Clinical features and distribution of the APC variant in duodenal and ampullary polyps in patients with familial adenomatous polyposis: a multicenter retrospective cohort study in Japan.

BACKGROUND: Management of duodenal or ampullary adenomas in patients with familial adenomatous polyposis (FAP) is a major challenge for clinicians. Insufficient data are available to evaluate the clinical manifestations and distribution of adenomatous polyposis coli (APC) variants in these patients. METHODS: We enrolled 451 patients with data regarding duodenal or ampullary polyps from 632 patients with FAP retrospectively registered in a nationwide Japanese multicenter study. Clinicopathological features and distribution of APC variants were compared between patients with and without duodenal or ampullary polyps. RESULTS: Duodenal and ampullary polyps were found in 59% and 18% of patients with FAP, respectively. The incidence of duodenal cancer was 4.7% in patients with duodenal polyps, and that of ampullary cancer was 18% in patients with ampullary polyps. Duodenal polyps were significantly associated with the presence of ampullary polyps and jejunal/ileal polyps. Duodenal polyps progressed in 35% of patients with a median follow-up of 776 days, mostly in those with early Spigelman stage lesions. Ampullary polyps progressed in 50% of patients with a follow-up of 1484 days. However, only one patient developed a malignancy. The proportion of patients with duodenal polyps was significantly higher among those with intermediate- or profuse-type APC variants than attenuated-type APC variants. The presence of duodenal polyps was significantly associated with ampullary and jejunal/ileal polyps in patients with intermediate- or profuse-type APC variants. CONCLUSIONS: Periodic endoscopic surveillance of the papilla of Vater and small intestine should be planned for patients with FAP with duodenal polyps.

Usefulness of genotyping APC gene for individualizing management of patients with familial adenomatous polyposis.

BACKGROUND: Colorectal polyp burden is crucial for the management of patients with familial adenomatous polyposis (FAP). However, accurate evaluation of polyp burden is difficult to standardize. This study aimed to examine the possible utility of genotype-oriented management of colorectal neoplasms in patients with FAP. METHODS: Clinicopathological data from genetically proven patients with FAP was analyzed using the database of a nationwide retrospective Japanese multicenter study. The cumulative incidence of CRC was evaluated between different genotype groups. Genotype-1 were defined as germline variants on attenuated FAP-associated regions (codons 1-177, alternative splice site of exon 10 (codon 312), 1581-2843) and Genotype-2 as the other variants. Weibull and Joinpoint analyses were performed to determine the annual percentage changes in CRC risk. RESULTS: Overall, 69 men and 102 women were included. Forty-eight patients underwent colorectal resection for the first CRC, and five patients underwent resection for first cancer in the remnant anorectal segment after prophylactic surgery. The 70-year cumulative incidence of CRC in all patients was 59.3%. Patients with Genotype-1 (n = 23) demonstrated a lower risk of CRC stages II-IV than those with Genotype-2 (n = 148, P = 0.04). The risk of stage II-IV CRC was estimated to increase markedly at the age of 49 years in the Genotype-1 patients and 34 years in the Genotype-2 patients, respectively. CONCLUSIONS: Different interventional strategies based on genotypes may be proposed for the clinical management of patients with FAP. This policy needs to be validated in further prospective studies focusing on long-term endoscopic intervention and optimal age at prophylactic (procto)colectomy.

Risk factors for adverse events associated with endoscopic submucosal dissection for superficial pharyngeal cancer.

BACKGROUND: Superficial pharyngeal cancer can be treated with curative intent while preserving function using minimally invasive peroral endoscopic resection techniques such as endoscopic submucosal dissection (ESD). However, severe adverse events occasionally occur, such as laryngeal edema requiring temporary tracheotomy and fistula formation. Therefore, we investigated the risk factors for adverse events associated with ESD for superficial pharyngeal cancer. METHODS: This retrospective observational study was conducted at a single institution, and 63 patients who underwent ESD were enrolled. The primary outcome was the risk factors for adverse events associated with ESD. The secondary outcomes were adverse events associated with ESD and their frequency. RESULTS: The overall adverse event rate was 15.9% (10/63). The incidence of laryngeal edema requiring prophylactic temporary tracheotomy was 11.1%, while laryngeal edema requiring emergency temporary tracheotomy, postoperative bleeding, aspiration pneumonia, fistula, abscess, and stricture formation occurred in 1.6% of patients, respectively. Logistic regression analyses showed that a history of radiotherapy for head and neck cancer was a risk factor for adverse events (odds ratio [OR], 16.67; 95% confidence interval [CI], 3.04-91.34; p = 0.001). After adjusting the model for differences in the baseline risk factors using the inverse probability of treatment weighting method, the adverse events were found to increase in association with a history of radiotherapy for head and neck cancer (OR, 39.66; 95% CI,5.85-268.72; p < 0.001). CONCLUSION: History of radiotherapy for head and neck cancer is an independent risk factor for adverse events associated with ESD for superficial pharyngeal cancer. Among adverse events, laryngeal edema requiring prophylactic temporary tracheotomy was particularly high.

Delineating the extent of esophageal squamous cell carcinoma.

BACKGROUND: Lugol chromoendoscopy has been conventionally used for the detection and delineation of esophageal squamous cell carcinoma (SCC). However, the boundaries of some lesions are unclear even with Lugol chromoendoscopy, and there is a risk of residual lesions or over-excision. This study aimed to evaluate the utility of narrow-band imaging (NBI) for the delineation of esophageal SCC in endoscopic resection. METHODS: Among 367 esophageal SCCs endoscopically resected between January and December 2019 at our institute, this retrospective study included consecutive lesions, which were first marked with NBI, followed by Lugol chromoendoscopy. The proportion of residual cancer, which was defined as histologically proven cancer confirmed adjacent to the scar within 1 year after endoscopic resection, was evaluated. To evaluate whether the marks added by Lugol chromoendoscopy after NBI marking were more reliable, we evaluated the presence of cancer in the iodine-unstained area outside the NBI-determined marks, i.e., the cancerous area missed by NBI. The presence of cancer in the iodine-stained areas inside the NBI-determined marks, i.e., the cancerous area missed by Lugol, was also evaluated. These were compared to assess the risk of residual cancer in endoscopic resection with NBI and Lugol chromoendoscopy. RESULTS: Among 304 lesions, 2 (0.7%) residual cancers were detected. The cancerous area missed by NBI and the cancerous area missed by Lugol were identified in 18 (6%) and 43 (14%) lesions, respectively (P = 0.001). CONCLUSIONS: NBI might be acceptable for delineating the extent of esophageal SCCs that are difficult to delineate with Lugol chromoendoscopy.

Curative value of underwater endoscopic mucosal resection for submucosally invasive colorectal cancer.

BACKGROUND AND AIM: Occasionally, colorectal tumors without characteristics of deep submucosal invasion are found to be invasive upon pathological evaluation after endoscopic resection (ER). Because the resection depth for underwater endoscopic mucosal resection (UEMR) has not been clarified, we evaluated the feasibility of UEMR for pathologically invasive colorectal cancer (pT1-CRC). METHODS: We retrospectively investigated data on the backgrounds and outcomes of patients with pT1-CRC who underwent UEMR between January 2014 and June 2019 at our institute. As a reference standard, the backgrounds and outcomes of pT1-CRCs that had undergone conventional EMR (CEMR) were also investigated. RESULTS: Thirty-one patients (median age, 68 years [range, 32-88 years]; 22 men [71%]) were treated with UEMR. Median lesion size was 17 mm (range, 6-50 mm). The endoscopic complete resection rate was 100%. The overall en bloc resection rate was 77%, and the VM0, HM0, and R0 resection rates were 81%, 58%, and 55%, respectively. In cases of pT1a (invasion <1000 µm)-CRC (n = 14), the en bloc, VM0, and R0 resection rates were 92%, 100%, and 71%, respectively. Seventeen patients (five with risk factors for lymph node metastasis and 12 without) were followed up, and no local recurrence and distant metastasis were observed during the follow-up period (median follow-up period, 18 months [range, 6-62 months]) after UEMR. The outcomes of UEMR seemed to be comparable with those of CEMR (n = 32). CONCLUSIONS: The VM0 rate of UEMR for pT1-CRC, especially for pT1a-CRC, without characteristics of deep submucosal invasion seems feasible.

Esophageal metal stent for malignant obstruction after prior radiotherapy.

The association between severe adverse events (SAEs) and prior radiotherapy or stent type remains controversial. Patients with esophageal or esophagogastric junctional cancer who underwent stent placement (2005-2019) were enrolled in this retrospective study conducted at a tertiary cancer institute in Japan. The exclusion criteria were follow-up period of < 1 month and insufficient data on stent type or cancer characteristics. We used Mann-Whitney's U test for quantitative data and Fisher's exact test for categorical data. Multivariate analysis was performed using a logistic regression model. 107 stents were placed. Low radial-force stents (L group) were used in 51 procedures and high radial-force stents (H group) in 56 procedures. SAEs developed after nine procedures, the median interval from stent placement being 6 days (range, 1-141 days). SAEs occurred more frequently in the H (14%: 8/56) than in the L group (2%: 1/51) (P = 0.03). In patients who had undergone prior radiotherapy, SAEs were more frequent in the H (36%: 4/11) than in the L group (0%: 0/13) (P = 0.03). Re-obstruction and migration occurred after 16 and three procedures, respectively; these rates did not differ significantly between groups (P = 0.59, P = 1, respectively). Low radial-force stents may reduce the risk of SAEs after esophageal stenting.

Continuous warfarin administration versus heparin bridging therapy in post colorectal polypectomy haemorrhage: a study protocol for a multicentre randomised controlled trial (WHICH study).

BACKGROUND: Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding. METHODS: We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events. DISCUSSION: The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy. TRIAL REGISTRATION: UMIN-CTR UMIN000023720 . Registered on 22 August 2016.

Diagnosis of pharyngeal cancer on endoscopic video images by Mask region-based convolutional neural network.

OBJECTIVES: We aimed to develop an artificial intelligence (AI) system for the real-time diagnosis of pharyngeal cancers. METHODS: Endoscopic video images and still images of pharyngeal cancer treated in our facility were collected. A total of 4559 images of pathologically proven pharyngeal cancer (1243 using white light imaging and 3316 using narrow-band imaging/blue laser imaging) from 276 patients were used as a training dataset. The AI system used a convolutional neural network (CNN) model typical of the type used to analyze visual imagery. Supervised learning was used to train the CNN. The AI system was evaluated using an independent validation dataset of 25 video images of pharyngeal cancer and 36 video images of normal pharynx taken at our hospital. RESULTS: The AI system diagnosed 23/25 (92%) pharyngeal cancers as cancers and 17/36 (47%) non-cancers as non-cancers. The transaction speed of the AI system was 0.03 s per image, which meets the required speed for real-time diagnosis. The sensitivity, specificity, and accuracy for the detection of cancer were 92%, 47%, and 66% respectively. CONCLUSIONS: Our single-institution study showed that our AI system for diagnosing cancers of the pharyngeal region had promising performance with high sensitivity and acceptable specificity. Further training and improvement of the system are required with a larger dataset including multiple centers.

Artificial intelligence for the detection of esophageal and esophagogastric junctional adenocarcinoma.

BACKGROUND AND AIM: Conventional endoscopy for the early detection of esophageal and esophagogastric junctional adenocarcinoma (E/J cancer) is limited because early lesions are asymptomatic, and the associated changes in the mucosa are subtle. There are no reports on artificial intelligence (AI) diagnosis for E/J cancer from Asian countries. Therefore, we aimed to develop a computerized image analysis system using deep learning for the detection of E/J cancers. METHODS: A total of 1172 images from 166 pathologically proven superficial E/J cancer cases and 2271 images of normal mucosa in esophagogastric junctional from 219 cases were used as the training image data. A total of 232 images from 36 cancer cases and 43 non-cancerous cases were used as the validation test data. The same validation test data were diagnosed by 15 board-certified specialists (experts). RESULTS: The sensitivity, specificity, and accuracy of the AI system were 94%, 42%, and 66%, respectively, and that of the experts were 88%, 43%, and 63%, respectively. The sensitivity of the AI system was favorable, while its specificity for non-cancerous lesions was similar to that of the experts. Interobserver agreement among the experts for detecting superficial E/J was fair (Fleiss' kappa = 0.26, z = 20.4, P < 0.001). CONCLUSIONS: Our AI system achieved high sensitivity and acceptable specificity for the detection of E/J cancers and may be a good supporting tool for the screening of E/J cancers.

Magnifying endoscopy with crystal violet staining for immune checkpoint inhibitor-associated colitis.

BACKGROUND AND AIM: There exists no evidence on the relationship between endoscopic and histologic findings. Furthermore, even after multiple biopsy specimens were obtained, histologic examination usually fails to show the characteristic features of immune checkpoint inhibitor-associated colitis. In this study, we explored the endoscopic and histologic findings of immune checkpoint inhibitor-associated colitis. METHODS: Patients diagnosed with immune checkpoint inhibitor-associated colitis at our hospital between March 2018 and December 2018 were retrospectively assessed. The degree of mucosal inflammation was evaluated using endoscopic inflammation grade (inactive, mild, moderate, or severe disease) and further observed using magnifying endoscopy with crystal violet staining. Pit structures were classified into three types: regularly arranged pits with circular or elliptical shape (R type), irregularly arranged pits with inhomogeneous size and morphology (IR type), and pits with reduced density or pits that partially disappeared (AD type). RESULTS: Eleven patients (median age, 71 years; range, 44-83 years) were diagnosed with immune checkpoint inhibitor-associated colitis. All characteristic histologic findings, including crypt distortion, crypt abscesses, and apoptotic bodies, were observed at sites with moderate-to-severe endoscopic inflammation but not at sites with inactive-to-mild endoscopic inflammation. Characteristic histologic features were observed in 0%, 50%, and 100% of R-type, IR-type, and AD-type mucosa, respectively. CONCLUSIONS: We revealed the possible utility of endoscopic images for selecting suitable target sites for biopsy and showed that endoscopic findings could reduce the time lag associated with tissue diagnosis and sampling errors due to biopsy.

Narrow band imaging under less-air condition improves the visibility of superficial esophageal squamous cell carcinoma.

BACKGROUND: The current virtual chromoendoscopy equipment cannot completely detect superficial squamous cell carcinoma (SCC) in the esophagus, despite its development in the recent years. Thus, in this study, we aimed to elucidate the appropriate air volume during endoscopic observation to improve the visibility of esophageal SCC. METHODS: This retrospective study included a total of 101 flat type esophageal SCCs identified between April 2017 and January 2019 at the Department of Gastrointestinal Oncology, Osaka International Cancer Institute. Video images of narrow band imaging (NBI) under both less-air and standard-air conditions were recorded digitally. Videos were evaluated by five endoscopists. Relative visibility between less-air and standard-air conditions of the brownish area, brownish color change of the epithelium, and dilated intrapapillary capillary loop (IPCL) were graded as 5 (definitely better under less-air condition) to 1 (definitely worse under less-air condition), with 3 indicating average visibility (equivalent to standard-air observation). RESULTS: The mean (standard deviation) visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs under less-air condition were 3.94 (0.58), 3.73 (0.57), and 4.13 (0.60), respectively, which were significantly better than that under standard-air condition (p < 0.0001). Esophageal SCC evaluated as ≥ 4 in the mean visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs accounted for 50% (51/101 lesions), 34% (34/101 lesions), and 67% (68/101 lesions), respectively. CONCLUSIONS: The present results suggested that NBI with less air might improve the visibility of flat type esophageal SCC compared with NBI with standard air. Less-air NBI observation may facilitate the detection of flat type esophageal SCC. TRIAL REGISTRATION: The present study is a non-intervention trial.

Real-time assessment of video images for esophageal squamous cell carcinoma invasion depth using artificial intelligence.

BACKGROUND: Although optimal treatment of superficial esophageal squamous cell carcinoma (SCC) requires accurate evaluation of cancer invasion depth, the current process is rather subjective and may vary by observer. We, therefore, aimed to develop an AI system to calculate cancer invasion depth. METHODS: We gathered and selected 23,977 images (6857 WLI and 17,120 NBI/BLI images) of pathologically proven superficial esophageal SCC from endoscopic videos and still images of superficial esophageal SCC taken in our facility, to use as a learning dataset. We annotated the images with information [such as magnified endoscopy (ME) or non-ME, pEP-LPM, pMM, pSM1, and pSM2-3 cancers] based on pathologic diagnosis of the resected specimens. We created a model using a convolutional neural network. Performance of the AI system was compared with that of invited experts who used the same validation video set, independent of the learning dataset. RESULTS: Accuracy, sensitivity, and specificity with non-magnified endoscopy (ME) were 87%, 50%, and 99% for the AI system and 85%, 45%, 97% for the experts. Accuracy, sensitivity, and specificity with ME were 89%, 71%, and 95% for the AI system and 84%, 42%, 97% for the experts. CONCLUSIONS: Most diagnostic parameters were higher when done by the AI system than by the experts. These results suggest that our AI system could potentially provide useful support during endoscopies.

Stratification of gastric cancer risk using a deep neural network.

BACKGROUND AND AIM: Stratifying gastric cancer (GC) risk and endoscopy findings in high-risk individuals may provide effective surveillance for GC. We developed a computerized image- analysis system for endoscopic images to stratify the risk of GC. METHODS: The system was trained using images taken during endoscopic examinations with non-magnified white-light imaging. Patients were classified as high-risk (patients with GC), moderate-risk (patients with current or past Helicobacter pylori infection or gastric atrophy), or low-risk (patients with no history of H. pylori infection or gastric atrophy). After selection, 20,960, 17,404, and 68,920 images were collected as training images for the high-, moderate-, and low-risk groups, respectively. RESULTS: Performance of the artificial intelligence (AI) system was evaluated by the prevalence of GC in each group using an independent validation dataset of patients who underwent endoscopic examination and H. pylori serum antibody testing. In total, 12,824 images from 454 patients were included in the analysis. The time required for diagnosing all the images was 345 seconds. The AI system diagnosed 46, 250, and 158 patients as low-, moderate-, and high risk, respectively. The prevalence of GC in the low-, moderate-, and high-risk groups was 2.2, 8.8, and 16.4%, respectively (P = 0.0017). Three experienced endoscopists also successfully stratified the risk; however, interobserver agreement was not satisfactory (kappa value of 0.27, indicating fair agreement). CONCLUSION: The current AI system detected significant differences in the prevalence of GC among the low-, moderate-, and high-risk groups, suggesting its potential for stratifying GC risk.

Application of Convolutional Neural Networks for Detection of Superficial Nonampullary Duodenal Epithelial Tumors in Esophagogastroduodenoscopic Images.

OBJECTIVES: A superficial nonampullary duodenal epithelial tumor (SNADET) is defined as a mucosal or submucosal sporadic tumor of the duodenum that does not arise from the papilla of Vater. SNADETs rarely metastasize to the lymph nodes, and most can be treated endoscopically. However, SNADETs are sometimes missed during esophagogastroduodenoscopic examination. In this study, we constructed a convolutional neural network (CNN) and evaluated its ability to detect SNADETs. METHODS: A deep CNN was pretrained and fine-tuned using a training data set of the endoscopic images of SNADETs (duodenal adenomas [N = 65] and high-grade dysplasias [HGDs] [N = 31] [total 531 images]). The CNN evaluated a separate set of images from 26 adenomas, 8 HGDs, and 681 normal tissue (total 1,080 images). The gold standard for both the training data set and test data set was a "true diagnosis" made by board-certified endoscopists and pathologists. A detected tumor was marked with a rectangular frame on the endoscopic image. If it overlapped at least a part of the "true tumor" diagnosed by board-certified endoscopists, the CNN was considered to have "detected" the SNADET. RESULTS: The trained CNN detected 94.7% (378 of 399) of SNADETs on an image basis (94% [280 of 298] of adenomas and 100% [101 of 101] of HGDs) and 100% on a tumor basis. The time needed for screening the 399 images containing SNADETs and all 1,080 images (including normal images) was 12 and 31 seconds, respectively. DISCUSSION: We used a novel algorithm to construct a CNN for detecting SNADETs in a short time.