Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Comparison of the Efficacy of Polaprezinc Plus Proton Pump Inhibitor and Rebamipide Plus Proton Pump Inhibitor Treatments for Endoscopic Submucosal Dissection-induced Ulcers.

GOALS: We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment. BACKGROUND: ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing. STUDY: Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used. RESULTS: The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006). CONCLUSION: The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD.

Prediction model for bleeding after endoscopic submucosal dissection of gastric neoplasms from a high-volume center.

BACKGROUND AND AIM: Bleeding after endoscopic submucosal dissection (ESD) is a main adverse event. To date, although there have been several studies about risk factors for post-ESD bleeding, there has been few predictive model for post-ESD bleeding with large volume cases. We aimed to design a prediction model for post-ESD bleeding using a classification tree model. METHODS: We analyzed a prospectively established cohort of patients with gastric neoplasms treated with ESD from 2007 to 2016. Baseline characteristics were collected for a total of 5080 patients, and the bleeding risk was estimated using variable statistical methods such as logistic regression, AdaBoost, and random forest. To investigate how bleeding was affected by independent predictors, the classification and regression tree (CART) method was used. The prediction tree developed for the cohort was internally validated. RESULTS: Post-ESD bleeding occurred in 262 of 5080 patients (5.1%). In multivariate logistic regression, ongoing antithrombotic use during the procedure, cancer pathology, and piecemeal resection were significant risk factors for post-ESD bleeding. In the CART model, the decisive variables were ongoing antithrombotic agent use, resected specimen size ≥49 mm, and patient age <62 years. The CART model accuracy was 94.9%, and the cross-validation accuracy was 94.8%. CONCLUSIONS: We developed a simple and easy-to-apply predictive tree model based on three risk factors that could help endoscopists identify patients at a high risk of bleeding. This model will enable clinicians to establish precise management strategies for patients at a high risk of bleeding and to prevent post-ESD bleeding.

A potential simple endoscopic antireflux method, "the Ripple Procedure" to reduce distensibility at the esophagogastric junction in a porcine model.

BACKGROUND AND AIMS: Currently available endoscopic or minimally invasive antireflux modalities are not widely accepted due to high procedure cost or inconsistent results. Therefore, a simpler and less technically demanding method is required. We evaluated the feasibility and efficacy of new endoscopic antireflux method (the Ripple Procedure) using functional lumen imaging probe (FLIP). METHODS: This 5-week survival study included 10 domestic pigs (control, n = 4; experimental [Ripple], n = 6). The procedure includes the following steps: (i) semicircular marking along the lesser curvature of the cardia; (ii) submucosal injection; and (iii) semicircular mucosal incision along the marking. Endoscopic and FLIP evaluations were performed preoperatively and on postoperative days (PODs) 14 and 35. Technical feasibility was evaluated, and FLIP parameters, including the distensibility index (DI) at the esophagogastric junction (EGJ) and histopathological findings, were compared between groups. RESULTS: The median procedure time was 28 (23.5-33.8) min. There was no significant difference in dysphagia score and body weight between groups. On POD 35, the Ripple group showed significantly lower EGJ DI at 30 mL [2.0 (1.3-2.5) vs 4.9 (2.7-5.0), P = 0.037]. The EGJ DI was significantly reduced at 30 mL, compared with that at the baseline level [- 59.0% (- 68.8% to - 32.1%) vs 27.8% (- 26.3% to 83.1%), P = 0.033]. Histologic evaluation revealed submucosal granulation tissues near the mucosal incision site, with increased intervening fibrosis between lower esophageal sphincter fibers in the Ripple group. CONCLUSION: The EGJ DI significantly decreased after the Ripple Procedure; hence, the procedure appears to be feasible and effective in this porcine model.

Long-term outcomes after noncurative endoscopic resection of early gastric cancer: the optimal time for additional endoscopic treatment.

BACKGROUND AND AIMS: We aimed to evaluate long-term outcomes with noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and surveillance strategies such as the optimal time for additional endoscopic treatment in patients with noncurative ESD. METHODS: Of 2527 patients who underwent gastric ESD for EGC, 512 (20.3%) patients with noncurative resection were reviewed. Noncurative resection is defined as positive resected margins on histology, lymphovascular infiltration, or beyond the expanded criteria for ESD. RESULTS: The mean ± standard deviation follow-up duration was 79.0 ± 55.7 months. A total of 264 patients (51.6%) and 50 patients (9.8%) underwent surgery and endoscopic treatment after noncurative resection, respectively, whereas 198 patients (38.7%) were observed. Cancer-specific survival and disease-free survival rates were significantly different among the surgery, other endoscopic treatment, and observation groups (96.7%, 86.8%, and 86.2%, respectively; P =.030; and 92.5%, 73.6%, and 63.0%, respectively; P < .001). When patients who underwent surgery were excluded, the disease-free survival rate of recurrence was not significantly different between the endoscopic treatment and observation groups (73.6% vs 63.0%; P = .548). To exclude the potential for the presence of lymph node metastasis, we further analyzed disease-free survival of local recurrence by comparing the patients with only a positive lateral resection margin. The disease-free survival rate was higher in the endoscopic treatment group than in the observation group (89.2% vs 69.1%; P = .023). Moreover, additional endoscopic treatment within 3 months showed significant associations with lower risk of local recurrence on multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002-0.260; P = .003). CONCLUSIONS: In patients with noncurative ESD, additional surgery showed a better long-term outcome; moreover, when a positive lateral resection margin was the only noncurative factor, additional endoscopic treatment within 3 months could be considered to improve disease-free survival.

Efficacy of hemostatic powder in preventing bleeding after gastric endoscopic submucosal dissection in high-risk patients.

BACKGROUND AND AIM: The prevention of post-endoscopic submucosal dissection (ESD) bleeding in high-risk patients is an important problem. This study evaluated the efficacy of polysaccharide hemostatic powder in preventing post-ESD bleeding in high-risk patients. METHODS: Patients at high risk for post-ESD bleeding were prospectively enrolled between December 2015 and July 2016. A high risk of post-ESD bleeding was considered if the patients were taking antithrombotic agents or had undergone a large resection (specimen size ≥ 40 mm). The endpoints were Forrest classification of the post-ESD ulcer on second-look endoscopy 2 days after the procedure and bleeding rates within 48 h and at 4 weeks. RESULTS: Forty-four patients underwent gastric ESD and treatment with hemostatic powder. Among them, 33 patients (70.5%) underwent large resection (≥ 40 mm) without antithrombotic therapy, and 13 patients (29.5%) received antithrombotic therapy. The mean resected specimen size was 55.3 ± 13.9 mm. The proportion of high-risk delayed bleeding lesions (Forrest IIa) at second-look endoscopy was 4.5% (2/44). The overall bleeding rate was 9.1% (4/44). There was no early bleeding event. The median (interquartile range) timing of bleeding after the procedure was 12.5 (interquartile range 10.3-15.5) days. The bleeding rate in the large resection (≥ 40 mm) group without antithrombotic therapy and the antithrombotic therapy group was 3.2% (1/33) and 23.1% (3/13), respectively. CONCLUSIONS: Hemostatic powder may be a promising new simple and effective method to prevent early post-ESD bleeding in high-risk patients, especially for those with larger resection. (Clinical trial registration number: NCT02625792).

Effect of the midazolam added with propofol-based sedation in esophagogastroduodenoscopy: A randomized trial.

BACKGROUND AND AIM: Although propofol has been widely used for sedation during esophagogastroduodenoscopy (EGD), adverse events including hypoxia and hypotension may be a concern in the propofol-based sedation. We aimed to analyze whether administration of midazolam would improve safety and efficacy of propofol-based sedation in EGD. METHODS: One hundred twenty patients who were scheduled to undergo diagnostic EGD were randomly assigned to either midazolam plus propofol (MP) or propofol alone groups. In the MP group, 2 mg of midazolam and 10 mg of propofol were given initially. In the propofol alone group, 40-60 mg of propofol was given initially. In both groups, 20 mg of propofol was given repeatedly to maintain moderate sedation as needed. Vital signs including oxygen saturation were monitored every 2 min. After the patients fully recovered, satisfaction score was investigated from endoscopists, nurses, and patients, respectively. RESULTS: The baseline characteristics did not differ between the MP and propofol alone groups. The mean required doses of propofol was (mean ± standard deviation) 0.3 ± 0.3 and 0.8 ± 0.2 mg/kg in the MP and propofol alone groups, respectively (P < 0.001). In addition, sedation-related adverse events and recovery time did not differ between the two groups. The proportion of satisfactory did not differ between the two groups (MP vs propofol alone; proportion; patient, 95.0% vs 93.3%, P > 0.999; endoscopist, 73.3% vs 80.0%, P = 0.064; nurse, 73.3% vs 76.7%, P = 0.551). CONCLUSION: Adding midazolam to propofol did not reduced the safety and efficacy, and sedation using propofol alone could be suitable for sedation during diagnostic EGD.

Effectiveness of the polysaccharide hemostatic powder in non-variceal upper gastrointestinal bleeding: Using propensity score matching.

BACKGROUND AND AIM: Recently, the application of hemostatic powder to the bleeding site has been used to treat active upper gastrointestinal bleeding (UGIB). We aimed to assess the effectiveness of the polysaccharide hemostatic powder (PHP) in patients with non-variceal UGIB. METHODS: We reviewed prospectively collected 40 patients with UGIB treated with PHP therapy between April 2016 and January 2017 (PHP group) and 303 patients with UGIB treated with conventional therapy between April 2012 and October 2014 (conventional therapy group). We compared the rate of successful hemostasis and the rebleeding between the two groups after as well as before propensity score matching using the Glasgow-Blatchford score and Forrest classification. RESULTS: Thirty patients treated with the PHP and 60 patients treated with conventional therapy were included in the matched groups. Baseline patient characteristics including comorbidities, vital signs, and bleeding scores were similar in the matched groups. The rate of immediate hemostasis and 7-day and 30-day rebleeding were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate hemostasis or rebleeding rate were noted between PHP in monotherapy and PHP combined with a conventional hemostatic method. At 30 days after the therapy, there were no significant PHP-related complications or mortality. CONCLUSIONS: Given its safety, the PHP proved feasible for endoscopic treatment of UGIB, having similar effectiveness as that of conventional therapy. The PHP may become a promising hemostatic method for non-variceal UGIB.

Comparison of long-term clinical outcomes between endoscopic and surgical resection for early-stage adenocarcinoma of the esophagogastric junction.

BACKGROUND: The aim of this study was to analyze long-term clinical and oncologic outcomes in patients with early-stage adenocarcinoma of the esophagogastric junction (AEG) managed with either endoscopic resection (ER) or surgery. METHODS: The inclusion criteria were AEG, meeting classic or expanded indications for ER of early gastric cancer, and complete resection. A total of 66 patients with Siewert type II AEG were included (ER group, n = 38; vs. surgery group, n = 28). RESULTS: The mean age of the ER group was greater than that of the surgery group (mean ± SD, 66.9 ± 9.7 vs. 58.5 ± 10.4 years, respectively; p = 0.001). Compared to the ER group, macroscopically flat or depressed-type lesions were more common (47.4 vs. 89.3%; p = 0.001), and mean lesion size was larger in the surgery group (13.3 ± 8.4 vs. 18.6 ± 11.0 mm; p = 0.039). One intensive care unit admission and subsequent surgery-related death occurred in the surgery group (1/28 vs. 0/38 in the ER group; p = 0.424). During follow-up, recurrence was detected in both groups (4/38 vs. 1/28; p = 0.385). Overall survival and 5-year disease-free survival did not differ between the groups (93.3 vs. 92.9%; p = 0.282 and 88.0 vs. 100.0%; p = 0.066). CONCLUSIONS: Once complete resection is achieved in patients with AEG who met the expanded criteria for endoscopic submucosal dissection of gastric cancer, there was no significant difference in clinical outcomes between ER and surgery.

Long-term outcomes of endoscopic submucosal dissection in comparison to surgery in undifferentiated-type intramucosal gastric cancer using propensity score analysis.

BACKGROUND: The treatment of intramucosal early gastric cancer with undifferentiated-type histologies (UD-EGCs) using endoscopic submucosal dissection (ESD) is controversial. This study aimed to compare the clinical and oncologic long-term outcomes of ESD and surgery for UD-EGCs. METHODS: A prospectively collected database of patients who underwent ESD or surgery between January 2006 and December 2012 was established. Patients who diagnosed with UD-EGC and satisfied the expanded indications of ESD were included. Clinical data from 111 patients treated with ESD and 382 patients underwent surgery were analyzed, and 1-1 propensity score-matched 81 pairs of patients were also compared. RESULTS: In both groups, two-thirds of the UD-EGCs had signet ring cell (SRC)-type histology and about 90% of UD-EGCs were flat or depressed types. The mean size of tumors was smaller in ESD group (9.7 vs. 13.2 mm; P < 0.001). After propensity score-matched, case-matching covariates were not significantly different between the groups. Disease-free survival (DFS) was significantly shorter in the ESD group, but overall survival (OS) was not different between the two groups both in overall comparison (DFS; P < 0.001 and OS; P = 0.078) and propensity score-matched analysis (DFS; P < 0.001 and OS; P = 0.850). According to histologic type, OS of SRC histology was not different between the group, both in overall comparison and propensity score-matched analysis (P = 0.286 and P = 0.210). On the other hands, OS of poorly differentiated adenocarcinoma was significantly shorter in ESD group in overall comparison (P = 0.007), but was not as so in propensity score-matched analysis (P = 0.088). CONCLUSIONS: ESD might be a complementary option for the treatment of UD-EGCs, especially in those with SRC-type histology based on strict expanded indications. Nonetheless, close endoscopic surveillance is required because of a high incidence of intragastric recurrence.

Comparative study between endoscopic submucosal dissection and surgery in patients with early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a standard treatment in patients with early gastric cancer (EGC) who have a negligible risk of lymph node metastasis. The aim of this study was to compare the short-term and long-term outcomes between ESD and surgery in patients with EGC that fulfilled the expanded indication of ESD on their final pathologic report. METHODS: We reviewed the clinical data of patients who underwent gastric ESD and surgery between January 2007 and December 2012. Patients with pathologically confirmed EGC that fulfilled the expanded indication of ESD on their final pathologic report were analyzed. RESULTS: Among 2023 patients, 817 (40.4%) underwent ESD and 1206 (59.6%) underwent surgery. The proportion of cases meeting the absolute indication was significantly higher in the ESD group than in the surgery group (66.0 vs. 26.2%). Lesions on the middle third, >3 cm in size, flat or depressed, and of undifferentiated histology were significantly more common in the surgery group than in the ESD group. The ESD group showed lower acute complication rates [8.1% (66 of 817) vs. 18.1% (218 of 1206), P ≤ 0.001] and procedure-related mortality [0 vs. 0.3% (4 of 1206), P = 0.153] than the surgical group. The annual incidence of recurrent gastric cancer was 2.18% in the ESD group and 0.19% in the surgery group. The 5-year overall and disease-specific survival rates were not significantly different between the ESD group and the surgery group (overall survival: 96.4 vs. 97.2%, P = 0.423; disease-specific survival: 99.6 vs. 99.2%, P = 0.203). CONCLUSIONS: Although EGC lesions had poorer features in the surgery group than in the ESD group, ESD was comparable to surgery for EGCs that fulfilled the expanded indication of ESD, with lower rates of acute complication and comparable overall survival.

Prediction model for non-curative resection of endoscopic submucosal dissection in patients with early gastric cancer.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a useful method for complete resection of early gastric cancer (EGC). However, there are still some patients who undergo additional gastrectomy after ESD because of non-curative resection. There is no model that can accurately predict non-curative resection of ESD. We aimed to create a model for predicting non-curative resection of ESD in patients with EGC. PATIENTS AND METHODS: We reviewed the medical records, including all gross findings of EGC, of patients who underwent ESD for EGCs. We divided the patients into a non-curative resection group and a curative resection group. The clinicopathologic characteristics were compared between the groups to identify the risk factors for non-curative resection of ESD. We created a scoring system based on logistic regression modeling and bootstrap validation. RESULTS: Of 1639 patients who had undergone ESD for EGCs, 272 were identified as being treated non-curatively with ESD. A large tumor size (≥20 mm), tumor location in the upper body of the stomach, the presence of ulcer, fusion of gastric folds, the absence of mucosal nodularity, spontaneous bleeding, and undifferentiated tumor histology were associated with non-curative resection of ESD. Points of risk scores were assigned for these variables based on the ß coefficient as follows: tumor size (≥20 mm), 2 points; tumor location in the upper body of the stomach, 1 point; ulcer, 2 points; fusion of gastric folds, 2 points; absence of mucosal nodularity, 1 point; spontaneous bleeding, 1 point; and undifferentiated histology, 2 points. Our risk scoring model showed good discriminatory performance on internal validation (bootstrap-corrected area under the receiver operating characteristic curve, 0.7004; 95% confidence interval, 0.6655-0.7353). CONCLUSIONS: We developed a validated prediction model that can be used to identify patients who will undergo non-curative resection of ESD. Our prediction model can provide useful information for making decisions about the treatment of EGC before performing ESD.

Additive endoscopic resection may be sufficient for patients with a positive lateral margin after endoscopic resection of early gastric cancer.

BACKGROUND AND AIMS: No well-established treatment strategies exist for lateral margin positivity (LM+) alone after endoscopic resection (ER) of early gastric cancer (EGC). Thus, we aimed to clarify a treatment strategy for non-curative resection (non-CR) with LM+ alone after ER in EGC. METHODS: Among 2065 patients with EGC treated by ER, 76 (3.6%) with only LM+ after non-CR of EGC were reviewed retrospectively. Of these, 28 underwent gastrectomy, 25 underwent argon plasma coagulation (APC), and 23 underwent repeat ER (re-ER). We analyzed the clinicopathologic characteristics of all patients and compared those who underwent additive surgery, APC, or re-ER. RESULTS: Of the 76 patients, 28 (36.8%) fulfilled the absolute criteria and 48 (63.2%) the expanded criteria for ER. Among the latter patients, the proportion undergoing additive surgery was 75.0%, higher than that of patients in the former group (P = .014). Residual cancer cells were observed in 70.6% of patients after additive surgery or re-ER. Residual cancer cells were observed significantly more often in patients with undifferentiated-type than in those with differentiated-type EGC (P = .02). However, no lymph node metastasis was observed in any patient after additive surgery. CONCLUSIONS: Our results suggest that endoscopic treatment may be a sufficient additive therapy for patients with LM+ alone after ER, irrespective of whether the absolute or expanded ER criteria are used. However, as complete ablation of remnant cells cannot be guaranteed, re-ER is a better additive treatment than APC.

Probe-based confocal laser endomicroscopy in the margin delineation of early gastric cancer for endoscopic submucosal dissection.

BACKGROUND AND AIM: We evaluated probe-based confocal laser endomicroscopy (pCLE) in the margin delineation of early gastric cancer (EGC) for endoscopic submucosal dissection in comparison with white-light imaging with chromoendoscopy (CE). METHODS: We conducted a prospective, randomized controlled study from November 2013 to October 2014 in a tertiary referral hospital. A total of 101 patients scheduled for endoscopic submucosal dissection due to differentiated EGC were randomized into pCLE and CE groups (pCLE 51, CE 50). Markings were made by electrocautery at the proximal and distal tumor margins, as determined by either pCLE or CE. The distance from the marking to the tumor margin was measured in the resected specimen histopathologically and was compared between the two groups by a linear mixed model. RESULTS: Among 104 lesions, 80 lesions with 149 markings (pCLE 68, CE 81) were analyzed after excluding undifferentiated EGCs (n = 8) and unidentifiable markings (n = 13). Although the complete resection rate showed no difference between the groups (94.6% vs 93.2%, P = 1.000), the median distance from the marking to the margin was shorter in the pCLE group (1.3 vs 1.8 mm, P = 0.525) and the proportion of the distance <1 mm was higher (43.9% vs 27.6%, P = 0.023) in the pCLE group. Finally, subgroup analysis with superficial flat lesions (18 lesions, 31 marking dots) showed a significantly decreased distance in the pCLE group (0.5 vs 3.1 mm, P = 0.007). CONCLUSIONS: Among EGCs with superficial flat morphology, in which the accurate evaluation of lateral extent is difficult with CE, pCLE would be useful for more precise margin delineation.

Additive treatment improves survival in elderly patients after non-curative endoscopic resection for early gastric cancer.

BACKGROUND AND STUDY AIMS: Endoscopic resection (ER) is accepted as a curative treatment option for selected cases of early gastric cancer (EGC). Although additional surgery is often recommended for patients who have undergone non-curative ER, clinicians are cautious when managing elderly patients with GC because of comorbid conditions. The aim of the study was to investigate clinical outcomes in elderly patients following non-curative ER with and without additive treatment. PATIENTS AND METHODS: Subjects included 365 patients (>75 years old) who were diagnosed with EGC and underwent ER between 2007 and 2015. Clinical outcomes of three patient groups [curative ER (n = 246), non-curative ER with additive treatment (n = 37), non-curative ER without additive treatment (n = 82)] were compared. RESULTS: Among the patients who underwent non-curative ER with additive treatment, 28 received surgery, three received a repeat ER, and six experienced argon plasma coagulation. Patients who underwent non-curative ER alone were significantly older than those who underwent additive treatment. Overall 5-year survival rates in the curative ER, non-curative ER with treatment, and non-curative ER without treatment groups were 84, 86, and 69 %, respectively. No significant difference in overall survival was found between patients in the curative ER and non-curative ER with additive treatment groups. The non-curative ER groups were categorized by lymph node metastasis risk factors to create a high-risk group that exhibited positive lymphovascular invasion or deep submucosal invasion greater than SM2 and a low-risk group without risk factors. Overall 5-year survival rate was lowest (60 %) in the high-risk group with non-curative ER and no additive treatment. CONCLUSIONS: Elderly patients who underwent non-curative ER with additive treatment showed better survival outcome than those without treatment. Therefore, especially with LVI or deep submucosal invasion, additive treatment is recommended in patients undergoing non-curative ER, even if they are older than 75 years.

Impact of the Surveillance Interval on the Survival of Patients Who Undergo Curative Surgery for Gastric Cancer.

BACKGROUND: For patients who undergo gastrectomy for gastric cancer, systematic follow-up evaluation to detect recurrent lesions is recommended, although the benefits of a surveillance program using short-term imaging studies have not been evaluated. METHODS: This study reviewed the clinical data of patients who underwent curative surgery for gastric cancer using a prospective database. Patients with recurrence were classified according to surveillance interval as follows: ≤3, 3-6, and 6-12 months. RESULTS: Of the 2785 patients who underwent curative surgery for gastric cancer, 376 (13.5 %) had intraabdominal recurrences, excluding the stomach. Multivariable analysis showed that a short surveillance interval did not increase the post-recurrence survival duration (with 6-12 months as the reference: ≤3 months: hazard ratio [HR] 0.954; 95 % confidence interval [CI] 0.689-1.323; 3-6 months: HR 0.994, 95 % CI 0.743-1.330). In addition, short surveillance intervals did not increase overall survival (with 6-12 months as the reference: ≤3 months: HR 0.969; 95 % CI 0.699-1.342; 3-6 months: HR 0.955; 95 % CI 0.711-1.285). In contrast to the surveillance interval, age, cancer stage, symptoms at recurrence, and recurrence time after gastrectomy were factors associated with both post-recurrence survival and overall survival. CONCLUSIONS: Although the detection of recurrence before symptoms helped to prolong both post-recurrence survival and overall survival, shortening the surveillance interval to less than 6 months did not improve either the patient's post-recurrence survival or overall survival. Hence, it is not recommended that asymptomatic patients undergo surveillance involving imaging studies more often than once a year.

Incidence and impact of scheduled endoscopic surveillance on recurrence after curative endoscopic resection for early gastric cancer.

BACKGROUND AND AIMS: The aim of this study was to identify the incidence of recurrent lesions after endoscopic submucosal dissection (ESD) and to determine whether scheduled endoscopic surveillance might control their development and treatment. METHODS: We reviewed the clinical data of patients who underwent gastric ESD between March 2007 and April 2014. RESULTS: A total of 1347 patients who underwent curative ESD for early gastric cancer that met the expanded indication for ESD were analyzed. Of these, recurrence at the previous ESD site occurred in 39 patients, whereas recurrence in the stomach at a site other than the ESD site occurred in 102 patients. Older age, intestinal metaplasia, flat or depressed lesions, and ESD criteria were associated with recurrence in the stomach in places other than the ESD site. The annual incidence was .84% for recurrence at the previous ESD site and 2.48% for recurrence in the stomach at other than the ESD site. In cases of local recurrence and metachronous lesions, there was a significant difference between the short- and long-surveillance interval group (≤12 months vs >12 months) in the proportions of recurrent adenocarcinoma (31.9% vs 60.9%, P = .021), additional gastrectomy (7.1% vs 46.2%, P = .033), and size (8.92 ± 4.17 mm vs 18.08 ± 10.47 mm, P = .010). CONCLUSIONS: Scheduled endoscopy surveillance is necessary for detecting recurrent lesions. In addition, scheduled endoscopy surveillance might help to detect recurrent lesions at a stage early enough for a curative resection.

The new modified ABCD method for gastric neoplasm screening.

BACKGROUND: The ABCD screening method was developed for risk stratification of gastric cancer. It is unclear whether the ABCD method can predict the risk of gastric neoplasms, including gastric adenomas, as observed for gastric cancer. We aimed to devise a modified ABCD method for predicting gastric neoplasms. METHODS: We reviewed 562 patients who had undergone upper gastrointestinal tract endoscopy and whose serum IgG anti-Helicobacter pylori antibody, gastrin, and pepsinogen (PG) I and PG II data were available. Patients were classified into the following four groups: H. pylori antibody negative and normal PG level (group A), H. pylori antibody positive and normal PG level (group B), H. pylori antibody positive and low PG level (group C), and H. pylori antibody negative and low PG level (group D). RESULTS: The PG I/PG II ratio was lower in patients with gastric neoplasms than in patients without these lesions (gastric adenoma vs gastric cancer vs no neoplasm, 3.7 ± 2.0 vs 3.8 ± 1.8 vs 4.9 ± 2.1, P < 0.001). The optimal cutoff values of the PG I/PG II ratio for predicting gastric neoplasms were 3.1 for H. pylori antibody negative patients and 4.1 for H. pylori antibody positive patients. A higher group grade was associated with a significantly higher proportion of gastric neoplasms [odds ratio (95 % confidence interval), group A, reference; group B, 1.783 (1.007-3.156); group C, 3.807 (2.382-6.085); and group D, 5.862 (2.427-14.155)]. CONCLUSIONS: The modified ABCD method using two different cutoff values according to the H. pylori antibody status was useful for predicting the presence of gastric neoplasms. This method might be a supplementary screening tool for both gastric adenoma and gastric cancer. However, further studies will be required to provide a definitive conclusion.

Is the recent WHO histological classification for gastric cancer helpful for application to endoscopic resection?

BACKGROUND: Endoscopic resection is performed in undifferentiated-type early gastric cancer (UD-EGC), including poorly differentiated (PD) adenocarcinoma and signet ring cell (SRC) carcinoma. We previously found that different approaches are needed for PD adenocarcinoma and SRC carcinoma for curative resection. However, according to the 2010 WHO classification, diffuse-type PD adenocarcinoma and SRC carcinoma are categorized in the "poorly cohesive carcinomas." Thus, we assessed whether the WHO classification is helpful when endoscopic resection is performed for treatment of UD-EGC. METHODS: We analyzed clinicopathological features of 1295 lesions with SRC carcinoma and PD adenocarcinoma treated by open surgery. We recategorized them into intestinal-type PD adenocarcinomas and poorly cohesive carcinomas (SRC carcinoma, diffuse-type PD adenocarcinoma). We also recategorized 176 lesions treated by endoscopic resection into intestinal-type PD adenocarcinomas and poorly cohesive carcinomas. RESULTS: According to the open surgery data, the rates of lymph node metastasis (LNM) and lymphovascular invasion were significantly lower in SRC carcinoma than in diffuse-type and intestinal-type PD adenocarcinomas. The rates of LNM and lymphovascular invasion were significantly higher in diffuse-type PD adenocarcinoma than in SRC carcinoma. Endoscopic resection data showed no recurrence if the carcinoma was curatively resected. However, the commonest cause of noncurative resection was different in SRC carcinoma and PD adenocarcinoma. A positive lateral margin was the commonest cause in SRC carcinoma versus a positive vertical margin in both intestinal-type and diffuse-type PD adenocarcinoma. CONCLUSIONS: The clinical behavior differs in diffuse-type PD adenocarcinoma and SRC carcinoma. On the basis of LNM and outcomes of endoscopic resection, the recent WHO classification may not be helpful when endoscopic resection is performed for treatment of UD-EGC.

Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated Patients With Supratherapeutic International Normalized Ratios?

The management of upper gastrointestinal bleeding (UGIB) in anticoagulated patients with supratherapeutic international normalized ratios (INRs) presents a challenge. The purpose of the study was to evaluate the safety of endoscopic therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated patients who underwent endoscopic treatment for UGIB were enrolled in the study. Patients were divided into 2 groups based on the occurrence of rebleeding within 30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from gastric cancer and bleeding at the duodenum were significantly related to rebleeding in a univariate analysis. Multivariate analysis determined that presenting symptoms other than melena (hematemesis, hematochezia, or others) (odds ratio, 3.93; 95% confidence interval, 1.44-10.76) and bleeding from gastric cancer (odds ratio, 6.10; 95% confidence interval, 1.27-29.25) were significant factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic therapy was not significantly associated with rebleeding in either univariate or multivariate analysis. Significant differences in bleeding-related mortality, additional intervention to control bleeding, length of hospital stay, and transfusion requirements were revealed between the rebleeding and no-rebleeding groups. There were no significant differences in therapeutic outcomes between patients with INR within the therapeutic range and those with supratherapeutic INR. Supratherapeutic INR at the time of endoscopic therapy did not change rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy for UGIB in anticoagulated patients, irrespective of INR at the time of endoscopic therapy.