Effects of colorectal endoscopic submucosal dissection on postoperative abdominal symptoms: a prospective observational study.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective procedure to resect large superficial gastrointestinal neoplasms. In gastric ESD, several studies showed the relationship between postoperative abdominal symptoms and endoscopic treatment. However, the influence of colorectal ESD on abdominal symptoms after treatment is still unknown. To the best of our knowledge, this is the first prospective multicenter study performed to investigate the impact of colorectal ESD on postoperative abdominal symptoms. This study aimed to clarify the association between change of abdominal symptoms and ESD. METHODS: This study was a prospective multicenter observational trial that enrolled 141 out of 171 patients who underwent colorectal ESD and answered the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire from March 2015 to August 2019. We evaluated abdominal symptoms in the patients using the GSRS questionnaire before ESD and a few weeks after ESD. RESULTS: Comparing the GSRS before and after ESD, overall scores changed from 1.58 ± 0.58 to 1.48 ± 0.48, and the five subscales (reflux syndrome, abdominal pain, indigestion syndrome, diarrhea syndrome, and constipation syndrome) were slightly improved. Overall scores, indigestion syndrome, and constipation syndrome were statistically significantly different before and after ESD (P < 0.05). CONCLUSIONS: In GSRS, a score of ≥ 3 is often treated as a clinically significant symptom. Therefore, our findings indicated that there was no clinically significant difference. For this reason, colorectal ESD does not affect postoperative abdominal symptoms and is considered a minimally invasive treatment. The analysis of the impact of colon ESD on gastrointestinal symptoms UMIN000016914.

Efficacy and safety of colorectal endoscopic submucosal dissection in patients with sarcopenia.

BACKGROUND: Endoscopic submucosal dissection (ESD) for early-stage colorectal cancer (CRC) has become a common and useful treatment. Although sarcopenia has been identified as an independent risk factor for complications after surgery for CRC, whether sarcopenia is also an independent risk factor for complications after colorectal ESD remains to be clarified. The aim of this study was to compare the outcomes of colorectal ESD in patients with and those without sarcopenia. METHODS: This is a retrospective cohort study. A total of 334 patients underwent colorectal ESD for 361 neoplasms at Hiratsuka City Hospital from March 2012 to October 2018. The neoplasms were divided into two groups depending on the presence or absence of sarcopenia in the patients. RESULTS: Overall, 334 patients underwent colorectal ESD for 361 neoplasms during the study period. We excluded 90 patients (90 neoplasms), and 244 patients (277 neoplasms) were included in the final analysis (134 from the sarcopenia group, 137 from the non-sarcopenia group). The en-bloc resection rate was high and was not significantly different between the sarcopenia group [126/134 (94.1%)] and the non-sarcopenia group [133/137 (97.1%)], P = 0.1778). The rate of perforation and the rate of delayed bleeding were not significantly different between the sarcopenia group and the non-sarcopenia group [6/134 (4.5%) vs. 9/137 (6.6%), P = 0.314, 4/134 (3%) vs. 6/137 (4.4%), P = 0.3885, respectively]. CONCLUSIONS: The presence of sarcopenia did not influence the rate of complications after ESD. Colorectal ESD is safe and effective even in patients with sarcopenia. Prospective multicenter studies are necessary to confirm our results.

Percent reduction of the ulcer size at 4 weeks is a predictor of the complete healing of endoscopic submucosal dissection-induced gastric ulcers.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is widely used as a treatment modality for gastric mucosal neoplasia. While proton pump inhibitors (PPIs) have been used for the control of artificial ulcers created by ESD (ESD-ulcers), complete healing of the ulcers is not always achieved in all the cases. The purpose of this study was to identify the clinical factors that are predictive of refractory ESD-ulcers. PATIENTS AND METHODS: We recruited 90 patients with 102 artificial ulcers that formed after the patients underwent ESD for gastric tumours. All the patients received a 20-mg capsule of esomeprazole daily until the 56th day after ESD, and underwent endoscopy at 1, 4, 6 and 8 weeks after the ESD. We analyzed the clinical factors that were associated with the complete healing at 8 weeks after the ESD (CH-8w). The ulcers in the scar stage were defined as the complete healing in this study. RESULTS: Of the 102 ESD-ulcers, 16.7% failed to show complete healing after the 8 weeks of PPI therapy. Univariate analysis identified the percent reduction of the ulcer size at 4 weeks after ESD (PR-4w) as being significantly associated with CH-8w. Multivariate analysis identified ulcer location in the lower-third of the stomach and PR-4w > 95% as being independently correlated with the CH-8w (odds ratio = 4.86 and 7.89, respectively). Analysis of the area under the receiver operating characteristic (AUROC) curve demonstrated that the AUROC curve of PR-4w for predicting the CH-8w was 0.78. CONCLUSION: Based on the results of our study, endoscopic observation at 4 weeks after ESD would help in the early identification of refractory ESD-ulcers.

Is a fecal occult blood test a useful tool for judging whether to perform capsule endoscopy in low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy?

BACKGROUND: Aspirin use is reportedly not to be associated with fecal immunochemical occult blood test (FIT) false-positive results for the detection of colorectal cancer. The need for additional small bowel exploration in FIT-positive, low-dose aspirin users with a negative colonoscopy is controversial. The aim of this study was to assess the ability of FIT to judge whether capsule endoscopy (CE) should be performed in low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy findings by comparing FIT results with CE findings. METHODS: A total of 264 consecutive low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy who were scheduled to undergo CE at five hospitals in Japan were enrolled. Patients had been offered FIT prior to the CE. The association between the FIT results and the CE findings was then assessed. RESULTS: One hundred and fifty-seven patients were included in the final analysis. Eighty-four patients (53.5 %) had positive FIT results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of positive FIT results for small bowel ulcers were 0.56, 0.47, 0.30, and 0.73, respectively. Furthermore, the NPV of positive FIT results for severe small bowel injury (Lewis score ≥790) was markedly high (0.90). When the analysis was performed only in low-dose aspirin users with anemia, the sensitivity of the positive FIT results was notably improved (0.72). CONCLUSIONS: Small bowel evaluation using CE is not recommended for FIT-negative, low-dose aspirin users. However, small bowel evaluation using CE should be considered in both FIT-positive and anemic low-dose aspirin users.

Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial.

BACKGROUND: The prevalence of, and mortality from, colorectal cancer is increasing worldwide, and new strategies for prevention are needed to reduce the burden of this disease. The oral diabetes medicine metformin might have chemopreventive effects against cancer, including colorectal cancer. However, no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention. Therefore, we devised a 1-year clinical trial to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer (assessed by adenoma and polyp recurrence) in patients with a high risk of adenoma recurrence. METHODS: This trial was a multicentre, double-blind, placebo-controlled, randomised phase 3 trial. Non-diabetic adult patients who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy were enrolled into the study from five hospitals in Japan. Eligible patients were randomly assigned (1:1) to receive oral metformin (250 mg daily) or identical placebo tablets by a stratified computer-based randomisation method, with stratification by institute, age, sex, and body-mass index. All patients, endoscopists, doctors, and investigators were masked to drug allocation until the end of the trial. After 1 year of administration of metformin or placebo, colonoscopies were done to assess the co-primary endpoints: the number and prevalence of adenomas or polyps. Our analysis included all participants who underwent random allocation, according to the intention-to-treat principle. This trial is registered with University Hospital Medical Information Network (UMIN), number UMIN000006254. FINDINGS: Between Sept 1, 2011, and Dec 30, 2014, 498 patients who had had single or multiple colorectal adenomas resected by endoscopy were enrolled into the study. After exclusions for ineligibility, 151 patients underwent randomisation: 79 were assigned to the metformin group and 72 to the placebo group. 71 patients in the metformin group and 62 in the placebo group underwent 1-year follow-up colonoscopy. The prevalence of total polyps (hyperplastic polyps plus adenomas) and of adenomas in the metformin group was significantly lower than that in the placebo group (total polyps: metformin group 27 [38·0%; 95% CI 26·7-49·3] of 71 patients, placebo group 35 [56·5%; 95% CI 44·1-68·8] of 62; p=0·034, risk ratio [RR] 0·67 [95% CI 0·47-0·97]; adenomas: metformin group 22 [30·6%; 95% CI 19·9-41·2] of 71 patients, placebo group 32 [51·6%; 95% CI 39·2-64·1] of 62; p=0·016, RR 0·60 [95% CI 0·39-0·92]). The median number of polyps was zero (IQR 0-1) in the metformin group and one (0-1) in the placebo group (p=0·041). The median number of adenomas was zero (0-1) in the metformin group and zero (0-1) in the placebo group (p=0·037). 15 (11%) of patients had adverse events, all of which were grade 1. We recorded no serious adverse events during the 1-year trial. INTERPRETATION: The administration of low-dose metformin for 1 year to patients without diabetes was safe. Low-dose metformin reduced the prevalence and number of metachronous adenomas or polyps after polypectomy. Metformin has a potential role in the chemoprevention of colorectal cancer. However, further large, long-term trials are needed to provide definitive conclusions. FUNDING: Ministry of Health, Labour and Welfare, Japan.

Frequency and risk factors for rebleeding events in patients with small bowel angioectasia.

BACKGROUND: Small bowel angioectasia is reported as the most common cause of bleeding in patients with obscure gastrointestinal bleeding. Although the safety and efficacy of endoscopic treatment have been demonstrated, rebleeding rates are relatively high. To establish therapeutic and follow-up guidelines, we investigated the long-term outcomes and clinical predictors of rebleeding in patients with small bowel angioectasia. METHODS: A total of 68 patients were retrospectively included in this study. All the patients had undergone CE examination, and subsequent control of bleeding, where needed, was accomplished by endoscopic argon plasma coagulation. Based on the follow-up data, the rebleeding rate was compared between patients who had/had not undergone endoscopic treatment. Multivariate analysis was performed using Cox proportional hazard regression model to identify the predictors of rebleeding. We defined the OGIB as controlled if there was no further overt bleeding within 6 months and the hemoglobin level had not fallen below 10 g/dl by the time of the final examination. RESULTS: The overall rebleeding rate over a median follow-up duration of 30.5 months (interquartile range 16.5-47.0) was 33.8% (23/68 cases). The cumulative risk of rebleeding tended to be lower in the patients who had undergone endoscopic treatment than in those who had not undergone endoscopic treatment, however, the difference did not reach statistical significance (P = 0.14). In the majority of patients with rebleeding (18/23, 78.3%), the bleeding was controlled by the end of the follow-up period. Multiple regression analysis identified presence of multiple lesions (≥3) (OR 3.82; 95% CI 1.30-11.3, P = 0.02) as the only significant independent predictor of rebleeding. CONCLUSION: In most cases, bleeding can be controlled by repeated endoscopic treatment. Careful follow-up is needed for patients with multiple lesions, presence of which is considered as a significant risk factor for rebleeding.

Metabolic factors accelerate colorectal adenoma recurrence.

BACKGROUND: Metabolic factors have been reported to increase the prevalence of colorectal adenomas, however, whether metabolic factors might also accelerate the recurrence after removal of adenomas has not yet been discussed. In this retrospective multicenter study, we clarified the risk factors for adenoma recurrence focusing on metabolic factors. METHODS: We analyzed the medical records of 43,195 patients who had undergone colonoscopy between January 2005 and December 2011 at 5 hospitals in Japan. Of these, the data of 1111 patients who had undergone removal of adenomas at the first screening colonoscopy, and then been followed up by colonoscopy 1 year and 2 years later were analyzed. RESULTS: The following 8 factors were demonstrated with a multivariate analysis as being associated with colorectal adenomas recurrence: for adenoma-related factors, 5 factors (villous features, grade of dysplasia, location and size of the largest removed adenoma, and number of the removed adenomas) were identified; for metabolic factors and other factors, 3 factors (age, body mass index (BMI), and fasting blood glucose (FBG)) were identified. A risk score (0-10 points) was developed based on these 8 factors. The risk of adenoma recurrence increased as the risk score increased. When the risk score was ≥3 (3-10) points, the odds ratio relative to <3 (0-2) points was 7.07 (95% CIs 5.30-9.43). CONCLUSIONS: In addition to adenoma-related factors (villous features, grade of dysplasia, location, size and number), 3 factors (age, BMI and FBG) were demonstrated to influence the recurrence rate of colorectal adenoma. When the risk score was ≥3, the risk of recurrence was significantly elevated.

Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry.

BACKGROUND: To develop appropriate management strategies for patients who take low-dose aspirin, it is important to identify the risk factors for GI injury. However, few studies have described the risk factors for small-bowel injury in these patients. OBJECTIVE: To investigate factors influencing the risk of small-bowel mucosal breaks in individuals taking continuous low-dose aspirin. DESIGN: Capsule endoscopy data were collected prospectively from 5 institutions. SETTING: Yokohama City University Hospital and 4 other hospitals. PATIENTS: A total of 205 patients receiving treatment with low-dose aspirin for over 3 months. INTERVENTIONS: Colonoscopic and upper GI endoscopy had been performed in all of the patients before the capsule endoscope evaluation. MAIN OUTCOME MEASUREMENTS: Risk factors for small-bowel mucosal breaks. RESULTS: Of the 198 patients (141 male; mean age 71.9 years) included in the final analysis, 114 (57.6%) had at least 1 mucosal break. Multivariate analysis identified protein pump inhibitor (PPI) use (OR 2.04; 95% confidence interval [CI], 1.05-3.97) and use of enteric-coated aspirin (OR 4.05; 95% CI, 1.49-11.0) as independent risk factors for the presence of mucosal breaks. LIMITATIONS: Cross-sectional study. CONCLUSION: PPI use appears to increase the risk of small-bowel injury in patients who take continuous low-dose aspirin. Clinicians should be aware of this effect of PPIs; new strategies are needed to treat aspirin-induced gastroenteropathy.

Characteristics of the small bowel lesions detected by capsule endoscopy in patients with chronic kidney disease.

Obscure gastrointestinal bleeding (OGIB) is one of the common complications in patients with chronic kidney disease (CKD), especially those who are on maintenance hemodialysis (HD). However, little is known about the characteristics of the small-bowel lesions in these patients, or of the factors that could predict the presence of such lesions. Therefore we enrolled a total of 42 CKD patients (including 19 HD patients and 23 non-HD patients), and compared the incidence of the small-bowel lesions among two groups. Furthermore, to identify predictive factors for the presence of small-bowel lesions, we performed multivariate logistic-regression-analyses. The incidence of small-bowel vascular lesions was significantly higher in CKD patients than in age-and-sex matched non-CKD patients (P < 0.001). On the other hand, there was any significant difference of the incidence of small-bowel lesions between HD and non-HD patients. In CKD patients, past history of blood transfusion (OR 5.66; 95% CI 1.10-29.1, P = 0.04) was identified as an independent predictor of the presence of vascular lesions, and history of low-dose aspirin use (OR 6.00; 95% CI 1.13-31.9, P = 0.04) was identified as that of erosive/ulcerated lesions. This indicated that proactive CE examination would be clinically meaningful for these patients.

Factors predicting the presence of small bowel lesions in patients with obscure gastrointestinal bleeding.

AIM: To identify the predictive factors for the presence of small bowel lesions in patients with obscure gastrointestinal bleeding (OGIB). METHODS: A total of 242 patients with OGIB (overt 149: occult 93) were retrospectively included in the present study. Capsule endoscopy (CE) was carried out to investigate the small bowel, and detected lesions were classified according to the P0-P2 system. Only P2 lesions were defined as significant lesions. Univariate and multivariate logistic regression analyses were carried out to define the predictive factors for the presence of small bowel lesions. RESULTS: In patients with overt OGIB, chronic kidney disease (CKD) ≥stage 4 (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.45-11.1, P = 0.007) was identified as an independent predictor of the presence of vascular lesions, and a history of non-steroidalanti-inflammatory drug (NSAID) use as that of erosive/ulcerated lesions (OR 4.73; 95% CI 1.47-15.2, P = 0.009). However, in patients with occult OGIB, no significant predictors of the presence of vascular lesions were identified, whereas a history of low-dose aspirin (LDA) (OR 3.57; 95% CI 1.21-10.5, P = 0.02) and proton pump inhibitor (PPI) use (OR 3.18; 95% CI 1.02-9.92, P = 0.05) were identified as independent predictors of the presence of erosive/ulcerated lesions. CONCLUSIONS: Our results indicated that bleeding pattern and clinical characteristics could contribute to predicting the origin of OGIB.

Capsule endoscopy with flexible spectral imaging color enhancement reduces the bile pigment effect and improves the detectability of small bowel lesions.

BACKGROUND: Capsule endoscopy with flexible spectral imaging color enhancement (CE-FICE) has been reported to improve the visualization and detection of small-bowel lesions, however, its clinical usefulness is still not established. Therefore, we conducted a study to evaluate whether CE-FICE contributes to improve the detectability of small-bowel lesions by CE trainees. METHODS: Four gastroenterology trainees without prior CE experience were asked to read and interpret 12 CE videos. Each of the videos was read by conventional visualization method and under three different FICE settings. To evaluate whether the lesion recognition ability of the CE trainees could be improved by the FICE technology, the lesion detection rate under each of the three FICE settings was compared with that by conventional CE. CE trainees tend to miss small-bowel lesions in bile-pigment-positive condition, therefore we evaluated whether CE-FICE contributes to reducing the bile-pigment effect. The bile-pigment condition was determined by the color values around the small-bowel lesions according to the results of the receiver-operating-characteristic analysis. Moreover, we also evaluated whether poor bowel preparion might affect the accuracy of lesion recognition by CE-FICE. RESULTS: Of a total of 60 angioectasias, CE trainees identified 26 by conventional CE, 40 under FICE setting 1, 38 under FICE setting 2, and 31 under FICE setting 3. Of a total of 82 erosions/ulcerations, CE trainees identified 38 by conventional CE, 62 under FICE setting 1, 60 under FICE setting 2, and 20 under FICE setting 3. Compared with conventional CE, FICE settings 1 and 2 significantly improved the detectability of angioectasia (P = 0.0017 and P = 0.014, respectively) and erosions/ulcerations (P = 0.0012 and P = 0.0094, respectively). Although the detectability of small-bowel lesions by conventional CE (P = 0.020) and under FICE setting 2 (P = 0.0023) was reduced by the presence of bile-pigments, that under FICE setting 1 was not affected (P = 0.59). Our results also revealed that in poor bowel visibility conditions, CE-FICE yielded a high rate of false-positive findings. CONCLUSIONS: CE-FICE may reduce the bile-pigment effect and improve the detectability of small-bowel lesions by CE trainees; the reliability of CE-FICE may be improved by good bowel preparation.