RESUMEN
Menthyl ester of valine (MV) has been developed as a plant defense potentiator to induce pest resistance in crops. In this study, we attempted to establish MV hydrochloride (MV-HCl) in lettuce and tomato crops. When MV-HCl solutions were used to treat soil or leaves of potted tomato and lettuce plants, 1 µM MV-HCl solution applied to potted plant soil was most effective in increasing the transcript level of defense genes such as pathogenesis-related 1 (PR1). As a result, leaf damage caused by Spodoptera litura and oviposition by Tetranychus urticae were significantly reduced. In addition, MV-HCl-treated plants showed an increased ability to attract Phytoseiulus persimilis, a predatory mite of T. urticae, when they were attacked by T. urticae. Overall, our findings showed that MV-HCl is likely to be effective in promoting not only direct defense by activating defense genes, but also indirect defense mediated by herbivore-induced plant volatiles. Moreover, based on the results of the sustainability of PR1 expression in tomato plants treated with MV-HCl every 3 days, field trials were conducted and showed a 70% reduction in natural leaf damage. Our results suggest a practical approach to promoting organic tomato and lettuce production using this new plant defense potentiator.
RESUMEN
Pyruvate dehydrogenase kinases (PDHKs) are fascinating drug targets for numerous diseases, including diabetes and cancers. In this report, we describe the result of our structure-based drug design from tricyclic lead compounds that led to the discovery of highly potent PDHK2 and PDHK4 dual inhibitors in enzymatic assay. The C3-position of the tricyclic core was explored, and the PDHK2 X-ray structure with a representative compound revealed a novel ATP lid conformation in which the phenyl ring of Phe326 mediated the interaction of the Arg258 sidechain and the compound. Compounds with amide linkers were designed to release the ATP lid by forming an intramolecular pi-pi interaction, and these compounds showed single-digit nM IC50 values in an enzymatic assay. We also explored the C4-position of the tricyclic core to reproduce the interaction observed with the C3-position substitution, and the pyrrolidine compound showed the same level of IC50 values. By optimizing an interaction with the Asn255 sidechain through a docking simulation, compounds with 2-carboxy pyrrole moiety also showed single-digit nM IC50 values without having a cation-pi interaction with the Arg258 sidechain.
Asunto(s)
Adenosina Trifosfato/farmacología , Amidas/farmacología , Diseño de Fármacos , Inhibidores de Proteínas Quinasas/farmacología , Adenosina Trifosfato/química , Amidas/química , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Relación Estructura-ActividadRESUMEN
A fragment-based lead discovery approach was applied to Pyruvate Dehydrogenase Kinases (PDHKs) to discover inhibitors against the ATP binding site with novel chemotypes. X-ray fragment screening toward PDHK4 provided a fragment hit 1 with a characteristic interaction in a deep pocket of the ATP binding site. While known inhibitors utilize several water molecules in a deep pocket to form water-mediated hydrogen bond interactions, the fragment hit binds deeper in the pocket with a hydrophobic group. Displacement of a remaining water molecule in the pocket led to the identification of lead compound 7 with a notable improvement in inhibition potency. This lead compound possessed high ligand efficiency (LE) and showed decent selectivity profile. Two additional lead compounds 10 and 13 with new scaffolds with tricyclic and bicyclic cores were generated by merging structural information of another fragment hit 2. The characteristic interaction of these novel inhibitors in a deep pocket provides new structural insights about PDHKs ATP binding site and opens a novel direction for the development of PDHKs inhibitors.
Asunto(s)
Adenosina Trifosfato/antagonistas & inhibidores , Descubrimiento de Drogas , Indoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Sitios de Unión/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Indoles/síntesis química , Indoles/química , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Relación Estructura-ActividadRESUMEN
Cubane (C8H8), a cubic alkane, has long attracted attention owing to its unique 3D structure. In order to utilize the cubane scaffold widely in science and technology, a powerful method for synthesizing diverse cubane derivatives is required. Herein, we report the synthesis of mono-, di-, tri-, and tetra-arylated cubanes. Directed ortho-metalation with lithium base/alkyl zinc and subsequent palladium-catalyzed arylation enabled C-H metalation and arylation of cubane. This reaction allows the late-stage and regioselective installation of a wide range of aryl groups, realizing the first programmable synthesis of diverse multiply arylated cubanes.
RESUMEN
We describe here a novel GPR119 agonist 24, which showed a potent and long-acting hypoglycemic effect in rats via oral dosing. For the discovery of 24, we chose compound 5, which possessed an oxadiazole linker, as a lead compound among our spirocyclic cyclohexane GPR119 agonist series, taking into account its lower plasma protein binding nature. 3,5-Difluoro and 4-methylsulfonylmethy groups on the left side phenyl group, and a gem-difluoro group on the right side of 24 are important for its agonist potency and metabolic stability, respectively.
Asunto(s)
Ciclohexanos/farmacología , Hipoglucemiantes/farmacología , Oxadiazoles/farmacología , Receptores Acoplados a Proteínas G/agonistas , Compuestos de Espiro/farmacología , Animales , Ciclohexanos/síntesis química , Ciclohexanos/farmacocinética , Estabilidad de Medicamentos , Humanos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/farmacocinética , Microsomas Hepáticos/metabolismo , Estructura Molecular , Oxadiazoles/síntesis química , Oxadiazoles/farmacocinética , Ratas Sprague-Dawley , Compuestos de Espiro/síntesis química , Compuestos de Espiro/farmacocinética , Relación Estructura-ActividadRESUMEN
We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which linked potency and lipophilicity. Subsequent optimization studies of 8 for improvement of solubility afforded representative 21. Compound 21 had no inhibitory activity against six CYP isoforms and showed favorable pharmacokinetic properties and hypoglycemic activity in rats.
Asunto(s)
Ciclohexanos/farmacología , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Hipoglucemiantes/farmacología , Receptores Acoplados a Proteínas G/agonistas , Compuestos de Espiro/farmacología , Animales , Ciclohexanos/síntesis química , Ciclohexanos/química , Inhibidores Enzimáticos del Citocromo P-450/síntesis química , Inhibidores Enzimáticos del Citocromo P-450/química , Sistema Enzimático del Citocromo P-450/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Ligandos , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Compuestos de Espiro/síntesis química , Compuestos de Espiro/química , Relación Estructura-ActividadRESUMEN
Brasilicardins, bacterial diterpenoid natural products that display highly potent immunosuppressive activity, are promising immunosuppressant drug candidates. Structurally, they can be described as hybrids of terpenoids, amino acids, and saccharides, and share a characteristic highly strained anti-syn-anti-fused perhydrophenanthrene terpenoid scaffold (ABC-ring system) with two quaternary asymmetric carbon atoms. A unified and stereoselective total synthesis of all four brasilicardins has been designed based on the strategic use of an intramolecular conjugate addition. The ABC-ring system was initially constructed with high stereocontrol by novel intramolecular conjugate additions of Weinreb amides and in situ generated (Z)-vinyl copper species. The late-stage common intermediate was subjected to stereoselective installation of the amino acid component, followed by introduction of the saccharide unit via glycosylation to accomplish the total synthesis of brasilicardinsâ A-D. Our synthesis offers opportunities to synthesize various brasilicardin analogues for biological and pharmacological investigations.
Asunto(s)
Aminoglicósidos/síntesis química , Diterpenos/síntesis química , Aminoglicósidos/química , Diterpenos/química , Conformación Molecular , EstereoisomerismoRESUMEN
BACKGROUND: Endoscopic submucosal dissection (ESD) has been used to treat patients with early gastric cancers (EGCs), including large and ulcerative lesions. Few published data exist on the long-term outcomes of this treatment with median follow-up periods of over 5 years; we therefore aimed to assess the long-term outcomes of EGC patients undergoing ESD. METHODS: A total of 1,956 consecutive patients with 2,210 EGC lesions at initial onset underwent ESD with curative intent at our hospital from 1999 to 2006. We performed a retrospective analysis of the 5-year survival of EGC patients undergoing curative ESD for absolute indications or for expanded indications. RESULTS: For the pathological curability, curative ESD for absolute indications, curative ESD for expanded indications of differentiated-type EGC, and curative ESD for undifferentiated-type EGC were achieved in 781, 713, and 43 patients, respectively. The median follow-up period was 83.3 months. Among the 1,537 patients, there were only two patients with recurrence, including one who developed a regional lymph node (LN) metastasis and one who developed a distant LN metastasis with local recurrence resulting in gastric cancer-related death. Seven died from metachronous gastric cancers. The 5-year rates of overall survival, disease-specific survival, and relative survival were 92.6, 99.9, and 105.0%, respectively. CONCLUSIONS: Based on the high rate of 5-year survival among EGC patients undergoing curative ESD for absolute indications or for expanded indications in the largest patient series with a median follow-up period of over 5 years, ESD could be employed as a standard treatment for EGC lesions.
Asunto(s)
Gastroscopía/métodos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Mucosa Gástrica , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Gástricas/patología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. METHODS: A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1 year after successful H. pylori eradication. RESULTS: Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5 years after successful H. pylori eradication was 15.0 %; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication. CONCLUSION: Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.
Asunto(s)
Gastrectomía/efectos adversos , Infecciones por Helicobacter/complicaciones , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Gástricas/epidemiología , Adulto , Anciano , Endoscopía , Femenino , Estudios de Seguimiento , Gastroscopía , Infecciones por Helicobacter/virología , Helicobacter pylori , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/cirugía , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Gástricas/etiología , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tasa de SupervivenciaRESUMEN
BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) using insulation-tipped knives (IT knives) to treat gastric lesions located on the greater curvature of the gastric body remains technically challenging because of the associated bleeding, control of which can be difficult and time consuming. To eliminate these difficulties, we developed a novel strategy which we have called the "near-side approach method" and assessed its utility. PATIENTS AND METHODS: We reviewed patients who underwent ESD for solitary early gastric cancer located on the greater curvature of the gastric body from January 2003 to September 2014. The technical results of ESD were compared between the group treated with the novel near-side approach method and the group treated with the conventional method. RESULTS: This study included 238 patients with 238 lesions, 118 of which were removed using the near-side approach method and 120 of which were removed using the conventional method. The median procedure time was 92 minutes for the near-side approach method and 120 minutes for the conventional method. The procedure time was significantly shorter in the near-side approach method arm. Although, the procedure time required by an experienced endoscopist was not significantly different between the two groups (100 vs. 110 minutes), the near-side approach group showed significantly shorter procedure time for a less-experienced endoscopist (90 vs. 120 minutes). CONCLUSIONS: The near-side approach method appears to require less time to complete gastric ESD than the conventional method using IT knives for technically challenging lesions located on the greater curvature of the gastric body, especially if the procedure is performed by less-experienced endoscopists.
RESUMEN
BACKGROUND AND STUDY AIMS: As more early gastric cancer (EGC) patients are being treated with endoscopic submucosal dissection (ESD), it is important to understand the outcomes of patients who develop metachronous gastric cancer (MGC). The aim of this study was to evaluate the long-term surveillance and treatment outcomes of MGC after curative gastric ESD. PATIENTS AND METHODS: The study included 1526 consecutive patients who underwent curative ESD resection of EGC. They were generally followed by annual or biannual esophagogastroduodenoscopy. The risk factors and treatment outcomes for MGC were assessed along with the 5-year, 7-year, and 10-year cumulative incidence functions of MGC and disease-specific survival (DSS). RESULTS: During a median follow-up period of 82.2 months, 238 patients developed MGC post-ESD resection of EGC. The 5-year, 7-year, and 10-year cumulative incidence functions of MGC were 9.5%, 13.1% and 22.7%, respectively. Male sex and multiple initial EGCs were independent risk factors for MGC in the Cox proportional hazard model. Of the 238 patients with MGC, 215 were treated with endoscopic resection, of which 183 achieved curative resection, although one patient later died of his initial EGC. A further 14 patients were treated surgically, three had metastatic disease and received palliative chemotherapy, and the remaining six were observed without any intervention. A total of seven patients died of MGC, five at least 5 years after their index ESD. The 5-year, 7-year, and 10-year DSSs were 99.2%, 98.6%, and 92.5%, respectively. CONCLUSIONS: The incidence of MGC increases with time after curative gastric ESD, therefore surveillance endoscopy should be continued indefinitely.
Asunto(s)
Adenocarcinoma , Mucosa Gástrica/patología , Gastroscopía , Neoplasias Primarias Secundarias , Neoplasias Gástricas , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Disección/efectos adversos , Disección/métodos , Femenino , Estudios de Seguimiento , Gastroscopía/efectos adversos , Gastroscopía/métodos , Humanos , Japón/epidemiología , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/mortalidad , Masculino , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/patología , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Two years after the initial ESD, a 0-IIc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric antrum. The estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated adenocarcinoma. ESD was performed for this lesion and en bloc resection with negative margins was achieved. Histopathological examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer (1600 µm), with lymphovascular invasion, consistent with the diagnosis of non-curative resection. Additional gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical resection. Systemic chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second ESD. Early gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well known. The present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer.
Asunto(s)
Adenocarcinoma/cirugía , Carcinoma Adenoescamoso/patología , Disección/métodos , Gastrectomía/métodos , Mucosa Gástrica/patología , Neoplasias Primarias Secundarias/patología , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Adenocarcinoma/patología , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Carcinoma Adenoescamoso/química , Carcinoma Adenoescamoso/secundario , Carcinoma Adenoescamoso/cirugía , Quimioterapia Adyuvante , Detección Precoz del Cáncer , Endoscopía del Sistema Digestivo , Resultado Fatal , Mucosa Gástrica/química , Mucosa Gástrica/cirugía , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/secundario , Masculino , Invasividad Neoplásica , Neoplasias Primarias Secundarias/química , Reoperación , Neoplasias Gástricas/química , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND AND STUDY AIMS: Compared with any other location in the gastrointestinal tract, the duodenum presents the most challenging site for endoscopic resection. The aim of this study was to analyze the clinical outcomes of duodenal endoscopic resection and to assess the feasibility of the technique as a therapeutic procedure. PATIENTS AND METHODS: A total of 113 consecutive patients with 121 nonampullary duodenal tumors underwent endoscopic resection by endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), or polypectomy between January 2000 and September 2013. Long-term outcomes were investigated in patients with more than 1 year follow-up. RESULTS: The median tumor size was 12âmm (range 3â-â50âmm). Lesions consisted of 63 adenocarcinomas/high-grade intraepithelial neoplasias (53â%) and 57 adenomas/low-grade intraepithelial neoplasias (48â%). Endoscopic resection included 106 EMRs (87â%), 8 ESDs (7â%), and 7 polypectomies (6â%). En bloc resection was achieved in 77 lesions (64â%), and 43 lesions (35â%) underwent piecemeal resection; one procedure was discontinued due to perforation. There were 14 cases of delayed bleeding after EMR (12â%), 1 perforation (1â%) during ESD, and 1 delayed perforation (1â%) after ESD, which required emergency surgery. Of the 76 patients who were followed for more than 1 year, none of the patients died from a primary duodenal neoplasm, and there were no local recurrences during the 51-month median follow-up period (range 12â-â163 months). CONCLUSIONS: Duodenal endoscopic resection was feasible as a therapeutic procedure, but it should only be performed by highly skilled endoscopists because of its technical difficulty. Piecemeal resection by EMR is acceptable for small lesions, based on these excellent long-term outcomes.
Asunto(s)
Adenocarcinoma/cirugía , Adenoma/cirugía , Carcinoma in Situ/cirugía , Disección/métodos , Neoplasias Duodenales/cirugía , Endoscopía Gastrointestinal/métodos , Adenocarcinoma/patología , Adenoma/patología , Poliposis Adenomatosa del Colon/cirugía , Anciano , Carcinoma in Situ/patología , Disección/efectos adversos , Neoplasias Duodenales/patología , Endoscopía Gastrointestinal/efectos adversos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Mucosa Intestinal/cirugía , Perforación Intestinal/etiología , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Carga TumoralRESUMEN
The introduction of colorectal endoscopic submucosal dissection (ESD) has expanded the application of endoscopic treatment, which can be used for lesions with a low metastatic potential regardless of their size. ESD has the advantage of achieving en bloc resection with a lower local recurrence rate compared with that of piecemeal endoscopic mucosal resection. Moreover, in the past, surgery was indicated in patients with large lesions spreading to almost the entire circumference of the rectum, regardless of the depth of invasion, as endoscopic resection of these lesions was technically difficult. Therefore, a prime benefit of ESD is significant improvement in the quality of life for patients who have large rectal lesions. On the other hand, ESD is not as widely applied in the treatment of colorectal neoplasms as it is in gastric cancers owing to the associated technical difficulty, longer procedural duration, and increased risk of perforation. To diversify the available endoscopic treatment strategies for superficial colorectal neoplasms, endoscopists performing ESD need to recognize its indications, the technical issues involved in its application, and the associated complications. This review outlines the methods and type of devices used for colorectal ESD, and the training required by endoscopists to perform this procedure.
Asunto(s)
Colectomía/métodos , Colonoscopía/métodos , Neoplasias Colorrectales/cirugía , Disección/métodos , Mucosa Intestinal/cirugía , Colectomía/educación , Colonoscopía/educación , Neoplasias Colorrectales/patología , Disección/educación , Educación de Postgrado en Medicina , Humanos , Mucosa Intestinal/patología , Resultado del TratamientoRESUMEN
Endoscopic submucosal dissection (ESD) is an established therapeutic technique for the treatment of gastrointestinal neoplasms. Because it is typically completed as en bloc resection, this technique provides a complete specimen for precise pathological evaluation. On the other hand, ESD is not as widely applied in treating colorectal neoplasms as with gastric cancers, due to its technical difficulty, longer procedure time, and increased risk of perforation. However, some devices that facilitate ESD and improve the safety of the procedure have been recently reported, and the use of the technique has gradually spread worldwide. Endoscopists who begin to perform ESD need to recognize the indications of ESD, the technical issue involved in this procedure, and its associated complications. This review outlines the methods and certain types of devices used for colorectal ESD.
RESUMEN
BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a relatively new therapy that has been accepted as the most effective treatment procedure for superficial colorectal neoplasms. Given the increasing acceptance and use of this procedure worldwide, the outcomes of colorectal ESD performed by trainees should be understood from a practical perspective and for developing strategies to introduce ESD to trainees. This study aimed to evaluate the clinical outcomes of ESD when conducted by less-experienced endoscopists. SUMMARY: We retrospectively reviewed the clinical outcomes of 164 patients with 164 colorectal neoplasms who underwent ESD carried out by 20 trainees performing their first colorectal ESDs between April 2005 and March 2012. For each operator, clinical data were collected between the first and 30th cases. For evaluating the technical aspects of the ESD procedure, the endoscopic characteristics of the lesions, procedure time, en bloc resection rate, R0 resection rate, invasion depth and complications were evaluated. The median procedure time was 95 min; about 75% of the lesions were resected within 120 min. Apparent perforation or electric damage in the muscularis propria was seen in 4% of lesions. In terms of factors with the potential to effect procedure time, lesion size and pathological invasion depth were significantly different between shorter and longer treatment times for granular-type laterally spreading tumors (LST). KEY MESSAGES: A granular-type LST of <40 mm is a good lesion for introducing colorectal ESD to trainees. Trainees should have a strong ability to make a depth diagnosis before starting ESD.