Clinicopathological characteristics of Lynch-like syndrome.

BACKGROUND: Lynch-like syndrome (LLS) has recently been proposed as a third type of microsatellite instability (MSI) tumor after Lynch syndrome (LS) and sporadic MSI colorectal cancer (CRC) without either a germline variant of mismatch repair (MMR) genes or hypermethylation of the MLH1 gene. The present study aimed to clarify and compare the clinicopathological characteristics of LLS with those of the other MSI CRC subtypes. METHODS: In total, 2634 consecutive patients with CRC who underwent surgical resection and subsequently received universal tumor screening (UTS), including MSI analysis were enrolled between January 2008 and November 2019. Genetic testing was performed in patients suspected of having Lynch syndrome. RESULTS: UTS of the cohort found 146 patients with MSI CRC (5.5%). Of these, excluding sporadic MSI CRC, 30 (1.1%) had a diagnosis of LS, and 19 (0.7%) had no germline pathogenic variants of the MMR gene. The CRC type in the latter group was identified as LLS. LLS occurred significantly more often in young patients, was left-sided, involved a KRAS variant and BRAF wild-type, and had a higher concordance rate with the Revised Bethesda Guidelines than sporadic MSI CRC. No significant differences were observed in terms of the clinicopathological factors between LLS and LS-associated MSI CRC; however, LLS had a lower frequency of LS-related neoplasms compared with LS. CONCLUSIONS: Distinguishing clinically between LS and LLS was challenging, but the incidence of neoplasms was higher in LS than in LLS, suggesting the need for different screening and surveillance methods for the two subtypes.

A Novel Hemostatic Peptide Solution for Common Acute Gastrointestinal Bleeding Diseases: First Case Series Study on the Treatment Results of Endoscopic Hemostasis by Nonexpert Endoscopists.

INTRODUCTION: We investigated the hemostatic effect and safety of a hemostatic peptide solution for the treatment of gastrointestinal bleeding requiring emergency endoscopy. METHODS: We retrospectively examined the patient backgrounds, hemostatic results, and procedural safety in patients who were treated with a hemostatic peptide solution for hemostasis during emergency endoscopies for gastrointestinal bleeding. All hemostatic procedures were performed by nonexpert physicians with less than 10 years of endoscopic experience. All of the cases were treated at a single institution over the months from January 2022 to January 2023. RESULTS: Twenty-six consecutive patients (17 males and 9 females) with a median age of 74 (45-95) years were included. Their conditions requiring emergency endoscopy were melena in 8 patients, hematochezia in 2, hematemesis in 8, anemia in 6, and bleeding during esophagogastroduodenoscopy in 2. The sites of bleeding were the esophagus in 3 patients, the stomach in 17, the duodenum in 3, the small intestine in 2, and the colon in 1. Hemostasis was obtained with another hemostasis device used in conjunction with the hemostatic peptide solution in 13 cases and with the hemostatic peptide solution alone in 13 cases. The hemostasis success rate was 100%, with no complications. Rebleeding occurred within 1 week in 4 cases. CONCLUSION: Hemostasis with the hemostatic peptide solution was safe and provided a temporary high hemostatic effect in emergency gastrointestinal endoscopy.

Changes in oral microflora following 0.3% cetylpyridinium chloride-containing mouth spray intervention in adult volunteers after professional oral care: Randomized clinical study.

OBJECTIVES: This study explored the changes in bacterial flora composition and total bacterial count in the saliva and tongue coating, along with the change in the tongue coating index (TCI) following an intervention with 0.3% cetylpyridinium chloride (CPC) mouth spray after professional oral care. MATERIALS AND METHODS: Fifty-two adult volunteers aged 30-60 years were equally divided into CPC spray (n = 26) and control (n = 26) groups. All subjects underwent scaling and polishing. The CPC spray group was administered four puffs of CPC spray to the tongue dorsum four times a day for 3 weeks. The control group performed only routine daily oral care (brushing) and did not use any other spray. Bacteriological evaluation of saliva and tongue coating was performed using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction. The tongue coating was evaluated to calculate the TCI. A per-protocol analysis was conducted for 44 subjects (CPC spray group, n = 23; control group, n = 21). RESULTS: At 1 and 3 weeks after CPC spray use, the flora of the saliva and tongue coating changed; the genus Haemophilus was dominant in the CPC spray group, whereas the genus Saccharibacteria was dominant in the control group. The sampling time differed among individual participants, which may have affected the bacterial counts. There was no significant intragroup change in TCI in either group. CONCLUSIONS: CPC spray affected the bacterial flora in the saliva and tongue coating, particularly with respect to an increase in the abundance of Haemophilus. However, CPC spray did not change the TCI. These results suggest that it may be optimal to combine CPC spray with a physical cleaning method such as using a tongue brush or scraper. Clinical Trial Registration: University Hospital Medical Information Network UMIN000041140.

Multiple ulcerative colitis-associated aseptic abscesses successfully treated with infliximab: a case report.

Aseptic abscesses are rare extraintestinal manifestations of inflammatory bowel disease. Herein, we present the case of a 69-year-old female patient with ulcerative colitis in whom multiple aseptic abscesses were successfully treated with infliximab. Aseptic abscesses associated with ulcerative colitis are difficult to differentiate from infectious abscesses. In the present case, we reached a diagnosis of aseptic abscesses associated with ulcerative colitis as antibiotics were ineffective and repeated Gram stains and cultures of blood and abscess were negative. Aseptic abscesses are commonly found in the spleen, lymph nodes, liver, and skin; however, in the present case, the periosteum was the major site. Prednisolone is often effective for aseptic abscesses; however, the present patient was initially treated with a combination of 40 mg/day of prednisolone and granulocyte and monocyte adsorption apheresis, with inadequate effect. Infliximab was administered as the patient was steroid-resistant, with strong effect. Subsequently, infliximab treatment has been continued, with no recurrence after 2 years. However, as there have been reports of cases of recurrence even after remission with treatment, careful follow-up in the future is therefore necessary.

Simple drainage versus drainage with minocycline infusion for symptomatic hepatic cysts.

Percutaneous treatment of symptomatic hepatic cysts includes simple drainage and drainage with sclerosing agents. We compared the efficacy of simple drainage with that of drainage with minocycline infusion for treating symptomatic hepatic cysts. We retrospectively evaluated 11 patients who underwent percutaneous drainage of symptomatic hepatic cysts. In seven cases, minocycline infusion was added at the discretion of the clinician. Cyst volume was evaluated before drainage, immediately after drainage, and after long-term follow-up. Cyst volume was calculated before treatment by multiplying the orthogonal diameters using the ellipsoid formula. Relapse was defined as the regrowth of the cyst with symptoms. Cyst volume immediately after drainage and after long-term follow-up was significantly less than that before treatment for the drainage with minocycline infusion group (p<0.05) but not for the simple drainage group. The relapse rates were 25% (1/4) for the simple drainage group and 0% for the drainage with minocycline infusion group. Drainage with minocycline infusion could be a promising option for treating symptomatic hepatic cysts, although simple drainage was not reliable.

Efficacy and Safety of a Novel Hemostatic Peptide Solution During Endoscopic Submucosal Dissection: A Multicenter Randomized Controlled Trial.

INTRODUCTION: To compare the effectiveness of the novel hemostatic peptide, TDM-621, with that of conventional hemostatic methods in treating intraoperative blood oozing during endoscopic submucosal dissection (ESD). METHODS: This multicenter, open-label, randomized controlled trial involved 227 patients with gastric and rectal epithelial tumors in whom ESD was indicated. Patients in whom the source of blood oozing was difficult to identify with waterjet washing during the procedure and required hemostasis with hemostatic forceps were randomly assigned to the TDM-621 and control groups. The TDM-621 group (in which hemostasis was achieved with TDM-621, followed by coagulation hemostasis with hemostatic forceps, as needed) was compared with the control group (in which hemostasis was achieved with hemostatic forceps). The primary end point was the mean number of coagulations with hemostatic forceps, determined by a blinded independent review committee. The secondary end points were the rate of achievement of hemostasis with only TDM-621, the dosage of TDM-621, and adverse events in the TDM-621 group. RESULTS: The mean number of coagulations with hemostatic forceps was significantly reduced in the TDM-621 group (1.0 ± 1.4) compared with that in the control group (4.9 ± 5.2) ( P < 0.001). The rate of hemostasis achievement with only TDM-621 was 62.2%; the mean dosage of TDM-621 was 1.75 ± 2.14 mL. The rates of grade ≥3 adverse events were 6.2% and 5.0% in the TDM-621 and control groups, respectively. DISCUSSION: TDM-621 is a useful, easily operable hemostatic peptide for treatment of blood oozing during gastric and rectal ESD, with no serious safety concerns.

Dual functions of discoidinolysin, a cholesterol-dependent cytolysin with N-terminal discoidin domain produced from Streptococcus mitis strain Nm-76.

Background: Some strains of Streptococcus mitis exhibit ß-hemolysis due to the ß-hemolytic activity of cholesterol-dependent cytolysin (CDC). Recently, a gene encoding an atypical lectinolysin-related CDC was found in S. mitis strain Nm-76. However, the product of this gene remains uncharacterized. We aimed to characterize this atypical CDC and its molecular functions and contribution to the pathogenicity of S. mitis strain Nm-76. Methods: Phylogenetic analysis of the CDC gene was conducted based on the web-deposited information. The molecular characteristics of CDC were investigated using a gene-deletion mutant strain and recombinant proteins expressed in Escherichia coli. Results: The gene encoding CDC found in Nm-76 and its homolog are distributed among many S. mitis strains. This CDC is phylogenetically different from other previously characterized CDCs, such as S. mitis-derived human platelet aggregation factor (Sm-hPAF)/lectinolysin and mitilysin. Because this CDC possesses an additional N-terminal domain, including a discoidin motif, it was termed discoidinolysin (DLY). In addition to the preferential lysis of human cells, DLY displayed N-terminal domain-dependent facilitation of human erythrocyte aggregation and intercellular associations between human cells. Conclusion: DLY functions as a hemolysin/cytolysin and erythrocyte aggregation/intercellular association molecule. This dual-function DLY could be an additional virulence factor in S. mitis.

Clinical usefulness of red dichromatic imaging in hemostatic treatment during endoscopic submucosal dissection: First report from a multicenter, open-label, randomized controlled trial.

OBJECTIVES: To verify the efficacy and safety of red dichromatic imaging (RDI) in hemostatic procedures during endoscopic submucosal dissection (ESD). METHODS: This is a multicenter randomized controlled trial of 404 patients who underwent ESD of the esophagus, stomach, colorectum. Patients who received hemostatic treatments by RDI during ESD were defined as the RDI group (n = 204), and those who received hemostatic treatments by white light imaging (WLI) were defined as the WLI group (n = 200). The primary endpoint was a shortening of the hemostasis time. The secondary endpoints were a reduction of the psychological stress experienced by the endoscopist during the hemostatic treatment, a shortened treatment time, and a non-inferior perforation rate, in RDI versus WLI. RESULTS: The mean hemostasis time in RDI (n = 860) was not significantly shorter than that in WLI (n = 1049) (62.3 ± 108.1 vs. 56.2 ± 74.6 s; P = 0.921). The median hemostasis time was significantly longer in RDI than in WLI (36.0 [18.0-71.0] vs. 28.0 [14.0-66.0] s; P = 0.001) in a sensitivity analysis. The psychological stress was significantly lower in RDI than in WLI (1.71 ± 0.935 vs. 2.03 ± 1.038; P < 0.001). There was no significant difference in the ESD treatment time between RDI (n = 161) and WLI (n = 168) (58.0 [35.0-86.0] vs. 60.0 [38.0-88.5] min; P = 0.855). Four perforations were observed, but none of them took place during the hemostatic treatment. CONCLUSIONS: Hemostatic treatment using RDI does not shorten the hemostasis time. RDI, however, is safe to use for hemostatic procedures and reduces the psychological stress experienced by endoscopists when they perform hemostatic treatment during ESD. UMIN000025134.

Evaluation of the visibility of bleeding points using red dichromatic imaging in endoscopic hemostasis for acute GI bleeding (with video).

BACKGROUND AND AIMS: We aimed to clarify whether red dichromatic imaging (RDI), a new type of image-enhanced endoscopy, improves the visibility of bleeding points in acute GI bleeding (AGIB) compared with white-light imaging (WLI). METHODS: Images and videos of bleeding points acquired with WLI and RDI during endoscopic hemostasis for AGIB were retrospectively compared. In images, the color difference between bleeding points and surrounding blood was analyzed. In videos, 4 expert and 4 trainee endoscopists evaluated the visibility on a scale of 1 (undetectable) to 4 (easily detectable). Furthermore, the correlation between the color difference and visibility score was evaluated. RESULTS: We analyzed 64 lesions. The color difference was significantly higher in RDI (13.11 ± 4.02) than in WLI (7.38 ± 3.68, P < .001). The mean visibility score for all endoscopists was significantly higher in RDI (3.12 ± .51) compared with WLI (2.72 ± .50, P < .001); this was also observed in experts (3.18 ± .51 vs 2.79 ± .54, P < .001) and trainees (3.05 ± .54 vs 2.64 ± .47, P < .001). The color difference and visibility score were moderately correlated for all endoscopists (γ = .56, P < .001) and for experts (γ = .53, P < .001) and trainees (γ = .57, P < .001). CONCLUSIONS: RDI improves the visibility of bleeding points in AGIB compared with WLI. RDI can help endoscopists at all levels of experience to recognize bleeding points by enhancing the color contrast relative to surrounding blood.

Endoscopic hand suturing for mucosal defect closure after gastric endoscopic submucosal dissection may reduce the risk of postoperative bleeding in patients receiving antithrombotic therapy.

OBJECTIVES: Endoscopic hand suturing (EHS) is expected to decrease the risk of post-endoscopic submucosal dissection (ESD) bleeding by closing mucosal defects. We investigated the efficacy of EHS after gastric ESD in patients with antithrombotic agents. METHODS: In this prospective single-arm trial, patients taking antithrombotic agents for cardiovascular disease, arrhythmia, cerebrovascular disease and/or peripheral arterial disease and having <3-cm gastric neoplasms were recruited. The mucosal defects after ESD were closed by EHS in which the needle was delivered through an overtube, and the mucosal rim of the defect was continuously sutured in a linear fashion by manipulating the needle grasped with the needle holder, followed by cutting the remnant suture and retrieval of the needle. The primary endpoint was the incidence of postoperative bleeding within 4 weeks after ESD. RESULTS: Twenty-two lesions in 20 patients (continuing antiplatelet agents in 11, anticoagulant agents in eight, both in one) underwent ESD followed by EHS. All defects (median size, 30 mm; range, 12-51 mm) were completely closed by EHS and remained closed on postoperative day 3. The median number of stitches was six (range, 4-8) and median suturing time was 36 (range, 24-60) min. There were no adverse events during/after EHS or postoperative bleeding. CONCLUSIONS: Postoperative bleeding was not observed in patients taking antithrombotic agents without perioperative cessation. EHS appears to be useful for prevention of post-gastric ESD bleeding in high-risk patients. (Clinical registration number: UMIN000024184).

Pseudomelanosis Duodeni Appearing after Oral Iron Therapy.

Pseudomelanosis duodeni is a rare condition characterized by the endoscopic appearance of diffuse dark pigmentation of the duodenal mucosa. It is typically seen in older women and has been reported to be associated with hypertension, chronic renal disease, diabetes mellitus, gastrointestinal hemorrhage, and the use of medications such as oral iron, furosemide, thiazide, hydralazine, and propranolol. We present a case of pseudomelanosis duodeni appearing after 2 years of oral iron therapy in an 85-year-old woman. Although oral iron supplementation seemed the strongest possible etiology, our patient had multiple comorbidities and was on other medications that have been described as associations. The majority of individuals taking oral iron or under these clinical conditions do not develop this entity; some other factors in patients may be responsible for its occurrence.

Visibility of the bleeding point in acute rectal hemorrhagic ulcer using red dichromatic imaging: A case report.

BACKGROUND: Red dichromatic imaging (RDI) is a novel image-enhanced endoscopy expected to improve the visibility of the bleeding point. However, it has not been thoroughly investigated. CASE SUMMARY: A 91-year-old man developed a sudden massive hematochezia and underwent emergent colonoscopy. An ulcer with pulsatile bleeding was found on the lower rectum. Due to massive bleeding, the exact location of the bleeding point was not easy to detect with white light imaging (WLI). Upon switching to RDI, the bleeding point appeared in deeper yellow compared to the surrounding blood. Thus, RDI enabled us for easier recognition of the bleeding point, and hemostasis was achieved successfully. Furthermore, we reviewed endoscopic images and evaluated the color difference between the bleeding point and surrounding blood for WLI and RDI. In our case, the color difference of RDI was greater than that of WLI (9. 75 vs 6. 61), and RDI showed a better distinguished bleeding point from the surrounding blood. CONCLUSION: RDI may improve visualization of the bleeding point by providing better contrast in color difference relative to surrounding blood.

Detection of Protein Aggregation using Fluorescence Correlation Spectroscopy.

Protein aggregation is a hallmark of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and so on. To detect and analyze soluble or diffuse protein oligomers or aggregates, fluorescence correlation spectroscopy (FCS), which can detect the diffusion speed and brightness of a single particle with a single molecule sensitivity, has been used. However, the proper procedure and know-how for protein aggregation detection have not been widely shared. Here, we show a standard procedure of FCS measurement for diffusion properties of aggregation-prone proteins in cell lysate and live cells: ALS-associated 25 kDa carboxyl-terminal fragment of TAR DNA/RNA-binding protein 43 kDa (TDP25) and superoxide dismutase 1 (SOD1). The representative results show that a part of aggregates of green fluorescent protein (GFP)-tagged TDP25 was slightly included in the soluble fraction of murine neuroblastoma Neuro2a cell lysate. Moreover, GFP-tagged SOD1 carrying ALS-associated mutation shows a slower diffusion in live cells. Accordingly, we here introduce the procedure to detect the protein aggregation via its diffusion property using FCS.

Efficacy of a new image-enhancement technique for achieving hemostasis in endoscopic submucosal dissection.

BACKGROUND AND AIMS: Hemostasis during endoscopic submucosal dissection (ESD) can sometimes be challenging and stressful for the endoscopist. Therefore, we aimed to assess the usefulness of dual red imaging (DRI), a new image enhancement technique that uses 3 wavelengths (540, 600, and 630 nm) to visualize bleeding points and to examine the efficacy of DRI in shortening the time required to achieve hemostasis (hemostasis time) during ESD. METHODS: DRI and white-light imaging (WLI) were used alternately for managing 378 bleeding events in 97 patients undergoing ESD. Hemostasis time for each hemostasis event was measured. Using portable eye-tracking glasses, 4 experienced endoscopists were shown random videos of intraoperative bleeding during ESD (20 cases each on WLI and DRI) and identified the bleeding point in each video. The mean distances of eye movement per unit of time until the bleeding point were identified in each video and compared between the WLI and DRI groups. RESULTS: Average hemostasis time was significantly shorter in the DRI group. The mean distance of eye movement was significantly shorter in the DRI group than in the WLI group for all endoscopists. CONCLUSIONS: DRI can offer useful images to help in clearly detecting bleeding points and in facilitating hemostasis during ESD. It is feasible and may help in successfully performing ESD that is safer and faster than WLI. (Clinical trial registration number: UMIN000018309.).

Feasibility of endoscopic submucosal dissection for colorectal neoplasia at anastomotic sites: a retrospective study.

BACKGROUND: Metachronous colorectal lesions sometimes occur at anastomotic sites following colorectal surgery, which increases the risk of developing colorectal cancer. However, these lesions are difficult to treat even with minimally invasive methods such as endoscopic submucosal dissection (ESD). Thus, we aimed to evaluate the outcomes of ESD for colorectal lesions at anastomotic sites following colorectal surgery. METHODS: We retrospectively investigated 11 patients with post-surgical colorectal lesions at anastomotic sites who later underwent ESD from May 2010 to April 2019 at Keio University Hospital, Tokyo, Japan. We examined the patients' background (tumor location, macroscopic type, tumor size, histological type, and depth of invasion) and treatment outcomes (procedure duration, en bloc resection rate, R0 resection rate, and adverse events). RESULTS: The patients' mean age was 66 years. There were two lesions in the transverse colon, six in the rectum, one in the anal canal, and two in the ileal pouch. The median tumor size was 25 mm. The macroscopic types were the protruded type (1 lesion) and the flat or depressed type (10 lesions). The pathological diagnoses were adenoma (4 lesions), intramucosal cancer (corresponding to high-grade dysplasia) (6 lesions), and muscularis propria cancer (1 lesion). The median procedure duration was 50 min; en bloc resection rate was 88.9% and R0 resection rate was 66.7%. The only adverse event was delayed post-ESD bleeding. CONCLUSIONS: A high en bloc resection rate without perforation was achieved with ESD for lesions at anastomotic sites. Although ESD for lesions at anastomotic sites is a technically challenging procedure because of severe submucosal fibrosis, this approach could prevent the need for repeated surgical resection.

Efficacy of mucosa-submucosa clip closure method after gastric endoscopic submucosal dissection.

BACKGROUND: We recently developed a new endoscopic closure technique using only conventional endo-clips for colorectal lesions. Little is known about the feasibility of the endoscopic mucosa-submucosa clip closure method for gastric lesions. AIM: To elucidate the efficacy of the endoscopic mucosa-submucosa clip closure method after gastric endoscopic submucosal dissection (ESD). METHODS: Twenty-two patients who underwent gastric ESD and mucosa-submucosa clip closure were included in this study. In this method, endo-clips are placed at the edges of a mucosal defect. Additional endo-clips are then applied in the same way to facilitate reduction of the defect size. Additional endo-clips are applied to both sides of the mucosal defect. Complete closure can be achieved. We have also developed a "location score" and "closure difficulty index" for assessment purposes. RESULTS: Complete closure was achieved in 68.2% of the patients (15/22). The location score in the failure group was significantly larger than that in the complete closure group (P = 0.023). The closure difficulty index in the failure group was significantly higher than that in the complete closure group (P = 0.007). When the cutoff value of the closure difficulty index was set at 99, the high closure difficulty index predicted failure with a sensitivity of 57.1%, specificity of 100%, and accuracy of 86.3%. CONCLUSION: The endoscopic mucosa-submucosa clip closure method was unreliable after gastric ESD, especially in cases with a high closure difficulty index.

Endoscopic suturing promotes healing of mucosal defects after gastric endoscopic submucosal dissection: endoscopic and histologic analyses in in vivo porcine models (with video).

BACKGROUND AND AIMS: Endoscopic suturing of mucosal defects after endoscopic submucosal dissection (ESD) is expected to prevent postoperative adverse events. We aimed to endoscopically and histologically evaluate the healing process of post-ESD mucosal defects closed with endoscopic hand suturing (EHS) in in vivo porcine models. METHODS: Twelve mucosal defects (2 cm in size) were created in 2 pigs (6 defects per pig). Initially, 2 defects were created: one was closed with EHS (sutured group) and the other was kept open (control group). On postoperative days (PODs) 7 and 14, 2 additional defects were created in each session, and they were treated in the same manner as in the initial procedure. On POD 21, the entire stomach, with the 6 lesion sites, was extracted for histologic evaluation after endoscopic observation. RESULTS: Endoscopically, all sutured sites remained closed in all sessions (PODs 7, 14, and 21). Histologically, on POD 14, the epithelium and muscularis mucosae were appropriately connected. The mucosae were covered with the epithelium without inversion of the mucosal edge in the sutured group, whereas the ulcer bed was exposed in the control group. Furthermore, the degree of neovascularity and fibroblasts in the submucosa was smaller in the sutured group than that in the control group. CONCLUSIONS: Our findings suggest that endoscopic suturing promotes healing of post-ESD mucosal defects histologically in in vivo porcine models. Thus, endoscopic mucosal closure after ESD might be clinically useful for the prevention of delayed perforation/bleeding if secure suturing is performed endoscopically.

Salvage endoscopic submucosal dissection for incompletely resected esophageal or gastric neoplasms (case series).

Background and study aims Given that positive lateral margins indicate possible residual carcinoma, salvage endoscopic submucosal dissection (ESD) should be considered for curative therapy. Presence of submucosal fibrosis, however, makes the procedure difficult to perform. We present our case series to discuss the feasibility of salvage ESD and the timing of the procedure.