The Management of Direct Oral Anticoagulants for Colorectal Endoscopic Submucosal Dissection: A Multicenter Observational Study.

BACKGROUND: There is a lack of reports on the use of direct oral anticoagulants (DOACs) during colorectal endoscopic submucosal dissection (ESD). AIMS: We aimed to assess whether the use of DOACs is associated with a higher incidence of delayed bleeding (DB) after ESD. METHODS: A total of 4175 colorectal neoplasms in 3515 patients were dissected at our hospitals during study period. We included 3909 lesions in the final analysis. The lesions were divided into two groups: the no-AT group (3668 neoplasms) and the DOAC group (241 neoplasms). We also compared the DOAC withdrawal group (154 neoplasms) and the DOAC continuation group (87 neoplasms). RESULTS: Among the 3909 lesions, DB occurred in a total of 90 cases (2.3%). The rate of DB was 2.2% (82/3668), and 3.3% (8/241), respectively. There were no significant differences in the rate of DB between the no-AT group and the DOAC group. In the DOAC group, there were no significant differences in the rate of DB between the withdrawal group (5.2%, 8/154) and the continuation group (0%, 0/87). The multivariable analysis identified the location of the lesion in the rectum (odds ratio [OR], 4.04; 95% confidence interval [CI], 2.614-6.242; p < 0.001) and lesions ≥ 30 mm in diameter (OR, 4.14; 95% CI, 2.349-7.34; p < 0.001) as independent risk factors for DB. CONCLUSIONS: Our findings suggest that DOAC use has no significant important on the rate of DB. Prospective studies are warranted to determine whether treatment with DOACs should be interrupted prior to colorectal ESD.

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.

New strategy for MS treatment with autoantigen-modified liposomes and their therapeutic effect.

As current treatments for multiple sclerosis (MS) remain chemotherapeutic ones directed toward symptoms, the development of a curative treatment is urgently required. Herein, we show an autoreactive immune cell-targetable approach using autoantigen-modified liposomes for the curative treatment of MS. In these experiments, experimental autoimmune encephalomyelitis (EAE) induced by autoantigenic myelin oligodendrocyte glycoprotein (MOG) peptide was used as a model of primary progressive MS, and MOG-modified liposomes encapsulating doxorubicin (MOG-LipDOX) were used as a therapeutic drug. The results showed that the progression of encephalomyelitis symptoms was significantly suppressed by MOG-LipDOX injection, whereas the other samples failed to show any effect. Additionally, invasion of inflammatory immune cells into the spinal cord and demyelination of neurons were clearly suppressed in the MOG-LipDOX-treated mice. FACS analysis revealed that the number of both MOG-recognizable CD4+ T cells in the spleen was obviously decreased after MOG-LipDOX treatment. Furthermore, the number of effector Th17 cells in the spleen was significantly decreased and that of regulatory Treg cells was concomitantly increased. Finally, we demonstrated that myelin proteolipid protein (PLP)-modified liposomes encapsulating DOX (PLP-LipDOX) also showed the therapeutic effect on relapsing-remitting EAE. These findings indicate that autoantigen-modified liposomal drug produced a highly therapeutic effect on EAE by delivering the encapsulated drug to autoantigen-recognizable CD4+ T cells and thus suppressing autoreactive immune responses. The present study suggests that the use of these autoantigen-modified liposomes promises to be a suitable therapeutic approach for the cure of MS.

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.

Risk factors for post-colorectal endoscopic submucosal dissection (ESD) coagulation syndrome: a multicenter, prospective, observational study.

BACKGROUND AND STUDY AIMS: Colorectal cancer (CRC) is one of the most common neoplasms and endoscopic submucosal dissection (ESD) is an effective treatment for early-stage CRC. However, it has been observed that patients undergoing ESD often complain of pain, even if ESD has been successfully performed. Risk factors for such pain still remain unknown. The aim of this study was to explore the risk factors for post-colorectal ESD coagulation syndrome (PECS). PATIENTS AND METHODS: This was a prospective multicenter observational trial (UMIN000016781) conducted in 106 of 223 patients who underwent ESD between March 2015 and April 2016. We investigated age, sex, tumor location, ESD operation time, lesion size, duration of hospitalization, and frequency of PECS. We defined PECS as local abdominal pain (evaluated on a visual analogue scale) in the region corresponding to the site of the ESD that occurred within 4 days of the procedure. RESULTS: PECS occurred in 15/106 (14.2 %), and 10 were women ( P  = 0.01, OR: 7.74 [1.6 - 36.4]), 7 had lesions in the cecum ( P  < 0.001, OR: 20.6 [3.7 - 115.2]), and 9 in whom ESD operation time was > 90 min ( P  = 0.002, OR: 10.3 [2.4 - 44.6]). Frequency of deviation from the prescribed clinical path was significantly higher (47 % [7/15] vs. 2 % [2/91], P  < 0.001, OR: 38.9 [6.9 - 219.6]), and hospital stay was significantly longer in the PECS group. . CONCLUSIONS: Female gender, location of lesion in the cecum, and ESD operation time > 90 minutes were significant risk factors independent of PECS. These findings are important to management of PECS. .

Continued Use of a Single Antiplatelet Agent Does Not Increase the Risk of Delayed Bleeding After Colorectal Endoscopic Submucosal Dissection.

BACKGROUND: With the aging of the population and rising incidence of thromboembolic events, the usage of antiplatelet agents is also increasing. There are few reports yet on the management of antiplatelet agents for patients undergoing colorectal endoscopic submucosal dissection (ESD). AIMS: The aim of this study is to evaluate whether continued administration of antiplatelet agents is associated with an increased rate of delayed bleeding after colorectal ESD. METHODS: A total of 1022 colorectal neoplasms in 927 patients were dissected at Yokohama City University Hospital and its three affiliate hospitals between July 2012 and June 2017. We included the data of 919 lesions in the final analysis. The lesions were divided into three groups: the no-antiplatelet group (783 neoplasms), the withdrawal group (110 neoplasms), and the continuation group (26 neoplasms). RESULTS: Among the 919 lesions, bleeding events occurred in a total of 31 (3.37%). The rate of bleeding after ESD was 3.3% (26/783), 4.5% (5/110), and 0% (0/26), respectively. There were no significant differences in the rate of bleeding after ESD among the three groups (the withdrawal group vs. the no-antiplatelet group, the continuation group vs. the no-antiplatelet group, and the withdrawal group vs. the continuation group). CONCLUSIONS: Continued administration of antiplatelet agents is not associated with any increase in the risk of delayed bleeding after colorectal ESD. Prospective, randomized studies are necessary to determine whether treatment with antiplatelet agents must be interrupted prior to colorectal ESD in patients who are at a high risk of thromboembolic events.