Postoperative bleeding in patients on antithrombotic therapy after gastric endoscopic submucosal dissection

To investigated the relationship between postoperative bleeding following gastric endoscopic submucosal dissection (ESD) and individual antithrombotic agents. METHODSA total of 2488 gastric neoplasms in 2148 consecutive patients treated between May 2001 and June 2016 were studied. The antithrombotic agents were categorized into antiplatelet agents, anticoagulants, and other antithrombotic agents, and we included combination therapies [e.g., dual antiplatelet therapy (DAPT)]. The risk factors associated with post-ESD bleeding, namely, antithrombotic agents overall, individual antithrombotic agents, withdrawal or continuation of antithrombotic agents, and bleeding onset period (during the first six days or thereafter), were analyzed using univariate and multivariate analyses. RESULTSThe en bloc resection and complete curative resection rates were 99.2% and 91.9%, respectively. Postoperative bleeding occurred in 5.1% cases. Bleeding occurred in 10.3% of the patients administered antithrombotic agents. Being male (P = 0.007), specimen size (P < 0.001), and antithrombotic agent used (P < 0.001) were independent risk factors for postoperative bleeding. Heparin bridging therapy (HBT) (P = 0.002) and DAPT/multidrug combinations (P < 0.001) were independent risk factors associated with postoperative bleeding. The bleeding rate of the antithrombotic agent continuation group was significantly higher than that of the withdrawal group (P < 0.01). Bleeding within postoperative day (POD) 6 was significantly higher in warfarin (P = 0.015), and bleeding after POD 7 was significantly higher in DAPT/multidrug combinations (P = 0.007). No thromboembolic events were reported. CONCLUSIONWe must closely monitor patients administered HBT and DAPT/multidrug combinations after gastric ESD, particularly those administered multidrug combinations after discharge.

Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients

BACKGROUND Persistent Helicobacter pylori(H.pylori)infection causes chronic inflammation,atrophy of the gastric mucosa,and a high risk of developing gastric cancer.In recent years,awareness of eradication therapy has increased in Japan.As H.pylori infections decrease,the proportion of gastric cancers arising from H.pylori uninfected gastric mucosa will increase.The emergence of gastric cancer arising in H.pylori uninfected patients though rarely reported,is a concern to be addressed and needs elucidation of its clinicopathological features.AIM To evaluate the clinicopathological features of early gastric cancer in H.pyloriuninfected patients.METHODS A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019.Of these,30 lesions in 30 patients were diagnosed as H.pylori-uninfected gastric cancer(Hp UIGC).We defined a patient as H.pylori-uninfected using the following three criteria:(1)The patient did not receive treatment for H.pylori,which was determined by investigating medical recordsand conducting patient interviews;(2)Lack of endoscopic atrophy;and(3)The patient was negative for H.pylori after being tested at least twice using various diagnostic methods,including serum anti-H.pylori-Ig G antibody,urease breath test,rapid urease test,and microscopic examination.RESULTS The frequency of Hp UIGC was 1.2%(30/2462)for the patients in our study.The study included 19 males and 11 females with a mean age of 59 years.The location of the stomach lesions was divided into three sections;upper third(U),middle third(M),lower third(L).Of the 30 lesions,15 were U,1 was M,and 14 were L.Morphologically,17 lesions were protruded and flat elevated type(0-I,0-IIa,0-IIa+IIc),and 13 lesions were flat and depressed type(0-IIb,0-IIc).The median tumor diameter was 8 mm(range 2-98 mm).Histological analysis revealed that22 lesions(73.3%)were differentiated type.The Hp UIGC lesions were classified into fundic gland type adenocarcinoma(7 cases),foveolar type welldifferentiated adenocarcinoma(8 cases),intestinal phenotype adenocarcinoma(7 cases),and pure signet-ring cell carcinoma(8 cases).Among 30 Hp UIGCs,24 lesions(80%)were limited to the mucosa;wherein,the remaining 6 lesions showed submucosal invasion.One of the submucosal invasive lesions showed more than 500μm invasion.The mucin phenotype analysis identified 7 Hp UIGC with intestinal phenotype and 23 with gastric phenotype.CONCLUSION We elucidated the clinicopathological characteristics of Hp UIGC,revealing recognition not only undifferentiated-type but also differentiated-type.In addition,intestinal phenotype tumors were also observed and could be an important tip.

Successful initial ablation therapy contributes to survival in patients with hepatocellular carcinoma

AIM： To evaluate the outcome predictors of percutaneous ablation therapy in patients with unresectable hepatocellular carcinoma （HCC）, especially to identify whether the initial treatment response contributes to the survival of the patients. METHODS： The study cohort included 153 patients with single （102） and two or three （51） HCC nodules 5 cm or less in maximum diameter. As an initial treatment, 110 patients received radiofrequency ablation and 43 patients received percutaneous ethanol injection. RESULTS： The Kaplan-Meier estimates of overall 3- and S-year survival rates were 75% and 59%, respectively. The log-rank test revealed statistically significant differences in the overall survivals according to ChildPugh class （P = 0.0275）, tumor size （P = 0.0130）, serum albumin level （P = 0.0060）, serum protein induced by vitamin K absence or antagonist Ⅱ level （P = 0.0486）, and initial treatment response （P = 0.0130）. The independent predictors of survival were serum albumin level （dsk ratio, 3.216; 950 CI, 1.407-7.353; P = 0.0056） and initial treatment response （risk ratio, 2.474; 95% CI, 1.076-5.692; P = 0.0330） based on the Cox proportional hazards regression models. The patients had a serum albumin level 3.5 g/dL and the 3- and 5-year survival rates of 86% and 82%. CONCLUSION： In HCC patients treated with percutaneous ablation therapy, serum albumin level and initial treatment response are the independent outcome predictors.

Histopathological validation of magnifying endoscopy for diagnosis of mixed-histological-type early gastric cancer

BACKGROUND The undifferentiated-type(UDT)component profoundly affects the clinical course of early gastric cancers(EGCs).However,an accurate preoperative diagnosis of the histological types is unsatisfactory.To date,few studies have investigated whether the UDT component within mixed-histological-type(MT)EGCs can be recognized preoperatively.AIM To clarify the histopathological characteristics of the endoscopically-resected MT EGCs for investigating whether the UDT component could be recognized preoperatively.METHODS This was a single-center retrospective study.First,we attempted to clarify the histopathological characteristics of the endoscopically-resected MT EGCs with emphasis on the UDT component.Histopathological examination investigated each lesion’s UDT component:(1)Whole mucosal layer occupation of the UDT component;(2)UDT component exposure to the surface of the mucosa;and(3)existence of a clear border between the differentiated-type and UDT components.Then,preoperative endoscopic images with magnifying endoscopy with narrowband imaging(ME-NBI)were examined to identify whether the endoscopic UDT component finding was recognizable within the area where it was present in the histopathological examination.The preoperative biopsy results and comparative relationships between endoscopic and histopathological findings were also examined.RESULTS In the histopathological examination,the whole mucosal layer occupation of the UDT component and exposure of the UDT component to the mucosal surface were observed in 67.3%(33/49)and 79.6%(39/49)of samples,respectively.A clear distinction of the border between the differentiated-type and UDT components could not be drawn in 65.3%(32/49)of MT lesions.In the endoscopic examination,the preoperative endoscopic images showed that only 24.5%(12/49)of MT EGCs revealed the UDT component within the area where it was present histopathologically.Histopathological UDT predominance was the single significant factor associated with the presence of the endoscopic UDT component finding(61.5%vs 11.1%,P=0.0009).Only 26.5%(13/49)of the lesions were diagnosed from the pretreatment biopsy as having a UDT component.Combined results of the pretreatment biopsy and ME-NBI showed the preoperative presence of the UDT component in 40.8%(20/49)of MT EGCs.CONCLUSION Recognition of a UDT component within MT EGCs is difficult even when pretreatment biopsy and ME-NBI are combined.Endoscopic resection plays a significant role in both treatment and diagnosis.

Coagulation syndrome: Delayed perforation after colorectal endoscopic treatments

Various procedure-related adverse events related to colonoscopic treatment have been reported. Previous studies on the complications of colonoscopic treatment have focused primarily on perforation or bleeding. Coagulation syndrome(CS), which is synonymous with transmural burn syndrome following endoscopic treatment, is another typical adverse event. CS is the result of electrocoagulation injury to the bowel wall that induces a transmural burn and localized peritonitis resulting in serosal inflammation. CS occurs after polypectomy, endoscopic mucosal resection(EMR), and even endoscopic submucosal dissection(ESD). The occurrence of CS after polypectomy or EMR varies according previous reports; most report an occurrence rate around 1%. However, artificial ulcers after ESD are largely theoretical, and CS following ESD was reported in about 9% of cases, which is higher than that for CS after polypectomy or EMR. Most cases of post-polypectomy syndrome(PPS) have an excellent prognosis, and they are managed conservatively with medical therapy. PPS rarely develops into delayed perforation. Delayed perforation is a severe adverse event that often requires emergency surgery. Since few studies have reported on CS and delayed perforation associated with CS, we focused on CS after colonoscopic treatments in this review. Clinicians should consider delayed perforation in CS patients.

Third-look endoscopy prevents delayed bleeding after endoscopic submucosal dissection under antithrombotic therapy

BACKGROUND Postoperative delayed bleeding(PDB) after gastric endoscopic submucosal dissection(ESD) is the most common adverse event in patients receiving antithrombotics even with second-look endoscopy. Moreover, with the increasing prevalence of cardiovascular and cerebrovascular diseases in an aging population with associated lifestyle-related diseases, an increasing number of patients receive antithrombotics. Several attempts have been made to prevent PDB in aging population;however, a consensus has yet to be reached.AIM To examine the efficacy of third-look endoscopy(TLE) for PDB prevention.METHODS One hundred patients with early gastric neoplasms receiving antithrombotics were prospectively enrolled and subjected to ESD with TLE between February 2017 and July 2019. The primary endpoint was PDB rate, which was compared with our preset threshold. Furthermore, we divided the bleeding period into early-and late-onset PDB(E-PDB and L-PDB, respectively) and analyzed its rate. As a secondary analysis, we compared PDB rates with those of a historical control group, using propensity score matching, and calculated the PDB rates per antithrombotic agent use in each group.RESULTS In total, 96 patients and 114 specimens were finally evaluated. The overall PDB rate was 7.9%(9/114) [90%CI: 4.7-13.1, P = 0.005], while the late-and early-onset PDB rates(L-PDB and E-PDB) were 5.3% [90%CI: 2.7-9.9, P < 0.0001] and 2.6% [90%CI: 1.1-6.4, P = 0.51], respectively. Propensity score matching generated 58 matched pairs for TLE and control groups. No differences were found in overall PDB incidence(10.3% vs 20.7%, P = 0.12), whereas L-PDB occurrence significantly differed(5.2% vs 17.2%, P = 0.04) between groups. Considering antithrombotics' use, the overall PDB rate was higher for direct oral anticoagulants and multiple antithrombotics in the control group, while L-PDB incidence was lower in the TLE group for these agents(8.7% vs 23.1% and 5.0% vs 29.4%, respectively).CONCLUSION TLE for gastric ESD reduces overall PDB, and especially L-PDB incidence, among patients receiving antithrombotics.