Optimization of Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection Strategies for Rectal Neuroendocrine Tumors Within 20 mm.

AIMS: No consensus regarding the optimal endoscopic resection approach for rectal neuroendocrine tumors (R-NETs) measuring 10-20 mm, this study aims to investigate this issue. METHODS: Patients with R-NETs underwent either endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). The primary endpoint was the complete resection rate, and the secondary endpoints were surgery-related complications and long-term outcomes. RESULTS: 96 patients met the inclusion criteria, 84 patients completed endoscopic resection, and 5 patients were excluded. 79 patients were enrolled and divided into EMR (n = 21) and ESD groups (n = 58). 100% of ESD excisions reached the primary endpoint, while 90.5% of EMR. Endoscopic submucosal dissection can achieve higher R0 rate and lower positive margin rate than EMR. The mean operative time of ESD and EMR was 35.22 ± 8.96 min and 13.14 ± 3.26 min, respectively. The complication rates of ESD and EMR were 3.4% and 4.8%, respectively. For R-NETs between 10 mm and 20 mm, the R0 rate of ESD was significantly higher than that of EMR (100% vs 71.4%, P = .01) and the margin positive rate of ESD was significant lower than that of EMR (4.8% vs 42.9%, P < .05). Both ESD and EMR obtained 100% R0 resection of less than 10 mm R-NET. The median follow-up was 13 months (3-84 months); 1 patient relapsed 25 months after EMR and was re-treated with ESD. CONCLUSION: For R-NETs with a diameter less than 10 mm, both EMR and ESD were safe and effective and EMR is convenient and fast, with advantages. ESD offers superiority for R-NETs between 10 and 20 mm and can be considered as the preferred method.

Efficacy and safety of fecal microbiota transplantation for chronic insomnia in adults: a real world study.

Objective: To assess the efficacy and safety of fecal microbiota transplantation (FMT) for adult chronic insomnia. Methods: Patients treated with FMT for chronic diseases were divided into chronic insomnia and non-insomnia group. The primary endpoint was the efficacy of FMT for insomnia 4 weeks after treatment, the secondary endpoints included the impacts of FMT on anxiety, depression, health-related quality of life, gut microbiota, and adverse events associated with FMT. Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) were utilized to assess the efficacy of FMT on insomnia, self-rating anxiety/depression scale [Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS)] was employed to evaluate anxiety and depression. Quality of life was evaluated by SF-36. 16S rRNA sequencing was employed to analyze the gut microbiota and correlation analysis was performed. Results: Forty patients met the inclusion criteria and seven were excluded. 33 patients were enrolled and stratified into chronic insomnia group (N = 17) and non-insomnia group (N = 16). Compared to baseline, FMT significantly ameliorated the ISI (17.31 ± 5.12 vs. 5.38 ± 5.99), PSQI (14.56 ± 2.13 vs. 6.63 ± 4.67), SAS (54.25 ± 8.90 vs. 43.68 ± 10.64) and SDS (57.43 ± 10.96 vs. 50.68 ± 15.27) score and quality of life of chronic insomnia patients. 76.47% (13/17) of insomnia patients achieved the primary endpoints. In chronic insomnia patients, the relative abundance of Eggerthella marked enhanced at baseline, while the relative abundance of Lactobacillus, Bifidobacterium, Turicibacter, Anaerostipes, and Eisenbergiella significantly increased after FMT treatment, the latter positive correlated with the efficacy of FMT. Encouragingly, FMT also improved the sleep quality of non-insomnia patients. Conclusion: Eggerthella may potentially serve as a distinctive genus associated with chronic insomnia. FMT maybe a novel treatment option for adults with chronic insomnia and provide an alternative to traditional treatments for insomnia. The effects were positive correlated with the augmentation of probiotics, such as Bifidobacterium, Lactobacillus, Turicibacter, and Fusobacterium.

Comparison of the long-term efficacy and safety of multiple endoscopic rubber band ligations in a single session for varying grades of internal hemorrhoids.

BACKGROUND: There is no consensus on the number of ligation bands for varying grades of internal hemorrhoids (IH) in a single session of endoscopic rubber band ligation (ERBL). AIMS: The aims of this study were to investigate this issue. METHODS: Patients with IH were treated with ERBL. The primary endpoint was no hemorrhoid symptoms 6 weeks after ERBL. The secondary endpoints were postoperative complications and recurrence. RESULTS: One hundred twenty-three eligible patients met the inclusion criteria, and 3 patients were excluded. The average bands were 3.9 ± 1.1, and grade II hemorrhoids required significantly fewer bands than grade III hemorrhoids (3.45 ± 0.85 vs 4.35 ± 1.06, P = 0.000). 78.8% of patients achieved the primary endpoint. The efficacy of grade II hemorrhoids was higher than that of grade III hemorrhoids (87.8% vs 69.2%). The incidence of postoperative complications was not significantly correlated with the grade of hemorrhoids (P = 0.201) and the number of bands (P = 0.886). The median follow-up time was 14.3 ± 7.9 (1.3-30.9) months. The overall recurrence rate was 25.0%, with grade III significantly higher than grade I-II (32.8% vs 14.6%, P = 0.027). For grade III hemorrhoids, the recurrence rate was lower with more than 4 bands of ligation than with less than 4 bands (26.5% vs 53.3%). CONCLUSIONS: The average ERBL treatment of IH requires nearly four bands, and grade II hemorrhoids require less banding than grade III hemorrhoids, while the efficacy was better. Increasing the number of bands improves the treatment efficacy for grade III IH, which could be a strategy to reduce the recurrence rate without increasing postoperative complications.

Optimization of screening strategies for colorectal cancer based on fecal DNA and occult blood testing.

BACKGROUND: Fecal DNA and occult blood testing have been gradually developed for colorectal cancer (CRC) screening. Comparison of different testing strategies for these methods in CRC screening is in urgent need. This study aims to examine the efficacy of different testing strategies including multi-target fecal DNA testing, qualitative and quantitative fecal immunoassay tests (FITs). METHODS: Fecal samples were collected from patients diagnosed by colonoscopy. Tests using fecal DNA, quantitative FIT or qualitative FIT were performed on same fecal samples. Efficiency of different testing strategies within different populations was investigated. RESULTS: For high-risk populations (CRC and advanced adenoma), the positive rate of the three methods alone was 74.3-80%; the positive predictive values (PPVs) ranged from 37.3% to 77.8%, and the negative predictive values (NPVs) ranged from 86.3% to 92.2%. For combined testing strategies, the positive rate was 71.4-88.6%, PPVs ranged from 38.3% to 86.2%, and NPVs ranged from 89.6% to 92.9%. Parallel fecal multi-target DNA test and quantitative FIT appears to be superior when using a combined testing strategy. For the normal population, no significant difference was identified in efficacy between these methods when used alone and in combination. CONCLUSIONS: Single testing strategy among the three methods is more suitable for the general population screening, and the combined testing strategy is more suitable for high-risk populations screening. The use of different combination strategies may have superiority in CRC high-risk population screening, but cannot conclude significant differences which may be attributed to the small sample size, large samples controlled trials are needed.

Borderline Brenner tumor with abnormally high serum level of carbohydrate antigen 199: a rare case report and literature review.

Ovarian Brenner tumor with abnormally increased serum carbohydrate antigen 19-9 (CA19-9) level is extremely rare. A 70-year-old woman with abnormally elevated serum CA199 (1289 U/ml) found in routine physical examination. Pelvic CT and MRI scan revealed a large mass with large patches of calcification in the right adnexal area, and the patient achieved total hysterectomy and bilateral adnexectomy. Grossly, the right ovary had a solid enlargement of about 7.0 cm × 6.0 cm × 5.0 cm with irregular nodules and smooth surface and the cut surface of the mass showed that the tumor is cystic and solid. Microscopically, the tumor showed a background of fibrous tissue hyperplasia with nested and adenoid cell clusters with uniform cell size and clear boundaries. The cells were translucent with eosinophilic cytoplasm and calcification. Immunohistochemical staining showed CK7, CA125, and P63 presented diffusely strongly positive staining, while negativity for CK20, GATA3, AR, P53, and CgA. Ki-67 showed weak positive staining, about 1%. The serum CA199 level decreased significantly on the 5th day after surgery. Postoperative pathology and immunohistochemistry confirmed borderline Brenner tumor. This is the first to report a case of borderline Brenner tumor with an abnormally high serum level of CA199 before surgery. In clinical practice, the possibility of ovarian Brenner tumor should be considered when abnormal elevation of serum CA199 level cannot be reasonably explained.

An innovative endoscopic management strategy for postoperative fistula after laparoscopic sleeve gastrectomy.

BACKGROUND: Postoperative fistula is a life-threatening complication that lacks a standard treatment strategy after laparoscopic sleeve gastrectomy (LSG). This observational study is the first to report the efficacy and safety of endoscopic full-thickness resection (EFTR) combined with purse-string sutures in treating this complication. PATIENTS AND METHODS: The old fistula was resected by EFTR, cut radially, and then sutured with a purse-string. The primary endpoint was complete fistula closure within two months. Endoscopic procedure-related complications were also recorded. RESULTS: Eight of 788 LSG patients developed fistulas with an incidence of 1.01%, primarily under the gastroesophageal junction, and the average distance from the center of the fistula to the cardia was 30 ± 6.3 mm. Two patients were cured by conservative treatment, and six received endoscopic sutures. The time from LSG to fistula diagnosis was 12.3 ± 14.4 days. The time from fistula diagnosis to endoscopic repair was 43.8 ± 55.8 days and 21.4 ± 10.0 days after eliminating the data of first case. The average fistula size was 12 ± 10 mm, the average endoscopic procedure duration was 40 ± 16 min, and the average number of endoscopic procedures required was 1.6 ± 0.8. Five patients achieved the primary endpoint, and one patient refused a third endoscopic suture after two sutures. The endoscopy success rate was 83.3%. No endoscopic procedure-related complications occurred. CONCLUSIONS: EFTR combined with purse-string sutures is an innovative, safe, and effective endoscopic strategy for postoperative fistula after LSG, avoiding reoperation and allowing early oral feeding.

The Diagnostic Value of Serum Gastrin-17 and Pepsinogen for Gastric Cancer Screening in Eastern China.

OBJECTIVE: To evaluate the diagnostic value of gastrin-17 (G-17) and pepsinogen (PG) in gastric cancer (GC) screening in China, especially eastern China, and to determine the best diagnostic combination and threshold (cutoff values) to screen out patients who need gastroscopy. METHODS: The serum concentrations of G-17 and pepsinogen I and II (PGI and PGII) in 834 patients were analyzed, and the PGI/PGII ratio (PGR) was calculated. According to pathological results, patients can be divided into chronic nonatrophic gastritis (NAG)/chronic atrophic gastritis (CAG)/intraepithelial neoplasia (IN)/GC groups. The differences in G-17, PG, and PGR in each group were analyzed, and their values in GC diagnosis were evaluated separately and in combination. RESULTS: There were differences in serum G-17, PGII, and PGR among the four groups (NAG/CAG/IN/GC) (P ≤ 0.001). In total, 54 GC cases were diagnosed, of which 50% were early GC. There was no significant difference in the PGI levels among the four groups (P = 0.377). NAG and CAG composed the chronic gastritis (CG) group. The G-17 and PGII levels in the IN and GC groups were higher than those in the CG group (both P ≤ oth C), while the PGR levels were lower (P ≤ lower). When distinguishing NAG from CAG, the best cutoff value for G-17 was 9.25 pmol/L, PGII was 7.06 µg/L, and PGR was 12.07. When distinguishing CG from IN, the best cutoff value for G-17 was 3.86 pmol/L, PGII was 11.92 µg/L, and PGR was 8.26. When distinguishing CG from GC, the best cutoff value for G-17 was 3.89 pmol/L, PGII was 9.16 µg/L, and PGR was 14.14. The sensitivity, specificity, accuracy, and positive and negative predictive values of G-17/PGII/PGR for GC diagnosis were 83.3%/70.4%/79.6%, 51.8%/56.3%/47.8%, 53.8%/57.2%/49.9%, 10.7%/10.9%/9.6%, and 97.8%/96.5%/97.1%, respectively. The sensitivity, specificity, accuracy, and positive predictive and negative predictive values of PGII/G-17 vs. PGR/G-17 vs. PGR/PGII in the diagnosis of GC were 63.0% vs. 70.4% vs. 64.8%, 70.5% vs. 70.1% vs. 60.4%, 70.0% vs. 70.1% vs. 60.7%, 12.9% vs. 14.0% vs. 10.2%, and 96.5% vs. 97.2% vs. 96.1%, respectively. CONCLUSION: The PGII and G-17 levels in patients with gastric IN and GC were significantly increased, while the serum PGR level was significantly decreased. Serological detection is effective for screening GC. The combination of different markers can improve the diagnostic efficiency. The highest diagnostic accuracy was G-17 combined with PGR, and the best cutoff values were G - 17 > 3.89 pmol/L and PGR < 14.14.

Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study.

BACKGROUND: To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC). RESULTS: Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6-38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26-131.7%) in both the FMT (range 6-38 months) and control groups (range 7-35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation. CONCLUSIONS: Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.

TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway.

BACKGROUND: The goal of the present study was to investigate the effects of TAK-242 on the gut microbiota and the TLR4/JAK2/STAT3 signaling pathway in mice with dextran sulfate sodium (DSS)-induced colitis. RESULTS: At the phylum level, Bacteroidetes, Firmicutes, Actinobacteria, Cyanobacteria, Epsilonbacteraeota and Proteobacteria were the primary microbiota in the five groups. TAK-242 treatment significantly enhanced Verrucomicrobia and Actinobacteria; significantly decreased Cyanobacteria, Epsilonbacteraeota and Proteobacteria; and particularly promoted the growth of Akkermansia. TAK-242 markedly alleviated DSS-induced colitis symptoms and colonic lesions by promoting IL-10 release, inhibiting IL-17 release, downregulating TLR4 and JAK2/STAT3 mRNA and protein expression and increasing JAK2/STAT3 phosphorylation. CONCLUSION: TAK-242 modulates the structure of the gut microbiota in colitis and may be a novel therapeutic candidate for ulcerative colitis.

Rectal Indomethacin and Spraying of Duodenal Papilla With Epinephrine Increases Risk of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND & AIMS: Rectal indomethacin and spraying of the duodenal papilla with epinephrine might reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We performed a randomized trial to compare the effects of the combination of indomethacin and epinephrine (IE) vs indomethacin plus saline (IS) in prophylaxis of post-ERCP pancreatitis (PEP). METHODS: We performed a double-blind trial at 10 centers in China, from February 2017 to October 2017, of 1158 patients with native papilla undergoing ERCP. The patients were assigned randomly to groups given IE (n = 576) or IS (n = 582). All patients received a single dose of rectal indomethacin within 30 minutes before ERCP; 20 mL of dilute epinephrine (IE group) or saline (IS group) then was sprayed on the duodenal papilla at the end of ERCP. The primary outcome was the incidence of overall PEP. Data were analyzed on an intention-to-treat principle. RESULTS: The study was terminated at the interim analysis for safety concerns and futility. The groups had similar baseline characteristics. PEP developed in 49 patients in the IE group (8.5%) and in 31 patients in the IS group (5.3%) (relative risk, 1.60, 95% CI, 1.03-2.47; P = .033). There were no significant differences between groups in proportions of patients with postsphincterotomy bleeding (2.1% in the IE group and 1.5% in the IS group) and biliary infection (1.2% in the IE group and 2.2% in the IS group). CONCLUSIONS: In a randomized trial, we found the combination of rectal indomethacin with papillary epinephrine spraying increased the risk of PEP compared with indomethacin alone. Spray epinephrine should not be used with rectal indomethacin for prevention of post-ERCP pancreatitis. ClincialTrials.gov no: NCT03057769.