Comparison of Fork-tip and Franseen needles for endoscopic ultrasound-guided fine-needle biopsy in pancreatic solid lesions: A propensity-matched analysis.

Objectives: There is no unanimity regarding the most appropriate needle to use for an endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). To date, new types of FNB needles have been designed, including the Fork-tip and Franseen needles. This study primarily aimed to compare the diagnostic accuracy and histological quality between the use of the Franseen and Fork-tip needles in EUS-FNB for solid pancreatic lesions. Materials and methods: We retrospectively analyzed 147 patients at our center for solid pancreatic lesions, 75 of whom underwent EUS-FNB using a 22-G Franseen needle, and 72 using a 22-G Fork-tip needle, from December 2019 to September 2021. The present study conducted a propensity-matched analysis and confounder adjustment. Results: The diagnostic accuracy of the Fork-tip group (93.3%, 42/45) was the same as that of the Franseen group. For the core tissue and blood scores, no significant difference was observed (p = 0.58, 0.25) between the two groups. The rate of changes in the operator from that of a trainee to an expert was less in the Fork-tip group (4.4%, 2/45) than in the Franseen group (15.6%, 7/45), but not significantly different (p = 0.16). Conclusions: In both groups, the diagnostic accuracy and histological quality were not significantly different. Additionally, there were no significant differences in the rate of operator changes. As both needles are useful, the choice of using either of them is equally good.

Can endoscopic retrograde cholangiopancreatography-related procedures for resolving acute cholangitis be effectively and safely performed in patients with surgically altered anatomy? Comparison study to evaluate the timing of short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography.

OBJECTIVES: Balloon enteroscopy (BE)-assisted endoscopic retrograde cholangiopancreatography (ERCP)-related procedures to resolve acute cholangitis (AC) in patients with surgically altered anatomy (SAA) are limited. There is a lack of evidence on whether the timing of BE-assisted ERCP affects clinical outcomes in patients with AC. This study aimed to evaluate the clinical outcomes of short-type single-balloon enteroscopy (short SBE)-assisted ERCP in patients with SAA and AC. METHODS: Patients with AC who underwent short SBE-assisted ERCP procedures between September 2011 and April 2022 were retrospectively reviewed. The outcomes of procedures undergone at ≤24 h and >24 h were compared. The primary outcome was the length of stay (LOS). RESULTS: Overall, 56 patients underwent procedures at ≤24 h, and 58 patients at >24 h. The procedural success and adverse event rates of short SBE-assisted ERCP were 87.7% (95% confidence interval [CI] 80.3-93.1%) and 4.4% (95% CI 1.4-9.9%), respectively. Patients with severe (Grade III) AC and systemic inflammatory response syndrome were more in early (at ≤24 h) ERCP groups. LOS and median time from ERCP procedures to discharge were shorter in the early group. Procedural success and adverse event rates between both groups had no significant differences. Multivariable linear regression analysis showed that ERCP performed at ≤24 h was associated with shorter LOS, while severe cholangitis and malignant biliary obstruction were associated with longer LOS. CONCLUSIONS: Short SBE-assisted ERCP is effective and safe in patients with SAA and AC. Early procedures seemed to attribute early improvement of general condition, thus shortening the LOS.

Endoscopic ultrasound­guided biliary drainage in patients with surgically altered anatomy: a systematic review and Meta­analysis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography is technically challenging to perform in patients with surgically altered anatomy (SAA). For these patients, endoscopic ultrasound-guided biliary drainage (EUS-BD) is one of the good indications. The aim of our systematic review and meta-analysis was to identify and evaluate evidence of the efficacy and safety of EUS-BD in patients with SAA. METHODS: A systematic review of the PubMed was conducted through to December 2021 to identify studies performing EUS-BD in patients with SAA. The primary outcome was the pooled technical success proportion in patients with SAA. The pooled clinical success and adverse event proportions in patients with SAA were also analyzed. RESULTS: The search identified 1195 possible records, with 18 studies meeting our criteria for analysis, reporting data for 409 patients with SAA who underwent EUS-BD. The pooled technical success, clinical success and adverse event proportions in patients with SAA were 97.8% (95% confidence interval [CI], 95.8-99.7%), 94.9% (95% CI, 91.8-98.1%), and 12.8% (95% CI, 7.4-18.1%), respectively. CONCLUSIONS: EUS-BD is effective for patients with SAA. However, adverse events should be considered when performing EUS-BD in these patients.

Multifunctional chemical inhibitors of the florigen activation complex discovered by structure-based high-throughput screening.

Structure-based high-throughput screening of chemical compounds that target protein-protein interactions (PPIs) is a promising technology for gaining insight into how plant development is regulated, leading to many potential agricultural applications. At present, there are no examples of using high-throughput screening to identify chemicals that target plant transcriptional complexes, some of which are responsible for regulating multiple physiological functions. Florigen, a protein encoded by FLOWERING LOCUS T (FT), was initially identified as a molecule that promotes flowering and has since been shown to regulate flowering and other developmental phenomena such as tuber formation in potato (Solanum tuberosum). FT functions as a component of the florigen activation complex (FAC) with a 14-3-3 scaffold protein and FD, a bZIP transcription factor that activates downstream gene expression. Although 14-3-3 is an important component of FAC, little is known about the function of the 14-3-3 protein itself. Here, we report the results of a high-throughput in vitro fluorescence resonance energy transfer (FRET) screening of chemical libraries that enabled us to identify small molecules capable of inhibiting FAC formation. These molecules abrogate the in vitro interaction between the 14-3-3 protein and the OsFD1 peptide, a rice (Oryza sativa) FD, by directly binding to the 14-3-3 protein. Treatment with S4, a specific hit molecule, strongly inhibited FAC activity and flowering in duckweed, tuber formation in potato, and branching in rice in a dose-dependent manner. Our results demonstrate that the high-throughput screening approach based on the three-dimensional structure of PPIs is suitable in plants. In this study, we have proposed good candidate compounds for future modification to obtain inhibitors of florigen-dependent processes through inhibition of FAC formation.

Gel immersion endoscopic submucosal dissection: clinical experience with 13 cases of superficial esophageal cancer.

Esophageal endoscopic submucosal dissection (ESD) of tumors located on the gravity side is technically challenging. Given that gel immersion ESD (GIESD) is performed by immersing lesions in gel, we hypothesized that it could be used to eliminate the disadvantage associated with submerging the gravity side. Here, we performed GIESD using VISCOCLEAR for superficial esophageal cancer on the gravity side of the esophagus, with monopolar devices. This study aimed to evaluate the short-term outcomes of GIESD for superficial esophageal cancer. Fifteen patients with 16 superficial esophageal cancers underwent GIESD by a single operator, and 13 cases were evaluated. All patients were male, and GIESD was performed in the middle (12/13, 92.3 %) and lower (1/13, 7.7 %) thoracic esophagus. The lesions were located on the left (7/13, 53.8 %), posterior (5/13, 38.5 %), and right (1/13, 7.7 %) esophageal walls. The median procedure time was 27 minutes (interquartile range [IQR], 14-68), and the median dissection speed was 20 mm 2 /min (IQR, 14-25.7). The median amount of gel used was 400 mL (IQR, 360-580), and no gel-related adverse events were observed. The median total dose of midazolam was 3 mg (IQR, 2-5). GIESD was completed with en bloc and R0 resections achieved in 100 % of the 13 cases. Delayed adverse events, such as bleeding or perforation, did not occur (0/13, 0 %).

Factors affecting complete stone extraction in the initial procedure in short type single-balloon enteroscopy-assisted endoscopic retrograde cholangiography for patients with Roux-en-Y gastrectomy.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of stone extraction in patients who underwent Roux-en-Y gastrectomy using short-type single-balloon enteroscopy (SBE) and to clarify the factors affecting complete stone extraction in the initial procedure. METHODS: The data of patients with Roux-en-Y gastrectomy who underwent endoscopic stone extraction using short SBE between September 2011 and January 2022 was analyzed. RESULTS: Overall, 85 patients were scheduled to undergo stone extraction. 77 patients were intended stone extraction after successful biliary cannulation. The complete stone extraction success in the initial procedure, overall complete stone extraction success including repeated procedures, and adverse event rates were 68.2% (95% confidence interval [CI], 57.2%-77.9%), 87.1% (95% CI, 78.0%-93.4%), and 8.2% (95% CI, 3.4%-16.2%), respectively. Multiple logistic regression analysis indicated that bile duct diameter affected the success of complete stone extraction after successful biliary cannulation in the initial procedure (odds ratio 0.53, 95% CI, 0.30-0.94, p = .03). CONCLUSIONS: Stone extraction in patients with Roux-en-Y gastrectomy using short SBE was effective. Patients with a large diameter bile duct required several sessions for complete stone extraction, suggesting that more dedicated devices are warranted for patients with surgically altered anatomy.

Effectiveness of a multi-loop traction device for colorectal endoscopic submucosal dissection performed by trainees: a pilot study.

Colorectal endoscopic submucosal dissection (ESD) is a difficult procedure, and its introduction to trainees has been debated. Although the criteria for performing colorectal ESD vary among institutions, it is often allowed after gaining experience performing surgeries in animals and upper gastrointestinal ESD. This pilot study aimed to compare the treatment outcomes of ESD performed by trainees using the multi-loop traction device (MLTD group) and those of conventional ESD performed by experts (control group). It also aimed to determine whether the MLTD can be used to safely introduce colorectal ESD to trainees. We included 26 colorectal ESD patients (13 in the MLTD group and 13 in the control group) treated at our hospital from October to December 2021. There were no significant differences in the procedure time (50 min vs. 30 min), dissection speed (19.9 mm2/min vs. 28.7 mm2/min), and intraoperative perforation (0% vs. 0%) of the two groups. Furthermore, the rate of ESD self-completion in the MLTD group was 100%. Therefore, the use of the MLTD allowed the safe introduction of colorectal ESD, even among endoscopists with no experience performing colorectal ESD. Consequently, the use of the MLTD may replace animal and upper gastrointestinal ESD when introducing colorectal ESD to trainees.

Sivelestat's effect on Candida albicans water-soluble fraction-induced vasculitis.

BACKGROUND: We investigated the efficacy of sivelestat sodium hydrate (SSH) as a treatment for Kawasaki disease, and its pharmacological action sites, in mice with Candida albicans water-soluble fraction-induced vasculitis. METHODS: Sivelestat sodium hydrate was administered intraperitoneally to Candida albicans water-soluble fraction-induced vasculitis model mice to assess its efficacy in preventing the development of coronary artery lesions based on the degree of inflammatory cell infiltration in the aortic root and coronary arteries (vasculitis score). The pharmacological sites of action were investigated based on changes in neutrophil elastase (NE) and intercellular adhesion molecule 1 (ICAM-1) positive areas, ICAM-1 and tumor necrosis factor-α mRNA expression levels in the upper heart, and the proportion of monocytes in the peripheral blood. RESULTS: The vasculitis score decreased below the lower limit of the 95% confidence interval of untreated mice in 69% of the SSH-treated mice. The NE- and ICAM-1-positive regions, and the mRNA expression of ICAM-1 and tumor necrosis factor-α were lower in the SSH-treated mice than in the untreated mice. The proportion of monocytes in the peripheral blood was higher in the SSH-treated mice than in the untreated mice, whereas monocyte migration to inflammation areas was suppressed in the SSH-treated mice. CONCLUSIONS: Our results showed that SSH might prevent the development of coronary artery lesions and ameliorate disease activity. In addition to its NE-inhibitory effect, SSH sites of action may also include monocytes.

Endoscopic closure using an over-the-scope clip for pancreatobiliary endoscopy-related large gastrointestinal perforation (with video).

Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) for pancreatobiliary diseases require advanced techniques. We usually use an oblique-viewing endoscope in such procedures. Sometimes, tumor invasion causes gastrointestinal strictures. Crossing a stricture using an oblique-viewing endoscope is more difficult than using a forward-viewing scope. Therefore, the frequency of scope perforation is higher than other endoscopic procedures. Although surgical repair for gastrointestinal perforations caused by endoscopes has been performed, patients with pancreatobiliary diseases are often elderly and in poor general condition; therefore, patients are hesitant to undergo surgical treatments. Recently, the usefulness of over-the-scope clipping (OTSC) as a minimally invasive rescue method has also been reported. In this study, we report cases of successful endoscopic closure using OTSC for gastrointestinal perforations caused by endoscopes in ERCP and EUS-related procedures. After those procedures, all cases showed no abnormalities in blood tests or symptoms, and emergency surgery was successfully avoided. Thus, endoscopic closure using OTSC for pancreatobiliary endoscopy-related gastrointestinal perforations is safe and effective. However, OTSC requires some expertise. A good assessment of defect size and careful insertion of the scope using OTSC attached to the upper esophagus are needed to avoid clip migration or disinsertion and esophageal tears. Therefore, endoscopic closure using OTSC could be the first choice of treatment for pancreatobiliary endoscopy-related gastrointestinal perforations. We should be familiar with its indication and perform it carefully and rapidly.

Effectiveness of clip-and-thread traction-assisted duodenal endoscopic submucosal dissection: a propensity score-matched study (with video).

BACKGROUND AND AIMS: The indications for endoscopic submucosal dissection (ESD) in superficial nonampullary duodenal epithelial tumors (SNADETs) remain controversial because the procedure is technically challenging. Moreover, the effectiveness of clip-and-thread traction-assisted ESD (TA-ESD) for SNADETs has not been assessed. The aim of the current study was to compare the effectiveness of duodenal TA-ESD and conventional ESD for SNADETs. METHODS: SNADETs treated with conventional ESD or TA-ESD between April 2017 and March 2021 at Saitama Medical University International Medical Center were evaluated retrospectively. RESULTS: There were 49 cases of conventional ESD and 32 cases of TA-ESD for SNADETs. Using a propensity score-matched design, we selected 26 pairs of cases with conventional ESD and TA-ESD. In the unmatched cohort, patients treated with TA-ESD were characterized by a higher R0 (no tumor identified at the lateral or vertical margins) resection rate (P = .004), more frequent poor submucosal lifting because of fibrosis (P = .014), and shorter follow-up period (P = .0004) than patients treated with conventional ESD. In the propensity score-matched pairs, patients treated with TA-ESD were characterized by a higher rate of R0 resection (P = .021) and a shorter follow-up period (P = .0061). The findings regarding R0 resection rates were confirmed by multivariate logistic regression models, which found a higher odds ratio (OR) for R0 resection in patients who underwent TA-ESD than in patients who underwent conventional ESD both in the unmatched cohort (OR, 17.0; 95% confidence interval, 1.6-178.8; P = .018) and in the propensity score-matched pairs (OR, 26.7; 95% confidence interval, 1.5-460.2; P = .024). CONCLUSIONS: Our findings suggest TA-ESD may increase the rate of R0 resection in patients with SNADETs in comparison with conventional ESD.

Current Status of Endoscopic Biliary Drainage in Patients with Distal Malignant Biliary Obstruction.

Distal malignant biliary obstruction is caused by various malignant diseases that require biliary drainage. In patients with operable situations, preoperative biliary drainage is required to control jaundice and cholangitis until surgery. In view of tract seeding, endoscopic biliary drainage is the first choice. Since neoadjuvant therapies are being developed, the time to surgery is increasing, especially in pancreatic cancer cases. Therefore, it requires long stent patency. Recently, preoperative biliary drainage using self-expandable metal stents has been reported as a useful modality to secure long stent patency. In patients with unresectable distal malignant biliary obstruction, self-expandable metal stent is the first choice for maintaining long stent patency. Although there are many comparison studies between a covered and an uncovered self-expandable metal stent, their use is still controversial. Recently, endoscopic ultrasound-guided biliary drainage has been performed as an alternative treatment. The clinical success and stent patency are favorable. We should take into consideration that both endoscopic retrograde cholangiopancreatography-guided biliary drainage and endoscopic ultrasound-guided biliary drainage have advantages and disadvantages and chose the drainage method depending on the patient's situation or the expertise of the endoscopist. Here, we discuss the current status of endoscopic biliary drainage in patients with distal malignant biliary obstruction.

A retrospective cohort study of factors influencing long procedure times in colorectal endoscopic submucosal dissection.

OBJECTIVE: To evaluate the outcomes and factors influencing colorectal endoscopic submucosal dissection (ESD) with a long procedure time. MATERIALS AND METHODS: In this single-center, retrospective study, we included 1,100 patients with 1,199 lesions who underwent colorectal ESD between April 2016 and December 2020. ESD was performed using an advanced system knife for lesions >20 mm. An S-O clip was used as the traction device. The long-time group (LP; procedure time >120 min) and normal-time group (NP; procedure time <120 min) were compared. RESULTS: The procedure times were 166.86 and 44.72 min in the LP and NP groups, respectively. The completion rate was higher in the NP group (96.5% vs. 83.5%, p = .001); the completed lesions were resected en bloc. Multivariate analysis revealed 18.8% and 7.8% of submucosal fibrosis in the LP and NP groups, respectively (odds ratio [OR] = 2.410, p = .026). Compared to the NP group, the LP group presented larger maximum lesion sizes and higher rates of R1 resection, and traction device use. Time to introduction of traction device use was longer in the LP than in the NP group (126.05 vs. 21.72 min; p < .001). Fibrosis tends to occur cecal lesions (OR 2.436, p = .011) and laterally spreading tumor-non-granular-pseudo-depressed (LST-NG-PD) (OR 2.6181, p = .001). CONCLUSIONS: Lesion size and fibrosis were factors associated with a long procedure time in colonic ESD. For fibrotic lesions (LST-NG-PD and cecal lesions), it is necessary to consider early use of traction devices and advisable to plan a strategy for the use of traction devices.

Novel assays to monitor gene expression and protein-protein interactions in rice using the bioluminescent protein, NanoLuc.

Luciferases have been widely utilized as sensitive reporters to monitor gene expression and protein-protein interactions. Compared to firefly luciferase (Fluc), a recently developed luciferase, Nanoluciferase (NanoLuc or Nluc), has several superior properties such as a smaller size and stronger luminescence activity. We compared the reporter properties of Nluc and Fluc in rice (Oryza sativa). In both plant-based two-hybrid and split luc complementation (SLC) assays, Nluc activity was detected with higher sensitivity and specificity than that with Fluc. To apply Nluc to research involving the photoperiodic regulation of flowering, we made a knock-in rice plant in which the Nluc coding region was inserted in-frame with the OsMADS15 gene, a target of the rice florigen Hd3a. Strong Nluc activity in response to Hd3a, and in response to change in day length, was detected in rice protoplasts and in a single shoot apical meristem, respectively. Our results indicate that Nluc assay systems will be powerful tools to monitor gene expression and protein-protein interaction in plant research.

Intraperitoneal Abscess as a Postoperative Complication of Gastric Endoscopic Submucosal Dissection.

We herein report a case of intraperitoneal abscess as a postoperative complication of gastric endoscopic submucosal dissection (ESD). A 70-year-old man who underwent ESD for early gastric cancer sought consultation for abdominal pain on postoperative day 28. Abdominal computed tomography revealed intraperitoneal abscess rupture. He underwent image-guided laparoscopic irrigation. His postoperative course was favorable, and he was discharged after 27 days. Intraoperatively, a white plaque adhering to the gastric wall was surrounded by a large pus volume and suspected to be ESD-associated. We present this case with a literature review of the association between intraperitoneal abscess and ESD.

Rice Gene Targeting by Homologous Recombination with Positive-Negative Selection Strategy.

Gene targeting (GT) is a technique that alter the structure of the specific genes at their original loci in the genome by homologous recombination (HR). It plays an important role in functional genomics because it enables precise modification of the endogenous genes into desired forms such as knockout, knock-in, introduction of point mutations, as well as generation of fusion genes. Also, site-directed mutagenesis by GT can also be applied as an excellent technique for molecular breeding and gene therapy, because it can directly reflect the knowledge acquired from functional genomics. In this section, we introduce well-established GT procedure in rice in combination with positive-negative-selection (PNS) strategy.