Cooperation between artificial intelligence and endoscopists for diagnosing invasion depth of early gastric cancer.

BACKGROUND AND STUDY AIMS: The diagnostic ability of endoscopists to determine invasion depth of early gastric cancer is not favorable. We designed an artificial intelligence (AI) classifier for differentiating intramucosal and submucosal gastric cancers and examined it to establish a diagnostic method based on cooperation between AI and endoscopists. PATIENTS AND METHODS: We prepared 500 training images using cases of mainly depressed-type early gastric cancer from 250 intramucosal cancers and 250 submucosal cancers. We also prepared 200 test images each of 100 cancers from another institution. We designed an AI classifier to differentiate between intramucosal and submucosal cancers by deep learning. We examined the performance of the AI classifier and the majority vote of the endoscopists as high confidence and low confidence diagnostic probability, respectively, and cooperatively combined them to establish a diagnostic method providing high accuracy. RESULTS: Internal evaluation of the training images showed that accuracy, sensitivity, specificity, and F1 measure by the AI classifier were 77%, 76%, 78%, and 0.768, and those of the majority vote of the endoscopists were 72.6%, 53.6%, 91.6%, and 0.662, respectively. A diagnostic method based on cooperation between AI and the endoscopists showed that the respective values were 78.0%, 76.0%, 80.0%, and 0.776 for the test images. The value of F1 measure was especially higher than those by AI or the endoscopists alone. CONCLUSIONS: Cooperation between AI and endoscopists improved the diagnostic ability to determine invasion depth of early gastric cancer.

Estimation of salt intake from spot urine may assist the risk assessment of gastric cancer.

Daily salt intake can be estimated by measuring sodium and creatinine concentrations in spot urine. Excessive salt intake is risk factor for gastric cancer. We examined the correlation between estimated salt intake from spot urine and risk of gastric cancer. This study included gastric cancer patients who underwent treatment at our hospital and patients in whom esophagogastroduodenoscopy was performed but gastric cancer was not observed. The history of H. pylori infection was known in these patients. Spot urine was collected, and daily salt intake was estimated from urine sodium and urine creatinine. Mean estimated salt intake was significantly higher in 120 gastric cancer patients (9.18 g/day) than in 80 non-gastric cancer patients (8.22 g/day). Multivariate analysis revealed estimated salt intake and H. pylori infection to be independent risk factors for gastric cancer. Among H. pylori-infected patients, salt intake was significantly higher in gastric cancer patients (9.25 g/day) than in non-gastric cancer patients (8.01 g/day). In conclusion, salt intake estimated from spot urine was high in patients with gastric cancer, especially in H. pylori infected patients. Spot urine is a simple examination and it may be applied as a new risk assessment of gastric cancer.

Image quality of a novel light-emitting diode (LED)-illuminated colonoscope.

BACKGROUND AND STUDY AIMS: Light-emitting diodes (LEDs) are used widely for their high luminous efficiency and durability. We developed a novel prototype high definition endoscope with white LEDs and evaluated the image quality it produced against a commercial endoscope with conventional light source. PATIENTS AND METHODS: The specifications of both colonoscopes were identical, except for the LED light source at the tip of the prototype. We examined 20 patients with rectal or sigmoid colon lesions and the image quality was evaluated in 40 images (one image from the LED colonoscope and one from the conventional colonoscope for each lesion) by three endoscopists. We additionally evaluated the 17 videos recorded with the LED colonoscope that were available. Image quality, mucosal and vascular color, and luminous distribution and intensity were scored on a 5-point scale. RESULTS: The mean score for vascular color given by one evaluator was significantly higher using the LED colonoscope than using the conventional colonoscope. The mean scores for mucosal color and luminous intensity from another evaluator were significantly lower with the LED colonoscope than with the conventional colonoscope. There were no significant differences in the luminous distribution scores for any of the evaluators. The image quality of the videos was evaluated as being similar with both colonoscopes. CONCLUSIONS: Image quality from the LED and conventional colonoscopes were similar, although the luminous intensity of the LEDs is inferior to that of the conventional light source at the present time.

Colonization of an acid resistant Kingella denitrificans in the stomach may contribute to gastric dysbiosis by Helicobacter pylori.

In the stomach of a gastric ulcer patient who had been administered an anti-acid, a gram-negative and urease-negative bacillus similar in size to Helicobacter pylori was infected together with H. pylori. According to biochemical test and 16S rRNA gene analysis, the urease-negative bacterium was identified as Kingella denitrificans, a human nasopharyngeal commensal. In contrast to the standard strain of K. denitrificans, the isolate showed catalase activity, did not produce acid from glucose, and exhibited acid tolerance. Acid tolerance of H. pylori was increased by cocultivation with the K. denitrificans isolate, but not with other isolates of K. denitrificans. Disruption of physiological and immunological niche by dysbiotic colonization of bacterium may provide pathological attributes to human stomach. Collectively, a careful administration of anti-acids to the elderly, especially those with atrophic gastritis, is necessary to avoid repression of the gastric barrier to bacteria.

Endoscopic Resection is Infeasible for Early Gastric Cancers with Undifferentiated Components.

BACKGROUND/AIMS: Aim of this study is to find subgroup of early gastric cancer with lymph node metastasis for which successive further surgical operation is needed after endoscopic resection. METHODOLOGY: A total of 559 lesions of early gastric cancer, which had undergone curative gastrectomy, were enrolled in this study. We retrospectively investigated 10 clinicopathological factors predictive of lymph node metastasis by univariate and multivariate analysis. We showed the frequency of lymph node metastasis of subgroups in combination of independent factors selected by multivariate analysis. RESULTS: Lymph node metastases were detected in 57 lesions (10.2%). Univariate analysis revealed that lesion size > 30 mm, undifferentiated components, sm massive invasion, lymphatic invasion and venous invasion were factors significantly correlated with lymph node metastasis. By multivariate analysis, risk factors for lymph node metastasis were lesion size > 30 mm, undifferentiated components, sm massive invasion, and lymphatic invasion, with odds ratios of 2.17, 2.30, 5.88 and 8.24, respectively. In lesions with undifferentiated components, LNM were found in all subgroups. CONCLUSIONS: When we treat early gastric cancers contained undifferentiated components, even if they are predominantly differentiated-type intramucosal lesions, an additional surgical procedure should be considered or careful follow-up is required.

In vitro bactericidal effects of near-ultraviolet light from light-emitting diodes on Helicobacter pylori.

We investigated whether near-ultraviolet light emitted from light-emitting diodes (LEDs) effects Helicobacter pylori viability and whether this new method can potentially apply to eradication therapy. Three H. pylori strains were used for near-ultraviolet (UV) LED irradiation experiments. Viability of isolates exposed to near-UV light was compared with controls by counting colony forming units. A time-dependent bactericidal effect of near-UV light was definitely observed. LED irradiation with near-UV light showed effective bactericidal activity against H. pylori strains. Eradication therapy with LED might provide a new avenue of treatment in patients refractory to eradication due to antibiotic resistance and/or adverse effects of antibiotics.

Endoscopic Diagnosis and Therapy for Epstein-Barr Virus-Associated Gastric Cancer.

Epstein-Barr-virus-associated gastric cancer (EBVaGC) represents almost 7% of all GC and is a distinct subtype of GC with extreme DNA hypermethylation. EBVaGC is a tumor-infiltrating lymphocyte-rich tumor with little lymph-node metastasis in its early stage and with a relatively favorable prognosis in its advanced stage. Using upper gastrointestinal endoscopy, we recognize EBVaGC as a mainly depressed type with SMT-like protrusion in the upper part of the stomach near the gastric mucosal atrophic border or remnant stomach. The EBVaGC recognition rate of 21.4% with the endoscopic motif is not high, and further progress in endoscopic diagnosis of EBVaGC is needed. As less invasive endoscopic therapy, the extension of the criteria of endoscopic submucosal dissection (ESD) for early EBVaGC with little lymph-node metastasis should be discussed. Endoscopic diagnosis of EBVaGC may be relevant for the selection of patients who could benefit from endoscopic treatment or chemotherapy.

Epstein-Barr virus detection in endoscopic submucosal dissection-proven early gastric cancer with mixed-type histology.

BACKGROUNDS: Early gastric cancer (EGC) with mixed-type histology is a significant risk factor for additional surgery after endoscopic submucosal dissection (ESD). On the other hand, Epstein-Barr virus-associated gastric cancer (EBVaGC) with mixed-type histology is a favorable risk factor with regard to lymph node metastasis. METHODS: We performed EBV detection in 13 ESD-proven lesions in 13 cases of early gastric cancer with mixed-type histology using EBV-encoded small RNA1 in situ hybridization (EBER1 ISH). RESULTS: EBVaGC was diagnosed in only one (7.7%) of the tested lesions. That EBVaGC patient underwent surgery and there was no residual lesion and no lymph metastasis. EBVaGC is not frequent in EGC with mixed-type histology. CONCLUSIONS: EBV testing of gastric biopsy specimens seems not to be useful to predict the mixed-type histology results of ESD. However, EBV testing for ESD specimens of EGC with mixed-type histology is expected to be useful for avoiding excessive additional surgery.

A novel colonoscope with high color-rendering white light-emitting diodes.

BACKGROUND: Light-emitting diodes (LEDs) are being used for a variety of new uses because of their cost-effectiveness and durability. We therefore considered using white LEDs as a light source for GI endoscopes to simplify the endoscopic system. OBJECTIVE: To assess the feasibility and safety of an LED-illuminated colonoscope. DESIGN: Pilot study of the LED colonoscope in healthy human volunteers and patients with colorectal lesions. SETTING: Yamaguchi University Hospital, Ube, Japan. INTERVENTIONS: We performed a total colonoscopy for 2 healthy volunteers and a sigmoidoscopy for 15 patients with colorectal lesions by using both LED and conventional colonoscopes. We assessed the feasibility and safety of the LED colonoscope by using a 5-grade scale. The 30 images of 15 colorectal lesions obtained by using each endoscope were evaluated in a blind, randomized order by 2 endoscopists. MAIN OUTCOME MEASUREMENTS: The mean scores of the LED colonoscope for the operability, ease of manipulation, image quality, and safety. RESULTS: We manufactured a prototype LED colonoscope with white LEDs on its tip. The LED colonoscope did not require an external light source or light-guide fiber bundle. The operability and ease of manipulation of the LED colonoscope were evaluated as similar to those of the conventional colonoscope. The color of the colonic mucosa and the vascular pattern were clearly visualized in the volunteers. For the 15 colorectal lesions, the mean score for image quality was not significantly different between the colonoscopes. The study was performed safely without any incident. LIMITATIONS: Single-center, small number of patients. CONCLUSIONS: The use of an LED colonoscope is feasible, and LED illumination may simplify the endoscope system.

Endoscopic and pathologic motifs for the clinical diagnosis of Epstein-Barr virus-associated gastric cancer.

Objectives: Based on the recent therapeutic trends for gastric cancer (GC), the clinical impact of the diagnosis of Epstein-Barr virus (EBV)-associated GC (EBVaGC) appears to be important. We retrospectively analyzed endoscopic and pathologic motifs of GC lesions to narrow the number of candidates for EBV testing. Methods: We performed EBV tests for 32 upper gastrointestinal lesions of 32 patients in the clinical setting. These tests were ordered by endoscopists or by pathologists without an endoscopist's order. EBV-encoded small RNA1 (EBER1) in situ hybridization was used for the EBV tests. The endoscopic motif for the EBV test was the location in the upper part of the stomach or remnant stomach, mainly the depressed type with a submucosal tumor-like protrusion of the lesion. The pathologic motif was carcinoma with lymphoid stroma (CLS) or CLS-like histology of the lesion. We retrospectively analyzed the results of EBV tests for the endoscopic and pathologic motifs. Results: The final pathological diagnoses of the 32 subjects were 26 GCs including CLS, gastric endocrine cell carcinoma, gastric hepatoid carcinoma, gastric T-cell lymphoma, gastritis of the remnant stomach, esophageal adenocarcinoma, and esophageal squamous cell carcinoma. When nontypical lesions were excluded, the EBER1-positive rate was 42.3% (11/26) in GCs. Of the 14 GC lesions ordered examined by endoscopists, three (21.4%) were EBVaGC. Eight of the 12 (66.7%) GCs ordered examined by pathologists were EBVaGC. Conclusions: The pathologic motif is expected to be useful and the endoscopic motif may be helpful for EBVaGC diagnosis.

Clinical impact of tumor invasion depth staging of esophageal squamous cell carcinoma using endoscopic ultrasonography.

BACKGROUND/AIMS: To demonstrate how EUS tumor staging has a practical effect on deciding the treatment strategy for esophageal carcinoma, we retrospectively evaluated the clinical impact of thin-probe EUS staging. METHODOLOGY: The results of EUS performed 54 times were classified according to clinical impact into three grades (none, supportive, and important) and analyzed to assess their impact on the treatment strategy on individual occasions. RESULTS: EUS was important in determining treatment strategy for 23 of 39 lesions (59.0%) in the EUS-superficial group and supportive for 16 lesions (41.0%). The clinical impact of EUS for 15 lesions in the EUS-deep group was graded important for 8 lesions (53.3%), supportive for 6 lesions (40.0%) and none for one lesion (6.7%). CONCLUSIONS: Thin-probe EUS is expected to have some clinical impact on the determination of treatment strategies for squamous cell carcinoma of the esophagus.

Application of Biopsy Samples Used for Helicobacter pylori Urease Test to Predict Epstein-Barr Virus-Associated Cancer.

Persistent gastric mucosal damage caused by Helicobacter pylori infection is a major risk factor for gastric cancer (GC). The Epstein-Barr virus (EBV) is also associated with GC. Most patients with EBV-associated GC are infected with H. pylori in East Asia. However, very few reports have described where and when both H. pylori and EBV infect the gastric mucosa. To clarify this, old biopsy samples used for the rapid urease test (RUT) were applied to count EBV genomic DNA (gDNA) copies using DNA probe quantitative polymerase chain reaction. DNA extracted from the gastric biopsy samples of 58 patients with atrophic gastritis was used to analyze the correlation between the degree of atrophic gastritis and the copy number of EBV gDNA. EBV was detected in 44 cases (75.9%), with viral copy numbers ranging from 12.6 to 4754.6. A significant correlation was found between patients with more than 900 copies of EBV gDNA and those with a more severe grade of atrophic gastritis (p = 0.041). This study shows that EBV can be detected in RUT samples in a manner that reduces patient burden.

[A case of advanced gastric cancer with histological complete response after S-1 chemotherapy].

A 58-year-old man of unresectable gastric cancer was treated with S-1 (120 mg/body/day) after gastrojejunostomy. After 5 courses of orally administration of S-1 for 4 weeks and withdrawal for 2 weeks, partial response (PR) was obtained clinically and distal gastrectomy was performed. The histological diagnosis showed no residue of carcinoma with both HE and immunohistochemical staining. The patient has been in good health and no recurrence has occurred for about 4 years and 4 months after resection.

Epstein-Barr Virus-associated Early Gastric Cancer Treated with Endoscopic Submucosal Dissection: A Possible Candidate for Extended Criteria of Endoscopic Submucosal Dissection.

A 73-year-old man visited our hospital for the treatment of an early gastric cancer (GC) lesion. We performed en bloc resection using endoscopic submucosal dissection (ESD) for his GC lesion. The present GC lesion was Epstein-Barr virus (EBV)-associated poorly differentiated-type adenocarcinoma invading into the submucosal layer. Recently, accumulating data has shown that the risk of lymph node metastasis from early EBV GC without local lymphovascular infiltration is low. The present patient has been in good health for over three years since ESD. Some cases of early EBV GC with invasion into the submucosal layer may be candidates for further extension of the ESD criteria.

Clinicopathologic Characteristics of Epstein-Barr Virus-Associated Gastric Cancer Over the Past Decade in Japan.

: Epstein-Barr virus (EBV) is a ubiquitous human herpes virus, but related with several types of malignancies. Among EBV-related malignancies, EBV-associated gastric carcinoma (EBVaGC) has the largest patient's number. We screened for EBV infection in 1067 GC lesions of 1132 patients who underwent surgical resection from 2007 to 2017 in Japan and examined clinicopathological features of EBVaGC. EBV infection was detected by in situ hybridization with EBV-encoded small RNA 1(EBER-1 ISH). EBV was infected in 80 GC lesions (7.1%). Mean age was significantly lower in patients with EBVaGC than with EBV-negative GC. EBVaGC was more frequent in men than in women. EBVaGC was found twice as frequent in the upper or middle stomach as in the lower stomach. Early EBVaGC was more frequent, and submucosally invaded cases were dominant. The presence of lymphatic vessel invasion was less in EBVaGC, but frequency of lymph node metastasis was similar. Carcinoma with lymphoid stroma (CLS) was found in 3.8% (43/1132) of all lesions with 60.5% of EBV positivity. The synchronous or metachronous multiple GC was frequent in EBVaGC. We clarified clinicopathologic characteristics of EBVaGC over the past decade in Japan. EBV infection should be examined in gastric cancer cases showing these characteristics.

The clinical meaning of mucin phenotype and Epstein-Barr virus infection in gastric cancer.

BACKGROUND/AIMS: Differentiated type adenocarcinomas producing gastric type mucin are receiving much attention because of their degree of clinical malignancy. Most Epstein-Barr virus (EBV)-associated gastric cancers are undifferentiated type, and correlate with gastric type mucin. We analyzed the clinical meaning of mucin phenotypes and the detection of EBV in gastric cancers. METHODOLOGY: The objects of study were 120 consecutive gastric cancer lesions, resected endoscopically (EMR group, n=54) or surgically (surgery group, n=66). The mucin phenotypes were determined using immunostaining for human gastric mucin (HGM), MUC2, and CD10. Changes in histological type within the lesions were examined. The presence of EBV was determined using in situ hybridization for EBV-encoded small RNA 1 (EBER-1). RESULTS: The incomplete intestinal phenotype accounted for 83% of the EMR group, and the gastric phenotype for only 13%. None of the EMR group lesions had changes in the degree of differentiation, and there was no EBER-1-positive lesion. In the surgery group, the gastric phenotype accounted for 29%, significantly more than in the EMR group (p=0.0363). The incomplete intestinal phenotype accounted for 64% of surgically resected lesions. Changes in the degree of differentiation were significantly more common in the surgery group (16/66) than in the EMR group (0/54) (p=0.0001), tending to be more common in the gastric phenotype lesions. There were 3 EBER-1-positive lesions in the surgery group, accounting for 5%, and all were HGM positive. CONCLUSIONS: There appears to be little need to determine the mucin phenotype or EBV status of endoscopically resected lesions. In cases of gastric cancer where surgical resection is indicated, however, where the preoperative findings indicate a depth of invasion to SM or greater, and/or an undifferentiated lesion, then mucin phenotyping of biopsy specimens may be useful in predicting the predominant histological type of the tumor.

Clinical Importance of Epstein⁻Barr Virus-Associated Gastric Cancer.

Epstein⁻Barr virus-associated gastric carcinoma (EBVaGC) is the most common malignancy caused by EBV infection. EBVaGC has definite histological characteristics similar to gastric carcinoma with lymphoid stroma. Clinically, EBVaGC has a significantly low frequency of lymph node metastasis compared with EBV-negative gastric cancer, resulting in a better prognosis. The Cancer Genome Atlas of gastric adenocarcinomas proposed a molecular classification divided into four molecular subtypes: (1) EBVaGC; (2) microsatellite instability; (3) chromosomal instability; and (4) genomically stable tumors. EBVaGC harbors a DNA methylation phenotype, PD-L1 and PD-L2 overexpression, and frequent alterations in the PIK3CA gene. We review clinical importance of EBVaGC and discuss novel therapeutic applications for EBVaGC.

Chronological Endoscopic and Pathological Observations in Russell Body Duodenitis.

A 64-year-old man was found to have a nodule in his right lung. He also complained of nausea and abdominal pain during the clinical course. Esophagogastroduodenoscopy revealed a duodenal ulcer associated with severe stenosis and a suspicion of malignancy. However, three subsequent biopsies revealed no evidence of malignancy. The fourth biopsy showed scattered large eosinophilic cells with an eccentric nucleus, leading to a diagnosis of Russell body duodenitis (RBD). RBD is an extremely rare disease, and little is known about its etiology and clinical course. The pathogenesis of RBD is discussed based on our experience with this case.

Usefulness of endoscopic ultrasound-guided fine-needle aspiration biopsy for the diagnosis of pancreatic cancer.

BACKGROUND: Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has come into widespread use, mainly in Western countries, as an efficient and safe method for the cytologic or histologic diagnosis of pancreatic cancer. However, it still has received relatively little attention in Japan. To evaluate the clinical status of EUS-FNAB in Japan, we retrospectively analyzed the results with regard to the ability of EUS-FNAB to diagnose pancreatic cancer, as well as its safety. METHODS: A total of 52 patients (37 male, 15 female; mean age, 62.5 years; range, 33-85 years) with focal pancreatic lesions underwent EUS-FNAB at our group of hospitals in one region of Japan. Final diagnosis was confirmed by histologic examination of surgical specimens or clinical follow-up. RESULTS: The final diagnoses were malignant tumors in 32 patients and benign ones in 20. Insertion of the needle into the lesion was successful in 50 of the 52 patients (96.2%). Adequate specimens were obtained by EUS-FNAB from 47 of the 50 pancreatic lesions (94.0%). With five false-negative and no false-positive results, the accuracy, sensitivity, specificity, and positive and negative predictive values were 89.4%, 82.1%, 100%, 100%, and 79.2%, respectively. No complications occurred. CONCLUSIONS: EUS-FNAB is an efficient and safe method for the histologic diagnosis of pancreatic cancer. It should be considered as one of the indispensable modalities for the histological diagnosis of pancreatic cancer in Japan, as it is in Western countries.

Endoscopic findings potentially predictive of gastric cancer in borderline lesions diagnosed by forceps biopsy.

BACKGROUND/AIMS: When a benign-malignant borderline lesion is diagnosed by the usual small gastric biopsy, there is sometimes difficulty in making a clinical decision. To clarify potentially useful findings to predict the existence of gastric cancer in borderline lesions diagnosed by forceps biopsy, we retrospectively analyzed endoscopic features. METHODOLOGY: We diagnosed 68 consecutive gastric benign-malignant borderline lesions (57 cases) by forceps biopsy and endoscopically resected them. The final diagnosis for 24 lesions (35.3%) was adenocarcinoma (adenocarcinoma group), and for 40 lesions (58.8%) was adenoma (adenoma group). Comparison with endoscopic findings for the groups was carried out using digitally filed endoscopic photos. RESULTS: We found six endoscopic findings (distal location, reddish surface color, lack of smoothness, lack of glossiness, focal roughness, and focal redness) having statistically significant relationships with adenocarcinoma at the final pathological diagnosis. In multivariate analysis, focal redness (p<0.01) and lack of glossiness (p<0.05) were found to have a significant relationship to gastric cancer. CONCLUSIONS: Endoscopic findings such as focal redness and lack of glossiness were potentially predictive of gastric cancer in borderline lesions diagnosed by forceps biopsy.