Evaluation of long-term survival in patients with severe comorbidities after endoscopic submucosal dissection for esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) is becoming widely popular as a less invasive treatment option for superficial esophageal squamous cell carcinoma. However, data on long-term survival after esophageal ESD in patients with severe comorbidities are limited. This study aimed to evaluate long-term survival after ESD in such patients. METHODS: Altogether, 584 consecutive patients underwent esophageal ESD at our institution from May 2004 to September 2016. Based on the American Society of Anesthesiologists Physical Status (ASA-PS) classification system, patients were grouped according to severe (ASA-PS ≥ 3) or non-severe comorbidities (ASA-PS 1/2). The overall survival (OS), disease-specific survival (DSS), and risk factors for mortality were compared between the groups using a propensity score matching analysis. RESULTS: In a matched cohort of 69 pairs, the 5-year OS rate was poorer in ASA-PS 3 patients than in ASA-PS 1/2 patients (63.9% vs. 92.5%, P < 0.01), while the 5-year DSS rate was similar between the groups (100% vs. 100%). The mortality rate was significantly higher in ASA-PS 3 patients than in ASA-PS 1/2 patients (hazard ratio 3.47; 95% confidence interval 1.79-6.74; P < 0.01). Death due to exacerbation of comorbidities was significantly more frequent in ASA-PS 3 patients than in ASA-PS 1/2 patients (42.4% vs. 8.3%, P < 0.04). CONCLUSION: Because of the exacerbation of comorbidities, patients with severe comorbidities had poorer long-term outcomes after esophageal ESD than those with non-severe comorbidities. Further studies will be necessary to evaluate esophageal ESD in patients with severe comorbidities.

Continuous warfarin administration versus heparin bridging therapy in post colorectal polypectomy haemorrhage: a study protocol for a multicentre randomised controlled trial (WHICH study).

BACKGROUND: Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding. METHODS: We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events. DISCUSSION: The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy. TRIAL REGISTRATION: UMIN-CTR UMIN000023720 . Registered on 22 August 2016.

Successful Eradication of Helicobacter pylori Could Prevent Metachronous Gastric Cancer: A Propensity Matching Analysis.

BACKGROUND AND AIM: Helicobacter pylori is the leading cause of gastric cancer, but it is still uncertain whether eradicating H. pylori in early gastric cancer (EGC) patients who underwent endoscopic resection can prevent metachronous gastric cancer (MGC). This study aimed to investigate the effect of H. pylori eradication to prevent MGC after endoscopic submucosal dissection (ESD). METHODS: In this propensity-matched retrospective observational study, 770 patients with EGC who received ESD were enrolled. The outcome was the incidence of MGC; this was compared between the persistent and eradicated groups. RESULTS: MGC was detected in 27 patients (7.8%) during a median period of 39.0 months (range 26.0-64.0). After propensity matching, 126 pairs of patients in each group were analyzed. The 5-year cumulative incidence rates of MGC were 13.2 and 3.9% in the persistent and eradicated groups, respectively (p= 0.021, log-rank test). On multivariate analysis, H. pylori eradication prevented MGC significantly (hazard ratio [HR] 0.32; p = 0.029). The results remained robust after inverse probability of treatment weighting analysis (HR 0.30; p = 0.020). CONCLUSIONS: Successful H. pylori eradication could prevent MGC after ESD for EGC.

Safety of Endoscopic Mucosal Resection Using a Bipolar Snare for Superficial Nonampullary Duodenal Epithelial Tumors and the Predictive Factors of Piecemeal Resection.

INTRODUCTION: Endoscopic mucosal resection for small superficial nonampullary duodenal epithelial tumors is a noninvasive treatment; however, perforations can occur. Bipolar snares can reduce the risk of perforation due to small tissue damage. Currently, only few studies have reported endoscopic mucosal resection for small superficial nonampullary duodenal epithelial tumors using a bipolar snare and the effect of preoperative findings. OBJECTIVE: To investigate (1) resectability and adverse events of endoscopic mucosal resection using a bipolar snare for small superficial nonampullary duodenal epithelial tumors and (2) the predictions of piecemeal resection. METHODS: Between 2007 and 2017, 89 patients with 107 lesions underwent endoscopic mucosal resection using a bipolar snare. Among them, 88 lesions of 77 patients were evaluated. The primary outcome was the incidence of en bloc resection and R0 resection and adverse events. Risk factors associated with piecemeal resection, including preoperative lesion findings, were also examined. RESULTS: The incidence rates of en bloc and R0 resections were 85.2 and 48.9%, respectively. Neither intraoperative or delayed perforations nor procedure-related mortality was noted. The nonlifting sign after submucosal injection was associated with an increase in piecemeal resection (odds ratio: 20.3, 95% confidence interval: 2.53-162; p = 0.005). CONCLUSION: Endoscopic resection for small superficial nonampullary duodenal epithelial tumors can cause perforation; however, endoscopic mucosal resection using a bipolar snare can be a safe treatment option as it does not cause perforations. The nonlifting sign after submucosal injection is a predictive factor for piecemeal resection.

Predictive factors for difficult endoscopic submucosal dissection for esophageal neoplasia including failure of en bloc resection or perforation.

BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as the standard treatment for early-stage esophageal neoplasia. However, esophageal perforation may occur, leading to mediastinitis and pneumothorax, which occasionally require emergency surgery. Moreover, failure of en bloc resection causes local recurrence. However, studies on the predictors of such difficulties during ESD are limited. Hence, we evaluated the predictors associated with the difficulty of ESD for esophageal neoplasia including failure of en bloc resection or perforation. METHODS: Data of 549 consecutive patients who were treated with ESD between May 2004 and March 2016 at a single institution were retrospectively studied. Exclusion criteria were the presence of metachronous esophageal neoplasia or missing data. The primary outcome was determining the predictors associated with the difficulty of ESD for esophageal neoplasia including failure of en bloc resection or perforation. RESULTS: Altogether, 543 patients with 736 lesions were evaluated. Failure of en bloc resection occurred in 6 patients (1.1%) with 6 lesions, and perforation occurred in 11 patients (2.0%) with 11 lesions (1.5%). Multivariate logistic regression analysis showed that large lesion diameter (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.21-1.84; p < 0.001) and previous chemoradiotherapy (OR 5.24; 95% CI 1.52-18.06; p = 0.009) were independent predictive factors. CONCLUSIONS: Larger lesions and previous chemoradiotherapy for esophageal cancer increased the risk for failure of en bloc resection or perforation in patients who underwent esophageal ESD.

Repeated Endoscopic Submucosal Dissection for Esophageal Neoplasia Located Close to a Previous Endoscopic Submucosal Dissection Scar.

INTRODUCTION: Endoscopic submucosal dissection (ESD) could become a standard treatment for early stage esophageal neoplasia. Recurrence sometimes develops close to a previous ESD scar. These lesions are predictably difficult to treat with ESD because of severe fibrosis. We evaluated the clinical outcomes of ESD for esophageal neoplasia located close to a previous ESD scar. METHODS: This was a retrospective observational study in a single institution. A total of 549 consecutive patients with 927 esophageal lesions were treated with ESD. The primary outcomes were resectability and adverse events of esophageal neoplasia located close to previous ESD scars (ESD scar group) than in primary esophageal ESD (primary group). Furthermore, predictive factors of perforation were examined. RESULTS: A total of 545 primary and 29 ESD scars in consecutive patients were evaluated. En bloc and complete (R0) resection rates in the ESD scar group were lower than those in the primary group (79.3% vs 98.3%, P < 0.01 and 75.9% vs 93.4%, P < 0.01). Perforations occurred more frequently in the ESD scar group (10.3% vs 2.0%, P = 0.03). The ESD scar group was a predictive factor for perforation (odds ratio = 10.37, 95% confidence interval: 2.15-49.94, P = 0.004). There were similar results for inverse probability of treatment weighting methods (odds ratio = 6.78, 95% confidence interval: 1.40-32.98, P = 0.018). DISCUSSION: ESD for esophageal neoplasia located close to a previous ESD scar was difficult to completely resect and increased the likelihood of perforation but could be a treatment option.

Endoscopic closure of refractory esophageal fistula after esophagectomy using polyglycolic acid sheets: a pilot study.

Background and study aims Esophageal fistulas after esophagectomy are associated with high mortality and poor quality of life. They are sometimes intractable to conservative management and surgery that increases mortality. Few studies have assessed use of polyglycolic acid (PGA) sheets with fibrin glue for esophageal fistulas. We investigated the safety of using PGA sheets with fibrin glue for esophageal fistulas after esophagectomy. Patients and methods This was a single-center prospective pilot study. Patients who had refractory esophageal fistulas after esophagectomy were included. PGA sheets were filled in the fistula using biopsy forceps. Fibrin glue was applied to the PGA sheets. We repeated the procedure 1 week later. The outcome measures were the incidence of adverse events (AEs) and closure of the fistula. Results Five patients were assessed. No adverse events were observed. The esophageal fistula was closed with the application of PGA sheets four times in 40 % (2/5) of the cases. Conclusions PGA sheets with fibrin glue were safe for esophageal fistula closure after esophagectomy and do not involve the risk of AEs.

Impact of preoperative biopsy sampling on severe submucosal fibrosis on endoscopic submucosal dissection for colorectal laterally spreading tumors: a propensity score analysis.

BACKGROUND AND AIMS: It is believed that preoperative biopsy sampling for superficial-type colorectal tumors should be avoided because submucosal fibrosis caused by biopsy sampling makes EMR impossible. However, few studies have reported the influence of biopsy sampling on colorectal endoscopic submucosal dissection (ESD). This study aimed to examine the effect of biopsy sampling on submucosal fibrosis and treatment outcomes of ESD for laterally spreading tumors (LSTs). METHODS: Between April 2005 and September 2015, 441 consecutive patients underwent colorectal ESD in Osaka City University Hospital. Using propensity score matching and inverse probability of treatment weighting (IPTW), we retrospectively evaluated risk factors for severe submucosal fibrosis and treatment outcomes for patients with LSTs, with or without preoperative biopsy sampling. RESULTS: A total of 428 LSTs resected using ESD were enrolled. After matching, there were 136 matched pairs of lesions that did or did not undergo biopsy sampling. Preoperative biopsy sampling increased severe fibrosis compared with that in the non-biopsy sampling group (20.6% vs 11.0%; P = .03) and was significantly associated with severe fibrosis after matching (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.07-4.10; P = .03). After adjustment with IPTW, biopsy sampling also increased the risk of severe fibrosis (OR, 2.33; 95% CI, 1.17-4.63; P = .02). However, no significant differences were observed between the 2 groups in treatment outcomes. CONCLUSIONS: Preoperative biopsy sampling for colorectal LSTs might cause severe submucosal fibrosis but has no adverse influence on clinical outcomes of ESD.

Long-term outcome of endoscopic submucosal dissection for early gastric cancer in patients with severe comorbidities: a comparative propensity score analysis.

BACKGROUND: Recently, endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) has been performed on patients with severe comorbidities because it is less invasive, although little is known regarding long-term outcomes. This study aimed to assess the long-term outcomes of ESD for patients with severe and non-severe comorbidities. METHODS: We enrolled 1081 patients who underwent ESD for EGC between February 2004 and June 2013. Based on the American Society of Anesthesiologists Physical Status (ASA-PS) classification, we defined patients with severe and non-severe comorbidities as ASA-PS 3 and 1/2, respectively. We retrospectively compared the overall survival, risk factors for mortality, and adverse events between these two groups using propensity score matching and inverse probability of treatment weighting. RESULTS: A total of 488 patients met the eligibility criteria. After matching, the ASA-PS 3 group showed a significantly shorter survival than the ASA-PS 1/2 group (5-year overall survival rate, 79.1 vs. 87.7%; p < 0.01). In addition, only the ASA-PS 3 group had a significant risk factor for mortality using both the Cox analysis [hazard ratio (HR), 2.56; 95% confidence interval (CI) 1.18-5.52; p = 0.02] and the IPTW method (HR, 3.14; 95% CI 1.91-5.14; p < 0.01). There was no significant difference in adverse events after matching between the two groups (p = 0.21). CONCLUSIONS: The long-term outcome of gastric ESD for patients with severe comorbidities was worse than for those with non-severe comorbidities. Further studies will be necessary to determine if ESD is truly warranted in these patients.

Colorectal polyps located across a fold are difficult to resect completely using endoscopic mucosal resection: A propensity score analysis.

BACKGROUND: Incomplete polyp resection during colorectal endoscopic mucosal resection (EMR) might contribute to the development of interval cancer. OBJECTIVE: This retrospective study aimed to determine the incidence of incomplete polyp resection during EMR of colorectal polyps located across a fold compared with that of colorectal polyps located between folds. METHODS: In total, 262 patients with 262 lesions that were ≥10 mm in diameter and treated with conventional EMR were enrolled. The main outcome was the incidence of incomplete polyp resections. Propensity score matching and inverse probability of treatment weighting (IPTW) were performed to reduce the effects of selection bias. RESULTS: Fifty-seven lesions (21.8%) were incompletely resected. After propensity score matching, the lesions located across a fold were at higher risk of incomplete resection than those between folds (26/68, 38.2% vs 7/68, 10.3%; odds ratio (OR): 3.71; 95% confidence interval (CI): 1.61-8.56; p < 0.01). These findings persisted after adjusting for the differences at baseline using the IPTW method (OR: 3.63; 95% CI: 1.72-7.63; p = 0.001). CONCLUSIONS: There is an increased risk of an incomplete polyp resection for a colorectal polyp that is located across a fold compared with that for a polyp that is located between folds.

Heparin-bridging therapy is associated with post-colorectal polypectomy bleeding in patients whose oral anticoagulation therapy is interrupted.

OBJECTIVES: The American and Japanese Societies for Gastrointestinal Endoscopy Guidelines recommend heparin-bridging therapy for patients whose oral anticoagulants are interrupted for endoscopic procedures. However, little is known about the potential association between heparin-bridging therapy and post-polypectomy bleeding (PPB). The aim was to investigate the incidence of PPB associated with heparin-bridging therapy administered to patients whose anticoagulants were interrupted. MATERIALS AND METHODS: This was a retrospective observational study using inverse propensity analysis. Between 2013 and 2015, 1004 patients with 2863 lesions were included. The primary outcomes were the rates of PPB and thromboembolism associated with heparin-bridging therapy. The risk factors associated with PPB were identified using multivariate logistic regression analysis involving probability of treatment weighting (IPTW). RESULTS: The patients were categorized into a heparin-bridging therapy group (78 patients with 255 lesions) or a control group (926 patients with 2608 lesions). The PPB rate in the heparin-bridging therapy group (10.2%, 8/78) was significantly higher than in the control group (1.1%, 11/926) (p <.01). Thromboembolism occurred in one patient in the control group. The multivariate analysis revealed that heparin-bridging therapy was an independent risk factor associated with PPB (odds ratio [OR], 8.21; 95% confidence interval [95% CI], 2.32-29.10; p <.01). IPTW showed heparin-bridging therapy increased PPB (OR, 7.68; 95% CI, 1.83-32.28; p <.01). CONCLUSIONS: Heparin-bridging therapy administered to patients whose oral anticoagulants were interrupted was associated with an increased PPB risk.

Prediction of esophageal stricture in patients given locoregional triamcinolone injections immediately after endoscopic submucosal dissection.

BACKGROUND AND AIM: Esophageal endoscopic submucosal dissection (ESD) to resect widespread lesions has increased the incidence of strictures, and some patients develop strictures despite receiving prophylactic locoregional triamcinolone injections. The present study evaluated the predictive factors for esophageal stricture formation in patients given prophylactic triamcinolone injections after ESD. METHODS: This was a retrospective observational study. Of 552 consecutive patients who underwent ESD, those who received prophylactic triamcinolone injections immediately after ESD were enrolled. Primary outcome was predictive factors for esophageal stricture formation in patients given prophylactic triamcinolone injections. RESULTS: We evaluated 101 en bloc resections involving 144 lesions in 96 patients. Strictures occurred following 17 (16.8%) resections. Wider circumferential mucosal defect (odds ratio [OR] 2.42, 95% confidence interval [CI]: 1.01-5.80; P = 0.048) was an independent predictive factor for stricture development. Cut-off value associated with stricture formation was five-sixths of the circumferential mucosal defect. Propensity analysis determined that frequency of esophageal strictures increased in patients with circumferential mucosal defects of more than five-sixths compared with those less than five-sixths (OR = 5.70, 95% CI: 1.61-20.18; P = 0.007). CONCLUSION: Resections involving circumferential mucosal defects of more than five-sixths increased the likelihood of stricture formation in patients given prophylactic locoregional triamcinolone injections after esophageal ESD.

A Metastatic Gastric Tumor from Ovarian Cancer.

Gastric metastasis from ovarian cancer has rarely been reported. We herein report the case of a 64-year-old woman with gastric metastasis from ovarian cancer that was diagnosed as surgical stage IA. Diagnostic and staging laparotomy showed mucinous carcinoma of the right ovary. At one month after surgery, bone metastasis was detected via scintigraphy. On esophagogastroduodenoscopy, a 10-mm elevated lesion with ulceration on the top was seen in the stomach. The immunohistochemical analysis of biopsy specimens showed that these metastases arose from ovarian cancer. We recommend that physicians remain aware of the possibility of gastric metastasis in patients with ovarian cancer.

Comparison of propofol with midazolam in endoscopic submucosal dissection for esophageal squamous cell carcinoma: a randomized controlled trial.

BACKGROUND: Interruption of sedation due to a poor response to modified neuroleptanalgesia (m-NLA) with midazolam often occurs during endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) because most patients have a history of heavy alcohol intake. Recently, propofol has been used feasibly and safely during endoscopic procedures. The aim of this study was to clarify the efficacy and safety of propofol compared with that of midazolam during ESD for ESCC. METHODS: This was a single-blind, randomized controlled trial in a single center. Patients with ESCC scheduled for ESD were included in the study. Patients were randomly assigned to one of two groups: the propofol group and the midazolam group. The main outcome was the incidence of discontinuation of the procedure due to a poor response to sedation. Secondary outcomes included risk factors for a poor response to sedation. RESULTS: Between April 2014 and October 2015, 132 patients (n = 66 per group) who underwent ESD for ESCC were enrolled in this study. The incidence of discontinuation due to a poor response to sedation in the propofol and midazolam groups was 0% (0/66) and 37.9% (25/66), respectively (p < 0.01). Multivariate analyses revealed that use of midazolam [Odds ratio (OR), 7.61; 95% confidence interval (CI), 2.64-21.92; p < 0.01] and age (OR, 0.93; 95% CI, 0.86-0.98; p < 0.01) were risk factors for a poor response to sedation. CONCLUSIONS: Our study indicates that, compared with midazolam, propofol is a more efficient sedative for m-NLA during ESD for ESCC.

Single Locoregional Triamcinolone Injection Immediately After Esophageal Endoscopic Submucosal Dissection Prevents Stricture Formation.

OBJECTIVES: Although endoscopic submucosal dissection (ESD) is an efficient treatment for superficial esophageal cancer, it is associated with stricture formation after wide-circumference resection that leads to a low quality of life. Although locoregional steroid injections prevent stricture formation, a randomized comparative study did not report any advantages associated with steroid injection. We evaluated the prophylactic efficacy of a single locoregional triamcinolone injection for stricture formation after esophageal ESD. METHODS: This was a retrospective matched case-control study using propensity score matching (PSM). Between April 2006 and July 2015, a total of 602 patients with superficial esophageal neoplasia underwent ESD. Among them, 189 patients with mucosal defects that spanned more than 2/3 of the esophageal circumference were included. After exclusion, 150 patients were enrolled. Triamcinolone acetonide (80 mg) was injected into the residual submucosal layer of the resected region immediately after ESD. PSM was performed to reduce the effects of selection bias for steroid injection. The primary outcome was the incidence of stricture formation. The secondary outcome was the number of balloon dilatation procedures required to resolve the stricture formation. RESULTS: Thirty-seven patients, with and without triamcinolone injection each, were matched after PSM. The incidence of stricture formation decreased from 45.9% (17/37) without triamcinolone injection to 18.9% (7/37) with triamcinolone injection (p=0.016). After matching, the mean number of balloon dilatation procedures required also decreased from 2.8±4.6 to 0.6±1.5 times (P<0.01). CONCLUSIONS: A single locoregional triamcinolone injection efficiently prevented stricture formation after esophageal ESD.