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.

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.

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.

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.

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.

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

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

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

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

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.

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.

Safety and Efficacy of Self-Expandable Metallic Stent Placement Using Low Radial Force Stent for Malignant Dysphagia after Radiotherapy.

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.

A novel diagnostic system for superficial nonampullary duodenal epithelial tumors sized ≤ 5 mm.

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.

Long-term outcomes of esophageal squamous cell carcinoma with invasion depth of pathological T1a-muscularis mucosae and T1b-submucosa by endoscopic resection followed by appropriate additional treatment.

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.

Incidence of metachronous cancer after endoscopic submucosal dissection: a comparison between undifferentiated-type and differentiated-type early gastric cancer.

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.

Artificial intelligence diagnostic system predicts multiple Lugol-voiding lesions in the esophagus and patients at high risk for esophageal squamous cell carcinoma.

BACKGROUND: It is known that an esophagus with multiple Lugol-voiding lesions (LVLs) after iodine staining is high risk for esophageal cancer; however, it is preferable to identify high-risk cases without staining because iodine causes discomfort and prolongs examination times. This study assessed the capability of an artificial intelligence (AI) system to predict multiple LVLs from images that had not been stained with iodine as well as patients at high risk for esophageal cancer. METHODS: We constructed the AI system by preparing a training set of 6634 images from white-light and narrow-band imaging in 595 patients before they underwent endoscopic examination with iodine staining. Diagnostic performance was evaluated on an independent validation dataset (667 images from 72 patients) and compared with that of 10 experienced endoscopists. RESULTS: The sensitivity, specificity, and accuracy of the AI system to predict multiple LVLs were 84.4 %, 70.0 %, and 76.4 %, respectively, compared with 46.9 %, 77.5 %, and 63.9 %, respectively, for the endoscopists. The AI system had significantly higher sensitivity than 9/10 experienced endoscopists. We also identified six endoscopic findings that were significantly more frequent in patients with multiple LVLs; however, the AI system had greater sensitivity than these findings for the prediction of multiple LVLs. Moreover, patients with AI-predicted multiple LVLs had significantly more cancers in the esophagus and head and neck than patients without predicted multiple LVLs. CONCLUSION: The AI system could predict multiple LVLs with high sensitivity from images without iodine staining. The system could enable endoscopists to apply iodine staining more judiciously.

Diagnostic performance in gastric cancer is higher using endocytoscopy with narrow-band imaging than using magnifying endoscopy with narrow-band imaging.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.0001; 82.1% [78.3-85.9%] versus 64.2% [60.4-69.8%], p < 0.0001; 88.7% [82.6-90.7%] versus 78.5% [75.4-85.1%], p = 0.0023; 79.0% [75.3-80.5%] versus 68.5% [66.4-71.6%], p < 0.0001, respectively). In the magnifying endoscopy with narrow-band imaging-trained group, these values were also higher with endocytoscopy with narrow-band imaging than with magnifying endoscopy with narrow-band imaging (p < 0.0001, p = 0.0001, p = 0.0143, and p < 0.0001, respectively). Diagnostic accuracy, sensitivity, and negative predictive value were higher with endocytoscopy with narrow-band imaging than with magnifying endoscopy with narrow-band imaging in the magnifying endoscopy with narrow-band imaging-untrained group (p = 0.0041, p = 0.0049, and p = 0.0098, respectively). CONCLUSIONS: Diagnostic performance was higher using endocytoscopy with narrow-band imaging than using magnifying endoscopy with narrow-band imaging. Our results may help change the technique used to diagnose gastric cancer.

Usefulness of Magnifying Endoscopy with Narrow-Band Imaging for Diagnosing Mixed Poorly Differentiated Gastric Cancers.

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.