31 of 1412(2.2%)lesions] after colorectal tumor resection. Piecemeal resection, tumor size of more than 2 cm, and the presence of villous components were associated with colorectal tumor recurrence after endoscopic resection. Of these three factors, the piecemeal resection procedure was identified as an independent risk factor for recurrence. Colorectal tumors resected into more than five pieces were associated with a high risk of recurrence since the average period from resection torecurrence in these cases was approximately 3 mo. The period to recurrence in cases resected into more than 5 pieces was much shorter than that in those resected into less than 4 pieces(3.8 ± 1.9 mo vs 7.9 ± 5.0 mo, P < 0.05).CONCLUSION Local recurrence of endoscopically treated colorectal tumors depends upon the outcome of first endoscopic procedure. Piecemeal resection was the only significant risk factor associated with local recurrence after endoscopic resection.

Evaluation of anti-migration properties of biliary covered self-expandable metal stents

AIM: To assess anti-migration potential of six biliary covered self-expandable metal stents(C-SEMSs) by using a newly designed phantom model. METHODS: In the phantom model, the stent was placed in differently sized holes in a silicone wall and retracted with a retraction robot. Resistance force to migration(RFM) was measured by a force gauge on the stent end. Radial force(RF) was measured with a RF measurement machine. Measured flare structure variables were the outer diameter, height, and taper angle of the flare(ODF, HF, and TAF, respectively). Correlations between RFM and RF or flare variables were analyzed using a linear correlated model.RESULTS: Out of the six stents, five stents were braided, the other was laser-cut. The RF and RFM of each stent were expressed as the average of five replicate measurements. For all six stents, RFM and RF decreased as the hole diameter increased. For all six stents, RFM and RF correlated strongly when the stent had not fully expanded. This correlation was not observed in the five braided stents excluding the laser cut stent. For all six stents, there was a strong correlation between RFM and TAF when the stent fully expanded. For the five braided stents, RFM after full stent expansion correlated strongly with all three stent flare structure variables(ODF, HF, and TAF). The laser-cut C-SEMS had higher RFMs than the braided C-SEMSs regardless of expansion state.CONCLUSION: RF was an important anti-migration property when the C-SEMS did not fully expand. Once fully expanded, stent flare structure variables plays an important role in anti-migration.

Refractory case of ulcerative colitis with idiopathic thrombocytopenic purpura successfully treated by Janus kinase inhibitor tofacitinib:A case report

BACKGROUND Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura(ITP) is a rare phenomenon. The management of UC with ITP can be challenging,since a decreased platelet count augments UC.CASE SUMMARY A 24-year-old man with UC and steroid-resistant ITP experienced UC flare.Although continuous infusion of cyclosporine was initiated, UC did not improve.The administration of tofacitinib subsequently led to the induction of remission.The patient has maintained remission of UC and ITP for over one year ontofacitinib treatment. Whole transcriptomic sequencing was performed forinflamed rectal mucosae obtained before and after the initiation of Janus kinase(JAK) inhibitor, suggesting that distinct molecular signatures seemed to beregulated by JAK inhibitors and other conventional therapies including tumornecrosis factor lockers.CONCLUSION Tofacitinib should be considered in refractory cases of UC with ITP.

Castor oil as booster for colon capsule endoscopy preparation reduction: A prospective pilot study and patient questionnaire

BACKGROUND Preparation for colon capsule endoscopy(CCE)requires a large liquid laxative volume for capsule excretion,which compromises the procedure's tolerability.AIM To assess the safety and utility of castor oil-boosted bowel preparation.METHODS This prospective cohort study including 20 patients(age range,16-80 years;six men and 14 women)suspected of having colorectal disease was conducted at Kindai University Hospital from September 2017 to August 2019.All patients underwent CCE because of the following inclusion criteria:previous incomplete colonoscopy in other facility(n=20),history of abdominal surgery(n=7),or organ abnormalities such as multiple diverticulum(n=4)and adhesion after surgery(n=6).The exclusion criteria were as follows:Dysphagia,history of allergic reactions to the drugs used in this study(magnesium citrate,polyethylene glycol,metoclopramide,and castor oil),possibility of pregnancy,possibility of bowel obstruction or stenosis based on symptoms,or scheduled magnetic resonance imaging within 2 wk after CCE.The primary outcome was the capsule excretion rate within the battery life,as evaluated by the total large bowel observation rate,large bowel transit time,and bowel creasing level using a fivegrade scale in different colorectal segments.The secondary outcomes were complications,colorectal lesion detection rates,and patients’tolerability.RESULTS The castor oil-based regimen was implemented in 17 patients.Three patients cancelled CCE because they could tolerate castor oil,but not liquid laxatives.The capsule excretion rate within the battery life was 88%(15/17).The mean large bowel transit time was 236 min.Approximately 70%of patients had satisfactory colon cleansing levels.CCE detected colon polyps(14/17,82%)and colonic diverticulum(4/12,33%).The sensitivity,specificity,and diagnostic accuracy rates for detecting colorectal polyps(size≥6 mm)were 76.9%,75.0%,and 76.4%,respectively.The sensitivity,specificity,and diagnostic accuracy rates for detection of diverticulum were 100%each.Twelve patients(71%)rated CCE as more than“good”,confirming the new regimen’s tolerability.No serious adverse events occurred during this study.CONCLUSION The castor oil-based regimen could reduce bowel preparation dose and improve CCE tolerability.

Promising anticancer therapy: combination of immune checkpoint inhibitors and molecular-targeted agents

Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer death worldwide,and prognosis remains unsatisfactory when the disease is diagnosed at an advanced stage.Sorafenib resistance is one of the main obstacles to the treatment of advanced HCC.Several studies have proposed that the activation of escape pathways from RAF/MEK/ERK/STAT3 might result in sorafenib resistance(1-3).Leung et al.showed that HCC cells with higher SHP2 expression was associated with a lower sensitivity towards sorafenib treatment(4).Consistently,SHP2 inhibitor SHP099 abrogated sorafenib resistance in cancer cells by blocking RAS/MEK/ERK and AKT signaling pathways(4).Unlike other tyrosine phosphatases,SHP2 functions as a positive regulator of proliferative signals.