Intramucosal Adenocarcinoma Research Articles

Persistent or recurrent Barrett's neoplasia after an endoscopic therapy session is associated with DNA content abnormality and can be detected by DNA flow cytometric analysis of paraffin-embedded tissue

Endoscopic therapy is currently the standard of care for the treatment of high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) in patients with Barrett's esophagus (BE). Visible lesions are treated with endoscopic mucosal resection (EMR), which is often coupled with radiofrequency ablation (RFA). However, endoscopic therapy may require multiple sessions (one session every 2-3 months) and does not always assure complete eradication of neoplasia. Furthermore, despite complete eradication, recurrences are not uncommon. This study assesses which potential risk factors can predict a poor response after endoscopic sessions. Forty-five BE patients who underwent at least one endoscopic session (EMR alone or ablation with or without preceding EMR) for the treatment of HGD/IMC, low-grade dysplasia (LGD), or indefinite for dysplasia (IND) were analyzed. DNA flow cytometry was performed on 82 formalin-fixed paraffin-embedded samples from the 45 patients, including 78 HGD/IMC, 2 LGD, and 2 IND. Eight non-dysplastic BE samples were used as controls. Three to four 60-micron thick sections were cut from each tissue block, and the area of HGD/IMC, LGD, or IND was manually dissected. Potential associations between clinicopathologic risk factors and persistent/recurrent HGD/IMC following each endoscopic session were examined using univariate and multivariate Cox models with frailty terms. Sixty (73%) of the 82 specimens showed abnormal DNA content (aneuploidy or elevated 4N fraction). These were all specimens with HGD/IMC (representing 77% of that group). Of these 60 HGD/IMC samples with abnormal DNA content, 42 (70%) were associated with subsequent development of persistent/recurrent HGD/IMC (n = 41) or esophageal adenocarcinoma (EAC; n = 1) within a mean follow-up time of 16 months (range: 1 month to 9.4 years). In contrast, only 6 (27%, all HGD/IMC) of the 22 remaining samples (all with normal DNA content) were associated with persistent/recurrent HGD/IMC. For outcome analysis per patient, 11 (24%) of the 45 patients developed persistent/recurrent HGD/IMC or EAC, despite multiple endoscopic sessions (mean: 3.6, range: 1–11). In a univariate Cox model, the presence of abnormal DNA content (hazard ratio [HR] = 3.8, p = 0.007), long BE segment ≥ 3 cm (HR = 3.4, p = 0.002), endoscopic nodularity (HR = 2.5, p = 0.042), and treatment with EMR alone (HR = 2.9, p = 0.006) were significantly associated with an increased risk for persistent/recurrent HGD/IMC or EAC. However, only abnormal DNA content (HR = 6.0, p = 0.003) and treatment with EMR alone (HR = 2.7, p = 0.047) remained as significant risk factors in a multivariate analysis. Age ≥ 60 years, gender, ethnicity, body mass index (BMI) ≥ 30 kg/m2, presence of hiatal hernia, and positive EMR lateral margin for neoplasia were not significant risk factors for persistent/recurrent HGD/IMC or EAC (p > 0.05). Three-month, 6-month, 1-year, 3-year, and 6-year adjusted probabilities of persistent/recurrent HGD/IMC or EAC in the setting of abnormal DNA content were 31%, 56%, 67%, 79%, and 83%, respectively. The corresponding probabilities in the setting of normal DNA content were 10%, 21%, 28%, 38%, and 43%, respectively. In conclusion, in BE patients with baseline HGD/IMC, both DNA content abnormality and treatment with EMR alone were significantly associated with persistent/recurrent HGD/IMC or EAC following each endoscopic session. DNA content abnormality as detected by DNA flow cytometry identifies HGD/IMC patients at highest risk for persistent/recurrent HGD/IMC or EAC, and it also serves as a diagnostic marker of HGD/IMC with an estimated sensitivity of 77%. The diagnosis of HGD/IMC in the setting of abnormal DNA content may warrant alternative treatment strategies as well as long-term follow-up with shorter surveillance intervals.

Intramucosal duodenal adenocarcinoma concomitant with Saint’s triad

Duodenal tubulovillous adenomas are rare and have malignant potential. Their successful management depends on the preoperative diagnosis and adequate excision. Endoscopic mucosal resection or submucosal dissection can control superficial tumors. Adenocarcinoma of the duodenum may originate in tubular or tubulovillous adenoma, and possible diagnostic challenges occur concerning the endoscopic biopsy findings. We report a 62-year-old female with chronic epigastric burning and a bolus sensation. Upper gastrointestinal endoscopy showed a non-ampullary duodenal tumor, and the biopsy study diagnosed a tubulovillous adenoma. Further mucosectomy revealed an intramucosal adenocarcinoma in a tubulovillous adenoma with a tumor-free pedicle. Besides the intestinal neoplasms, the patient had the diagnosis of classical Saint’s triad; and the manifestations were hiatus hernia, gallbladder disorder, and colonic diverticula. The objective is to report two scarcely described conditions and comment on controversial points of view about the concomitance of Saint’s triad and malignancy. Case reports can reduce late diagnosis, enhancing the suspicion index on rare diseases.

Retroflexion in the duodenal bulb combined with tunnel and double-clip traction: the key to successful endoscopic submucosal dissection of a malignant gastric adenoma protruding through the pylorus.

An 81-year-old man was referred for resection of a prepyloric lesion, described as a large pseudopolypoid gastric fold, with low grade dysplasia adenoma on biopsies. Examination showed a flat, centrally depressed lesion without ulceration, protruding completely through the pylorus ([Video 1]). The distal side of the lesion could not be assessed in forward view, despite the use of a transparent cap. A careful retroflexion in the bulb, with underwater examination (gastroscope GIF-H190; Olympus, Tokyo, Japan), allowed perfect visualization of the distal margin ([Fig. 1 a]). After submucosal injection of glycerol solution with indigo carmine, distal incision was carefully made in retroflexion in the duodenum, with a DualKnife J 1.5 mm (Olympus) ([Fig. 1 b]). Then, we proceeded to the proximal incision and submucosal dissection in a tunnel with visualization of the pylorus muscle arch ([Fig. 1 c]). Counter-traction was applied with two clips (Resolution 360°; Boston Scientific, Marlborough, Massachusetts, USA) and rubber band to expose the posterior edges ([Fig.1 d]). During the procedure, the axis of the counter-traction was modified to allow good exposure of the superior and anterior parts of the lesion. En bloc resection was achieved ([Fig. 2 a]). Histological examination confirmed complete resection of intestinal-type pyloric adenoma with intramucosal adenocarcinoma ([Fig. 2 b]).

Endoscopic treatment of intramucosal adenocarcinoma in hyperplastic gastric polyp

The prevalence of gastric polyps during upper gastrointestinal endoscopies is 6%, and 17% correspond to gastric hyperplastic polyps. They are usually incidentally found during upper gastrointestinal endoscopy; yet, large polyps may become symptomatic. The prevalence of gastric cancer in gastric hyperplastic polyps is 2.1%. The aim of this paper is to describe an atypical presentation of this disease with review of the literature. A 73-year-old male patient with anemia and subsequent diagnosis of early gastric cancer in a gastric hyperplastic polyp was treated with endoscopic polypectomy with endoloop.Minimally invasive treatment by endoscopic resection is sufficient in this type of patients.

Outcomes of Radiofrequency Ablation Compared to Liquid Nitrogen Spray Cryotherapy for the Eradication of Dysplasia in Barrett's Esophagus.

Current guidelines recommend endoscopic eradication therapy (EET) for Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma using either radiofrequency ablation (RFA) or liquid nitrogen spray cryotherapy (LNSC). The aims of this multicenter study are to compare the rate and number of treatment sessions of RFA vs. LNSC to achieve CE-D and CE-IM and assess outcomes for those who switched therapy. This is a retrospective cohort study of patients with BE undergoing EET. Demographics, baseline variables, endoscopy details, and histology information were abstracted. One hundred and sixty-two patients were included in this study with 100 patients in the RFA group and 62 patients in the LNSC group. The rate of CE-D and CE-IM did not differ between the RFA group and LNSC group (81% vs. 71.0%, p = 0.14) and (64% vs. 66%, p = 0.78), respectively. The number of sessions to achieve CE-D and CE-IM was higher with LNSC compared to RFA (4.2 vs. 3.2, p = 0.05) and (4.8 vs. 3.5, p = 0.04), respectively. The likelihood of developing recurrent dysplasia was higher among patients who did not achieve CE-IM (12%) compared to those who did achieve CE-IM (4%), p = 0.04. Similar findings were found in those who switched treatment modalities. EET is highly effective in eradication of Barrett's associated dysplasia and neoplasia.Both RFA and LNSC achieved similar rates of CE-D and CE-IM although LNSC required more sessions. Also, achievement of CE-IM was associated with less recurrence rates of dysplasia.

Impact of bariatric surgery on surveillance and treatment outcomes of Barrett's esophagus: A stage-matched cohort study.

Obesity could increase the risk of Barrett's esophagus (BE). Roux-en-Y gastric bypass (RYGB) could alter the natural course of BE. Data on BE progression after RYGB are scarce. To study endoscopic surveillance and endoscopic eradication therapy (EET) outcomes of BE in post-RYGB patients versus controls with obesity. Academic referral centers, a retrospective cohort study. Patients who underwent RYGB with biopsy-proven BE or intramucosal esophageal adenocarcinoma (IM-EAC) with an endoscopic follow-up of at least 12 months were identified from a prospectively maintained database between January 1992 and February 2019 at 3 tertiary care centers. RYGB patients were matched 1-to-2 to patients with obesity (body mass index > 30 kg/m2) by the initial BE stage at diagnosis. Surveillance and EET outcomes were compared. A total of 147 patients were included (49 RYGB and 98 BE stage-matched controls with obesity). For endoscopic surveillance, the rate of disease progression to high-grade dysplasia /IM-EAC was significantly lower in the RYGB patients than controls (2.6% versus 40.2%, respectively; P < .0001), with a comparable median follow-up time (85 months versus 80 months, respectively). This effect persisted in a multivariate analysis, with a hazard ratio of .09 (95% confidence interval, .01-.69). For EET, no difference in the rate of achieving complete remission of intestinal metaplasia was observed between the RYGB and control groups (71.2% versus 81.3%, respectively; P = .44). RYGB appears to be a protective factor for disease progression to neoplastic BE during endoscopic surveillance. However, disease progression was still observed after RYGB, warranting continuing endoscopic surveillance. EET appeared to be equally effective between RYGB patients and controls with obesity.

Radiofrequency ablation for intraductal extension of ampullary adenomatous lesions: proposal for a standardized protocol.

Background and study aims Intraductal extension of ampullary adenoma represents a challenging endoscopic issue. Intraductal radiofrequency ablation (RFA) has been recently suggested, but evidence and standardization of this technique are still lacking. This study aimed to provide a long-term evaluation of clinical efficacy and safety of intraductal RFA ablation with a standardized algorithm of treatment. Patients and methods Data were prospectively collected from consecutive patients with intraductal extension of adenomatous ampullary lesions from January 2016 to November 2018. Endpoints of the study were clinical success evaluated on histology results at the last follow-up, technical success, and adverse events assessment. Results Nine patients with intraductal (biliary ± pancreatic) extension of ampullary adenomas were treated with RFA during the study period. Histology on the papillectomy specimen confirmed intraductal involvement with low-grade dysplasia (LGD) in five cases (56 %), high-grade dysplasia (HGD) in three (33 %), and HGD with intramucosal adenocarcinoma in one patient (11 %). Additional argon plasma coagulation to ablate the adenoma on the duodenal mucosa was applied in five patients (56 %). Technical success was 100 %. One patient (11 %) with failed pancreatic stenting, developing acute pancreatitis after RFA, recovered with medical therapy. After a median follow-up of 21 months (IQR 20–31), six patients (67 %) achieved clinical success being free of recurrence, whereas one was diagnosed with persistence of adenocarcinoma, one with recurrent HGD, and one with recurrent LGD. Conclusions In our experience, intraductal RFA achieved acceptable results after a 2-year follow-up. Further studies are required to confirm our results and to select those patients most likely to respond.

Endoscopic resection of Barrett's adenocarcinoma: Intramucosal and low-risk tumours are not associated with lymph node metastases.

BackgroundSuperficial oesophageal adenocarcinoma can be resected endoscopically, but data to define a curative endoscopic resection are scarce.ObjectiveOur study aimed to assess the risk of lymph node metastasis depending on the depth of invasion and histological features of oesophageal adenocarcinoma.MethodsWe retrospectively included all patients undergoing an endoscopic resection for T1 oesophageal adenocarcinoma among seven expert centres in France in 2004–2016. Mural invasion was defined as either intramucosal or submucosal tumours; the latter were further divided into superficial submucosal (<1000 mm) and deep submucosal (>1000 mm). Absence or presence of lymphovascular invasion and/or poorly differentiated cancer (G3) defined a low‐risk or a high‐risk tumour, respectively. For submucosal tumours, invasion depth and histological features were systematically confirmed after a second dedicated histological assessment (new 2‐mm thick slices) performed by a second pathologist. Occurrence of lymph node metastasis was recorded during the follow‐up from histological or PET CT reports when an invasive procedure was not possible.ResultsIn total, 188 superficial oesophageal adenocarcinomas were included with a median follow‐up of 34 months. No lymph node metastases occurred for intramucosal oesophageal adenocarcinomas (n = 135) even with high‐risk histological features. Among submucosal oesophageal adenocarcinomas, only tumours with lymphovascular invasion or poorly differentiated cancer or with a depth of invasion >1000 μm developed lymph node metastasis tumours (n = 10/53%; 18.9%; hazard ratio 12.04). No metastatic evolution occurred under a 1000‐mm threshold for all low‐risk tumours (0/25), nor under 1200 mm (0/1) and three over this threshold (3/13%, 23.1%).ConclusionIntramucosal and low‐risk tumours with shallow submucosal invasion up to 1200 mm were not associated with lymph node metastasis during follow‐up. In case of high‐risk features and/or deep submucosal invasion, endoscopic resections are not sufficient to eliminate the risk of lymph node metastasis, and surgical oesophagectomy should be carried out. These results must be confirmed by larger prospective series.

Endoscopic management of Barrett's dysplasia and early neoplasia: efficacy, safety and long-term outcomes in a UK tertiary centre.

Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) are effective treatments for dysplastic Barrett's esophagus (BE). This study evaluates efficacy, durability and safety in a single high-volume UK tertiary centre with 15-years' experience. Prospective data were collected from Nottingham University Hospitals 2004-2019 for endotherapy of dysplastic BE or intramucosal adenocarcinoma. Procedural outcome measures include complete resection, complications and surgery rates. Efficacy outcomes include complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM), recurrence, treatment failure rates, durability of RFA, median follow up and tumor-associated mortality. A total of 319 lesions were resected; 671 RFAs were performed on 239 patients. Median age was 67 (±9.5) years, male:female ratio was 5:1 and median BE length was C3 [interquartile range (IQR): 6] M6 (IQR: 5). The most common lesion was Paris IIa (64%) with a median size of 10 mm (3-70). Final histology was adenocarcinoma in 50%. Complete resection rates were 96%. The multiband mucosectomy technique (91%) was most commonly used. The median number of RFA sessions was 3 (IQR: 2). The rates of CR-D and CR-IM were 90.4%% and 89.8% achieved after a median of 20.1 (IQR: 14) months. The most common complications: EMR was bleeding 2.2% and RFA was stricture (5.4%) requiring a median of 2 (range 1-7) dilatations. Median follow up post CR-IM/CR-D was 38 months (14-60). Metachronous lesions developed in 4.7% after CR-D and tumor-related mortality was 0.8%. Dysplasia and intestinal metaplasia-free survival at 5 years was 95 and 90%, respectively. BE endotherapy is minimally invasive, effective, safe and deliverable in a day-case setting.

A133 GASTRIC ESD: PRELIMINARY EXPERIENCE IN A TERTIARY CENTER IN QUEBEC

Abstract Background Endoscopic submucosal dissection (ESD) is an endoscopic procedure developed in Asian countries to treat early gastric cancer (EGC). Western countries have less experience with this challenging technique. Aims The goal of this study is to evaluate the effectiveness of ESD as a preliminary experience. Methods This is an unicentric retrospective study of all consecutive gastric ESD for adenomas or EGC from 07/2017 to 08/2020. The primary endpoints were en bloc and R0 resection rates. Results Nineteen patients (mean age 74.2 (54–88), sex ratio 3F/16M) and 23 lesions were included. Mean diameter was 25 mm (10–90). Treatment was previously performed in 7 cases (30.4%), by ESD (5) or EMR (2). The procedure, performed under general anaesthesia, lasted on average 148 minutes (45–412). En bloc resections were performed in 16 cases (69.6%); 5 cases (21.7%) were converted to P-EMR and there was a failure to resect the lesion because of deep invasion or perforation in 2 cases (8.7%). Pathologic examination demonstrated 2 low-grade dysplasia, 4 high-grade dysplasia and 15 adenocarcinomas: intramucosal (8), sm1 (2), sm2 (2), sm3 (1) or sm deep (2). R0 and curative resection rates were 43.5% and 39.1% respectively. The complication rate related to the procedure was 30.4% including 5 perforations and 2 delayed bleeding: all were managed endoscopically. Five patients (21.7%) underwent subsequent gastrectomy for non-curative resection (4) or failed resection (1); 3 had no residual disease on final pathology, 1 had high grade dysplasia and 1 had intramucosal adenocarcinoma. One patient went to palliative care because he was unfit for surgery. Follow-up endoscopy was completed in all 17 patients who underwent endoscopic resection (mean 10 months (2–24)). Recurrence occurred in 23.5% (4/17); all were successfully treated by another ESD. Conclusions In our preliminary experience, the rate of en bloc and R0 resection were 70% and 44%. Compared to other studies, these low en bloc and curative resection rates may be explained by technically difficult lesions during the learning curve and might improve with experience. Nevertheless, surgery has been avoided in 13/19 patients (68%) with endoscopic intervention. Funding Agencies None

Liquid nitrogen spray cryotherapy for intramucosal carcinoma and extensive gastric intestinal metaplasia with dysplasia.

Background and AimsGastric intestinal metaplasia with dysplasia (GIM-D) that is visible as a discrete limited lesion on endoscopy is readily treated using endoscopic mucosal resection or endoscopic submucosal dissection. However, there are few options for more extensive and invisible dysplasia. Ablating a wide swath of tissue with argon plasma coagulation or radiofrequency ablation can be challenging and carries risks, including postprocedure ulceration. Liquid nitrogen spray cryotherapy is an established treatment for dysplasia in Barrett’s esophagus, but its use for GIM-D has not been previously reported.MethodsThree patients with intramucosal adenocarcinoma and GIM-D underwent a total of 10 sessions of spray cryotherapy. In all cases, spray cryotherapy was performed after passing an orogastric decompression tube into the stomach for active suctioning. Ablations were performed in cycles of 20 to 40 seconds, with at least 45 seconds between cycles to allow for tissue thawing. Between 2 and 7 ablations were performed during each procedure. Before each procedure, Sydney protocol biopsy specimens were obtained. No patient reported any postprocedure adverse events.ResultsThe first patient underwent 3 sessions of spray cryotherapy; there was no evidence of GIM-D after 1 session, no evidence of gastric intestinal metaplasia after 3 sessions, and no recurrence after 29 months. The second patient underwent 5 sessions of spray cryotherapy; after 1 session there was no adenocarcinoma, and at 14 months there was only GIM-D. The third patient underwent 2 spray cryotherapy sessions, and after 1 session there was gastric intestinal metaplasia but no GIM-D.ConclusionsVery few treatment modalities exist for extensive GIM-D. We present 3 cases in which off-label spray cryotherapy was used to treat extensive high-grade dysplasia with good treatment effect and patient tolerance. This adds to the body of literature supporting spray cryotherapy as a safe, well-tolerated, and effective treatment for extensive GIM-D.

Underwater endoscopic mucosal resection of adenomas and colorectal serrated lesions: a prospective clinical study.

BackgroundUnderwater endoscopic mucosal resection (UEMR) without submucosal injection has been described as an alternative technique to the endoscopic resection of adenomas and colorectal serrated lesions. We aimed to assess the feasibility, safety, and efficacy of UEMR in a Brazilian setting.MethodsThis was a prospective observational study of consecutive patients who underwent UEMR between January and July 2019, in a single tertiary care center. Inclusion criteria were lesions without endoscopic stigmata of deep submucosal invasion in patients referred for endoscopic resection of colorectal adenomas, and serrated lesions detected in a previous colonoscopy. The following features were assessed: complete resection rate, en bloc resection rate, resection time, adverse events, and resection infeasibility.ResultsA total of 36 patients underwent UEMR for 51 colorectal lesions. The mean/median lesion size was 16.24/13 mm and the mean/median resection time was 16.97/9.19 min. Histopathology revealed the following: tubular adenoma (43.1%), tubulovillous adenoma (13.7%), serrated lesions (41.2%), and intramucosal adenocarcinoma (2%). Complete resection was achieved in 86.3% of cases; 52.9% of the lesions were removed en bloc, while 47.1% were resected in a piecemeal fashion. UEMR was feasible in 96.1% of cases and failed on 2 occasions, requiring conversion to standard endoscopic mucosal resection. Minor intraoperative bleeding occurred in 5 patients (9.8%) and only 1 presented with delayed bleeding (2%), all controlled endoscopically.ConclusionUEMR for removal of adenomas and colorectal serrated lesions was demonstrated to be feasible, safe and effective.

Endoscopic features of buried Barrett’s mucosa

Buried Barrett's mucosa is defined as intestinal metaplasia that is "buried" under the normal-appearing squamous epithelium. This can occur in Barrett's esophagus with or without previous endoscopic therapy. Dysplasia and neoplasia within buried Barrett's mucosa have also been reported. However, endoscopic features of buried Barrett's mucosa have not been described. At our tertiary referral center for Barrett's esophagus, several endoscopic features have been observed in patients who were found to have buried Barrett's mucosa on histology. These features are squamous epithelium which is (1) darker pink on white-light and darker brown on narrow-band imaging and/or (2) has a slightly raised or nodular appearance. It was also observed that either of these 2 features is frequently seen adjacent to a Barrett's mucosa island. This study aimed to (1) evaluate the diagnostic accuracy of these endoscopic features, and (2) evaluate the frequency of endoscopically identifiable buried Barrett's mucosa in patients with dysplastic Barrett's esophagus, before and after endoscopic eradication therapy. This was a retrospective analysis of a prospectively observed cohort of all cases of dysplastic Barrett's esophagus referred to St Vincent's Hospital, Melbourne. Endoscopy documentation software and histopathology reports of esophageal biopsy and EMR specimens between March 2013 and March 2019 were searched for terms "buried" or "subsquamous" Barrett's mucosa. Endoscopic reports, images, and histopathology reports of suspected buried Barrett's mucosa were then reviewed to apply the endoscopic features and correlate with the histologic diagnosis. In a cohort of 506 patients with dysplastic Barrett's esophagus, 33 (7%) patients (73% male, median age at referral 70.5 years) had buried Barrett's mucosa on histology. Twenty-seven (82%) patients had previous treatment for dysplastic Barrett's esophagus; radiofrequency in 2 (6%), EMR in 4 (12%), and both modalities in 21 (64%). Six (18%) had no previous treatment. Histologically confirmed buried Barrett's mucosa was suspected at endoscopy in 26 patients (79%). Endoscopic features were (1) darker pink or darker brown mucosa underneath squamous epithelium (24%), (2) raised areas underneath squamous mucosa (27%), and both features present concurrently (27%). These features were associated with adjacent islands of Barrett's esophagus in 48%. Forty-four cases of buried Barrett's mucosa were suspected endoscopically, and these were sampled by biopsy (50%) and EMR (50%). Buried Barrett's mucosa was confirmed in 26 cases, with a positive predictive value of endoscopic suspicion of 59%. Eighteen cases of endoscopically suspected buried Barrett's mucosa had no buried Barrett's mucosa on histology; inflammation or reflux was identified in 12 (67%) patients. Dysplasia was identified within buried Barrett's mucosa in 12 (36%) patients; 5 intramucosal adenocarcinoma, 1 high-grade dysplasia, and 6 low-grade dysplasia. Endoscopic features of buried Barrett's mucosa were observed in 11 of 12 cases harboring dysplasia or neoplasia, compared with 15 of 21 cases of buried Barrett's mucosa without dysplasia. In this retrospective analysis of prospectively observed patients with dysplastic Barrett's esophagus, buried Barrett's mucosa was identified in 7%, including treatment-naive patients. The proposed endoscopic features of buried Barrett's mucosa were seen in 79% of patients with histology confirmed disease. These endoscopic features may predict the presence of buried Barrett's mucosa, which may contain dysplasia or neoplasia. An overlap between the endoscopic features of inflammation, reflux, and buried Barrett's mucosa was observed. Future prospective studies are required to develop and validate endoscopic criteria for identifying buried Barrett's mucosa.

Comparative Outcomes of Cap Assisted Endoscopic Resection and Endoscopic Submucosal Dissection in Dysplastic Barrett’s Esophagus

Endoscopic resection is an important component of the endoscopic treatment of Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma. Endoscopic resection can be performed by cap-assisted endoscopic mucosal resection (cEMR) or endoscopic submucosal dissection (ESD). We compared the histologic outcomes of ESD vs cEMR, followed by ablation. We queried a prospectively maintained database of all patients undergoing cEMR and ESD followed by ablation at our institution from January 2006 to March 2020 and abstracted relevant demographic and clinical data. Our primary outcomes included the rate of complete remission of dysplasia (CRD): absence of dysplasia on surveillance histology, and complete remission of intestinal metaplasia (CRIM): absence of intestinal metaplasia. Our secondary outcome included complication rates. We included 537 patients in the study: 456 underwent cEMR and 81 underwent ESD. The cumulative probabilities of CRD at 2 years were 75.8% and 85.6% in the cEMR and ESD groups, respectively (P < .01). Independent predictors of CRD were as follows: ESD (hazard ratio [HR], 2.38; P < .01) and shorter BE segment length (HR, 1.11; P < .01). The cumulative probabilities of CRIM at 2 years were 59.3% and 50.6% in the cEMR and ESD groups, respectively (P > .05). The only independent predictor of CRIM was a shorter BE segment (HR, 1.16; P < .01). BE patients with dysplasia or intramucosal adenocarcinoma undergoing ESD reach CRD at higher rates than those treated with cEMR, although CRIM rates at 2 years and complication rates were similar between the 2 groups.

Long-term model of colitis-associated colorectal cancer suggests tumor spread mechanism and nature of cancer stem cells.

Although chemical-induced animal models of colorectal cancer (CRC) suggest a lot about the disease, more efforts are required to establish metastasis models. Azoxymethane (AOM) and dextran sodium sulfate (DSS)-treated (AOM/DSS) Crl:CD-1 mice were sacrificed after 10 or 20 weeks in our previous study, and most colon tumors exhibited intramucosal adenocarcinomas. Our observations were extended until 30 weeks to study a colitis-associated advanced CRC mouse model, and explore whether linker threonine-phosphorylated Smad2/3 (pSmad2/3L-Thr) immunostaining-positive cells were involved in the progressive course of colitis-associated CRC as cancer stem cells. AOM/DSS mice were sacrificed at 10, 20 and 30 weeks after AOM administration. Following the histopathological analysis, immunohistochemical staining was performed for the following markers: CD34, podoplanin, β-catenin, E-cadherin, Ki67, Bmi1 and pSmad2/3L-Thr. Compared with AOM/DSS mice at 10 and 20 weeks, submucosal tumor infiltration and tumor invasion into vessels were markedly increased at 30 weeks. In the parts of colon tumors from AOM/DSS mice, particularly in mice at 30 weeks, the positive signal of E-cadherin was clearly reduced in the cell membranes. The percentage of Ki67-positive tumor cells in mucosal areas of AOM/DSS mice was higher than that in the sites of submucosal infiltration. In mucosal areas of colon tumors, pSmad2/3L-Thr-positive cells were scattered among tumor cells. At sites of submucosal infiltration and vessel invasion of these tumors, pSmad2/3L-Thr-positive cells were also observed among tumor cells. In colon tumors from AOM/DSS mice at 30 weeks, the percentage of pSmad2/3L-Thr-positive cells among the nuclear β-catenin-positive tumor cells was higher than that among the cytoplasmic β-catenin-positive tumor cells. For both non-neoplastic and neoplastic epithelial cells, pSmad2/3L-Thr-positive cells exhibited immunohistochemical co-localization with Bmi1. The present study developed an advanced CRC mouse model that exhibited tumor infiltration into the submucosa and invasion into vessels. The present study re-confirmed the theory that pSmad2/3L-Thr-positive cells may be cancer stem cells.

Clinical significance of recurrent gastroesophageal junction intestinal metaplasia after endoscopic eradication of Barrett’s esophagus

After endoscopic eradication of Barrett's esophagus (BE), recurrence of intestinal metaplasia at the gastroesophageal junction (GEJIM) is common. The clinical significance of this finding is unclear. We assessed whether recurrent GEJIM is associated with increased risk of subsequent dysplasia and whether endoscopic treatment lowers this risk. A retrospective, multicenter, cohort study was performed of treated BE patients who achieved complete eradication of intestinal metaplasia (IM). Postablation follow-up was performed at standard intervals. Recurrent GEJIM was defined as nondysplastic IM on gastroesophageal junction biopsy specimens without endoscopic evidence of BE. Patients were categorized as "never-GEJIM," "GEJIM-observed," or "GEJIM-treated." Endoscopic treatment for recurrent GEJIM was at the endoscopists' discretion. The primary outcome was dysplasia recurrence. Analyses were performed using log-rank tests and Cox proportional hazards modeling. Six hundred thirty-three patients were analyzed; median follow-up was 47 months (interquartile range, 24-69). Most patients (81%) had high-grade dysplasia or intramucosal adenocarcinoma before treatment. Dysplasia recurrence was 2.2% per year. GEJIM-observed patients had the lowest rate of recurrence (.6%/y) followed by GEJIM-treated (2.2%/y) and never-GEJIM (2.6%/y) (log-rank P= .07). In multivariate analyses, compared with never-GEJIM, the risk of dysplasia recurrence was significantly lower in GEJIM-observed patients (adjusted hazard ratio, .19; 95% confidence interval, .05-.81) and not different in GEJIM-treated patients (adjusted hazard ratio, .81; 95% confidence interval, .39-1.67). Older age and longer initial BE length were independently associated with recurrence. Recurrent GEJIM after endoscopic eradication of BE was not associated with an increased risk of subsequent dysplasia. Future studies are warranted to determine if observation is appropriate for this finding.

S1670 A Unique Case of Neuroendocrine Tumor of the Colon Masquerading as Intramucosal Adenocarcinoma

S1670 A Unique Case of Neuroendocrine Tumor of the Colon Masquerading as Intramucosal Adenocarcinoma

S3577 A Case of Early Adenocarcinoma of Gastric Cardia

INTRODUCTION: Gastric cancer can be classified as cardia and non-cardia subtypes according to the anatomic site. One of the main etiological factors involved in the development of both cardia cancers and Esophageal adenocarcinomas (EACs) is central obesity. We discuss a case of a patient who presented with hematochezia and was diagnosed with gastric cardia adenocarcinoma. CASE DESCRIPTION/METHODS: A 60 year-old obese African American male was admitted for hematochezia and loose stools. The patient started having the symptoms 3 days before presentation after eating at a restaurant. His symptoms resolved a day after the admission. Review of symptoms was positive for acid reflux. Family and surgical history were insignificant. He drank socially and had 30 pack-year smoking history. He denied taking any medications for acid reflux and any endoscopic intervention in the past. His vitals were acceptable and physical examination including digital rectal exam was unremarkable. Hemoglobin was 13 and the rest of the blood tests, stool studies were within normal limits. Due to a history of acid reflux and hematochezia, the patient underwent endoscopic intervention. Diverticulosis was noted on colonoscopy. A 8mm nodule was noted in the cardia and biopsy was suggestive of focal high-grade dysplasia. The patient underwent EUS and Endoscopic-submucosal dissection (ESD). Histopathological findings were suggestive of early, well-differentiated, intramucosal adenocarcinoma, with extensive high-grade dysplasia. Immunostains were suggestive of infiltrating single or small groups of tumor cells (AE1, AE3); negative for vascular (CD31), lymphatic (D240), or submucosal invasion (desmin). DISCUSSION: Gastric cardia cancer may develop in patients with chronic GERD without H. pylori infection. High volume reflux content including bile acids play a major role in carcinogenesis. Our patient was a chronic smoker and never sought treatment for acid reflux. In addition to imaging studies, EUS is used for locoregional staging. ESD should be carefully considered after comprehensive pretreatment workup and staging. The common complications of ESD are pain, bleeding, and perforation. Bleeding is the most common complication. Stricture formation is common if ESD is performed at cardia as in our case. The incidence of cardia cancers and esophageal adenocarcinoma (EAC) continues to increase with chronic GERD and obesity being a common risk factor. Early endoscopic intervention can be diagnostic and curative.Figure 1Figure 2Figure 3.: Post-Endoscopic submucosal dissection.

S0405 Wide Area Transepithelial Sampling in Adjunct to Forceps Biopsy in Post Treatment Barret’s Esophagus: Increasing Diagnostic Yield

INTRODUCTION: Previous studies have shown that WATS-3D as an adjunct to both targeted and random FB increases the diagnostic yield for the detection of dysplasia. However, till date, there have been no published studies that assess the use of WATS-3D after endoscopic ablation or endoscopic mucosal resection (EMR). The aim of this study is to evaluate whether the addition of WATS-3D to standard FB would improve the yield of detecting intestinal metaplasia, dysplasia or carcinoma in patients undergoing post-ablation/EMR surveillance endoscopy and if this changes the medical management. METHODS: A single center, retrospective cohort study was conducted. Consecutive patients undergoing WATS-3D procedure after post-ablation between 2018 and 2019 with a known prior history of BE with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and/or intramucosal adenocarcinoma (IMCA) were included. Data was collected on endoscopic information, pathologic evaluation of slides, and other demographic variables. RESULTS: A total of 37 subjects with a confirmed history of BE with a prior endoscopic intervention underwent EGD with FB and WATS-3D sampling. Biopsies from FB and WATS-3D were compared: negative for dysplasia or positive for metaplasia/dysplasia (Table 2). The readings were concordant on both FB and WATS-3D in 28/37 subjects or 75.6% of the samples. One additional case was detected only by FB showing LGD, representing a yield of FB alone of 2.7%. Eight additional cases were detected only by WATS-3D. Seven of them showed intestinal metaplasia and one showed indefinite for dysplasia. This increment represents an increased yield of detected metaplasia of 350% (=7/2) with WATS-3D. The absolute increase of 7 cases of metaplasia, results in a number needed to treat (NNT) of 37/7 = 5.2. Three of those additional 8 cases detected by WATS-3D, had an increase in the interval of follow-up (Table 3). The former constitutes a change in management of 37.5% of those additional 8 cases. CONCLUSION: Our study shows that WATS-3D as an adjunct to FB increases the diagnostic yield for the detection of intestinal metaplasia in patients undergoing post-ablation/resection surveillance endoscopy by 350% (=7/2) (NNT: 5.2). In addition, WATS-3D had a direct impact of change in the medical management with closer follow up in 37.5% of those additional 8 cases. Further multicenter prospective studies are needed to evaluate the diagnostic benefit of WATS-3D in surveillance endoscopies.Table 1.: Clinical and demographic characteristics of subjects with BE (n = 37)Table 2.: Forceps biopsy and WATS-3D biopsy reads: negative for dysplasia, positive for metaplasia or dysplasiaTable 3.: Interval of follow-up and change in management

S2074 Liquid Nitrogen Spray Cryotherapy Is a Safe and Effective Treatment Modality for Extensive Gastric Intestinal Metaplasia With Dysplasia

INTRODUCTION: Gastric intestinal metaplasia with dysplasia (GIM-D) that is visible as a discrete limited lesion on endoscopy is readily treated using endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). However, there are few options for more extensive and invisible dysplasia. Ablating a wide swath of tissue with argon plasma coagulation (APC) or radiofrequency ablation (RFA) can be challenging and carry risks, including post-procedure ulceration. Liquid Nitrogen Spray Cryotherapy (LSNC) is an established treatment for dysplasia in Barrett’s esophagus, but its use for GIM-D has not been previously reported. CASE DESCRIPTION/METHODS: Three patients with GIM-D underwent a total of ten sessions of LNSC. In all cases, LNSC was performed after passing an orogastric decompression tube in the stomach for active suctioning. Ablations were performed in cycles of 20-40 seconds, with at least 45 seconds in between cycles to allow for tissue thawing. Between two to seven ablations were performed during each procedure. Prior to each procedure, Sydney protocol biopsies were obtained. No patient reported any mild, moderate, or severe post-procedure complications. Patient 1: 73-year-old with a 15 mm intramucosal adenocarcinoma in the fundus, resected using band ligation EMR. Random biopsies in the fundus demonstrated low-grade GIM-D. The patient underwent 3 sessions of LNSC throughout the fundus. There was no evidence of GIM-D after 1 session, no evidence of GIM after 3 sessions, and no recurrence after 29 months of follow up (Table 1). Patient 2: 72-year-old with pre-pyloric intramucosal adenocarcinoma, with a positive margin after ESD, extensive surrounding high-grade dysplasia (HGD) in the antrum. He underwent 5 sessions of LSNC to this area and surrounding antrum (Figure 1). After 1 session, there was no adenocarcinoma. At 14 months, there is GIM but no GIM-D. Patient 3: 71-year-old with HGD of the gastric antrum and incisura, and persistent GIM-D despite EMR. He underwent 2 sessions of LSNC over 3 months. After 1 session, there was GIM but no GIM-D. DISCUSSION: Very few treatment modalities exist for extensive GIM-D. LNSC appears to be a safe, well tolerated, and effective treatment for extensive GIM-D. Our series provides a scientific rationale to pursue larger studies evaluating LNSC for GIM-D.Table 1.: Liquid nitrogen spray cryotherapy treatment detailsFigure 1.: A. Gastric intestinal metaplasia with high grade dysplasia throughout the antrum, and ulceration at the prior resection site (*) B. Liquid nitrogen spray cryotherapy, which allows for ablation of a wide swath of the antrum.