Publications by authors named "Satoru Nonaka"

69 Publications

APC mutations are common in adenomas but infrequent in adenocarcinomas of the non-ampullary duodenum.

J Gastroenterol 2021 Nov 12;56(11):988-998. Epub 2021 Sep 12.

Division of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background: Recent studies highlighted the clinicopathological heterogeneity of non-ampullary duodenal adenomas and adenocarcinomas, but the detailed process of the malignant transformation remains unclear.

Methods: We analyzed 144 adenomas and 54 adenocarcinomas of the non-ampullary duodenum for immunohistochemical phenotypes, genetic alterations, and mismatch repair (MMR) status to probe their histogenetic relationship.

Results: The median ages of patients with adenoma and adenocarcinoma were the same (66 years). Adenomas were histologically classified as intestinal-type adenoma (n = 124), pyloric gland adenoma (PGA, n = 10), gastric-type adenoma, not otherwise specified (n = 9), and foveolar-type adenoma (n = 1). Protein-truncating APC mutations were highly frequent in adenomas (85%), with the highest prevalence in intestinal-type adenomas (89%), but rare in adenocarcinomas (9%; P = 2.1 × 10). Close associations between phenotypic marker expression and genetic alterations were observed in adenomas, but not in adenocarcinomas, excluding the common association between GNAS mutations and MUC5AC expression. MMR deficiency was more frequent in adenocarcinomas (20%) than in adenomas (1%; P = 2.6 × 10). One MMR-deficient adenoma and three MMR-deficient adenocarcinomas occurred in patients with Lynch syndrome. Additionally, three other patients with an MMR-deficient adenocarcinoma fulfilled the revised Bethesda criteria.

Conclusion: The discrepant APC mutation frequency between adenomas and adenocarcinomas suggests that APC-mutated adenomas, which constitute the large majority of non-ampullary duodenal adenomas, are less prone to malignant transformation. Non-ampullary duodenal adenocarcinomas frequently exhibit MMR deficiency and should be subject to MMR testing to determine appropriate clinical management, including the identification of patients with Lynch syndrome.
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http://dx.doi.org/10.1007/s00535-021-01823-xDOI Listing
November 2021

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

Endoscopy 2021 Sep 8. Epub 2021 Sep 8.

Cancer Center, School of Medicine, Keio University, Tokyo, Japan.

Background And Study Aim: There is no enough data for endoscopic resection (ER) of superficial duodenal epithelial tumors (SDETs) due to its rarity. There are two main kinds of ER techniques for SDETs: EMR and ESD. In addition, modified EMR techniques, underwater EMR (UEMR) and cold polypectomy (CP), are getting popular. We conducted a large-scale retrospective multicenter study to clarify detailed outcomes of duodenal ER.

Patients And 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 Kaplan-Meier method.

Results: In total, 3107 patients (including 1017 receiving 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 7.3% for CP, UEMR, EMR and ESD, respectively. The delayed AE rate was significantly higher for ESD group than non-ESD group among lesions less than 19 mm (7.4% vs 1.9%, p<0.0001), but not among lesions larger than 20 mm (6.1% vs 7.1%, p=0.6432). The local recurrence rate was significantly lower in ESD group than non-ESD group (p<0.001). Furthermore, for lesions larger than 30 mm, the cumulative local recurrence rate at 2 years was 22.6% in non-ESD group compared to only 1.6% in ESD group (p<0.0001).

Conclusions: ER outcomes for SDETs were generally acceptable. ESD by highly experienced endoscopists might be an option for very large SDETs.
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http://dx.doi.org/10.1055/a-1640-3236DOI Listing
September 2021

Novel hybrid endoscopy-assisted larynx-preserving esophagectomy for cervical esophageal cancer (with video).

Jpn J Clin Oncol 2021 Jul;51(7):1171-1175

Division of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan.

Hybrid endoscopy-assisted larynx-preserving esophagectomy is developed for cervical esophageal squamous cell carcinoma encroaching or extending above the upper esophageal sphincter. First, a cervical incision was surgically performed followed by cervical lymph node dissection. Second, the margin of cervical esophageal squamous cell carcinoma was endoscopically identified with iodine staining and marked endoscopically followed by semi-circumferential or circumferential endoscopic full-thickness excision around the lumen of the esophagus. The distal margin was surgically resected and reconstruction was performed. Among six consecutive patients with cervical esophageal squamous cell carcinoma undergoing hybrid endoscopy-assisted larynx-preserving esophagectomy, proximal surgical margin was histologically negative in five patients. During a median follow-up period of 15.5 months, all patients tolerated oral intake and were alive without evidence of recurrence. None of the patients experienced aspiration pneumonia, vocal disorder or postoperative anastomotic stricture. Hybrid endoscopy-assisted larynx-preserving esophagectomy could be a clinically feasible treatment for cervical esophageal squamous cell carcinoma providing accurate proximal resection margin with the benefit of laryngeal function preservation.
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http://dx.doi.org/10.1093/jjco/hyab045DOI Listing
July 2021

Optimal selection of endoscopic resection in patients with esophageal squamous cell carcinoma: endoscopic mucosal resection versus endoscopic submucosal dissection according to lesion size.

Dis Esophagus 2021 May;34(5)

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

En bloc resection is essential for accurate pathological evaluation in patients with superficial esophageal squamous cell carcinoma (SESCC). This retrospective study aimed to clarify optimal treatment selection of endoscopic resection according to lesion size. A total of 760 patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) between January 2011 and December 2015. Among them, this retrospective study included 196 solitary index SESCC lesions ≤20 mm, with the deepest invasion to the mucosa or superficial submucosa endoscopically. The lesions were classified according to size measured via endoscopy as follows; group A: lesions ≤10 mm, group B: lesions ≥11 mm but ≤15 mm, and group C: lesions ≥16 mm but ≤20 mm. The short- and long-term outcomes were investigated for EMR and ESD subgroups. In patients undergoing EMR and ESD, en bloc resection rates for group A and B were not different (98.8 vs. 100%, 93.3 vs. 100%, respectively). However, the en bloc resection rate was significantly lower in EMR than that in ESD for group C (64.3 vs. 100%, P < 0.001). Furthermore, the use of adjunctive ablative therapy rate was significantly higher in EMR than that in ESD in group C (35.7 vs. 0%, P < 0.001). The 5-year cumulative local recurrence rate of group C was significantly higher than that of group A + B after EMR (P < 0.01). EMR was an adequate treatment for SESCC lesions ≤15 mm. On the other hand, ESD could be necessary to achieve en bloc resection for lesions ≥16 mm to avoid local recurrence.
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http://dx.doi.org/10.1093/dote/doaa096DOI Listing
May 2021

Reduced Intravenous Fluorescein Dose for Upper and Lower Gastrointestinal Tract Probe-Based Confocal Laser Endomicroscopy.

Clin Endosc 2021 May 8;54(3):363-370. Epub 2020 Sep 8.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

Background/aims: Probe-based confocal laser endomicroscopy (pCLE) requires the administration of intravenous (IV) fluorescein. This study aimed to determine the optimal dose of IV fluorescein for both upper and lower gastrointestinal (GI) tract pCLE.

Methods: Patients 20 to 79 years old with gastric high-grade dysplasia (HGD) or colorectal neoplasms (CRNs) were enrolled in the study. The dose de-escalation method was employed with five levels. The primary endpoint of the study was the determination of the optimal dose of IV fluorescein for pCLE of the GI tract. The reduced dose was determined based on off-line reviews by three endoscopists. An insufficient dose of fluorescein was defined as the dose of fluorescein with which the pCLE images were not deemed to be visible. If all three endoscopists determined that the tissue structure was visible, the doses were de-escalated.

Results: A total of 12 patients with gastric HGD and 12 patients with CRNs were enrolled in the study. Doses were de-escalated to 0.5 mg/kg of fluorescein for both non-neoplastic duodenal and colorectal mucosa. All gastric HGD or CRNs were visible with pCLE with IV fluorescein at 0.5 mg/kg.

Conclusion: In the present study, pCLE with IV fluorescein 0.5 mg/kg was adequate to visualize the magnified structure of both the upper and lower GI tract.
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http://dx.doi.org/10.5946/ce.2020.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182239PMC
May 2021

Endoscopic Closure Utilizing Endoloop and Endoclips After Gastric Endoscopic Submucosal Dissection for Patients on Antithrombotic Therapy.

Dig Dis Sci 2021 07 14;66(7):2336-2344. Epub 2020 Aug 14.

Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Objectives: Antithrombotic therapy is a well-known independent risk factor for bleeding after endoscopic submucosal dissection (ESD) of early gastric cancer (EGC). A novel method of ulcer base closure using an endoloop and endoclips has been reported. This study aimed to evaluate the effectiveness of endoscopic closure using an endoloop and endoclips in preventing post-ESD bleeding in patients undergoing gastric ESD on antithrombotic therapy.

Methods: This was a single center, retrospective study. Patients on antithrombotic therapy who underwent gastric ESD were divided into two groups, the closure group and the non-closure group. We analyzed procedural outcomes, post-ESD bleeding rate and factors associated with post-ESD bleeding.

Results: Among 400 ESDs with EGCs in 311 patients, 131 ESDs in 110 patients were in the closure group, and 269 ESDs in 217 patients were in the non-closure group (16 patients were overlapped in both groups). Post-ESD bleeding rate was 11.5% (15/131) in the closure group, and 11.9% (32/269) in the non-closure group (p = 0.89). Total sustained closure rate during second look endoscopy was 47.8% (33/69). Post-ESD bleeding rate tended to be lower in the closure group than in the non-closure group for lesions located in the greater curvature (3.6% vs. 11.1%, p = 0.11). In addition, sustained closure rate was significantly higher in the greater curvature than in the lesser curvature (72.0% vs. 34.1%, p < 0.01). Multivariate analysis revealed resection size > 40 mm and heparin bridge were the independent risk factor for post-ESD bleeding.

Conclusion: Ulcer base closure using endoloop and endoclips did not prevent post-ESD bleeding in patients on antithrombotic therapy.
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http://dx.doi.org/10.1007/s10620-020-06508-8DOI Listing
July 2021

A new reliable acoustic respiratory monitoring technology during upper gastrointestinal tract therapeutic endoscopy with CO insufflation.

J Clin Monit Comput 2021 08 15;35(4):877-884. Epub 2020 Jun 15.

Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan.

Previous studies documented the effectiveness and benefits of capnography monitoring during propofol-based sedation for colonoscopy to reduce the incidence of hypoxemia. However, the performance of capnography during longer duration endoscopic therapy of upper gastrointestinal tract cancers under CO insufflation it is not well known. In this study, we compare a new device with acoustic monitoring technology to standard capnography monitoring. We retrospectively analyzed 49 patients who underwent endoscopic resection of early upper gastrointestinal tract cancer between December 2013 and October 2014. All 49 patients were monitored using both acoustic monitoring technology and standard capnography. We investigated the duration of the periods with unmeasurable respiratory rate during the overall procedure. When comparing standard capnography monitoring to the new acoustic monitoring technology, the ratio of the unmeasurable time was significantly lower in RRa (36.9% vs. 21.6%, p < 0.01). The ratio of unmeasurable respiratory rate by capnography was strongly correlated to the ratio of unmeasurable PETCO level by capnography (R = 0.847). There were no severe events or adverse events (grade 2 or more) during all 49 procedures. The acoustic monitoring technology provides a more reliable respiratory monitoring when compared to standard capnography during endoscopic resection of upper gastrointestinal tract cancers under CO insufflation, even if the procedures were prolonged and complex.
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http://dx.doi.org/10.1007/s10877-020-00547-2DOI Listing
August 2021

Safety and usefulness of endoscopic submucosal dissection for early esophageal cancers in elderly patients aged 80 years or older.

Esophagus 2021 Jan 29;18(1):81-89. Epub 2020 May 29.

Endoscopy Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background And Aim: Endoscopic submucosal dissection (ESD) for early gastrointestinal (GI) cancers is widely performed as a standard treatment in Japan. Given the increasing life expectancy worldwide, it is naturally regarded that the rate of elderly patients diagnosed with early GI cancer has increased. Available guidelines do not specifically outline how to manage endoscopic therapy for the elderly. The aim of this study was to assess the safety and usefulness of ESD for superficial esophageal squamous cell carcinoma (SESCC) in elderly patients.

Methods: We retrospectively investigated 393 consecutive patients, who underwent 426 ESD for 444 SESCCs from January 2011 to August 2016 at our institution. For this study, patients were divided into 2 groups based on their age; ≥ 80 years (Group aged ≥ 80 years, n = 42) and < 80 years (group aged < 80 years, n = 351). Patient demographics, sedation methods, technical outcomes, adverse events, sedatives, dosages given, overall survival, and disease-specific survival were then examined.

Results: The ESD procedure time was significantly longer for group aged ≥ 80 years than for group aged < 80 years (110 min [range 29-260] vs 85 min [24-504], p = 0.006); however, there was no significant differences between other technical items and adverse events. The 3-year overall survival and disease-specific survival were favorable in both groups.

Conclusions: Esophageal ESD for elderly patients aged ≥ 80 years can be safely performed. Mid-term outcome was favorable. Our study suggests that esophageal ESD might be a useful treatment for SESCCs.
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http://dx.doi.org/10.1007/s10388-020-00750-9DOI Listing
January 2021

Sporadic pyloric gland adenoma associated with a large fundic gland polyp: genetic evidence for stepwise progression.

Gastric Cancer 2020 11 15;23(6):1102-1106. Epub 2020 May 15.

Division of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Pyloric gland adenoma (PGA) is an uncommon variant of gastric adenoma exhibiting pyloric gland/mucous neck cell differentiation. We present a sporadic PGA associated with a large fundic gland polyp (FGP) in a woman in her 40 s without Helicobacter pylori infection. The polyp, measuring 25 mm in size, was located in the middle gastric body and was removed by endoscopic submucosal dissection. Histological examination revealed three morphologically distinct components: FGP, FGP with large cysts, and PGA. A genetic analysis identified a truncating APC mutation in all the three components, supporting their histogenetic relationship. Additionally, a GNAS mutation was detected in two components, FGP with large cysts and PGA, whereas a KRAS mutation was exclusively found in the PGA component. Thus, despite the unusual presentation, the PGA component harbored prototypical genetic alterations. The differential genetic alterations observed in the three components imply that they represent stepwise progression from FGP to PGA.
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http://dx.doi.org/10.1007/s10120-020-01082-4DOI Listing
November 2020

Long-term outcomes of patients with recurrent squamous cell carcinoma of the esophagus undergoing salvage endoscopic resection after definitive chemoradiotherapy.

Surg Endosc 2021 04 30;35(4):1766-1776. Epub 2020 Apr 30.

Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan.

Background: Salvage endoscopic resection (ER) has been reported to be effective for patients with local failure of esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT). This study aimed to evaluate the long-term outcomes of salvage ER for patients with local failure of ESCC and to identify risk factors associated with disease recurrence after salvage ER.

Methods: This study included 45 patients undergoing salvage ER after dCRT during 2000 to 2017. After ER, all patients were required to undergo surveillance esophagogastroduodenoscopy (EGD) once or twice every year, and a computed tomography (CT) examination was repeated every 3 to 6 months. We assessed short-term outcomes and long-term outcomes.

Results: Of the 45 patients in this study, the baseline clinical T stage before dCRT was T1 in 80%, 66% of the patients did not have nodal metastasis. The median time from CRT to the detection of local failure was 11 months (range 2-130 months). The en-bloc resection rate was 46%, and the R0 resection rate was 38%, respectively. Stricture occurred after salvage ER for one case, while adverse events such as bleeding or perforation and ER-related death did not occur. After a median observation period of 57 months, recurrence free survival at 3 years was 58%, overall survival was 72%, and disease specific survival was 81%. In multivariate analysis, clinical N stage before CRT was the only independent risk factor of recurrence after salvage ER (p = 0.04).

Conclusions: Salvage ER might be effective local treatment in patients with local failure after dCRT. For the patients with clinical N stage, frequent surveillance should be performed.
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http://dx.doi.org/10.1007/s00464-020-07571-yDOI Listing
April 2021

Efficacy of Current Traction Techniques for Endoscopic Submucosal Dissection.

Gut Liver 2020 11;14(6):673-684

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

This systematic review aimed to assess the efficacy of the current approach to tissue traction during the endoscopic submucosal dissection (ESD) of superficial esophageal cancer, early gastric cancer, and colorectal neoplasms. We performed a systematic electronic literature search of articles published in PubMed and selected comparative studies to investigate the treatment outcomes of tractionassisted versus conventional ESD. Using the keywords, we retrieved 381 articles, including five eligible articles on the esophagus, 13 on the stomach, and 12 on the colorectum. A total of seven randomized controlled trials and 23 retrospective studies were identified. Clip line traction and submucosal tunneling were effective in reducing the procedural time during esophageal ESD. The efficacy of traction methods in gastric ESD varied in terms of the devices and strategies used depending on the lesion location and degree of submucosal fibrosis. Several prospective and retrospective studies utilized traction devices without the need to reinsert the colonoscope. When pocket creation is included, the traction devices and methods effectively shorten the procedural time during colorectal ESD. Although the efficacy is dependent on the organ and tumor locations, several traction techniques have been demonstrated to be efficacious in facilitating ESD by maintaining satisfactory traction during dissection.
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http://dx.doi.org/10.5009/gnl19266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667936PMC
November 2020

ESD as first-intent resection method: also for the duodenum?

Endosc Int Open 2019 Dec 10;7(12):E1761-E1762. Epub 2019 Dec 10.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1055/a-1012-6455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904242PMC
December 2019

Conventional versus traction-assisted endoscopic submucosal dissection for large esophageal cancers: a multicenter, randomized controlled trial (with video).

Gastrointest Endosc 2020 01 21;91(1):55-65.e2. Epub 2019 Aug 21.

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

Background And Aims: Endoscopic submucosal dissection (ESD) is widely used as a minimally invasive treatment for large esophageal cancers, but prolonged procedure duration and life-threatening adverse events remain matters of concern. We aimed to determine whether traction-assisted ESD (TA-ESD) is superior to conventional ESD in terms of technical outcomes.

Methods: A superiority, randomized, phase III trial was conducted at 7 institutions across Japan. Patients with large esophageal cancer (defined as tumor diameter >20 mm) were eligible for this study. Enrolled patients were randomly assigned to undergo conventional ESD or TA-ESD. The primary endpoint was ESD procedure duration.

Results: Two hundred forty-one patients were recruited and randomized. On applying exclusion criteria, 117 and 116 patients who underwent conventional ESD and TA-ESD, respectively, were included in the baseline analysis. In 1 patient, conventional ESD was discontinued because of severe perforation. Thus, the final analysis included 116 patients per group (primary analysis). The ESD procedure duration was significantly shorter for TA-ESD than for conventional ESD (44.5 minutes vs 60.5 minutes, respectively; P < .001). Moreover, no adverse events were noted in the TA-ESD group. The rate of horizontal margin involvement did not differ between the groups (10.3% vs 6.9% for conventional ESD and TA-ESD, respectively; P = .484).

Conclusions: TA-ESD was superior to conventional ESD in terms of procedure duration and was not associated with any adverse events. TA-ESD should be considered the procedure of choice for large esophageal cancers. (Clinical trial registration number: UMIN000024080.).
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http://dx.doi.org/10.1016/j.gie.2019.08.014DOI Listing
January 2020

A case of mixed-type early gastric cancer with recurrence following curative endoscopic submucosal dissection for expanded indication.

Endosc Int Open 2019 Jun 12;7(6):E841-E845. Epub 2019 Jun 12.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

In Japan, intramucosal gastric adenocarcinoma with ulcerative finding having a predominantly differentiated type with an undifferentiated component, tumor diameter ≤ 3 cm, and no lymphovascular invasion is included in the expanded pathological criteria for curative endoscopic treatment. This indication is based on retrospective examination of surgical resection cases, and is determined to have a negligible risk of lymph node metastasis (LNM). We performed endoscopic submucosal dissection on a 78-year-old man with early gastric cancer in 2011, and pathology revealed a well-differentiated tubular adenocarcinoma (21 × 10 mm in diameter), with poorly differentiated adenocarcinoma components, limited to the mucosa, fibrosis by ulcer scar in the submucosal layer, no lymphovascular invasion, and tumor-free margins. Resection was determined to be curative under expanded indications of the gastric cancer treatment guidelines, 4 edition. However, 55 months after the initial diagnosis, invasive local and distant recurrence was noted. Ultimately, the patient died of gastric cancer 3 months after recurrence.
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http://dx.doi.org/10.1055/a-0900-3835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561759PMC
June 2019

Clinical feasibility of endoscopic submucosal dissection with minimum lateral margin of superficial esophageal squamous cell carcinoma.

Endosc Int Open 2019 Apr 15;7(4):E396-E402. Epub 2019 Mar 15.

National Cancer Center Hospital, Endoscopy Division, Tokyo, Japan.

 Esophageal stricture following endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell cancer (SESCC) has been associated with wide mucosal defects greater than three-quarters of the luminal circumference. Some patients developed dysphagia and required repeated endoscopic balloon dilation even after steroid therapy. As iodine staining clearly visualized the margin of SESCC, we made a longitudinal mucosal incision close to the margin of the lesion to avoid a mucosal defect involving over three-quarters of the luminal circumference for large lesions. This retrospective study aimed to clarify the clinical feasibility of ESD with minimum lateral margin of SESCC.  Between 2005 and 2013, 94 patients with 94 initial SESCCs had lesions greater than half of the luminal circumference. Of those, 70 patients with 70 SESCCs had achieved endoscopic clearance for the initial SESCC. In this study, endoscopic clearance was defined as en bloc resection of SESCC histologically confined to the mucosa without lymphovascular invasion and with a free deep margin regardless of the lateral margin. This study evaluated the short- and long-term outcomes in patients undergoing endoscopic clearance.  In total, 61.4 % (43/70) of the patients had mucosal defects involving over three-quarters of the luminal circumference and 38.5 % (27/70) had a positive or indeterminate lateral margin. However, there was no local or nodal recurrence during the median follow-up period of 3.8 years; the 3-year overall survival rate was 98.5 % and the 3-year disease-free survival rate was 100 %.  Using our institutions' strategy, ESD for SESCCs with minimum lateral margins was oncologically acceptable; this approach could reduce the known risk factor of post-ESD stricture.
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http://dx.doi.org/10.1055/a-0838-5064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420336PMC
April 2019

Risk of Lymph Node Metastasis in Patients with the Superficial Spreading Type of Esophageal Squamous Cell Carcinoma.

Digestion 2020 25;101(3):239-244. Epub 2019 Mar 25.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

Background: Little is known about the clinicopathological characteristics of superficial spreading-type esophageal carcinoma extending ≥5 cm along the long axis of the esophagus. This study was aimed at investigating the frequency of lymph node metastasis (LNM) in patients with superficial spreading-type esophageal carcinoma.

Methods: We reviewed the data of 320 patients with superficial esophageal squamous cell carcinoma who had undergone esophagectomy with lymph node dissection at our hospital between 1986 and 2010. The incidence of LNM was compared between the spreading (≥5 cm) and nonspreading (< 5 cm) types.

Results: The multivariate analysis revealed significant differences in the likelihood of LNM depending on the lymphovascular invasion, the infiltrative growth pattern (INF)-c, and the depth. There was no difference in the LNM frequency between nonspreading and spreading type in the patients with epithelium (EP)-lamina propria, muscularis mucosa (MM)-submucosa (SM)1 and SM2/3 lesions. The frequencies of LNMs (nonspreading-type vs. spreading-type tumors) in the patients with MM-SM1 lesions were 7/47 (14.9%) versus 4/25 (16%) and those in the patients with SM2/3 lesions were 22/58 (37.9%) versus 4/14 (28.9%), when the lesions did not have lymphovascular invasion and INF-c.

Conclusions: Endoscopic resection can be selected for -EP-SM1 lesions, regardless of whether the lesions are of the spreading type or nonspreading type.
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http://dx.doi.org/10.1159/000499017DOI Listing
March 2021

Conventional versus traction-assisted endoscopic submucosal dissection for gastric neoplasms: a multicenter, randomized controlled trial (with video).

Gastrointest Endosc 2018 May 9;87(5):1231-1240. Epub 2017 Dec 9.

Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

Background And Aims: The aim of this study was to clarify whether dental floss clip (DFC) traction improves the technical outcomes of endoscopic submucosal dissection (ESD).

Methods: A superiority, randomized control trial was conducted at 14 institutions across Japan. Patients with single gastric neoplasm meeting the indications of the Japanese guidelines for gastric treatment were enrolled and assigned to receive conventional ESD or DFC traction-assisted ESD (DFC-ESD). Randomization was performed according to a computer-generated random sequence with stratification by institution, tumor location, tumor size, and operator experience. The primary endpoint was ESD procedure time, defined as the time from the start of the submucosal injection to the end of the tumor removal procedure.

Results: Between July 2015 and September 2016, 640 patients underwent randomization. Of these, 316 patients who underwent conventional ESD and 319 patients who underwent DFC-ESD were included in our analysis. The mean ESD procedure time was 60.7 and 58.1 minutes for conventional ESD and DFC-ESD, respectively (P = .45). Perforation was less frequent in the DFC-ESD group (2.2% vs .3%, P = .04). For lesions located in the greater curvature of the upper or middle stomach, the mean procedure time was significantly shorter in the DFC-ESD group (104.1 vs 57.2 minutes, P = .01).

Conclusions: Our findings suggest that DFC-ESD does not result in shorter procedure time in the overall patient population, but it can reduce the risk of perforation. When selectively applied to lesions located in the greater curvature of the upper or middle stomach, DFC-ESD provides a remarkable reduction in procedure time.
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http://dx.doi.org/10.1016/j.gie.2017.11.031DOI Listing
May 2018

Feasibility of endoscopic resection using bipolar snare for nonampullary duodenal tumours in familial adenomatous polyposis patients.

Fam Cancer 2018 10;17(4):517-524

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

The management of duodenal and colorectal tumours is important in patients with familial adenomatous polyposis (FAP). Endoscopic resection (ER) should be carefully performed because the risk of complications during or after (ER) of nonampullary duodenal tumours is higher than that of stomach or colorectal lesions in general. Thus, we evaluated the feasibility of endoscopic resection using bipolar snare (ERB) for nonampullary duodenal tumours in FAP patients. Eleven FAP patients who underwent ERB for nonampullary duodenal tumours at our hospital between October 2013 and December 2016 were retrospectively analysed based on clinicopathological features. ER was generally indicated for endoscopically diagnosed tumours > 20 mm, biopsy-confirmed high-grade dysplasia or carcinomas > 10 mm, and multiple tumours. Nineteen endoscopic treatments were performed and 134 nonampullary duodenal tumours were resected. The median patient age at initial treatment was 40 years (range 20-64), and median size of the largest tumour in each procedure was 16 mm (range 9-40). Of the 101 pathologically evaluated lesions, 10 tumours were high-grade tubular adenomas, 87 were low-grade tubular adenomas, 1 was an adenocarcinoma, and 3 were non-neoplastic mucosal polyps. No intraoperative or delayed perforations were observed. Melena was encountered in one patient and managed without emergent endoscopic intervention. ERB for nonampullary duodenal tumours of FAP patients is feasible and effective, even for large lesions with high-grade dysplasia. Long-term outcomes of ERB, including local recurrence and prognosis, should be monitored.
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http://dx.doi.org/10.1007/s10689-017-0063-1DOI Listing
October 2018

Tumor location is a risk factor for lymph node metastasis in superficial Barrett's adenocarcinoma.

Endosc Int Open 2017 Sep 12;5(9):E868-E874. Epub 2017 Sep 12.

Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan.

Background And Study Aims : Endoscopic treatment is indicated for superficial Barrett's adenocarcinoma (BA) with a negligible risk of lymph node metastasis (LNM). However, risk factors associated with LNM in superficial BA are still not well characterized. The aim of the current study was to clarify risk factors for LNM of superficial BA.

Patients And Methods : A retrospective study was conducted in 87 consecutive patients with BA that was resected at National Cancer Center Hospital, Tokyo, Japan between 1990 and 2013. We assessed tumor size, macroscopic type, histological type, tumor depth of invasion, lymphovascular invasion and tumor location to analyze factors associated with LNM. Tumor location was classified into following 2 groups according to Siewert classification: 1) BA of the esophagogastric junction (EGJ-BA) as those having their center within 1 cm proximal from the EGJ; and 2) Esophageal-BA as those having their center at 1 cm or more proximal to the EGJ. EGJ was defined as distal end of the palisade vessels.

Results:  LNM was detected in 10 (11 %) patients. Univariable analysis revealed that tumor size, tumor depth of invasion, histological type of mixed differentiated and undifferentiated-type adenocarcinoma, lymphovascular invasion and tumor location of esophageal-BA were significantly associated with LNM. Multivariable analysis revealed that tumor location of esophageal-BA [odds ratio 7.8 (95 %CI: 1.3 - 48.1)] was a potential risk factor for LNM.

Conclusions : The current study demonstrated that tumor location is a potential risk factor for LNM in BA. Therefore, indications for endoscopic treatment of esophageal-BA and EGJ-BA could be different.
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http://dx.doi.org/10.1055/s-0043-115388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595573PMC
September 2017

Metachronous Gastric Cancer Following Curative Endoscopic Resection of Early Gastric Cancer.

Clin Endosc 2018 May 18;51(3):253-259. Epub 2017 Sep 18.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

This review article summarizes knowledge about metachronous gastric cancer (MGC) occurring after curative endoscopic resection (ER) of early gastric cancer (EGC), treatment outcomes of patients who developed MGC, and efficacy of Helicobacter pylori eradication to prevent MGC. The incidence of MGC following curative ER increases over time and is higher than in patients undergoing gastrectomy. Increasing age and multifocal EGC are independent risk factors for developing MGC. An MGC following curative ER is usually a small (<20 mm) and differentiated intramucosal cancer. Most MGC lesions are found at an early stage on semiannual or annual surveillance endoscopy and are successfully treated by further ER, with excellent long-term outcomes. Eradication of H. pylori may reduce the risk of MGC following ER of EGC, but further prospective studies with long-term outcomes are required. Surveillance endoscopy following gastric ER should be continued indefinitely, due to the risk of MGC even after successful H. pylori eradication. Risk stratification and tailored endoscopic surveillance schedules need to be developed.
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http://dx.doi.org/10.5946/ce.2017.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997077PMC
May 2018

Clinical outcomes of gastric polyps and neoplasms in patients with familial adenomatous polyposis.

Endosc Int Open 2017 Mar;5(3):E137-E145

Department of Surgical Pathology, Hyogo College of Medicine, Hyogo, Japan.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by a germline mutation in the adenomatous polyposis coli (APC) gene, characterized by the presence of more than 100 adenomatous polyps in the colorectum. The upper gastrointestinal tract is an extracolonic site for malignancy in patients with FAP. The frequency of death in Japanese patients with FAP because of gastric cancer is 2.8 % and that because of colon cancer is 60.6 %. Few studies have reported upper gastrointestinal diseases in patients with FAP. In the present study, we investigated the clinical outcomes of patients with FAP diagnosed with gastric neoplasms. We enrolled 80 patients with FAP who underwent esophagogastroduodenoscopy from October 1997 to December 2011. We investigated patient characteristics, endoscopic findings of gastric lesions, treatment outcomes, and long-term courses.  Fundic gland polyposis was observed in 51 patients (64 %) and gastric neoplasms in 22 patients (28 %), including 20 with non-invasive and 2 with invasive neoplasm. Of the 26 neoplasms, 11 were treated by endoscopic resection (ER) and 4 by surgical resection. Metachronous gastric neoplasms were observed in 7 patients (15 lesions) and treated by ER, except for in 1 patient. No patients died of gastric lesions during a median follow-up period of 6.5 years (range, 0 - 14). Because gastric lesions including gastric cancers in patients with FAP did not cause any deaths, they can be considered to have favorable prognoses. Early detection of gastric neoplasms through an appropriate follow-up interval may have contributed to these good outcomes.
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http://dx.doi.org/10.1055/s-0042-119809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339024PMC
March 2017

Prospective trial of biodegradable stents for refractory benign esophageal strictures after curative treatment of esophageal cancer.

Gastrointest Endosc 2017 Sep 27;86(3):492-499. Epub 2017 Jan 27.

Office of Clinical Research Support, National Cancer Center Hospital East, Chiba, Japan.

Background And Aims: Biodegradable stents are reportedly effective for refractory benign esophageal strictures; however, little is known about their use in patients with refractory stricture after endoscopic submucosal dissection (ESD) or chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the effectiveness of biodegradable stents for these patients.

Methods: Patients with refractory benign esophageal stricture with a dysphagia score (DS) of 2 or worse and for whom the passage of a standard size endoscope was not possible were eligible. The primary endpoint was the proportion of those who improved their DSs (% DS improved) at 12 weeks after stent placement, and the secondary endpoints were the proportion of those who improved their DSs at 24 weeks, dysphagia-free survival (DFS), and adverse events.

Results: Eighteen patients (men:women, 15:3; median age, 72 years; range, 53-80) were enrolled. Twelve patients improved their DS at 12 weeks (% DS improved, 66.7%; 90% CI, 44.6%-84.4%). Also, 8 of 11 patients (72.7%) after esophagectomy, 4 of 6 patients (66.7%) after ESD, and 3 of 4 patients (75%) after CRT improved at 12 weeks. Three patients who were treated with esophagectomy maintained their DS improvement at 24 weeks (% DS improved, 16.7%; 95% CI, 3.6%-41.4%). The median DFS was 14.1 weeks (95% CI, 13.0-19.0). One patient who had ESD and CRT developed an esophagobronchial fistula 3 months after stent placement.

Conclusions: Biodegradable stents are effective and tolerable for refractory benign esophageal strictures after treatment for esophageal cancer; however, long-term efficacy was limited, especially after ESD or CRT. (Clinical trial registration number: UMIN000008054.).
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http://dx.doi.org/10.1016/j.gie.2017.01.011DOI Listing
September 2017

Clinical outcomes and prognostic factors in gastric cancer patients aged ≥85 years undergoing endoscopic submucosal dissection.

Gastrointest Endosc 2017 May 15;85(5):963-972. Epub 2016 Oct 15.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

Background And Aims: Although the number of gastric cancer patients aged ≥85 years indicated for endoscopic submucosal dissection (ESD) has increased, little is known about the outcomes and prognostic factors. This study aimed to investigate the clinical outcomes and prognostic factors for overall survival (OS) of patients aged ≥85 years who underwent ESD for gastric cancer.

Methods: We retrospectively reviewed 108 patients aged ≥85 years with 149 gastric cancers treated by ESD between 1999 and 2014 at our institution. The clinical outcomes and prognosis were evaluated. Furthermore, the relationships between patient and lesion characteristics with OS were determined using the Kaplan-Meier method and a Cox proportional hazards model.

Results: All patients had Eastern Cooperative Oncology Group performance status (PS) of 0 to 1. En bloc, R0, and curative resections were achieved in 98.0%, 91.3%, and 72.7%, respectively, without severe adverse events requiring surgery. During a median follow-up period of 40.2 months (range, 1.8-108.7 months), 23 patients died, including 2 of gastric cancer. The 3-year (54.3% vs 95.9%) and 5-year (54.3% vs 76.3%) OS rates were significantly lower in patients with a low (<44.6) as opposed to a higher (≥44.6) prognostic nutritional index (PNI) (P < .001). The PNI was independently prognostic of OS (hazard ratio, 7.0; 95% confidence interval, 2.2-22.9; P = .001).

Conclusions: ESD is feasible for gastric cancer patients aged ≥85 years with good PS. However, low PNI was found to be prognostic of reduced OS, indicating the need to evaluate the PNI in determining whether to perform ESD.
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http://dx.doi.org/10.1016/j.gie.2016.10.013DOI Listing
May 2017

Clinical outcomes of early gastric cancer patients after noncurative endoscopic submucosal dissection in a large consecutive patient series.

Gastric Cancer 2017 Jul 8;20(4):679-689. Epub 2016 Oct 8.

Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan.

Background: Clinical outcomes of early gastric cancer (EGC) patients after noncurative endoscopic submucosal dissection (ESD) have not been fully elucidated; we therefore aimed to clarify these outcomes.

Methods: A total of 3058 consecutive patients with 3474 clinically diagnosed EGCs at initial onset underwent ESD with curative intent at our hospital between 1999 and 2010. We retrospectively assessed the following clinical outcomes of noncurative gastric ESD patients with a possible risk of lymph node (LN) metastasis by dividing patients into two groups with different treatment strategies (additional gastrectomy and simple follow-up): presence of LN metastasis at the time of gastrectomy, incidence of LN and distant metastases during the follow-up period, clinicopathological factors associated with metastasis, and 5-year disease-specific survival (DSS).

Results: After exclusion of 75 noncurative ESD patients with only a positive horizontal margin, 569 noncurative ESD patients with a possible risk of LN metastasis were identified. Among the 356 patients undergoing additional gastrectomy, LN metastasis was identified in 18 patients. A positive vertical margin with submucosal invasion (odds ratio 3.6) and lymphovascular invasion (odds ratio 3.5) were significantly associated with LN metastasis. The 5-year DSS rate was 98.8 %. Among the 212 patients who underwent simple follow-up, LN and/or distant metastases were found in eight patients. In this group, lymphovascular invasion (hazard ratio 6.6) was significantly associated with metastasis with a 5-year DSS rate of 96.8 %.

Conclusions: Additional gastrectomy should be performed particularly in noncurative gastric ESD patients with lymphovascular invasion or a positive vertical margin with submucosal invasion.
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http://dx.doi.org/10.1007/s10120-016-0651-zDOI Listing
July 2017

Factors associated with incomplete gastric endoscopic submucosal dissection due to misdiagnosis.

Endosc Int Open 2016 Jul 29;4(7):E788-93. Epub 2016 Jun 29.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

Background And Study Aims: Endoscopic submucosal dissection (ESD) is widely accepted for treating early gastric cancer (EGC); however, there can be cases of incomplete resection due to not only technical problems, but also misdiagnosis. Our aim was to identify factors associated with incomplete gastric ESD due to misdiagnosis.

Patients And Methods: A total of 2,268 patients with solitary EGCs at initial onset underwent ESD with curative intent at our hospital from 1999 to 2008. We retrospectively assessed the clinicopathological factors by comparing the two groups of incomplete ESD cases due to misdiagnosis (cases with a positive lateral margins [LM] [Group A] or those with a positive vertical margins [VM] [Group B]) with complete ESD cases using multivariable analysis.

Results: Complete ESD was achieved in 2,097 patients. The 171 patients with incomplete ESDs were divided into 109 with a positive LM and 80 with a positive VM (overlapped). Except 49 cases with a positive LM due to technical problems, a positive LM due to misdiagnosis was identified in 60 cases (Group A). Excluding 32 cases with a positive VM due to technical problems, a positive VM due to misdiagnosis was found in 48 cases (Group B). Significant independent factors (odds ratios [OR]; 95 % confidence intervals [CI]) for each group were as follows: Group A: size > 20 mm (5.4; 3.0 - 9.9), undifferentiated-type (4.1; 1.8 - 9.0), submucosal invasion (2.0; 1.1 - 3.4) and location of upper/middle (1.9; 1.0 - 3.6); Group B: size > 20 mm (3.0; 1.6 - 5.5), undifferentiated-type (3.0; 1.1 - 8.0) and location of upper/middle (2.4; 1.2 - 4.8).

Conclusions: Endoscopists must be aware of these factors associated with incomplete gastric ESD due to misdiagnosis to further decrease their incidence.
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http://dx.doi.org/10.1055/s-0042-108191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993884PMC
July 2016

Characteristics and Clinical Outcomes of Duodenal Neoplasia in Japanese Patients With Familial Adenomatous Polyposis.

J Clin Gastroenterol 2017 May/Jun;51(5):407-411

*Endoscopy Division ‡Colorectal Surgery Division, National Cancer Center Hospital, Tokyo †Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Background: After colorectal cancer and desmoid tumors, duodenal adenocarcinoma is the next leading cause of death in familial adenomatous polyposis (FAP) patients, but it has not been thoroughly investigated.

Patients And Methods: To investigate the clinical course of duodenal neoplasia, including adenoma and cancer, we investigated 77 Japanese FAP patients treated at the National Cancer Center Hospital, Tokyo, Japan. We evaluated the clinicopathologic features, Spigelman severity score, and management of duodenal neoplasms. Data were acquired from a prospectively enrolled database.

Results: Fifty-one (66%) of the 77 FAP patients had duodenal neoplasia during this observational period, and 47 of 51 patients had extra-ampulla duodenal neoplasia; 42 (58%) had duodenal neoplasms (extra-ampulla), 4 had duodenal adenomas with high-grade dysplasia (HGD), and 1 had invasive carcinoma. Among the 45 patients (extra-ampulla) with duodenal adenoma with HGD or low-grade dysplasia, 8 (18%) patients were treated using endoscopic resection (ER). During the short observation period, ER was performed only in HGD cases. None of the patients died from duodenal neoplasia. In total, during the surveillance period, duodenal HGD was detected in 5 (63%) of 8 patients graded as Spigelman stage IV; HGD was not detected in stage 0 (n=33), I (n=0), II (n=12), or III (n=20) patients.

Conclusions: Short-interval endoscopic surveillance and appropriate ER may help prevent duodenal invasive carcinoma. In addition, there was little development of invasive carcinoma during the follow-up. The Spigelman classification is beneficial for the risk assessment of duodenal neoplasia in Japanese FAP patients.
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http://dx.doi.org/10.1097/MCG.0000000000000555DOI Listing
April 2019

Management and associated factors of delayed perforation after gastric endoscopic submucosal dissection.

World J Gastroenterol 2015 Nov;21(44):12635-43

Haruhisa Suzuki, Ichiro Oda, Masau Sekiguchi, Seiichiro Abe, Satoru Nonaka, Shigetaka Yoshinaga, Takeshi Nakajima, Yutaka Saito, Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.

Aim: To identify the actual clinical management and associated factors of delayed perforation after gastric endoscopic submucosal dissection (ESD).

Methods: A total of 4943 early gastric cancer (EGC) patients underwent ESD at our hospital between January 1999 and June 2012. We retrospectively assessed the actual management of delayed perforation. In addition, to determine the factors associated with delayed perforation, after excluding 123 EGC patients with perforations that occurred during the ESD procedure, we analyzed the following clinicopathological factors among the remaining 4820 EGC patients by comparing the ESD cases with delayed perforation and the ESD cases without perforation: age, sex, chronological periods, clinical indications for ESD, status of the stomach, location, gastric circumference, tumor size, invasion depth, presence/absence of ulceration, histological type, type of resection, and procedure time.

Results: Delayed perforation occurred in 7 (0.1%) cases. The median time until the occurrence of delayed perforation was 11 h (range, 6-172 h). Three (43%) of the 7 cases required emergency surgery, while four were conservatively managed without surgical intervention. Among the 4 cases with conservative management, 2 were successfully managed endoscopically using the endoloop-endoclip technique. The median hospital stay was 18 d (range, 15-45 d). There were no delayed perforation-related deaths. Based on a multivariate analysis, gastric tube cases (OR = 11.0; 95%CI: 1.7-73.3; P = 0.013) were significantly associated with delayed perforation.

Conclusion: Endoscopists must be aware of not only the identified factors associated with delayed perforation, but also how to treat this complication effectively and promptly.
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http://dx.doi.org/10.3748/wjg.v21.i44.12635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658618PMC
November 2015

Novel strategy of endoscopic submucosal dissection using an insulation-tipped knife for early gastric cancer: near-side approach method.

Endosc Int Open 2015 Oct 2;3(5):E425-31. Epub 2015 Sep 2.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

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.
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http://dx.doi.org/10.1055/s-0034-1392567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612249PMC
October 2015
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