Diagnostic Performance of Near-Infrared Fluorescent Marking Clips in Laparoscopic Gastrectomy.

INTRODUCTION: Accurate tumor localization and resection margin acquisition are essential in gastric cancer surgery. Preoperative placement of marking clips in laparoscopic gastrectomy as well as intraoperative gastroscopy can be used for gastric cancer surgery. However, these procedures are not available at all institutions. We conducted a prospective clinical trial to investigate the diagnostic performance of near-infrared fluorescent clips (ZEOCLIP FS) in laparoscopic gastrectomy. MATERIALS AND METHODS: Patients with gastric cancer or neuroendocrine tumor in whom laparoscopic distal, pylorus-preserving, or proximal gastrectomy was planned were enrolled (n = 20) in this study. Fluorescent clips were placed proximal and/or distal to the tumor via gastroscopy on the day before surgery. During surgery, the clips were detected using a fluorescent laparoscope, and suturing was performed where fluorescence was detected. The clip locations were then confirmed via gastroscopy, and the stomach was transected. The primary endpoint was the detection rate of the marking clips using fluorescence, and the secondary endpoints were complications and distance between the clips and stitches. RESULTS: Among the 20 patients enrolled, distal and pylorus-preserving gastrectomies were performed in 18 and 2 patients, respectively. All clips were detected in 15 patients, indicating a detection rate of 75.0% (90% confidence interval: 54.4%-89.6%). Furthermore, no complications related to the clips were observed. The median distance between the clips and stitches was 5 (range, 0-10) mm. CONCLUSIONS: We report the feasibility and safety of preoperative placement and intraoperative detection of near-infrared fluorescent marking clips in laparoscopic gastrectomy.

Evaluating the usefulness of considering the size and morphological type of type B2 vessel area based on Japan Esophageal Society classification in estimating tumor invasion depth in superficial esophageal squamous cell carcinomas: study protocol for a prospective observational study (Japan BEES study).

BACKGROUND: Accurate evaluation of tumor invasion depth is essential to determine the appropriate treatment strategy for patients with superficial esophageal cancer. The pretreatment tumor depth diagnosis currently relies on the magnifying endoscopic classification established by the Japan Esophageal Society (JES). However, the diagnostic accuracy of tumors involving the muscularis mucosa (MM) or those invading the upper third of the submucosal layer (SM1), which correspond to Type B2 vessels in the JES classification, remains insufficient. Previous retrospective studies have reported improved accuracy by considering additional findings, such as the size and macroscopic type of the Type B2 vessel area, in evaluating tumor invasion depth. Therefore, this study aimed to investigate whether incorporating the size and/or macroscopic type of the Type B2 vessel area improves the diagnostic accuracy of preoperative tumor invasion depth prediction based on the JES classification. METHODS: This multicenter prospective observational study will include patients diagnosed with MM/SM1 esophageal squamous cell carcinoma based on the Type B2 vessels of the JES classification. The tumor invasion depth will be evaluated using both the standard JES classification (standard-depth evaluation) and the JES classification with additional findings (hypothetical-depth evaluation) for the same set of patients. Data from both endoscopic depth evaluations will be electronically collected and stored in a cloud-based database before endoscopic resection or esophagectomy. This study's primary endpoint is accuracy, defined as the proportion of cases in which the preoperative depth diagnosis matched the histological depth diagnosis after resection. Outcomes of standard- and hypothetical-depth evaluation will be compared. DISCUSSION: Collecting reliable prospective data on the JES classification, explicitly concerning the B2 vessel category, has the potential to provide valuable insights. Incorporating additional findings into the in-depth evaluation process may guide clinical decision-making and promote evidence-based medicine practices in managing superficial esophageal cancer. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Registry of the University Hospital Medical Information Network (UMIN-CTR) under the identifier UMIN000051145, registered on 23/5/2023.

Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort.

INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Long- vs short-segment Barrett's esophagus-derived adenocarcinoma: clinical features and outcomes of endoscopic submucosal dissection.

BACKGROUND: The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. METHODS: We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3 cm or ≥ 3 cm, respectively. RESULTS: Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0 min vs. 60.5 min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). CONCLUSIONS: The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required.

Prognostic factors for patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Little is known about prognostic factors for patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer. Therefore, this study aimed to identify such prognostic factors. METHODS: We retrospectively evaluated the long-term outcomes and prognostic factors of 143 patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer at a single-center between October 2005 and September 2020. Using the Kaplan-Meier method and a Cox proportional hazards regression model, we examined the relationships of patient characteristics and endoscopic curability (additional gastrectomy recommended [eCuraC-2] or not recommended) with overall survival. RESULTS: The median age of the patients was 86 years, and most patients were men (65%). The eCuraC-2 rate was 14.7%. During the follow-up period, 55 patients died; however, only two patients died due to gastric cancer. The 3-year and 5-year overall survival rates were 91.5% and 74.7%, respectively. Male sex (hazard ratio, 2.23; 95% confidence interval, 1.16-4.30), American Society of Anesthesiologists Physical Status of 3 (hazard ratio, 2.57; 95% confidence interval, 1.32-4.99), body mass index < 18.9 kg/m2 (hazard ratio, 2.21; 95% confidence interval, 1.11-4.40), and eCuraC-2 (hazard ratio, 3.04; 95% confidence interval, 1.37-6.75) were identified as independent prognostic factors. Moreover, patients with eCuraC-2 had significantly more poor prognostic factors than those who did not. CONCLUSIONS: The decision to perform endoscopic submucosal dissection for patients with the aforementioned prognostic factors should be carefully considered because follow-up without endoscopic submucosal dissection is possible.

Risk stratification for synchronous/metachronous recurrence after endoscopic submucosal dissection for Barrett's esophageal adenocarcinoma using the length of Barrett's esophagus.

BACKGROUND: In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus. METHODS: We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences. RESULTS: The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively). CONCLUSIONS: Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings.

Multicenter retrospective analysis of complications and risk factors in endoscopic resection for esophageal cancer across Japan.

BACKGROUND: Endoscopic resection (ER) is a minimally invasive treatment for esophageal cancer that sometimes causes complications. To understand the real-world incidence and risk factors for these complications, a nationwide survey was conducted across Japan. METHODS: This retrospective multicenter study included patients who underwent ER for esophageal cancer from April 2017 to March 2018 (2017 complication analysis) and April 2021 to March 2022 (2021 complication analysis). The study assessed the complication rates and conducted risk factor analyses for endoscopic submucosal dissection (ESD) using data for these patients, with exclusions based on specific criteria to ensure data accuracy. RESULTS: In the 2021 complication analysis, there were two mortalities highly likely attributable (0.03%) to ER and one mortality possibly attributable (0.01%) to ER. Intraoperative perforation, delayed bleeding, and pneumonia occurred in 137 cases (1.8%), 44 cases (0.6%), and 130 cases (1.7%), respectively. In the multivariate analysis for complications after ESD, low ER volume of the facility was an independent risk factor for perforation, while lesion location in the cervical or upper thoracic esophagus was an independent factor for reduced risk of perforation. Age ≥ 80 years was a risk factor for pneumonia, while use of traction techniques was a factor for reduced risk of pneumonia. Lesions located in the middle thoracic esophagus had a lower risk of stricture, and the risk of stricture increased as the circumferential extent of the lesion increased. CONCLUSIONS: This large-scale study provided detailed insights into the complications associated with esophageal ER and identified significant risk factors.

Curative Management After Endoscopic Resection for Esophageal Squamous Cell Carcinoma Invading Muscularis Mucosa or Shallow Submucosal Layer-Multicenter Real-World Survey in Japan.

INTRODUCTION: Curative management after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), which invades the muscularis mucosa (pMM-ESCC) or shallow submucosal layer (pSM1-ESCC), has been controversial. METHODS: We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data were based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER. RESULTS: A total of 992 patients with pMM-ESCC (n = 749) and pSM1-ESCC (n = 243) were registered. According to the multivariate Cox proportional hazards analysis, pSM1-ESCC (hazard ratio = 1.88, 95% confidence interval 1.15-3.07, P = 0.012) and LVI (hazard ratio = 6.92, 95% confidence interval 4.09-11.7, P < 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1-233), among patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients with additional treatment were significantly better than those of patients without additional treatment; 85.4% vs 61.5% ( P < 0.0001), 80.5% vs 53.3% ( P < 0.0001), and 98.5% vs 93.1% ( P = 0.004), respectively. There was no difference in survival rate between the chemoradiotherapy and surgery groups. DISCUSSION: pSM1 and LVI were risk factors for metastasis after ER for ESCC. To improve the survival, additional treatment immediately after ER, such as chemoradiotherapy or surgery, is effective in patients with these risk factors.

Association between perioperative management of antiplatelet agents and risk of post-endoscopic submucosal dissection bleeding in early gastric cancer: analysis of a nationwide multicenter study.

BACKGROUND AND AIMS: Data are lacking regarding post-endoscopic submucosal dissection (ESD) bleeding in patients with early gastric cancer (EGC) who take antiplatelet agents (APAs), particularly in those taking thienopyridine and cilostazol. We aimed to clarify the association between the status of APA medication and post-ESD bleeding risk. METHODS: This study is a secondary analysis using data from a recently conducted nationwide multicenter study in Japan. We retrospectively reviewed patients treated with APAs or on no antithrombotic therapy recruited from 33 institutions who underwent ESD for EGC between November 2013 and October 2016. The primary outcome of this study was the relationship between the rate of post-ESD bleeding and the status of each APA medication. RESULTS: A total of 9736 patients were included in the analysis. Among 665 aspirin users, the continuation group was significantly associated with post-ESD bleeding (odds ratio [OR], 2.79; 95% confidence interval [CI], 1.77-4.37). Among 227 thienopyridine users, the aspirin or cilostazol replacement group was not significantly associated with post-ESD bleeding (OR, 1.85; 95% CI, .72-4.78). Among 158 cilostazol users, there was no significant association with post-ESD bleeding, irrespective of medication status. The rate of post-ESD bleeding was approximately 10% to 20% irrespective of the status of APA administration among dual-antiplatelet therapy users. No patients experienced thromboembolic events in this study. CONCLUSIONS: Replacement of thienopyridine with aspirin or cilostazol may be acceptable for minimizing both the risk of post-ESD bleeding and thromboembolism in patients with EGC. In patients on cilostazol monotherapy undergoing ESD, continuation of therapy may be acceptable.

Effect of Helicobacter pylori eradication evaluated using magnifying endoscopy with narrow-band imaging in mixed-type early gastric Cancer.

BACKGROUND: The effect of Helicobacter pylori (H.pylori) eradication therapy on mixed-histological-type gastric cancer remains unclear. This study aimed to clarify the effect of H. pylori eradication therapy on mixed-histological-type early gastric cancer using endoscopic and histological findings. METHODS: This single-center, retrospective study included patients with mixed-histological-type gastric cancer who underwent endoscopic submucosal dissection at the Cancer Institute Hospital. We compared detailed magnifying endoscopy with narrow-band imaging findings between eradicated and non-eradicated groups of patients with differentiated-type- and undifferentiated-type-predominant cancers. Subsequently, we performed histological evaluations of the non-cancerous epithelium covering differentiated-type components. RESULTS: A total of 124 patients with mixed-type early gastric cancer were enrolled (eradicated group: 62 differentiated-type-predominant cancer patients and 8 undifferentiated-type-predominant cancer patients; non-eradication group: 40 differentiated-type-predominant cancer patients and 14 undifferentiated-type-predominant cancer patients). Regarding differentiated-type-predominant cancer, differentiated-type findings were detected in all patients in eradicated and non-eradicated groups. The difference in the detection rate of undifferentiated-type findings between both groups was not significant in differentiated-type-predominant cancer patients. In differentiated-type-predominant cancers, the percentage of non-cancerous epithelium covering differentiated-type components was higher in the eradicated group than in the non-eradicated group (median: 60% vs. 40%, p < 0.001). CONCLUSIONS: Although the pathological findings of differentiated-type-predominant cancer were affected by H. pylori eradication, eradication did not affect the diagnosis of differentiated-type-predominant early gastric cancer using magnifying endoscopy with narrow-band imaging. ME-NBI is useful for the early detection of D-MIX EGCs and diagnosis of histological types during endoscopy, regardless of whether H. pylori eradication therapy has been administered.

Genomic features of Helicobacter pylori-naïve diffuse-type gastric cancer.

Helicobacter pylori (HP) is a major etiologic driver of diffuse-type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP-naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP-exposed and HP-naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP-exposed and 27 HP-naïve DGCs from sporadic, early-stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP-exposed and 17 HP-naïve samples had been preserved as fresh-frozen samples. HP infection status was determined using stringent criteria. HP-exposed DGCs exhibited an increased single nucleotide variant burden (HP-exposed DGCs; 1.97 [0.48-7.19] and HP-naïve DGCs; 1.09 [0.38-3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm-level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA-ARHGAP pathway misregulation was exclusive to HP-exposed DGCs (p = 0.0167). HP-exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP-exposed DGCs. HP-naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP-naïve and HP-exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Outcomes after partially covered self-expandable metal stent placement for recurrent duodenal obstruction.

BACKGROUND: Outcomes of partially covered self-expandable metal stents (SEMS) as an additional stent after recurrent duodenal obstruction (RDO) have not been elucidated. In this study, we compared outcomes of partially covered and uncovered SEMS placement after RDO in patients with malignant duodenal obstruction and explored factors affecting re-recurrent obstruction and overall survival in this population. METHODS: We conducted a retrospective study of patients undergoing SEMS placement for RDO at a cancer institute in Japan from July 2014 to June 2021. Clinical variables and outcomes of patients undergoing partially covered and uncovered SEMS placement were compared. RESULTS: Sixty-one patients underwent SEMS placement after RDO, for which the COMVI stent was used in 38 cases and uncovered stents were used in 23 cases. Stent ingrowth was the most common cause of RDO (51.4%). Stent migration only occurred after partially covered stent placement (20% vs. 0%, p = 0.018). Choice of SEMS had no impact on time to re-RDO (median 2.8 vs. 4.1 months, p = 0.776) or overall survival (median 2.6 vs. 2.4 months, p = 0.703). Median overall survival was longer in patients receiving chemotherapy after second stenting (4.6 vs. 1.8 months, p < 0.001) and shorter in those with early RDO, regardless of the SEMS used. Use of the partially covered stent had no impact on survival or time to RDO. CONCLUSIONS: While outcomes after partially covered SEMS placement for RDO were not significantly different from uncovered SEMS, migration remains a concern when they are used as a second stent. Chemotherapy after second stenting was associated with longer overall survival but not with longer time to re-RDO.

Clinical factors associated with noncurative endoscopic submucosal dissection for the expanded indication of intestinal-type early gastric cancer: Post hoc analysis of a multi-institutional, single-arm, confirmatory trial (JCOG0607).

OBJECTIVES: The multi-institutional, single-arm, confirmatory trial JCOG0607 showed excellent efficacy of endoscopic submucosal dissection (ESD) for the expanded indication of intramucosal intestinal-type early gastric cancer (EGC), which consists of two groups: lesions >2 cm if clinical finding of ulcer (cUL)-negative, or those ≤3 cm if cUL-positive because of the expected low risk of lymph node metastasis. However, the proportion of noncurative resections (NCR) requiring additional surgery was high (32.4%). This post hoc analysis aimed to explore the clinical factors associated with NCR. METHODS: As the expanded indication includes two different groups, we explored the clinical factors associated with NCR separately in cUL-negative (>2 cm) and cUL-positive (≤3 cm) groups using the log-linear model. RESULTS: Two hundred and sixty cUL-negative and 206 cUL-positive EGCs were analyzed. The proportions of NCR were 33.8% in the cUL-negative group and 29.6% in the cUL-positive group. A multivariable analysis demonstrated that moderately differentiated predominant histology diagnosed in pretreatment biopsy (risk ratio [RR] 1.93, 95% confidence interval [CI] 1.34-2.77, P < 0.001) and lesion in the upper stomach (RR 1.75, 95% CI 1.03-2.96, P = 0.038) in the cUL-negative EGCs, and tumor size >2 cm (RR 1.78, 95% CI 1.22-2.58, P = 0.003) and female sex (RR 1.62, 95% CI 1.07-2.44, P = 0.021) in the cUL-positive EGCs were independent factors associated with NCR. CONCLUSIONS: Clinical risk factors associated with NCR were different between cUL-negative and cUL-positive EGCs. To avoid NCR, we need to take these factors into account when deciding expanded indications for ESD.

Prediction of the invasion depth of superficial nonampullary duodenal adenocarcinoma.

OBJECTIVES: Distinguishing between intramucosal cancer and submucosal invasive cancer is vital for optimal treatment selection for patients with superficial nonampullary duodenal adenocarcinoma (SNADAC); however, standard diagnostic systems for diagnosing invasion depth are as yet undetermined. METHODS: Of 205 patients with SNADAC who underwent treatment at our institution between 2006 and 2022, 188 had intramucosal cancer and 17 had submucosal invasive cancer. The clinical, endoscopic, and pathological features used in the preoperative diagnosis of invasion depth and the diagnostic performance of endoscopic ultrasonography (EUS) were retrospectively analyzed in 85 patients. RESULTS: The oral side of the papilla tumor location, protruded or mixed macroscopic type, and moderately-to-poorly differentiated adenocarcinoma based on biopsy specimens were significantly more frequent in submucosal invasive cancer than in intramucosal cancer (88% vs. 48%; 94% vs. 42%; 47% vs. 0%, respectively). From the relationship between the endoscopic features and the submucosal invasive cancer incidence, submucosal invasion risk was stratified as: (i) low-risk (risk, 2%), all lesions located on the anal side of the papilla and superficial macroscopic type on the oral side of the papilla; and (ii) high-risk (risk, 23%), protruded or mixed macroscopic type on the oral side of the papilla. Based on the biopsy specimens, all eight patients with moderately-to-poorly differentiated adenocarcinoma had submucosal invasive cancer. Furthermore, EUS was not associated with invasion depth's diagnostic accuracy improvements. CONCLUSION: Optimal treatment indications for SNADAC can be selected based on the risk factors of submucosal invasion by tumor location, macroscopic type, and biopsy diagnosis.

Comprehensive registry of esophageal cancer in Japan, 2015.

BACKGROUND: The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes of patients who underwent any treatment during 2015 in Japan. METHODS: We analyzed patients' data who had visited the participating hospitals in 2015. We collected the data using the National Clinical Database with a web-based data collection system. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification by the Union of International Cancer Control (UICC) for cancer staging. RESULTS: A total of 9368 cases were registered from 355 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 86.7% and 7.4%, respectively. The 5-year survival rates of patients treated by endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.2%, 33.5%, 24.2%, and 59.9%, respectively. Esophagectomy was performed in 5172 cases. Minimally invasive approaches were selected for 60.6%, and 54.4% underwent thoracoscopic esophagectomy. The operative mortality (within 30 days after surgery) was 0.79% and the hospital mortality was 2.3%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system because pStage IV included the patients with supraclavicular lymph node metastasis (M1 LYM). CONCLUSION: We hope this report improves all aspects of diagnosing and treating esophageal cancer in Japan.

Additive effect of evaluating microsurface and microvascular patterns using magnifying endoscopy with narrow-band imaging in gastric cancer: a post-hoc analysis of a single-center observational study.

BACKGROUND: No studies have compared the performance of microvascular and microsurface patterns alone with their combination in patients undergoing magnifying endoscopy with narrow-band imaging for diagnosing gastric cancer. This study aimed to clarify the differences in diagnostic performance among these methods. METHODS: Thirty-three participating endoscopists who had received specialized training in magnifying endoscopy evaluated the microvascular and microsurface patterns of images of 106 cancerous and 106 non-cancerous lesions. If classified as "irregular," the lesion was diagnosed as gastric cancer. To evaluate diagnostic performance, we compared the diagnostic accuracy, sensitivity, and specificity of these methods. RESULTS: Performance-related items did not differ significantly between microvascular and microsurface patterns. However, the diagnostic accuracy and sensitivity were significantly higher when using a combination of these methods than when using microvascular (82.1% [76.4-86.7] vs. 76.4% [70.3-81.6] and 69.8% [60.5-77.8] vs. 63.2% [53.7-71.8]; P < 0.001 and P = 0.008, respectively) or microsurface (82.1% [76.4-86.7] vs. 73.6% [67.3-79.1] and 69.8% [60.5-77.8] vs. 52.8% [43.4‒62.1]; both, P < 0.001) patterns alone. The additive effect on diagnostic accuracy and sensitivity was 5.7‒8.6% and 6.6‒17.0%, respectively. CONCLUSIONS: We demonstrate the superiority of the combination of microvascular and microsurface patterns over microvascular or microsurface patterns alone for diagnosing gastric cancer. Our data support the use of the former method in clinical practice. Although a major limitation of this study was its retrospective, single-center design, our findings may help to improve the diagnosis of gastric cancer.

The effect of antithrombotic drug use on delayed bleeding with esophageal endoscopic resection.

BACKGROUND AND AIM: Whether antithrombotic drugs increase the risk of post-esophageal endoscopic resection bleeding is unknown. This study examined the effect of antithrombotic drugs, aspirin, thienopyridine, direct oral anticoagulants (DOAC), and warfarin, on post-esophageal endoscopic resection bleeding. METHODS: We enrolled 957 patients (1202 esophageal tumors) treated with endoscopic resection and classified them based on antithrombotic drug use as no use, aspirin, thienopyridine, DOAC, and warfarin. Patients using antiplatelet drugs (i.e. aspirin and thienopyridine) were further sub-classified based on their continued or discontinued use before endoscopic resection. The bleeding rates were compared between these groups to assess the effects of antithrombotic drug use and interruption of antiplatelet therapy on post-esophageal endoscopic resection bleeding. RESULTS: The post-endoscopic resection bleeding rate was 0.3% (95% CI, 0.1-1) in the group without antithrombotic drug use, 4.5% (95% CI, 0.1-23) in the aspirin-continued group, 2.9% (95% CI, 0.1-15) in the aspirin-discontinued group, 0% (95% CI, 0-78) in the replaced thienopyridine with aspirin group, 0% (95% CI, 0-26) in the thienopyridine-discontinued group, 13% (95% CI, 1.6-38) in the DOAC group, and 0% (95% CI, 0-45) in the warfarin group. The post-endoscopic resection bleeding rate in the DOAC group was significantly higher than that in the group without antithrombotic drugs (P = 0.003). The post-endoscopic resection bleeding rates did not differ between the other groups. CONCLUSIONS: Our results suggest that discontinuing aspirin is not necessary for esophageal endoscopic resection while we must be careful regarding DOAC.

Pretreatment risk factors for endoscopic noncurative resection of gastric cancers with undifferentiated-type components.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is recommended for the treatment of early gastric cancers with an undifferentiated-type component, clinically diagnosed as intramucosal lesions ≤ 2 cm, without ulceration. In the JCOG1009/1010 trial, ESD could be performed with stomach preservation in 70% of such patients whose pathological findings met the curative resection criteria. However, additional gastrectomy was required for the remaining 30%. We identified the pretreatment risk factors for noncurative resection. METHODS: Post-hoc analysis indicated that 336 patients were identified in the JCOG1009/1010 trial; among them, 243 and 93 patients were categorized into the curative or noncurative resection groups, respectively, based on the pathological findings of the resected specimens. We explored the pretreatment risk factors for noncurative resection and investigated their associated pathological findings. RESULTS: Multivariable analysis revealed that a pretreatment tumor size > 1 cm was an independent risk factor for noncurative resection (odds ratio, 3.538; 95% confidence interval, 2.020-6.198, P < 0.0001). Patients with a pretreatment tumor size > 1 cm (n = 172) had a histological tumor size > 2 cm (22.1% vs 4.3%, odds ratio, 6.313; 95% confidence interval, 2.73-14.599, P < 0.0001) and submucosal invasion (17.4% vs 9.1%, odds ratio, 2.000; 95% confidence interval, 1.032-3.877, P = 0.040) more frequently as noncurative resection findings compared with those with a tumor size < 1 cm (n = 164). CONCLUSIONS: Because pretreatment tumor size > 1 cm is an independent risk factor for noncurative resection, endoscopists should be aware that noncurative resection is not uncommon in ESD and fully explain the potential necessity for additional gastrectomy to patients before the procedure.

The degree of mucosal atrophy is associated with post-endoscopic submucosal dissection bleeding in early gastric cancer.

BACKGROUND AND AIM: Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post-ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post-ESD bleeding and the degree of gastric mucosal atrophy based on H. pylori infection status. METHODS: We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post-ESD bleeding. RESULTS: There were 3935 H. pylori-positive patients and 4235 H. pylori-negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post-ESD bleeding in H. pylori-negative patients (odds ratio: 1.51, P = 0.007), but not in H. pylori-positive patients (odds ratio: 0.91, P = 0.600). Further, in H. pylori-negative, but not H. pylori-positive, patients, the rate of post-ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers. CONCLUSIONS: Nonsevere gastric mucosal atrophy was a risk factor for post-ESD bleeding in early gastric cancer in H. pylori-negative patients but not in H. pylori-positive patients.

Evaluation of Microvascular Patterns Alone Using Endocytoscopy with Narrow-Band Imaging for Diagnosing Gastric Cancer.

INTRODUCTION: Although endocytoscopy (EC) with narrow-band imaging (NBI) is effective in diagnosing gastric cancer, no diagnostic system has been validated. We explored a specific diagnostic system for gastric cancer using EC with NBI. METHODS: Equal numbers of images from cancerous and noncancerous areas (114 images each) were assessed by endoscopists with (development group: 33) and without (validation group: 28) specific training in magnifying endoscopy with NBI. Microvascular and microsurface patterns (MS) in each image were evaluated. Lesions were diagnosed as cancerous when patterns were deemed "irregular." The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of a diagnosis according to patterns on EC with NBI (microvascular pattern [MV] alone, MS alone, and both) were evaluated and compared between groups to determine the diagnostic performance. RESULTS: In the development and validation groups, diagnoses based on the MV alone had significantly higher accuracy (91.7% vs. 76.3%, p < 0.0001 and 92.5% vs. 67.5%, p < 0.0001, respectively) and sensitivity (88.6% vs. 68.3%, p < 0.0001 and 89.5% vs. 38.6%, p < 0.0001, respectively) than those based on the MS alone. In both groups, there were no significant differences in diagnostic accuracy between using the MV alone and both patterns. DISCUSSION/CONCLUSION: Evaluation of the MV alone is a simple and accurate diagnostic method for gastric cancer. This system could find widespread applications in clinical practice.