Resectability of Small Duodenal Tumors: A Randomized Controlled Trial Comparing Underwater Endoscopic Mucosal Resection and Cold Snare Polypectomy.

INTRODUCTION: Underwater endoscopic mucosal resection (UEMR) and cold snare polypectomy (CSP) are novel endoscopic procedures for superficial nonampullary duodenal epithelial tumors (SNADET). However, consensus on how to use both procedures appropriately has not been established. In this study, we evaluated treatment outcomes of both procedures, including resectability. METHODS: In this single-center randomized controlled study conducted between January 2020 and June 2022, patients with SNADET ≤12 mm were randomly allocated to UEMR and CSP groups. The primary end point was sufficient vertical R0 resection (SVR0), which was defined as R0 resection including a sufficient submucosal layer. We compared treatment outcomes including SVR0 rate between groups. RESULTS: The SVR0 rate was significantly higher in the UEMR group than in the CSP group (65.6% vs 41.5%, P = 0.01). By contrast, the R0 resection rate was not significantly different between study groups (70.3% vs 61.5%, P = 0.29). The submucosal layer thickness was significantly greater in the UEMR group than in the CSP group (median 546 [range, 309-833] µm vs 69 [0-295] µm, P < 0.01). CSP had a shorter total procedure time (median 12 [range, 8-16] min vs 1 [1-3] min, P < 0.01) and fewer total bleeding events (9.4% vs 1.5%, P = 0.06). DISCUSSION: UEMR has superior vertical resectability compared with CSP, but CSP has a shorter procedure time and fewer bleeding events. Although CSP is preferable for most small SNADET, UEMR should be selected for lesions that cannot be definitively diagnosed as mucosal low-grade neoplasias.

Conserved gatekeeper methionine regulates the binding and access of kinase inhibitors to ATP sites of MAP2K1, 4, and 7: Clues for developing selective inhibitors.

Mitogen-activated protein kinase kinases (MAP2Ks) 1, 4, and 7 are potential targets for treating various diseases. Here, we solved the crystal structures of MAP2K1 and MAP2K4 complexed with covalent inhibitor 5Z-7-oxozeaenol (5Z7O). The elucidated structures showed that 5Z7O was non-covalently bound to the ATP binding site of MAP2K4, while it covalently attached to cysteine at the DFG-1 position of the deep ATP site of MAP2K1. In contrast, we previously showed that 5Z7O covalently binds to MAP2K7 via another cysteine on the solvent-accessible edge of the ATP site. Structural analyses and molecular dynamics calculations indicated that the configuration and mobility of conserved gatekeeper methionine located at the central ATP site regulated the binding and access of 5Z7O to the ATP site of MAP2Ks. These structural features provide clues for developing highly potent and selective inhibitors against MAP2Ks. Abbreviations: ATP, adenosine triphosphate; FDA, Food and Drug Administration; MAP2Ks, mitogen-activated protein kinase kinases; MD, molecular dynamics; NSCLC, non-small cell lung cancer; 5Z7O, 5Z-7-oxozeaenol; PDB, protein data bank; RMSD, root-mean-square deviation.

Total Synthesis of Bipenicilisorin and Assignment of the Absolute Configuration.

The first total synthesis of bipenicilisorin (1) isolated from Penicillium chrysogenum SCSIO 41001 via its monomer natural product, penicilisorin (2), was achieved. Penicilisorin was synthesized in four steps from a o-bromobenzaldehyde derivative via the Pd-catalyzed one-pot fluorocarbonylation/lactonization/ß-elimination cascade reaction. Iodination of penicilisorin gave 7-iodopenicilisorin which was dimerized by Pd-catalyzed homodimerization to provide (±)-bipenicilisorin. The unknown absolute configuration of naturally occurring (+)-bipenicilisorin was examined by optical resolution of the (±)-synthetic bipenicilisorin and a comparison of experimental and theoretical electronic circular dichroism (ECD) spectra. These results support the absolute configuration of the natural product to be Sa. A cytotoxic activity test of (+)-and (-)-bipenicilisorin using A549 cells revealed that (+)-1 has a lower IC50 value than (-)-1.

Substrate-Dependent Alteration in the C- and O-Prenylation Specificities of Cannabis Prenyltransferase.

CsPT4 is an aromatic prenyltransferase that synthesizes cannabigerolic acid (CBGA), the key intermediate of cannabinoid biosynthesis in Cannabis sativa, from olivetolic acid (OA) and geranyl diphosphate (GPP). CsPT4 has a catalytic potential to produce a variety of CBGA analogs via regioselective C-prenylation of aromatic substrates having resorcylic acid skeletons including bibenzyl 2,4-dihydroxy-6-phenylethylbenzoic acid (DPA). In this study, we further investigated the substrate specificity of CsPT4 using phlorocaprophenone (PCP) and 2',4',6'-trihydroxydihydrochalcone (THDC), the isomers of OA and DPA, respectively, and demonstrated that CsPT4 catalyzed both C-prenylation and O-prenylation reactions on PCP and THDC that share acylphloroglucinol substructures. Interestingly, the kinetic parameters of CsPT4 for these substrates differed depending on whether they underwent C-prenylation or O-prenylation, suggesting that this enzyme utilized different substrate-binding modes suitable for the respective reactions. Aromatic prenyltransferases that catalyze O-prenylation are rare in the plant kingdom, and CsPT4 was notable for altering the reaction specificity between C- and O-prenylations depending on the skeletons of aromatic substrates. We also demonstrated that enzymatically synthesized geranylated acylphloroglucinols had potent antiausterity activity against PANC-1 human pancreatic cancer cells, with 4'-O-geranyl THDC being the most effective. We suggest that CsPT4 is a valuable catalyst to generate biologically active C- and O-prenylated molecules that could be anticancer lead compounds.

Studies on Comprehensive Total Synthesis of Natural and Pseudo-Natural Products for Drug Discovery.

Natural products are important for the development of pharmaceuticals and agrochemicals; thus, their synthesis and medicinal chemistry research is critical. Developing a total synthesis pathway for natural products confirms their structure and provides the opportunity to modify the structure in a targeted manner. A simple modification of a single oxidation step can increase the biological activity, or the complexity of the molecule can alter the property. Herein, we discuss the asymmetric total synthesis of dihydroisocoumarin-type natural products, the creation of novel antibacterial compounds through partial structural modification, and the development of antioxidants with high activity and low toxicity through dimerization strategies.

Novel quantitative assessment indicators for efficiency and precision of endoscopic submucosal dissection in animal training models by analyzing an electrical surgical unit.

OBJECTIVES: Although endoscopic submucosal dissection (ESD) training is important, quantitative assessments have not been established. This study aimed to explore a novel quantitative assessment system by analyzing an electrical surgical unit (ESU). METHODS: This was an ex vivo study. Step one: to identify the novel efficiency indicators, 20 endoscopists performed one ESD each, and we analyzed correlations between their resection speed and electrical status. Step two: to identify the novel precision indicators, three experts and three novices performed one ESD each, and we compared the stability of the electrical status. Step three: three novices in step two performed 19 additional ESDs, and we analyzed the learning curve using novel indicators. RESULTS: Step one: the percentage of total activation time (AT) of ESU in the procedure time (ß coefficient, 0.80; P < 0.01) and AT required for submucosal dissection (ß coefficient, -0.57; P < 0.01) were significantly correlated with the resection speed. Step two: coefficient of variation of the AT per one pulse (0.16 [range, 0.13-0.17] vs. 0.26 [range, 0.20-0.41], P = 0.049) and coefficient of variation of the peak electric power per pulse during mucosal incision (0.14 [range, 0.080-0.15] vs. 0.25 [range, 0.24-0.28], P = 0.049) were significantly lower in the experts than in the novices. Regarding the learning curve, the percentage of total AT of ESU in the procedure time and AT required for submucosal dissection had a trend of improvement. CONCLUSION: Novel indicators identified by analyzing ESU enable quantitative assessment for endoscopist's skill.

Novel perfusion system using continuous liquid-suction catheter attachment in colorectal endoscopic submucosal dissection with water pressure method (with video).

Water pressure method (WPM) is useful for colorectal endoscopic submucosal dissection (ESD), characterized not only by underwater conditions but also by active water pressure via the waterjet function. However, the extension of the colorectum by injecting excess water and contaminating the operative field by stool and bleeding have been issues. This study aimed to evaluate the feasibility of a novel perfusion system using a continuous liquid-suction catheter attachment (CLCA) in colorectal ESD with WPM. We retrospectively reviewed cases in which the perfusion system was used in colorectal ESD with WPM between August 2022 and September 2023. We evaluated clinical characteristics, treatment outcomes, volume of injection by the waterjet function, volume of suction by the endoscope and CLCA, and concentration of floating matter in the operative field over time. Thirty-one cases were enrolled. The median lesion size was 30 (range, 15-100) mm. In all cases, en bloc resection was achieved without perforation. The median injection volume was 2312 (range, 1234-13,866) g. The median suction volumes by the endoscope and CLCA were 918 (range, 141-3162) and 1147 (range, 254-11,222) g, respectively. The median concentration of floating matter in the operative field (measured in 15 cases) was 15.3 (range, 7.3-112) mg/mL when the endoscope arrived at the lesion and 8.0 (range, 3.2-16) mg/mL after endoscopically washing at the beginning of the ESD. It ranged from 7.6 to 13.4 mg/dL every 20 min during ESD. This perfusion system could prevent the extension of the lumen and maintain a good field of view in colorectal ESD with WPM.

Modified double-layered suturing for a mucosal defect after colorectal endoscopic submucosal dissection (Origami method) (with video).

BACKGROUND AND AIMS: Through-the-scope clips (TTSCs) are among the most common devices used to close colorectal post-endoscopic submucosal dissection (ESD) defects. Although TTSCs are easy to deliver, even to the proximal colon, simple clipping of large defects results in mucosa-mucosa closure, which could be unreliable. We developed a novel endoscopic closure technique using a modified double-layered suturing called the origami method (OGM). This method closes not only the mucosal layer but also the muscle layer with only TTSCs, which can obtain robust closure even for large defects. This study aimed to evaluate the feasibility of this new closure method for colorectal post-ESD defects. METHODS: This retrospective observational study was conducted at a tertiary care hospital. We reviewed the cases of the OGM attempted after colorectal ESD at our institute between October 2021 and October 2022 and measured the clinical characteristics and outcomes of enrolled cases. RESULTS: The OGM was attempted in 47 cases after colorectal ESD. Thirty-one cases (66%) were in the proximal colon, 5 (11%) in the distal colon, 6 (13%) in the upper rectum, and 5 (10%) in the lower rectum. The median defect size was 38 mm, with the largest being 85 mm. Complete closure was achieved in 44 cases (94%), including all lower rectum cases. No perforations were caused by clips during closure, and delayed perforation and bleeding were not observed. CONCLUSIONS: This new closure method is feasible and recommended. The OGM could achieve reliable closure of large defects in any location, including the proximal colon and thick-walled lower rectum, using only TTSCs.

Closure of large mucosal defects for prevention of strictures after duodenal endoscopic submucosal dissection (with video).

BACKGROUND AND AIMS: Although lesions occupying a large circumference are associated with the risk of post-endoscopic submucosal dissection (ESD) strictures, the corresponding data for duodenal lesions are unknown. We aimed to analyze the incidence of post-ESD strictures after wide-field duodenal ESD. METHODS: In this retrospective study of duodenal lesions treated with ESD between July 2010 and August 2021, we included lesions that resulted in mucosal defects occupying more than half of the circumference and excluded lesions located in bulbs and involving Vater's papilla. We analyzed the incidence rates of stricture and luminal narrowing, in addition to bleeding and perforation as the outcomes in this study. Stricture was defined as the inability of the endoscope to pass through the lumen. A single endoscopist reviewed all endoscopic images and judged the degree of luminal narrowing. RESULTS: Eighty lesions were included, of which 2 involved mucosal defects occupying more than 90% of the circumference. The wound was closed, at least partially, in 90% in all lesions and in 86% of lesions with a mucosal defect occupying more than 75% of the circumference. None of the lesions caused delayed perforation and stricture, whereas 2 lesions caused delayed bleeding. Only 6 lesions caused luminal narrowing. When examined by the degree of closure, the rate of luminal narrowing increased with complete closure, incomplete closure, and nonclosure (4.9%, 9.1%, and 25.0%, respectively). CONCLUSIONS: Suturing may prevent post-ESD bleeding and perforation as well as stricture formation in cases of duodenal tumors, with mucosal defects occupying a large circumference.

Intensive endoscopic resection strategy for multiple duodenal polyposis associated with familial adenomatous polyposis.

BACKGROUND AND AIM: Multiple duodenal polyposis associated with familial adenomatous polyposis (FAP) is a high risk of duodenal cancer development. We evaluated the feasibility of intensive endoscopic resection that is a comprehensive treatment strategy combining multiple kinds of endoscopic treatments. METHODS: This is a retrospective observational study. From January 2012 to July 2022, a total of 28 consecutive patients in FAP who underwent endoscopic resection for multiple duodenal polyposis more than twice were included. Various endoscopic treatments, such as cold polypectomy (CP), endoscopic mucosal resection (EMR), underwater EMR (UEMR), endoscopic submucosal dissection (ESD), and endoscopic papillectomy (EP), were applied depending on lesions size and location. We evaluated individual information from patients' medical records, including patient characteristics, lesion characteristics, details of endoscopic treatment, pathologic findings, and Spigelman index (SI). We compared the differences in the number of treatments and observation periods with and without SI decrease. RESULTS: A total of 1040 lesions were removed by 138 sessions of endoscopic resections. The median follow-up period was 3.2 years. At the beginning of the endoscopic intervention, median SI was 9 (6-11) and the proportion of Spigelman stage (SS) IV was 61%. Repeated endoscopic treatments finally reduced SI in 26 patients (93%), and the proportion of SS IV significantly decreased to 13% with every endoscopic treatment. The mean SI change was -4.2 points per year (95% confidence interval: -0.6 to -5.9). There were no patients required surgical duodenectomy during the follow-up period. CONCLUSION: Intensive resection has a potential of downstaging duodenal lesions associated with FAP.

Association between oral function and nutrition in gastric cancer patients undergoing chemotherapy.

OBJECTIVES: This study aimed to clarify the relationship between the oral assessment guide (OAG), a simple method for assessing oral function and poor nutrition in gastric cancer patients and investigate the reduction of oral mucositis through appropriate oral function management. SUBJECTS AND METHODS: Gastric cancer patients who underwent chemotherapy at the Nagoya Ekisaikai Hospital between January 2015 and December 2020 were evaluated. The prognostic nutritional index (PNI), as the objective variable, was used to assess nutritional status. The explanatory variables were sex, age, smoking status, body mass index (BMI), number of remaining teeth, cancer stage, albumin level, C-reactive protein level, white blood cell count and the OAG score. RESULTS: PNI was significantly associated with age, number of remaining teeth, cancer stage and the OAG score (p < 0.05) among the 217 patients. There were significant differences in age, BMI, cancer stage and the OAG score among the patients. An abnormal BMI and an advanced cancer stage were more common in older patients, and abnormal OAG scores were associated with a lower PNI. CONCLUSIONS: For gastric cancer patients undergoing postoperative chemotherapy, worse oral functional status is associated with worse PNI and nutritional status.

Novel closure method for a large mucosal defect after endoscopic resection: String clip suturing method with an anchor.

Duodenal endoscopic submucosal dissection (ESD) is a high-risk technique; however, prophylactic closure of mucosal defects reduces the risk. Unfortunately, we have encountered cases where closure is difficult, especially in large lesions. Therefore, we developed a novel closure technique, a string clip suturing method with an anchor (SCSM-A). This study aimed to elucidate the feasibility of this method. Five patients underwent this method for the closure of mucosal defects after duodenal ESD. The initial string clip was deployed at the anal end of the mucosal defects and the second clip was deployed at the other end of the mucosal defect. A third clip was deployed on the muscular layer in the middle of the mucosal defect. The free end of the string was pulled, and additional clips were deployed around the first to the third clips for complete closure. Because of grasping the muscle layer, SCSM-A can be employed for secure closure without creating a pocket. We reviewed the background and clinical course of hospitalization of patients who underwent this method. The resected specimens ranged from 52 to 103 mm in diameter. Complete closure of the mucosal defects was possible in all the cases. There were no adverse events, and no cases required additional treatment. All the patients were discharged within 7 days. The new method achieved secure closure even for large mucosal defects after duodenal ESD. This is a technique that can be applied to other organs, e.g., the colon.

Prospective cross-organ analysis for the causes of fever and increased inflammatory response after endoscopic resection.

OBJECTIVES: Fever and increased inflammatory responses sometimes occur following endoscopic resection (ER). However, the differences in causes according to the organ are scarcely understood, and several modified ER techniques have been proposed. Therefore, we conducted a comprehensive prospective study to investigate the cause of fever and increased inflammatory response across multiple organs after ER. METHODS: We included patients who underwent gastrointestinal endoscopic submucosal dissection (ESD) and duodenal endoscopic mucosal resection at our hospital between January 2020 and April 2022. Primary endpoints were fever and increased C-reactive protein (CRP) levels following ER. The secondary endpoints were risk factors for aspiration pneumonia. Blood tests and radiography were performed on the day after ER, and computed tomography was performed if the cause was unknown. RESULTS: Among the 822 patients included, aspiration pneumonia was the most common cause of fever and increased CRP levels after ER of the upper gastrointestinal tract (esophagus, 53%; stomach, 48%; and duodenum, 71%). Post-ER coagulation syndrome was most common after colorectal ESD (38%). On multivariate logistic regression analysis, lesions located in the esophagus (odds ratio [OR] 3.57; P < 0.001) and an amount of irrigation liquid of ≥1 L (OR 3.71; P = 0.003) were independent risk factors for aspiration pneumonia. CONCLUSIONS: Aspiration pneumonia was the most common cause of fever after upper gastrointestinal ER and post-ER coagulation syndrome following colorectal ESD. Lesions in the esophagus and an amount of irrigation liquid of ≥1 L were independent risk factors for aspiration pneumonia.

Clinical course and management of adverse events after endoscopic resection of superficial duodenal epithelial tumors: Multicenter retrospective study.

OBJECTIVES: This study aimed to elucidate the clinical course and management of adverse events (AEs) after endoscopic resection (ER) for superficial duodenal epithelial tumors (SDETs). METHODS: Consecutive patients who underwent ER of SDETs between January 2008 and July 2018 at 18 Japanese institutions were retrospectively enrolled. The study outcomes included the clinical course, management, and risk of surgical conversion with perioperative AEs after ER for SDETs. RESULTS: Of the 226 patients with AEs, the surgical conversion rate was 8.0% (18/226), including 3.7% (4/108), 1.0% (1/99), and 50.0% (12/24) of patients with intraoperative perforation, delayed bleeding, or delayed perforation, respectively. In the multivariate logistic analysis, involvement of the major papilla (odds ratio [OR] 12.788; 95% confidence interval [CI] 2.098-77.961, P = 0.006) and delayed perforation (OR 37.054; 95% CI 10.219-134.366, P < 0.001) were significant risk factors for surgical conversion after AEs. Delayed bleeding occurred from postoperative days 1-14 or more, whereas delayed perforation occurred within 3 days in all cases. CONCLUSIONS: The surgical conversion rate was higher for delayed perforation than those for other AEs after ER of SDETs. Involvement of the major papilla and delayed perforation were significant risk factors for surgical conversion following AEs. In addition, reliable prevention of delayed perforation is required for 3 days after duodenal ER to prevent the need for surgical interventions.

Sick sinus syndrome diagnosed after a sinus arrest during treatment for zygomatic fracture: a case report.

BACKGROUND: Intraoperative sinus arrest is rarely seen during zygomatic fracture treatment. The patient was diagnosed with sick sinus syndrome based on repeated postoperative sinus arrest, which could have resulted in death if diagnosed late, making this case very significant to report. CASE PRESENTATION: Sick sinus syndrome is an arrhythmia associated with reduced automaticity of the sinoatrial node or impaired sinoatrial node conduction. We report the case of a 67-year-old man diagnosed with the syndrome after a sinus arrest that occurred during a zygomatic fracture treatment. The patient had cheek pain and mouth opening disorder, dizziness after fainting and sustaining a facial injury. Preoperative examination determined that the syncope was due to drug-induced arrhythmia, and surgery was authorized after drug withdrawal. During the operation, sinus arrest was observed due to trigeminal vagal reflex, and heart rate was restarted by stopping the operation and chest compressions. After the surgery, the patient showed symptoms of dizziness and palpitations, and sinus arrest following atrial fibrillation and supraventricular tachycardia, which was diagnosed as sick sinus syndrome, and a pacemaker was implanted. Currently, 8 years have passed since the surgery, and there are no symptoms of mouth opening disorder, dizziness, or palpitations. CONCLUSIONS: In the case of maxillofacial injuries due to syncope, cardiogenic syncope is a possibility, and repeated syncope is a risk for death due to delayed diagnosis. There are no reports of maxillofacial trauma leading to a diagnosis of sick sinus syndrome. The purpose of this case report is to disseminate the importance of diagnosing the cause of syncope as well as injury treatment.

Outcomes of endoscopic resection for superficial duodenal tumors: 10 years' experience in 18 Japanese high volume centers.

BACKGROUND: Data on endoscopic resection (ER) for superficial duodenal epithelial tumors (SDETs) are insufficient owing to their rarity. There are two main ER techniques for SDETs: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). In addition, modified EMR techniques, such as underwater EMR (UEMR) and cold polypectomy, are becoming popular. We conducted a large-scale retrospective multicenter study to clarify the detailed outcomes of duodenal ER. METHODS: Patients with SDETs who underwent ER at 18 institutions from January 2008 to December 2018 were included. The rates of en bloc resection and delayed adverse events (AEs; defined as delayed bleeding or perforation) were analyzed. Local recurrence was analyzed using the Kaplan-Meier method. RESULTS: In total, 3107 patients (including 1017 undergoing ESD) were included. En bloc resection rates were 79.1 %, 78.6 %, 86.8 %, and 94.8 %, and delayed AE rates were 0.5 %, 2.2 %, 2.8 %, and 6.8 % for cold polypectomy, UEMR, EMR and ESD, respectively. The delayed AE rate was significantly higher in the ESD group than in non-ESD groups for lesions < 19 mm (7.4 % vs. 1.9 %; P < 0.001), but not for lesions > 20 mm (6.1 % vs. 7.1 %; P = 0.64). The local recurrence rate was significantly lower in the ESD group than in the non-ESD groups (P < 0.001). Furthermore, for lesions > 30 mm, the cumulative local recurrence rate at 2 years was 22.6 % in the non-ESD groups compared with only 1.6 % in the ESD group (P < 0.001). CONCLUSIONS: ER outcomes for SDETs were generally acceptable. ESD by highly experienced endoscopists might be an option for very large SDETs.

Efficacy of capnographic and bispectral index monitoring on trans-oral therapeutic endoscopy: A prospective observational study.

BACKGROUND AND AIM: Oral therapeutic and invasive endoscopy requires deep sedation to reduce patient distress due to prolonged examination and procedures. The usefulness of capnography and bispectral index (BIS) monitoring in the early hypoxia detection in oral therapeutic and invasive endoscopy has yet to be evaluated. This study aimed to investigate the clinical impact of capnography and BIS monitoring on hypoxic events during oral therapeutic and invasive endoscopic procedures. METHODS: This is a prospective observational study. Trans-oral non-intubated therapeutic and/or invasive endoscopic procedures were performed with conventional monitoring (pulse oximetry, pulse, and blood pressure) as well as additional monitoring (BIS and end-tidal CO2 concentration). Hypoxia is defined as oxygen saturation of <90% that lasts >15 s. The clinical impact of capnography and BIS monitoring on hypoxic events during oral therapeutic and invasive endoscopic procedures were investigated with the risk factors for hypoxia in each patient. RESULTS: Patients with hypoxia had significantly more apneas detected using capnography than other patients. The multivariate analysis revealed the detected apnea by capnography as an independent risk factor for hypoxia (odds ratio: 3.48[95% confidence interval: 1.24-9.78], P = 0.02). The BIS was not significantly different as a risk factor for hypoxia; however, per-event analysis revealed significantly decreased BIS values over time in 3 min before hypoxic events. CONCLUSIONS: Apnea detected by capnography was an independent predictor of hypoxia. The BIS value was not associated with hypoxia events; however, it showed a significant downward trend before hypoxia events.

Stereoselective Syntheses of trans-Anhydromevalonic Acid and trans-Anhydromevalonyl Group-Containing Natural Products.

Collective total syntheses of trans-anhydromevalonic acid (tAHMA) and trans-anhydromevalonyl (tAHM) group-containing natural products (pestalotiopin A, pestalotiopamide C, pestalotiopamide D, farinomalein E, eleutherazine B, and trichocyclodipeptide A) were achieved using tAHMA esters as key intermediates. To this end, tAHMA tert-butyl ester was newly prepared by Z-vinyltosylation of tert-butyl 3-oxo-5-((triisopropylsilyl)oxy)pentanoate followed by the Negishi cross-coupling reaction with Me2Zn. tAHMA esters were converted to the target natural products via esterification or amidation. Comparison of the spectroscopic data of synthetic and natural products confirmed the E-configuration of the tAHM moieties in the natural products.

Feasibility Study of Partial Submucosal Injection Technique Combining Underwater EMR for Superficial Duodenal Epithelial Tumors.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) and Underwater EMR have been reported as effective endoscopic treatment for superficial duodenal tumor (SDET). However, a notable problem of EMR for SDET is technical difficulty for the lesion with non-lifting sign, and it of UEMR is that en bloc resection rate is relatively low. Therefore, we performed partial submucosal injection combining UEMR (PI-UEMR). The aim of this study is to evaluate feasibility and safety of this technique for duodenal tumor. METHODS: This is a prospective observational study from tertiary care hospital. We performed PI-UEMR in patients with SDET that is 13-20 mm in diameter, or less than 13 mm with technical difficulty for EMR and UEMR from January 2019 to March 2020. Primary outcome was en bloc resection rate. Secondary outcomes were R0 resection rate, mean total procedure time, intra- and post-procedure complication. RESULTS: Thirty patients were included in this study. Mean age was 62 ± 12 years old. Three fourths lesions were located at anal side from major papilla. Median lesion size was 12 mm [IQR 10-16 mm]. Twenty-four cases were taken endoscopic biopsy in prior hospital and observed biopsy scar. En bloc resection rate was 97%. Ro resection rate was 83%. Mean total procedure time was 17 ± 12 min. And there was an only one case of complication, intra-procedure bleeding that was controllable endoscopically. CONCLUSIONS: PI-UEMR might be very useful and safe technique of endoscopic resection for SDET including relatively large lesions.

Feasibility of endoscopic resection for large pedunculated duodenal lesions (with video).

BACKGROUND: A standard treatment method for pedunculated duodenal lesions has not yet been established. This study aimed to evaluate the feasibility of endoscopic resection (ER) for pedunculated duodenal lesions, especially for large lesions. METHODS: This study retrospectively reviewed cases of pedunculated duodenal lesions treated with ER at our institute between July 2010 and January 2021. We collected data on the clinical characteristics and treatment outcomes. In addition, the cases were divided based on the treatment provided for the lesion, i.e., the ESD and snare resection groups, and we compared the data between the two groups. RESULTS: Thirty-eight cases were included in this study. The overall en bloc resection rate was 95%. No perforation occurred in any of the cases. There were 10 cases treated with ESD, which were considered difficult to achieve en bloc resection using snare forceps, and 28 cases treated with snare resection. Although the median lesion size was significantly larger in the ESD group than in the snare resection group (27 [range 23-66] vs. 19 [range 6-55] mm, P = 0.0052), treatment outcomes were not significantly different between the two groups. Among the 10 cases treated using ESD, en bloc resection was achieved in all cases, along with specimen retrieval without any perforations, despite the large size of the lesions. CONCLUSION: ER could be performed to achieve a high en bloc resection rate without any perforations in pedunculated duodenal lesions, even in extremely large (e.g., ≧ 60 mm) lesions, suggesting that ER is feasible and may be an alternative to surgical resection for large pedunculated duodenal lesions.