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.

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.

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.

The five-year survival rate after endoscopic submucosal dissection for superficial esophageal squamous cell neoplasia.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell neoplasia (ESCN) because of a high complete resection rate. However, there were a few reports about the long-term outcomes of these patients due to short follow-up periods. AIMS: We aimed to evaluate the 5-year survival after ESD for superficial ESCN. METHODS: This was a retrospective cohort study performed at a single institution. Between 2006 and 2009, 94 patients with superficial ESCN underwent ESD. Eighty-three patients (93.3%) who had completed an extended period of observation of at least 5 years were enrolled. The main outcomes were the 5-year survival rates. The secondary outcomes were the cumulative incidence rate of metachronous ESCN, and the clinical outcomes. RESULTS: The 5-year relative overall survival rate was 99.0%, whereas the cause specific survival rate was 100% during 72.9 months of median follow up period. Subgroup analysis showed that the 5year survival of patients with EP/LPM and MM/SM1 (submucosal invasion ≤200µm) were 100% and 89.0%, respectively. The cumulative incidence rate of metachronous ESCN at 5 years was 16.8%. CONCLUSION: ESD for superficial ESCN is a curative treatment with a favorable 5-year survival rate.

A comparison between capsule endoscopy and double balloon enteroscopy using propensity score-matching analysis in patients with previous obscure gastrointestinal bleeding.

BACKGROUND: Recently, diagnosis of obscure gastrointestinal bleeding (OGIB) has improved greatly due to introduction of capsule endoscopy (CE) and double balloon enteroscopy (DBE). However, the efficacy of CE over DBE in patients with previous OGIB remains unclear. This study aimed to compare, in terms of diagnostic yield, the efficacy of DBE with that of CE in patients with previous OGIB. PATIENTS AND METHODS: We enrolled 223 consecutive patients with previous OGIB who were treated between May 2007 and March 2012. We retrospectively evaluated the respective diagnostic yields of CE and DBE in patients with previous OGIB using propensity score-matching analysis. We compared the diagnostic yield of CE with that of DBE. RESULTS: The diagnostic yields were 41.9% in DBE group and 11.6% in CE group, respectively (p < .01). On logistic regression analysis, DBE was significantly superior to CE after matching (Odds ratio [OR], 4.25; 95% confidence interval [CI], 1.43-12.6; p < .01), even after adjustment for propensity score (OR, 5.65; 95% CI, 1.56?20.5; p < .01). CONCLUSIONS: Our results indicate that DBE might be more useful and perhaps safer than CE in achieving a positive diagnosis in patients with previous OGIB.

Prediction of Poor Response to Modified Neuroleptanalgesia with Midazolam for Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIMS: Modified neuroleptanalgesia (m-NLA) with midazolam is often used for sedation and analgesia during endoscopic submucosal dissection (ESD) for gastrointestinal neoplasia. However, interruption due to poor response to midazolam is often experienced during ESD for esophageal squamous cell carcinoma (ESCC) because most patients with ESCC have a history of heavy alcohol intake. We examined the incidence and risk factors for poor response to m-NLA with midazolam and pethidine hydrochloride. METHODS: This retrospective cross-sectional study was conducted at a single institution. Between April 2007 and July 2013, 151 patients with superficial ESCC who underwent ESD under sedation using m-NLA with midazolam and pethidine hydrochloride were enrolled. Poor response to sedation was defined as the use of a second drug when Ramsay Sedation Score 1-2. RESULTS: Poor response to sedation occurred in 66.2% patients. Most cases of poor response were controlled by using additional flunitrazepam. Multivariate logistic regression analysis showed that cumulative alcohol intake and major specimen size were independent risk factors for poor response to sedation (OR 3.63, 95% CI 1.20-10.99, and OR 3.23, 95% CI 1.26-8.25). CONCLUSION: Our study indicated that cumulative alcohol intake and major specimen size were associated with poor response to m-NLA with midazolam and pethidine hydrochloride.

Locoregional steroid injection prevents stricture formation after endoscopic submucosal dissection for esophageal cancer: a propensity score matching analysis.

BACKGROUND: Although endoscopic submucosal dissection (ESD) has become accepted for the treatment of superficial esophageal cancer, the incidence of stricture formation caused by ESD for widespread lesions is high and leads to a low quality of life. A few studies reported that locoregional steroid injections are useful for the prevention of such stricture formation compared with historical controls. We evaluated the efficacy of prophylactic locoregional steroid injections for stricture formation caused by ESD using quasi-randomized analysis. METHODS: This matched case-control study included 461 superficial esophageal cancers from 305 patients who underwent ESD between 2006 and 2013. We used two methods of locoregional steroid injection to prevent stricture formation after ESD. A propensity score matching analysis was performed to reduce the effects of a selection bias for steroid injections and other potential confounding factors. In addition, generalized estimating equations were used to analyze repeated measures data. We compared the incidence of stricture formation with or without steroid injections. RESULTS: Forty-two lesions were treated with locoregional steroid injection (dexamethasone/triamcinolone, 23/19) after ESD and esophageal stricture formation occurred in 36 lesions. Fifty-six lesions treated with or without steroid injections were matched after propensity score matching. Locoregional steroid injection reduced the incidence of stricture formation to 10.7% (3/28) of patients compared with 35.7% (10/28) in the control group (odds ratio 4.63, 95% confidence interval 1.11-19.25, p = 0.035). CONCLUSIONS: Locoregional steroid injections could be efficient for the prevention of stricture formation after ESD for superficial esophageal cancer.

Comparison of Risk Factors Between Small Intestinal Ulcerative and Vascular Lesions in Occult Versus Overt Obscure Gastrointestinal Bleeding.

BACKGROUND AND AIMS: The detailed risk factors such as bleeding pattern, comorbidities, and medication usage of patients with obscure gastrointestinal bleeding (OGIB) are largely unknown. We evaluated the risk factors related to ulcerative and vascular lesions of the small intestine diagnosed by capsule endoscopy or balloon-assisted endoscopy in OGIB cases. METHODS: We retrospectively evaluated 390 OGIB cases (occult, n = 101; overt, n = 289) in our hospital between January 2005 and March 2011 using univariate and multivariate logistic regression analyses to determine the related risk factors. RESULTS: In occult (n = 36) and overt (n = 120) OGIB cases, some lesions were detected in the small intestine. Ulcerative and vascular lesions were detected in both occult (n = 25, 69.4 %; n = 8, 22.2 %, respectively) and overt (n = 57, 47.5 %; n = 39, 32.5 %, respectively) cases. For ulcerative lesions, non-steroidal anti-inflammatory drugs were identified as a risk factor in overt cases [odds ratio (OR) 2.974, 95 % confidence interval (CI) 1.522-5.809, P = 0.001]. For vascular lesions, lowest hemoglobin level (OR 0.634, 95 % CI 0.422-0.953, P = 0.028) and hematologic disease (OR 8.575, 95 % CI 1.076-68.309, P = 0.042) were identified as risk factors in occult cases, whereas hemodialysis (OR 3.71, 95 % CI 1.315-10.467, P = 0.013) was identified in overt cases. Additionally, liver cirrhosis was noted as a risk factor in both occult (OR 7.453, 95 % CI 1.213-45.773, P = 0.013) and overt (OR 4.900, 95 % CI 2.099-11.443, P < 0.001) OGIB cases. CONCLUSION: There are differences in risk factors related to ulcerative versus vascular lesions in the small intestine in occult and overt OGIB cases. Differences were seen in both medication usage and comorbidities.

Optimal management for patients not meeting the inclusion criteria after endoscopic submucosal dissection for gastric cancer.

BACKGROUND: The necessity of additional gastrectomy for patients not meeting the inclusion criteria after endoscopic submu cosal dissection (ESD) is controversial. The aim of this study was to elucidate the risk factors for lymph node metastasis (LNM) and residual cancer (RC) in patients not meeting the inclusion criteria after ESD and to determine additional treatment strategies. METHODS: Of 1443 gastric cancer patients who underwent ESD between 2004 and 2013, 167 patients diagnosed as having a lesion not meeting the inclusion criteria after ESD were retrospectively analyzed. Of the 167 cases, 100 cases underwent additional gastrectomy, and 67 cases were observed without surgery. RESULTS: Overall, 9.0 % (9/100) and 9.0 % (9/100) of patients not meeting the inclusion criteria after ESD presented with LNM and RC, respectively, but neither was observed in 83 patients (83.0 %). Multivariate analysis revealed that lymphovascular involvement (LVI) (OR 38.38; 95 % CI 1.94-761.43, p = 0.017) and undifferentiated type (OR 45.58; 95 % CI 2.88-720.94, p = 0.007) were independent risk factors for LNM, and positive horizontal margin was an independent risk factor for RC (OR 9.48; 95 % CI 1.72-52.13, p = 0.010). In differentiated types without LVI, no cases had LNM (0/38) in the additional gastrectomy group, and there was no lymph node or distant recurrence (0/39) in the observation group. CONCLUSIONS: Additional treatment is necessary for patients with LVI, undifferentiated type, and positive horizontal margin. Careful follow-up may be acceptable for patients with the differentiated type without LVI, especially for the elderly or patients with severe comorbidities.

Rectal biopsy, rather than ileal, is appropriate to confirm the diagnosis of early gastrointestinal graft-versus-host disease.

OBJECTIVE: Once gastrointestinal (GI) graft-versus-host disease (GVHD) occurs after hematopoietic stem cell transplantation, it may be life-threatening. Therefore, an earlier accurate diagnosis of macroscopic and microscopic features using an appropriate modality improves the prognosis of patients with suspected GI-GVHD. PATIENTS AND METHODS: In patients experiencing watery diarrhea within 100 days after hematopoietic stem cell transplantation, we evaluated the severity of mucosal injury at the proximal ileum, terminal ileum, and rectum according to previously reported criteria using transanal single balloon endoscopy. GI-GVHD was diagnosed by the presence of gland apoptosis without inflammatory or infectious factors in the biopsied specimens obtained from their respective site regardless of the mucosal lesion. RESULTS: Consecutive suspected GI-GVHD patients with watery diarrhea (11 men and 5 women, mean age: 45.6 years, coexistent symptoms: nausea [38%] and exanthema [69%]) were enrolled. GI-GVHD was identified pathologically in 11 patients (69%), all of whom had pathological findings of GI-GVHD at the rectum. However, eight patients (73%) had pathological findings of GI-GVHD at both the ileum and the rectum and none had pathological findings of GI-GVHD at the ileum alone. The accuracies for a pathological diagnosis of GI-GVHD based on endoscopic features were 44%, 44%, and 38% at the proximal ileum, terminal ileum, and rectum, respectively. The severity of mucosal injury had no association with the diagnostic rate of pathological GI-GVHD at any site. CONCLUSIONS: A pathological evaluation of the rectum but not the ileum may be important and useful for the accurate diagnosis of early GI-GVHD.

The prevalence of adverse events associated with double-balloon enteroscopy from a single-centre dataset in Japan.

BACKGROUND: There are few comprehensive reports detailing the prevalence of major adverse events associated with a double-balloon enteroscopy procedure. METHODS: We retrospectively investigated the prevalence of major adverse events in 538 patients (262 males and 276 females; median age, 65 years; age range, 12-95 years) who underwent double-balloon enteroscopy at our Institution between April 2008 and October 2011. RESULTS: Of the 17 adverse events recorded (3.2%), acute pancreatitis (n=5; 0.9%) occurred during both diagnostic (n=3) and therapeutic (n=2) anterograde double-balloon enteroscopy, and all of them were treated conservatively. For these cases, the average duration of the examination was 135 min, which was longer than for the other patients (97 min) (P=0.046). Intestinal bleeding (1.3%) was observed in 6 cases after endoscopic polypectomy and in 1 case following a biopsy procedure during a diagnostic double-balloon enteroscopy. The prevalence rates of intestinal perforation and other complications were 0.2% and 0.7%, respectively. CONCLUSIONS: The rate of adverse events associated with double-balloon enteroscopy was high compared to that associated with conventional upper/lower gastrointestinal endoscopy (0.042%/0.078%). The occurrence of acute pancreatitis may be significantly dependent on the duration of double-balloon enteroscopy examination.

Endoscopic resection of a vocal cord polyp with a bipolar snare in a patient with cervical disc herniation.

A 55-year-old male with progressively worsening hoarseness was found to have a vocal cord polyp of >10 mm in diameter on the right true cord. It was necessary to remove the polyp in order to prevent airway obstruction by prolapse. However, the patient was a poor candidate for resection by standard otolaryngologic procedures because of the large size of the polyp and because he had a symptomatic cervical disc herniation. Therefore, endoscopic resection under general anesthesia using a bipolar electrocautery snare was selected. This case was our first attempt to treat a vocal cord polyp using this technique, and we found that polypectomy with the bipolar snare was an efficient and safe method for the treatment of this lesion.

Endoscopic radial incision and cutting method for refractory esophageal stricture after endoscopic submucosal dissection of superficial esophageal carcinoma.

A 59-year-old woman and a 69-year-old man had esophageal strictures that were refractory to over 10 therapeutic attempts with endoscopic balloon dilation (EBD) after endoscopic submucosal dissections (ESD) for superficial esophageal carcinoma (SEC). The strictured lesions in both patients improved remarkably with a new endoscopic modality (endoscopic radial incision and cutting [ERIC]), which was carried out one to three times, and stricture recurrence was not noted throughout the follow-up period. ERIC is a safe and efficient method for treating refractory strictures after EBD caused by ESD for SEC.

Possible antistenotic effect of tranilast in a patient with small bowel tuberculosis to prevent intestinal obstruction due to stenosis progression by antituberculous chemotherapy.

Small intestinal tuberculosis is a rare disorder of the small intestine. We report the development of deep small bowel tuberculosis in a rheumatoid arthritis patient who was taking methotrexate. The diagnosis of small bowel tuberculosis was ascertained by typical endoscopic findings and production of interferon gamma in the peripheral blood. The patient was successfully treated with antituberculous chemotherapy combined with an antifibrotic agent, tranilast, to suppress the progression of intestinal stenosis toward symptomatic stricture.