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Endoscopic resection (ER) for early gastric cancer (EGC) can preserve the stomach; however, the remaining stomach can develop second gastric cancer. Few reports have prospectively investigated the incidence and treatment outcomes of second gastric cancer.This post-hoc analysis used the dataset of the single-arm confirmatory trial, JCOG0607. The key inclusion criteria for JCOG0607 were solitary differentiated-type EGC and no previous gastrectomy or endoscopic treatment for EGC. Three hundred seventeen patients who underwent curative ER were included in this study. Surveillance endoscopy was performed 1 to 3 months after the initial ER and subsequently annually for at least 5 years. A lesion detected ≤1 year and1 year after the initial ER was defined as overlooked gastric cancer (OGC) and metachronous gastric cancer (MGC), respectively.During a median follow-up period of 6.0 years (interquartile range, 5.1-7.0), 30 OGCs and 61 MGCs were detected in 24 and 48 patients, respectively. The cumulative incidence of OGC at 1 year and MGC at 5 years was 7.6% and 12.7%, respectively. ER and gastrectomy were performed in 85 lesions and 6 lesions, respectively. Pathologic evaluation showed 78 mucosal cancers, 12 submucosal cancers, and 1 advanced cancer. Eventually, 28 OGCs and 52 MGCs fulfilled the pathologic criteria for curative ER.Our study was the first to reveal the actual incidence of second gastric cancer after curative ER for differentiated-type gastric cancer. Most lesions could be treated with ER. Continuous endoscopic surveillance after curative ER is important to detect second 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.

Background An association between specific endoscopic findings and high-grade dysplasia/carcinoma in superficial nonampullary duodenal epithelial tumors ≤ 5 mm in size has not been reported. We sought to identify the endoscopic findings associated with high-grade dysplasia/carcinoma in patients with superficial nonampullary duodenal epithelial tumors ≤ 5 mm. Methods We retrospectively assessed the data of 84 patients (88 lesions; low-grade dysplasia: n = 35, high-grade dysplasia/carcinoma: n = 53) with superficial nonampullary duodenal epithelial tumors who underwent initial treatment at a single center (from July 2009 to April 2021). All the patients had lesions sized ≤ 5 mm. We assumed that the endoscopic findings were independently associated with high-grade dysplasia/carcinoma and determined the accuracy, sensitivity, and specificity of a combination of independent factors for diagnosing high-grade dysplasia/carcinoma and low-grade dysplasia. Results Multivariate logistic regression of significant factors in the univariate analysis revealed that lesions with depressed morphology (odds ratio: 23.9, 95% confidence interval: 2.8-204.2; p = 0.0037) and a reddish color (odds ratio: 175.7, 95% confidence interval: 11.4-2697.1; p = 0.0002) were independently associated with high-grade dysplasia/carcinoma. McNemar's test revealed that combining the macroscopic type and color provided significantly higher sensitivity for diagnosing high-grade dysplasia/carcinoma than color alone (98.1%, 95% confidence interval: 90.1-99.7 vs. 71.7%, 95% confidence interval: 58.4-82.0; p = 0.0002). Conclusions Reddish and depressed-type lesions before treatment were associated with high-grade dysplasia/carcinoma. Combining the macroscopic type and color can help detect high-grade dysplasia/carcinoma. These findings could help clinicians determine the best therapeutic strategy for patients with smaller (≤ 5 mm) superficial nonampullary duodenal epithelial tumors in clinical settings.

OBJECTIVES Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. METHODS Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). RESULTS In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. CONCLUSIONS Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.

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 WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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.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.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.Our results suggest that discontinuing aspirin is not necessary for esophageal endoscopic resection while we must be careful regarding DOAC.

BACKGROUND AND AIM This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). METHODS We retrospectively reviewed 10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated. RESULTS Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1). CONCLUSION We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.

Background Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett’s esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society—Barrett’s esophagus working group (JES-BE) for superficial Barrett’s esophagus-related neoplasms. Methods The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. Results The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. Conclusion The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician’s experience level.

Diagnosis using artificial intelligence (AI) with deep learning could be useful in endoscopic examinations. We investigated the ability of AI to detect superficial esophageal squamous cell carcinoma (ESCC) from esophagogastroduodenoscopy (EGD) videos. We retrospectively collected 8428 EGD images of esophageal cancer to develop a convolutional neural network through deep learning. We evaluated the detection accuracy of the AI diagnosing system compared with that of 18 endoscopists. We used 144 EGD videos for the two validation sets. First, we used 64 EGD observation videos of ESCCs using both white light imaging (WLI) and narrow-band imaging (NBI). We then evaluated the system using 80 EGD videos from 40 patients (20 with superficial ESCC and 20 with non-ESCC). In the first set, the AI system correctly diagnosed 100% ESCCs. In the second set, it correctly detected 85% (17/20) ESCCs. Of these, 75% (15/20) and 55% (11/22) were detected by WLI and NBI, respectively, and the positive predictive value was 36.7%. The endoscopists correctly detected 45% (25–70%) ESCCs. With AI real-time assistance, the sensitivities of the endoscopists were significantly improved without AI assistance (p

Introduction: Curative rates of endoscopic treatment for undifferentiated-type early gastric cancer (EGC), particularly mixed poorly differentiated adenocarcinoma (MIXED-POR), are lower than those of endoscopic treatment for the differentiated type. Magnifying endoscopy with narrow-band imaging (ME-NBI) is useful for diagnoses of the histological type. This study aimed to investigate the detection rates of MIXED-POR among undifferentiated-type EGCs using biopsy and ME-NBI in order to improve curative rates through endoscopic treatment. Methods: We analyzed 267 lesions initially subjected to endoscopic submucosal resection (ESD) and histologically diagnosed as undifferentiated-type EGCs between July 2005 and December 2016 at our hospital. We obtained written informed consent from all participants. Biopsy and ME-NBI findings were compared to distinguish pure signet ring cell carcinoma (PURE-SIG) and MIXED-POR. ME-NBI findings were divided into 2 categories depending on the presence of irregular vessels. Results of biopsy and ME-NBI (combination method) were also analyzed, and detection rates of MIXED-POR and PURE-SIG were evaluated in terms of sensitivity, specificity, and accuracy. Results: Overall, 114 lesions were analyzed. Fifty-eight lesions (50.9%) were identified as MIXED-POR. With biopsy, the detection rate of MIXED-POR was significantly lower than that of PURE-SIG (p < 0.0001). ME-NBI detected significantly more MIXED-POR with irregular vessels than PURE-SIG (p < 0.0001). The combination method could detect significantly more MIXED-POR than PURE-SIG (p < 0.0001). The sensitivity and accuracy for MIXED-POR diagnosis were significantly higher with the combination method than with biopsy alone (p < 0.0001). Discussion/Conclusion: Combining biopsy and ME-NBI improved the accuracy of pretreatment diagnosis before ESD in undifferentiated-type cancer.

Image recognition using artificial intelligence (AI) has progressed significantly due to innovative technologies such as machine learning and deep learning. In the field of gastric cancer (GC) management, research on AI-based diagnosis such as anatomical classification of endoscopic images, diagnosis of Helicobacter pylori infection, and detection and qualitative diagnosis of GC is being conducted, and an accuracy equivalent to that of physicians has been reported. It is expected that AI will soon be introduced in the field of endoscopic diagnosis and management of gastric cancer as a supportive tool for physicians, thus improving the quality of medical care.

Artificial intelligence (AI) that surpasses human ability in image recognition is expected to be applied in the field of gastrointestinal endoscopes. Accordingly, its research and development (RD) is being actively conducted. With the development of endoscopic diagnosis, there is a shortage of specialists who can perform high-precision endoscopy. We will examine whether AI with excellent image recognition ability can overcome this problem.Since 2016, papers on artificial intelligence using convolutional neural network (CNN in other word Deep Learning) have been published. CNN is generally capable of more accurate detection and classification than conventional machine learning. This is a review of papers using CNN in the gastrointestinal endoscopy area, along with the reasons why AI is required in clinical practice. We divided this review into four parts: stomach, esophagus, large intestine, and capsule endoscope (small intestine).Potential applications for the AI include colorectal polyp detection and differentiation, gastric and esophageal cancer detection, and lesion detection in capsule endoscopy. The accuracy of endoscopic diagnosis will increase if the AI and endoscopist perform the endoscopy together.

Management strategies for primary non-ampullary duodenal adenocarcinoma (NADAC) in early stage are not well established given its low incidence. This study aimed to elucidate clinicopathological features of early NADAC, including risk for lymph nodal metastasis (LNM). In total, 166 patients with early NADAC underwent initial treatment at our institution between 2006 and 2019, of whom 153 had intramucosal (M-) and 13 had submucosal (SM-) NADAC. These endoscopic and pathological features were retrospectively analyzed. Risk factors for LNM were evaluated in 46 early NADAC patients who underwent surgery with lymph node dissection. Compared with M-NADAC, SM-NADAC was significantly more frequently located at the proximal side of the papilla, with mixed elevated and depressed macroscopic type, histologically poorly differentiated tumor and lymphovascular invasion (LVI) (85% vs. 47%, P = 0.009; 54% vs. 5%, P

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an increased risk of developing Lauren's diffuse-type gastric carcinoma and lobular breast carcinoma. Although signet-ring cell carcinoma (SRCC) in situ (SRCC-pTis) has been reported as a characteristic lesion in HDGC cases with CDH1 germline mutations (CDH1 pathogenic variant), and a precursor of conventional intramucosal SRCC (SRCC-pT1a), its histopathologic features and specificity have not been sufficiently clarified. Here, we examined gastrectomy samples from 6 Japanese HDGC patients with CDH1 germline mutation, belonging to 4 families, and analyzed SRCC lesions histologically and immunohistochemically. Of the 274 foci found in the 6 samples, SRCC-pT1a accounted for 225 lesions (range: 8 to 107, mean 45.7 lesions per patient), while 46 foci were of SRCC-pTis (range: 1 to 15, mean 7.67 foci per patient). All SRCC-pTis foci were observed in the fundic gland area and on the superficial side of the mucosa. Histologically, tumor cells of SRCC-pTis were found between normal foveolar epithelial cells and the basement membrane, following a typical pagetoid spread pattern. Immunohistochemically, E-cadherin expression was lost in SRCC-pTis (27/28, 96.4%) more frequently than in SRCC-pT1a (95/197, 48.2%; P

Background We previously reported for the first time the usefulness of artificial intelligence (AI) systems in detecting gastric cancers. However, the “original convolutional neural network (O-CNN)” employed in the previous study had a relatively low positive predictive value (PPV). Therefore, we aimed to develop an advanced AI-based diagnostic system and evaluate its applicability for the classification of gastric cancers and gastric ulcers. Methods We constructed an “advanced CNN” (A-CNN) by adding a new training dataset (4453 gastric ulcer images from 1172 lesions) to the O-CNN, which had been trained using 13 584 gastric cancer and 373 gastric ulcer images. The diagnostic performance of the A-CNN in terms of classifying gastric cancers and ulcers was retrospectively evaluated using an independent validation dataset (739 images from 100 early gastric cancers and 720 images from 120 gastric ulcers) and compared with that of the O-CNN by estimating the overall classification accuracy. Results The sensitivity, specificity, and PPV of the A-CNN in classifying gastric cancer at the lesion level were 99.0 % (95 % confidence interval [CI] 94.6 %−100 %), 93.3 % (95 %CI 87.3 %−97.1 %), and 92.5 % (95 %CI 85.8 %−96.7 %), respectively, and for classifying gastric ulcers were 93.3 % (95 %CI 87.3 %−97.1 %), 99.0 % (95 %CI 94.6 %−100 %), and 99.1 % (95 %CI 95.2 %−100 %), respectively. At the lesion level, the overall accuracies of the O- and A-CNN for classifying gastric cancers and gastric ulcers were 45.9 % (gastric cancers 100 %, gastric ulcers 0.8 %) and 95.9 % (gastric cancers 99.0 %, gastric ulcers 93.3 %), respectively. Conclusion The newly developed AI-based diagnostic system can effectively classify gastric cancers and gastric ulcers.

Objectives Detecting early gastric cancer is difficult, and it may even be overlooked by experienced endoscopists. Recently, artificial intelligence based on deep learning through convolutional neural networks (CNNs) has enabled significant advancements in the field of gastroenterology. However, it remains unclear whether a CNN can outperform endoscopists. In this study, we evaluated whether the performance of a CNN in detecting early gastric cancer is better than that of endoscopists. Methods The CNN was constructed using 13,584 endoscopic images from 2639 lesions of gastric cancer. Subsequently, its diagnostic ability was compared to that of 67 endoscopists using an independent test dataset (2940 images from 140 cases). Results The average diagnostic time for analyzing 2940 test endoscopic images by the CNN and endoscopists were 45.5 ± 1.8 s and 173.0 ± 66.0 min, respectively. The sensitivity, specificity, and positive and negative predictive values for the CNN were 58.4%, 87.3%, 26.0%, and 96.5%, respectively. These values for the 67 endoscopists were 31.9%, 97.2%, 46.2%, and 94.9%, respectively. The CNN had a significantly higher sensitivity than the endoscopists (by 26.5%; 95% confidence interval, 14.9-32.5%). Conclusion The CNN detected more early gastric cancer cases in a shorter time than the endoscopists. The CNN needs further training to achieve higher diagnostic accuracy. However, a diagnostic support tool for gastric cancer using a CNN will be realized in the near future.

Objectives The prognosis for pharyngeal cancer is relatively poor. It is usually diagnosed in an advanced stage. Although the recent development of narrow-band imaging (NBI) and increased awareness among endoscopists have enabled detection of superficial pharyngeal cancer, these techniques are still not prevalent worldwide. Nevertheless, artificial intelligence (AI)-based deep learning has led to significant advancements in various medical fields. Here, we demonstrate the diagnostic ability of AI-based detection of pharyngeal cancer from endoscopic images in esophagogastroduodenoscopy. Methods We retrospectively collected 5403 training images of pharyngeal cancer from 202 superficial cancers and 45 advanced cancers from the Cancer Institute Hospital, Tokyo, Japan. Using these images, we developed an AI-based diagnostic system with convolutional neural networks. We prepared 1912 validation images from 35 patients with 40 pharyngeal cancers and 40 patients without pharyngeal cancer to evaluate our system. Results Our AI-based diagnostic system correctly detected all pharyngeal cancer lesions (40/40) in the patients with cancer, including three small lesions smaller than 10 mm. For each image, the AI-based system correctly detected pharyngeal cancers in images obtained via NBI with a sensitivity of 85.6%, much higher sensitivity than that for images obtained via white light imaging (70.1%). The novel diagnostic system took only 28 s to analyze 1912 validation images. Conclusions The novel AI-based diagnostic system detected pharyngeal cancer with high sensitivity. It could facilitate early detection, thereby leading to better prognosis and quality of life for patients with pharyngeal cancers in the near future.

Epstein-Barr virus-positive gastric cancer (EBVGC) comprises approximately 9% of all gastric cancers and is associated with a low prevalence of lymph node metastasis (LNM). Given that limited data concerning LNM in EBV-related early GC are available, EBV status is not considered an indicator for endoscopic submucosal dissection (ESD). In this review, we focused on pT1 EBVGC and on gastric carcinoma with lymphoid stroma (GCLS), and discuss expanded ESD indications and curative resection criteria. In pT1b EBVGC, the incidence of LNM was low (6/180 patients, 3.3%; 95% confidence interval [CI] 1.2-7.1), especially in lymphovascular invasion-negative EBVGC (1/109 patients, 0.9%). No patients with pT1a EBVGC had LNM (0/38 patients, 0%; 95% CI 0-7.6), even those who did not meet the current curative ESD criteria. Although the frequency of LNM in GCLS was low (5.0-10.6%), the incidence of LNM in non-EBV GCLS was relatively high (10.0-20.0%); therefore, EBV status can be considered a more important factor than GCLS. In summary, the clinicopathological characteristics of EBVGC differ from those of conventional GC, and EBV negativity is a risk factor for LNM in early GC. Therefore, patients in this group are likely to be promising candidates for ESD, and we recommend that EBV status evaluation be included in early GC treatment guidelines.

It has been recently reported that deep invasive submucosal (T1b) colorectal cancer (CRC) without other pathological risk factors for lymph node metastasis has a low rate of lymph node metastasis, increasing the possibility of endoscopic submucosal dissection (ESD) in the future. However, ESD for T1b CRC is technically difficult, and some lesions cannot be resected en bloc. This study aimed to identify the risk factors associated with vertical incomplete ESD in T1b CRC.We retrospectively studied 140 pathological T1b CRC lesions that underwent initial ESD at our institution between January 2011 and October 2020, and categorized them into positive vertical margin (PVM) and negative vertical margin (NVM) groups. The risk factors for PVM were examined using univariate and multivariate analyses, and a subgroup analysis for T1b CRC with an obvious depressed surface was performed.Multivariate analysis revealed obvious depression (hazard ratio [HR]: 7.4; 95% confidence interval [CI]: 2.47-22.5) and severe fibrosis (HR: 11.4; 95% CI: 3.95-33.0) as significant risk factors for PVM. Length of depressed surface ≥12 mm (HR: 6.19; 95% CI: 1.56 -24.6) was identified as an independent predictor of PVM for T1b CRC with an obvious depression.Pathological T1b CRC cases with an obvious depression and severe fibrosis are at a high risk of vertical incomplete ESD.

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 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 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.

Introduction: We aimed to investigate the safety and efficacy of self-expandable metallic stent (SEMS) placement in patients with prior radiotherapy (RT) using the Niti-S stent, which is characterized by low radial force, in comparison to patients without prior RT. Methods: A consecutive series of 83 patients who were treated by SEMS placement using Niti-S stent for severe malignant esophageal obstruction or fistula were enrolled. The adverse event rates and efficacy were retrospectively compared between patients with/without prior RT before SEMS placement (RT group [n = 32] versus non-RT group [n = 51]). Results: The incidence rate of major adverse events in the RT group was 6.3% and was not significantly different from that in the non-RT group (5.9%, p = 0.95). Among the RT group, 84.4% were able to resume oral intake within a median of 2 days. Among the patients with fistula, 78.6% could resume oral intake and survive for 73 days after SEMS placement. Cox proportional hazard regression analysis identified significant factors affecting overall survival to be prior RT (hazard ratio [HR]: 1.96), low performance status (HR: 3.87), and subsequent anticancer treatment after SEMS placement (HR: 0.41). However, compared to the non-RT group, the RT group had received longer duration of anticancer treatment before SEMS placement and a lower rate of subsequent anticancer treatment after SEMS placement. Conclusions: With the Niti-S stent, the incidence of major adverse events was sufficiently low even for patients after RT. SEMS with low radial force would be an effective palliative treatment option for patients, regardless of prior RT.

Rectal multiple neuroendocrine tumors (M-NETs) are rare, with only few epidemiologic reports on the topic. Therefore, their clinicopathological features are not completely known, and the appropriate treatment strategy has not been established. This study aimed to compare the clinicopathological malignant potential (lymphatic or venous invasion-positive and lymph node metastasis rates) of M-NETs with that of solitary NETs (S-NETs). We retrospectively investigated 369 patients with NETs of the rectum. Patients who underwent colonoscopy at the Cancer Institute Hospital between January 1979 and 2016 and diagnosed with S-NETs were included, and S-NETs were found in 348 patients. Patients with M-NETs were classified into two groups as follows: patients with

Early detection of early gastric cancer (EGC) allows for less invasive cancer treatment. However, differentiating EGC from gastritis remains challenging. Although magnifying endoscopy with narrow band imaging (ME-NBI) is useful for differentiating EGC from gastritis, this skill takes substantial effort. Since the development of the ability to convolve the image while maintaining the characteristics of the input image (convolution neural network: CNN), allowing the classification of the input image (CNN system), the image recognition ability of CNN has dramatically improved. To explore the diagnostic ability of the CNN system with ME-NBI for differentiating between EGC and gastritis. A 22-layer CNN system was pre-trained using 1492 EGC and 1078 gastritis images from ME-NBI. A separate test data set (151 EGC and 107 gastritis images based on ME-NBI) was used to evaluate the diagnostic ability [accuracy, sensitivity, positive predictive value (PPV), and negative predictive value (NPV)] of the CNN system. The accuracy of the CNN system with ME-NBI images was 85.3%, with 220 of the 258 images being correctly diagnosed. The method’s sensitivity, specificity, PPV, and NPV were 95.4%, 71.0%, 82.3%, and 91.7%, respectively. Seven of the 151 EGC images were recognized as gastritis, whereas 31 of the 107 gastritis images were recognized as EGC. The overall test speed was 51.83 images/s (0.02 s/image). The CNN system with ME-NBI can differentiate between EGC and gastritis in a short time with high sensitivity and NPV. Thus, the CNN system may complement current clinical practice of diagnosis with ME-NBI.

This study aimed to clarify the pretreatment factors associated with overtreatment with surgery in patients with differentiated-type early gastric cancer. This single-centre, retrospective study included 781 patients with differentiated-type early gastric cancer treated by surgical resection between April 2005 and May 2017. Postoperative pathological results were used to divide patients into the accurate surgical indication group and overtreatment with surgery group; the groups were compared with respect to accurate diagnosis and misdiagnosis based on tumour diameter (≤30 mm or >30 mm), diagnosis of depth, diagnosis of ulcerative findings, and diagnosis of main histology. There were 224 patients in the overtreatment with surgery group. Multivariate analysis revealed significant differences in misdiagnosis of tumour diameter, misdiagnosis of depth, misdiagnosis of ulcerative findings, and misdiagnosis of main histology between the accurate surgical indication group and overtreatment with surgery group. Significant factors for pretreatment misdiagnosis leading to overtreatment in differentiated-type early gastric cancer were tumour diameter, depth, and main histology. It may be acceptable to perform endoscopic resection for patients with pretreatment tumour diameter ≤30 mm, mucosal invasion of pretreatment depth, and undifferentiated-type cancers containing differentiated-type components of pretreatment histology because this reduces overtreatment with surgery.

Based on Japanese guidelines for endoscopic submucosal dissection (ESD) in undifferentiated-type early gastric cancer (UD-EGC), UD-predominant mixed-type (M-UD) EGC is considered high risk for lymph node metastasis (LNM). However, differences in LNM risk between pure UD (P-UD) and M-UD remain unclear. This study assessed risk factors for LNM considering differences between P-UD and M-UD and identified pathological features related to the lowest LNM risk. This single-center, retrospective study included 1425 patients with UD-EGC treated with surgical resection between April 2005 and May 2017. We divided patients into those with and without LNM and compared background characteristics and post-operative pathological results between groups. Patients were further stratified based on depth, tumor diameter, ulcerative findings, lymphatic invasion, vascular invasion, and histological type to clarify post-operative pathological features associated with the lowest LNM risk. When comparing background characteristics and post-operative pathological results, multivariate analysis showed that, in patients with LNM, tumor diameters were significantly larger, and there were higher rates of submucosal invasion, lymphatic invasion, and M-UD histological type. In patients with absence of ulcerative findings, absence of lymphatic invasion, and absence of vascular invasion, no LNM occurred among those with intramucosal P-UD tumor diameters of 1–40 mm (1–20 mm: 95% confidence interval [CI], 0–5.5%; 21–40 mm: 95% CI, 0–6.1%). Intramucosal P-UD EGC patients with absence of ulcerative findings, absence of lymphatic invasion, absence of vascular invasion, and tumor diameters of ≤ 40 mm did not show LNM. We suggest expanding indications for ESD to include these patients.

Lymphovascular invasion (LVI) is a strong predictive factor for lymph node metastasis (LNM) in early gastric cancer (GC). This study investigated the risk for LNM in pT1b GC without LVI based on Epstein-Barr virus (EBV) status in addition to conventional clinicopathological parameters.In total, 847 consecutive patients of pT1b GC without LVI who underwent surgery at three high-volume centers between 2005 and 2014 were retrospectively analyzed. Clinicopathological parameters and EBV status were evaluated, and univariate and multivariate analyses were performed to estimate LNM risk. With regard to the presence of those three parameters, risk stratification for LNM was performed and compared with a previously proposed risk classification that included low-risk (LNM 3.0%), intermediate-risk (LNM ≥ 3.0 and 19.6%), and high-risk (LNM ≥ 19.6%) groups.EBV-positive GC (EBVGC) accounted for 11.3% (96 of 847) of cases; LNM was lower in EBVGC than in non-EBVGC (1 of 96, 1.0% vs. 71/751, 9.5%). In the multivariate analysis, non-EBVGC [odds ratio (OR) 10.8, 95% confidence interval (CI) 1.48-78.9], age 65 years (OR 2.13, 95% CI 1.30-3.48), and tumor diameter 3 cm (OR 2.26, 95% CI 1.36-3.74) were independent risk factors for LNM. Patients with EBVGC were at low risk for LNM whereas those with all of three independent risk factors were at high risk (36 of 168, 21.4%, 95% CI 15.5-28.4).LNM risk stratification that includes EBV status is useful for clinical decision-making in pT1b GC cases without LVI.

Endoscopic submucosal dissection (ESD) is the preferred treatment for esophageal squamous cell carcinoma (ESCC). However, ESD can be difficult when patients move due to insufficient sedation. We conducted a prospective confirmatory single arm study to evaluate the efficacy of using dexmedetomidine (DEX) in combination with midazolam as a novel sedation for ESD. Endoscopic submucosal dissection was performed without intubation in 65 patients. The primary outcome was the proportion of patients who did not move or require restraint during ESD, compared to historical control of ESD performed under midazolam sedation. Secondary outcomes included the frequency of complications and self-report questionnaires from patients and endoscopists. Restraint was not required in 97% of patients sedated using the combination of DEX and midazolam. Depressed respiration, low blood pressure, and bradycardia occurred in 23, 37, and 26% of patients, respectively. All patients recovered without severe complication. Occurrence of low blood pressure and bradycardia were higher, while respiratory depression was lower for the combination group than for the historical control group. The amount of midazolam used was significantly lower than in the control. Of note, 94% of patients had no painful sensations, with 3 reporting chest pain and 3 having a recollection of the procedure. Endoscopists were satisfied with the sedation in 94% of cases. All lesions were resected in en bloc fashion, without perforation. The combination of DEX and midazolam provided effective sedation for ESD for ESCC.

Objectives Sodium alginate (SA) solution has characteristic viscoelasticity. We aimed to determine efficacy and safety of 0.6% SA for submucosal injection during endoscopic submucosal dissection (ESD) in patients with localized neoplastic lesion in the esophageal and gastric mucosa. Methods We conducted a randomized controlled study at six major hospitals in Japan including 130 patients with endoscopically localized neoplastic lesion in the esophageal and gastric mucosa and eligible for ESD. Patients were randomly assigned to SA or 0.4% sodium hyaluronate (SH) group (control); ESD was performed using a submucosal injection of SA/SH. As a primary outcome measure, non-inferiority of SA against SH was investigated using en bloc complete resection in ESD and formation and maintenance of mucosal elevation upon injection as an efficacy index. Adverse events during the study were evaluated as safety outcome measures. This study was registered with Pharmaceuticals and Medical Devices Agency (clinical trial no. 28-277/2016-18; clinical trial identification no. KP2013-009_C001). Results Efficacy rate of submucosal injection during ESD was 91.7% (55/60) and 88.7% (55/62) in the SA and SH groups, respectively, demonstrating non-inferiority of SA against SH. Adverse events for which a causal relationship with submucosal injection solution could not be eliminated were noted in 8.2% (5/61) and 4.7% (3/64) in the SA and SH groups, respectively, but symptoms disappeared without treatment/after drug administration in both groups. Conclusions In Japan, 0.4% SH is the only commercially approved formulation for submucosal injection during ESD. The study results may expand submucosal injection solution options in clinical practice.

The double-tracer method has been established for sentinel node (SN) mapping in gastric cancer surgery. However, there remain several unresolved issues that prevent its widespread use in clinical practice. In this study, we aimed to demonstrate the feasibility of single-tracer SN mapping in laparoscopic surgery for gastric cancer, using indocyanine green (ICG) fluorescence imaging with a one-step nucleic acid amplification (OSNA) assay intraoperatively. Patients with clinical T1N0M0 gastric adenocarcinoma preoperatively were considered for inclusion if they had a single primary lesion 4 cm or less in maximal diameter. Immunohistochemical staining with the anti-cytokeratin 19 antibody was performed on preoperative biopsy specimens, and patients with faint positive reactions were excluded. Intraoperatively, single-tracer SN biopsy with ICG fluorescence imaging was performed, followed by laparoscopic gastrectomy with modified D1+ or D2 lymph node dissection. Twenty eligible patients underwent SN biopsy and laparoscopic gastrectomy. SNs were identified in 17 cases (85%), with a median number of three SNs per patient. The median times for SN mapping and OSNA assay were 19 and 35 min, respectively. OSNA assay detected one metastatic lymph node, but all other nodes were negative. No adverse effects were observed in relation to SN mapping. Single-tracer SN mapping by ICG fluorescence imaging with intraoperative diagnosis by OSNA assay is feasible and safe. SNs can be identified in most patients, without producing false-negative results. Further clinical trial to demonstrate the sensitivity is ongoing.

Background and Aims The prognosis of esophageal cancer is relatively poor. Patients are usually diagnosed at an advanced stage when it is often too late for effective treatment. Recently, artificial intelligence (AI) using deep learning has made remarkable progress in medicine. However, there are no reports on its application for diagnosing esophageal cancer. Here, we demonstrate the diagnostic ability of AI to detect esophageal cancer including squamous cell carcinoma and adenocarcinoma. Methods We retrospectively collected 8428 training images of esophageal cancer from 384 patients at the Cancer Institute Hospital, Japan. Using these, we developed deep learning through convolutional neural networks (CNNs). We also prepared 1118 test images for 47 patients with 49 esophageal cancers and 50 patients without esophageal cancer to evaluate the diagnostic accuracy. Results The CNN took 27 seconds to analyze 1118 test images and correctly detected esophageal cancer cases with a sensitivity of 98%. CNN could detect all 7 small cancer lesions less than 10 mm in size. Although the positive predictive value for each image was 40%, misdiagnosing shadows and normal structures led to a negative predictive value of 95%. The CNN could distinguish superficial esophageal cancer from advanced cancer with an accuracy of 98%. Conclusions The constructed CNN system for detecting esophageal cancer can analyze stored endoscopic images in a short time with high sensitivity. However, more training would lead to higher diagnostic accuracy. This system can facilitate early detection in practice, leading to a better prognosis in the near future.

Colorectal endoscopic submucosal dissection (ESD) requires advanced endoscopic skill. For safer and more reliable ESD implementation, various traction devices have been developed in recent years. The purpose of this research was to evaluate whether an ESD training program using a traction device (TD) would contribute to the improvement of trainees' skill acquisition.The differences in treatment outcomes and learning curves by the training program were compared before and after the introduction of TD (control group: January 2014 to March 2016; TD group: April 2016 to June 2018).A total of 316 patients were included in the analysis (TD group: 202 cases; control group: 114 cases). The number of cases required to achieve proficiency in ESD techniques was 10 in the TD group and 21 in the control group. Compared to the control group, the TD group had a significant advantage in ESD self-completion rate (73.8% vs. 58.8%), dissection speed (19.5 mmThe rate of colorectal ESD self-completion by trainees improved immediately after the start of the training program using a traction device compared to the conventional method, and the dissection speed tended to increase linearly with ESD experience. We believe that ESD training using a traction device will help ESD techniques to be performed safely and reliably among trainees.

Totally laparoscopic gastrectomy (TLG), which involves a complete intracorporeal gastric transection and the creation of an anastomosis, has been gradually adopted. However, a potential limitation of intracorporeal transection is the lack of tactile feedback, and whether this limitation influences oncological outcomes is unclear. The aim of this study is to evaluate the short- and long-term oncological safety of TLG using endoscopy-guided intracorporeal gastric transection for clinical stage (cStage) I gastric cancer. A total of 1875 consecutive patients who underwent laparoscopic gastrectomy for cStage I gastric cancer between January 2007 and March 2015 were enrolled in this study. Marking clips were preoperatively placed and a transection line was determined by perceiving it tactually in laparoscopy-assisted gastrectomy (LAG) or endoscopically in TLG. After propensity score matching, 1366 patients (683 each for LAG and TLG groups) were selected to primarily test the non-inferiority of TLG to that of LAG for relapse-free survival (RFS). In the propensity-matched population, the 5-year RFS rates of the LAG and TLG groups were 94.3% (95% confidence interval (CI) 92.2–95.8%), and 95.6% (95% CI 93.8–96.9%), respectively. The hazard ratio (TLG/LAG) was 0.77 (95% CI 0.48–1.24, P for non-inferiority

Anastomotic leak is a potentially life-threatening complication following esophageal cancer surgery. In this study, we aimed to clarify the efficacy of endoscopic filling with polyglycolic acid (PGA) sheets and fibrin glue for anastomotic leak after esophageal cancer surgery. Consecutive patients who underwent endoscopic filling with PGA sheets and fibrin glue for anastomotic leak after esophageal cancer surgery between August 2014 and January 2020 were included in the study, with its efficacy retrospectively reviewed. We performed endoscopic filling using two methods: (1) filling the fistula with PGA sheets, followed by the application of a fibrinogen and thrombin solution (conventional method) and (2) filling the fistula with PGA sheets pre-soaked in a fibrinogen solution, followed by the application of a thrombin solution (pre-soak method). A total of 14 patients underwent endoscopic filling procedures within the study period. The endoscopic filling procedures were successfully performed in all cases and no adverse events associated with the procedures were observed. Fistula closure was obtained in 10 (71%) cases. In the 10 successful cases, the median number of procedures was 1 (range 1–3) and the median time from the first procedure to oral intake was 7.5 days (range 4–36 days). The success rate of the pre-soak method was significantly higher than that of the conventional method (90% vs. 25%, P = 0.041). Endoscopic filling with PGA sheets and fibrin glue is a safe and effective treatment for the closure of an anastomotic leak. The pre-soak method can achieve successful endoscopic filling.

In Japan, preoperatively diagnosed T1a-muscularis mucosae or T1b-submucosa 1 (MM/SM1) esophageal squamous cell carcinoma (ESCC) is a relative indication for endoscopic resection (ER). We evaluated long-term outcomes in patients after ER for non-circumferential ESCC with a preoperative diagnosis of MM/SM1 invasion. We retrospectively reviewed 66 patients with a preoperative diagnosis of non-circumferential MM/SM1 ESCC endoscopically resected between 2010 and 2015. Patients were divided into low- (adequate follow-up) and high-risk (requiring additional treatment) groups for lymph node metastasis according to risk factors (submucosal invasion, lymphovascular invasion, or droplet infiltration) and long-term outcomes were analyzed. Pathological invasion to T1a-lamina propria mucosa, MM/SM1, and T1b-SM2 was seen in 22, 38, and 6 lesions, respectively. Overall, 71.2% patients were classified into the “adequate follow-up” group. Of these, only one patient had a lymph node recurrence, which was successfully treated by additional therapy. The remaining 28.8% patients were classified into the “requiring additional treatment” group, where no recurrences were observed after additional treatments. After a median follow-up of 58.6 months, no deaths happened due to ESCC. The 3- and 5-year overall survival rates were 93.6% and 88.7%, respectively. ER is a valid initial treatment for non-circumferential ESCC with preoperatively diagnosed MM/SM1 invasion.

While endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC. The key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC. Three hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1–99.8). ESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.

Background Patients with Lynch syndrome are at an increased risk of developing colorectal cancer, and the adenoma-carcinoma sequence is accelerated in these patients. However, the clinicopathological characteristics of colorectal neoplasms in Lynch syndrome patients are not well-known. Methods A total of 325 consecutive colorectal neoplasms were endoscopically removed from 68 patients with Lynch syndrome between June 2005 and May 2018 and retrospectively reviewed. Results Of the 325 lesions, 94 (29%), 220 (68%) and 11 (3%) were from patients with MLH1, MSH2 and MSH6 mutations, respectively. The median lesion size was 5 mm (range 2–40 mm), with 229 (71%) lesions having a non-polypoid morphology. The frequencies of advanced neoplasms, including high-grade adenomas, intramucosal carcinomas and submucosal invasive carcinomas were 14, 34, 97 and 93% for lesions with diameters of Conclusions Our results suggest that the malignant transformation interval from low-grade adenomas to advanced neoplasms is similar in all parts of the colon. Furthermore, since one-third of neoplastic lesions with diameters of ≥5 and

For diagnosing gastric cancer, differences in the diagnostic performance between endocytoscopy with narrow-band imaging and magnifying endoscopy with narrow-band imaging have not been reported. We aimed to clarify these differences by analyzing diagnoses made by endoscopists in Japan. This single-center retrospective cohort study used 106 cancerous and 106 non-cancerous images obtained via both modalities (total, 424 images) for diagnosis. Sixty-one endoscopists with varying experience levels from 45 institutions were included. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were evaluated to determine the diagnostic performance of each modality and compared using the Mann–Whitney U test. Among all endoscopists, diagnostic accuracy, sensitivity, positive predictive value, and negative predictive value were higher with endocytoscopy with narrow-band imaging than with magnifying endoscopy with narrow-band imaging (percentage [95% confidence interval]: 78.8% [76.4–83.0%] versus 72.2% [69.3–73.6%], p

BACKGROUND Endoscopic assessment is crucial in diagnosing clinical complete response after neoadjuvant therapy in rectal cancer. OBJECTIVE The purpose of this research was to evaluate the benefits of adding narrow-band imaging endoscopy to conventional chromoendoscopy in predicting pathologic complete response in the surgical specimen. DESIGN This was a prospective nonrandomized study. SETTINGS This was an ad hoc study of a prospective phase II trial at a single comprehensive cancer center that evaluated oncologic outcomes of a neoadjuvant therapy for rectal cancer. PATIENTS Patients with high-risk stage II to III low rectal cancer who received neoadjuvant modified folinic acid, fluorouracil, and oxaliplatin plus bevacizumab followed by chemoradiotherapy and surgery were included. INTERVENTION Tumor response after neoadjuvant therapy was evaluated using conventional white light endoscopy plus chromoendoscopy then followed by using narrow-band imaging based on a predefined diagnostic protocol. MAIN OUTCOME MEASURES Diagnostic accuracy for predicting pathologic complete response and inter-rater agreement between an expert and trainee endoscopists were compared between the assessments using conventional white light endoscopy plus chromoendoscopy and the assessment adding narrow-band imaging. RESULTS In total, 61 patients were eligible for the study, and 19 had pathologic complete response (31.1%). Although the addition of narrow-band imaging correctly converted the diagnosis in 3 patients, overall diagnostic improvement in predicting pathologic complete response was limited (conventional chromoendoscopy vs adding narrow-band imaging: accuracy, 70.5% vs 75.4%; sensitivity, 63.2% vs 73.7%; specificity, 73.8% vs 76.2%; positive predictive value, 52.2% vs 58.3%; and negative predictive value, 81.6% vs 86.5%). A κ value for the inter-rater agreement improved from 0.599 to 0.756 by adding narrow-band imaging. LIMITATIONS This was a single-center study with a relatively small sample size. CONCLUSIONS Despite the limited improvement in diagnostic accuracy, adding narrow-band imaging to chromoendoscopy improved inter-rater agreement between the expert and nonexpert endoscopists. Narrow-band imaging is a reliable and promising modality for universal standardization of the diagnosis of clinical complete response. See Video Abstract at http://links.lww.com/DCR/B275. ADICION DE IMAGENES DE BANDA ESTRECHA A LA CROMOENDOSCOPIA PARA LA EVALUACION DE LA RESPUESTA TUMORAL A LA TERAPIA NEOADYUVANTE EN EL CANCER DE RECTO: La evaluacion endoscopica es fundamental para valorar la respuesta clinica completa despues de la terapia neoadyuvante en el cancer de recto.Evaluar los beneficios de agregar endoscopia de imagen de banda estrecha a la cromoendoscopia convencional para predecir la respuesta patologica completa en la muestra quirurgica.Estudio prospectivo no aleatorizado.Un estudio ad hoc de un ensayo prospectivo de fase II en un solo centro integral de cancer que evaluo los resultados oncologicos de una terapia neoadyuvante para el cancer rectal.Pacientes con cancer rectal bajo de alto riesgo en estadio II-III que recibieron acido folinico neoadyuvante modificado, fluorouracilo y oxaliplatino mas bevacizumab seguido de quimiorradioterapia y cirugia.La respuesta tumoral despues de la terapia neoadyuvante se evaluo mediante endoscopia de luz blanca convencional mas cromoendoscopia, seguido de imagenes de banda estrecha basadas en un protocolo de diagnostico predefinido.La precision diagnostica para predecir la respuesta patologica completa y el acuerdo entre evaluadores entre un experto y un endoscopista en entrenamiento se compararon entre las evaluaciones utilizando endoscopia de luz blanca convencional mas cromoendoscopia y la evaluacion agregando imagenes de banda estrecha.En total, 61 pacientes fueron elegibles para el estudio, y 19 tuvieron una respuesta patologica completa (31.1%). Aunque la adicion de imagenes de banda estrecha convirtio correctamente el diagnostico en 3 pacientes, la mejora diagnostica general en la prediccion de la respuesta patologica completa fue limitada (cromoendoscopia convencional versus adicion de imagenes de banda estrecha: precision, 70.5% versus 75.4%; sensibilidad, 63.2% versus 73.7%; especificidad, 73.8% versus 76.2%; valor predictivo positivo, 52.2% versus 58.3%; y valor predictivo negativo, 81.6% versus 86.5%). Un valor de kappa para el acuerdo entre evaluadores mejoro de 0.599 a 0.756 al agregar imagenes de banda estrecha.Un estudio de centro unico con un tamano de muestra relativamente pequeno.A pesar de la mejora limitada en la precision diagnostica, agregar imagenes de banda estrecha a la cromoendoscopia mejoro el acuerdo entre evaluadores entre los endoscopistas expertos y no expertos. La imagenologia de banda estrecha es una modalidad confiable y prometedora para la estandarizacion universal del diagnostico de respuesta clinica completa. Consulte Video Resumen en http://links.lww.com/DCR/B275.

Background and Aims Endoscopic submucosal dissection (ESD) has become an important and minimally invasive treatment for early gastric cancer (EGC) with a negligible risk of metastasis not only for differentiated-type (D-type) cancer but also for undifferentiated-type (UD-type) cancer. We aimed to investigate the incidence and characteristics of metachronous cancer after ESD for UD-type cancer, which has not yet been elucidated. Methods In total, 175 patients who underwent ESD for UD-type EGC were enrolled. For comparison, 350 patients who underwent ESD for D-type EGC during the same period were randomly selected. These patients underwent a follow-up EGD annually. The median observation period was 6.0 years and 5.4 years, respectively. Results The annual incidence of metachronous cancer after ESD for UD-type and D-type cancer was .9% and 5.3%, respectively. Among the patients who underwent ESD for UD-type cancer, 30.9% of patients were uninfected with Helicobacter pylori, whereas all patients who underwent ESD for D-type cancer were infected with H pylori. All patients who developed metachronous cancer were infected with H pylori. UD-type metachronous cancer developed more frequently in patients after ESD for UD-type cancer than after ESD for D-type cancer, and the curative resection rate of ESD was significantly lower in these cases. Conclusions Metachronous cancers developed only in H pylori-infected patients in this cohort. Although metachronous cancer incidence was significantly less frequent in patients after ESD for UD-type cancer, the curative resection rate of ESD was significantly lower. Routine surveillance should be conducted more carefully after ESD for UD-type cancer, especially in H pylori-infected patients.

Background and Aims The performance of magnifying endoscopy with narrow-band imaging (ME-NBI) using a computer-aided diagnosis (CAD) system in diagnosing early gastric cancer (EGC) is unclear. Here, we aimed to clarify the differences in the diagnostic performance between expert endoscopists and the CAD system using ME-NBI. Methods The CAD system was pretrained using 1492 cancerous and 1078 noncancerous images obtained using ME-NBI. One hundred seventy-four videos (87 cancerous and 87 noncancerous videos) were used to evaluate the diagnostic performance of the CAD system using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). For each item, comparisons were made between the CAD system and 11 experts who were skilled in diagnosing EGC using ME-NBI with clinical experience of more than 1 year at our hospital. Results The CAD system demonstrated an AUC of 0.8684. The accuracy, sensitivity, specificity, PPV, and NPV were 85.1% (95% confidence interval [95% CI], 79.0-89.6), 87.4% (95% CI, 78.8-92.8), 82.8% (95% CI, 73.5-89.3), 83.5% (95% CI, 74.6-89.7), and 86.7% (95% CI, 77.8-92.4), respectively. The CAD system was significantly more accurate than 2 experts, significantly less accurate than 1 expert, and not significantly different from the remaining 8 experts. Conclusions The overall performance of the CAD system using ME-NBI videos in diagnosing EGC was considered good and was equivalent to or better than that of several experts. The CAD system may prove useful in the diagnosis of EGC in clinical practice.

We recently reported the clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using surgical specimens; patients with homogeneously HER2 positive gastric cancer benefitted more from trastuzumab. However, the majority of patients are diagnosed by endoscopic biopsy, and surgical specimens are not available in these patients. The aim of this study is to verify clinical significance of HER2 heterogeneity on trastuzumab efficacy using biopsy specimens.Eighty-seven patients, who received trastuzumab-based chemotherapy and whose endoscopic biopsy specimens were available for HER2 assessment, were consecutively enrolled. When all tumor cells in all biopsy specimens overexpressed HER2 protein, it was defined as homogeneously HER2 (homo-HER2) positive group, and the others were defined as heterogeneously HER2 (hetero-HER2) positive group. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were evaluated.Thirty-four patients (39%) were diagnosed as the homo-HER2 group and 53 patients (61%) were the hetero-HER2 group. After the median follow-up period of 17.8 months, the median PFS and OS were 7.6 and 17.8 months, respectively. Significant survival differences were shown between the two groups; the homo-HER2 group showed significantly longer PFS (10.8 vs. 6.1 months, HR 0.469 95% CI 0.29-0.77, p = 0.003) and OS (29.3 vs. 14.4 months, HR 0.352 95% CI 0.20-0.61, p 0.001). ORR was 68.6% in this cohort. Higher response rate (85.2% vs 58.1%, p = 0.020) and deeper response (- 49.0% vs - 40.0%, p = 0.018) were also found in the homo-HER2 group.Similar to surgical specimens, we verified clinical significance of HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens.

Background and aims Precise endoscopic assessment of complete response to neoadjuvant chemoradiotherapy before surgery is important for optimizing surgical and non-surgical treatment. We prospectively evaluated the accuracy of the newly proposed endoscopic criteria to identify complete response, using magnifying chromoendoscopy. Methods New endoscopic criteria were created to define endoscopic complete response, near complete response and incomplete response, using magnifying chromoendoscopy. The criteria contained notable endoscopic findings, including shape of the scar, state of the ulcer, finding of white moss, presence of residual protruded nodules, regenerated pits of the scar, presence of neoplastic pit patterns, and extension of rectal wall. Seventy-nine patients with rectal cancer who received neoadjuvant chemoradiotherapy were prospectively evaluated 1–3 days before resection. Diagnostic accuracy to identify pathological complete response and interobserver agreement among a supervising colonoscopist and two trainees were investigated. Results Pathological complete response was obtained in 17 patients (21.5%). The diagnostic accuracy of endoscopic complete response was 85%, with a sensitivity of 47%, specificity of 97%, positive predictive value of 80% and negative predictive value of 77%. The kappa-value for interobserver agreement across 3 doctors was 0.57 (standard error, 0.74; 95% confidence interval, 0.39–0.76). Conclusion The newly proposed endoscopic criteria using magnifying chromoendoscopy achieved excellent diagnostic accuracy to determine good responders to neoadjuvant chemoradiotherapy in rectal cancer, with fair interobserver agreement. The criteria could be clinically useful to select patients for non-surgical management.

Image recognition using artificial intelligence with deep learning through convolutional neural networks (CNNs) has dramatically improved and been increasingly applied to medical fields for diagnostic imaging. We developed a CNN that can automatically detect gastric cancer in endoscopic images. A CNN-based diagnostic system was constructed based on Single Shot MultiBox Detector architecture and trained using 13,584 endoscopic images of gastric cancer. To evaluate the diagnostic accuracy, an independent test set of 2296 stomach images collected from 69 consecutive patients with 77 gastric cancer lesions was applied to the constructed CNN. The CNN required 47 s to analyze 2296 test images. The CNN correctly diagnosed 71 of 77 gastric cancer lesions with an overall sensitivity of 92.2%, and 161 non-cancerous lesions were detected as gastric cancer, resulting in a positive predictive value of 30.6%. Seventy of the 71 lesions (98.6%) with a diameter of 6 mm or more as well as all invasive cancers were correctly detected. All missed lesions were superficially depressed and differentiated-type intramucosal cancers that were difficult to distinguish from gastritis even for experienced endoscopists. Nearly half of the false-positive lesions were gastritis with changes in color tone or an irregular mucosal surface. The constructed CNN system for detecting gastric cancer could process numerous stored endoscopic images in a very short time with a clinically relevant diagnostic ability. It may be well applicable to daily clinical practice to reduce the burden of endoscopists.

Background: In recent years, effective outcomes of endoscopic submucosal dissection (ESD) for esophagogastric junction cancer including short-segment Barrett’s esophagus (SSBE) cancer have been reported. However, the efficacy of ESD for long-segment Barrett’s esophagus (LSBE) cancer is unknown. Aim: To clarify the treatment outcomes of ESD for LSBE cancer versus SSBE cancer. Methods: A total of 86 patients with 91 superficial Barrett’s esophageal adenocarcinomas who underwent ESD were enrolled; of these, 68 had underlying SSBE and 18 had LSBE. Procedure outcomes and prognosis were compared. Results: There was no significant difference in age and tumor diameter among patients. The only complication observed was stricture, but it was not significant (2 vs. 9%). No significant difference was observed in the negative horizontal margin rates (94.1 vs. 95.7%), R0 resection rates (83.8 vs. 82.6%), curative resection rates (72.1 vs. 73.9%), and noncurative factors. Both LSBE and SSBE cancer showed favorable 3-year overall survival rates (95.0 vs. 94.4%) in the median observation period of 28.5 months. Conclusions: ESD for LSBE cancer achieved procedure outcomes and short-term prognosis comparable to SSBE. ESD has the potential to be an effective therapeutic option for esophageal neoplasms in patients with LSBE.

BACKGROUND AND AIM In Japan, an increase in the number of routine esophagogastroduodenoscopy procedures is expected because several studies have reported that endoscopy screening has reduced gastric cancer mortality. Magnifying narrow-band imaging has been reported to be effective for accurate diagnosis of gastric abnormalities such as cancers, adenomas, and intestinal metaplasia. However, the efficacy of this method in routine esophagogastroduodenoscopy has not been clarified. METHODS We divided 3763 patients into two groups. The non-magnification group included 1842 patients who underwent endoscopy screening using GIF-H260/LUCERA-SPECTRUM between October 2014 and February 2015, whereas the magnification group included 1921 patients who underwent screening using GIF-H290Z/LUCERA-ELITE between March 2015 and May 2015. In the magnification group, diagnosis of cancer was conducted using the VS classification system. We did not carry out a biopsy when results were confirmed as non-cancer using magnifying narrow-band imaging. If cancer was diagnosed, or when a cancer or non-cancer diagnosis was difficult, we carried out a biopsy. We analyzed and compared the diagnostic performance between the two groups. RESULTS Gastric biopsy rate was significantly lower in the magnification group (29%) than in the non-magnification group (41%) (P < 0.001). Positive predictive value (PPV) for gastric cancer was significantly higher in the magnification group (5.5%) than in the non-magnification group (2.5%) (P < 0.001). Furthermore, PPV for gastric epithelial neoplasia was significantly higher in the magnification group (7.9%) than in the non-magnification group (3.2%) (P < 0.001). CONCLUSION Magnifying narrow-band imaging improves the diagnostic performance of routine esophagogastroduodenoscopy.

Colorectal endoscopic submucosal dissection (ESD) is technically demanding while ensuring safety, especially in cases with fibrosis and/or poor maneuverability. To overcome such difficulties, we developed a novel method called the pocket-creation method with a traction device (PCM with TD). We then evaluated the effectiveness and safety of PCM with TD in colorectal ESD compared to other conventional methods.In total, 324 colorectal lesions treated with ESD from July 2018 to June 2019 were included. The following three treatment strategies were used: conventional ESD (CE), CE with TD, and PCM with TD. Patient backgrounds and treatment outcomes were retrospectively compared and analyzed.As ESD methods, CE, CE with TD, and PCM with TD account for 58% (187/324), 24% (78/324), and 18% (59/324), respectively. No significant difference was observed among the three groups in en bloc and R0 resection rates or adverse events. The rate of lesions with fibrosis and poor maneuverability was significantly higher in the PCM with TD group (CE group vs CE with TD group vs PCM with TD group: fibrosis, 24% vs 47% vs 64%, p 0.001; poor maneuverability, 5.3% vs 13% vs 20%, p = 0.002). Dissection speed was significantly higher in the PCM with TD than in the CE with TD group (p = 0.003).PCM with TD can achieve a stable en bloc resection rate and R0 dissection rate without adverse events even in the hands of trainees, irrespective of the size and location of the lesion, presence of fibrosis, and under poor maneuverability conditions.

We aimed to clarify the differences in therapeutic outcomes of patients with pure undifferentiated-type and mixed undifferentiated-type cancers who underwent endoscopic submucosal dissection (ESD), and whether pre-treatment diagnosis of mixed undifferentiated-type cancer is associated with requiring additional surgery after ESD. Patients subjected to ESD as initial treatment between May 2005 and March 2017 were enrolled. There were 277 undifferentiated-type cancers (265 patients). Histologically, 258 lesions were pure-type and 19 were mixed-type. We compared therapeutic outcomes and pre-treatment factors (tumour diameter, tumour depth, ulcerative findings, tumour location, and the macroscopic, and histological type of the biopsy specimen) between pure-type and mixed-type lesions, and between cases not requiring additional surgeries and cases requiring additional surgeries. Tumour diameter >20 mm, submucosal invasion, and the presence of ulcerative findings made pre-treatment diagnosis more difficult for mixed-type than for pure-type lesions. In cases requiring additional surgery, pre-treatment diagnosis of mixed-type lesions was significantly more likely than pre-treatment diagnosis of pure-type lesions. For mixed-type lesions, pre-treatment histological diagnosis and careful consideration are necessary to determine indications for ESD to avoid additional surgery after ESD.

Objectives Serrated lesions of the colorectum often have complex histological morphology, and some groups include subtypes with different molecular biology. This study aimed to characterize serrated lesions with heterogeneous histology that was dominated by a traditional serrated adenoma (TSA) component. Methods Representative lesions were selected based on both endoscopic and histological features. If a lesion had more than one component, each of the different structural parts was considered as a separate sample. DNA was extracted from 177 samples of 60 lesions and amplified to screen for BRAF and K/NRAS mutations. Results Heterogeneous TSA samples were classified into four categories: sessile serrated lesion with TSA (SA-1); TSAs with microvesicular hyperplastic polyp (SA-2); TSAs with unclassified adenoma, characterized by tubulo-serrated histology (SA-3); and TSAs with conventional adenomas (SA-4). On endoscopy, SA-1 lesions had sessile-elevated morphology with the small reddish elevations; SA-2 lesions had a pedunculated appearance with a whitish mucosal component at the stalk; SA-3 lesions had a sessile-elevated component surrounded by flat spreading margins; and SA-4 lesions had mixed adenomatous morphology. Eighteen of the 19 category SA-1 and -2 lesions (95%) had BRAF mutations, and all of the SA-3 and -4 lesions had K/NRAS mutations. Conclusions Traditional serrated adenomas were classified into two phenotypes according to their molecular characteristics: microvesicular serrated subtypes with BRAF mutations (SA-1 and -2 lesions) and subtypes containing tubulo-serrated/conventional adenoma with K/NRAS mutations (SA-3 and -4 lesions). Each subtype had characteristic macroscopic and microscopic morphologies and was distinct on endoscopy.

In Japan, endoscopic resection (ER) is often used to treat esophageal squamous cell carcinoma (ESCC) when invasion depths are diagnosed as EP-SM1, whereas ESCC cases deeper than SM2 are treated by surgical operation or chemoradiotherapy. Therefore, it is crucial to determine the invasion depth of ESCC via preoperative endoscopic examination. Recently, rapid progress in the utilization of artificial intelligence (AI) with deep learning in medical fields has been achieved. In this study, we demonstrate the diagnostic ability of AI to measure ESCC invasion depth. We retrospectively collected 1751 training images of ESCC at the Cancer Institute Hospital, Japan. We developed an AI-diagnostic system of convolutional neural networks using deep learning techniques with these images. Subsequently, 291 test images were prepared and reviewed by the AI-diagnostic system and 13 board-certified endoscopists to evaluate the diagnostic accuracy. The AI-diagnostic system detected 95.5% (279/291) of the ESCC in test images in 10 s, analyzed the 279 images and correctly estimated the invasion depth of ESCC with a sensitivity of 84.1% and accuracy of 80.9% in 6 s. The accuracy score of this system exceeded those of 12 out of 13 board-certified endoscopists, and its area under the curve (AUC) was greater than the AUCs of all endoscopists. The AI-diagnostic system demonstrated a higher diagnostic accuracy for ESCC invasion depth than those of endoscopists and, therefore, can be potentially used in ESCC diagnostics.