Publications by authors named "Kenneth K Wang"

246 Publications

CT radiomic features of photodynamic priming in clinical pancreatic adenocarcinoma treatment.

Phys Med Biol 2021 Jul 14. Epub 2021 Jul 14.

Thayer School of Engineering at Dartmouth, Hanover, New Hampshire, UNITED STATES.

Photodynamic therapy (PDT) offers localized focal ablation in unresectable pancreatic tumors while tissues surrounding the treatment volume experience a lower light dose, termed photodynamic priming (PDP). While PDP does not cause tissue damage, it has been demonstrated to promote vascular permeability, improve drug delivery, alleviate tumor cell density, and reduce desmoplasia and the resultant internal pressure in pre-clinical evaluation. Preclinical data supports PDP as a neoadjuvant therapy beneficial to subsequent chemotherapy or immunotherapy, yet it is challenging to quantify PDP effects in clinical treatment without additional imaging and testing. This study investigated the potential of radiomic analysis using CT scans acquired before and after PDT to identify areas experiencing PDT-induced necrosis as well as quantify PDP effects in the surrounding tissues. A total of 235 CT tumor slices from 7 patients undergoing PDT for pancreatic tumors were examined. Radiomic features assessed included intensity metrics (CT number in Hounsfield Units) and texture analysis using several Gray-Level Co-Occurrence Matrix (GLCM) parameters. Pre-treatment scans of tumor areas that resulted in PDT-induced necrosis showed statistically significant differences in intensity and texture-based features that could be used to predict the regions that did respond (paired t-test, response vs no response, p < 0.001). Evaluation of PDP effects on the surrounding tissues also demonstrated statistically significant differences, in tumor mean value, standard deviation, and GLCM parameters of contrast, dissimilarity and homogeneity (t-test, pre vs post, p < 0.001). Using leave-one-out cross validation, six intensity and texture-based features were combined into a support-vector machine model which demonstrated reliable prediction of treatment effects for 6 out of 7 patients (ROC curve, AUC = 0.93). This study provides pilot evidence that texture features extracted from CT scans could be utilized as an effective clinical diagnostic prediction and assessment of PDT and PDP effects in pancreatic tumors. (clinical trial NCT03033225).
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http://dx.doi.org/10.1088/1361-6560/ac1458DOI Listing
July 2021

Comparative Cost Effectiveness of Reflux-Based and Reflux-Independent Strategies for Barrett's Esophagus Screening.

Am J Gastroenterol 2021 Jun 9. Epub 2021 Jun 9.

Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: Minimally invasive tests for Barrett's esophagus (BE) detection have raised the prospect of broader nonreflux-based testing. Cost-effectiveness studies have largely studied men aged 50 years with chronic gastroesophageal reflux disease (GERD) symptoms. We evaluated the comparative cost effectiveness of BE screening tests in GERD-based and GERD-independent testing scenarios.

Methods: Markov modeling was performed in 3 scenarios in 50 years old individuals: (i) White men with chronic GERD (GERD-based); (ii) GERD-independent (all races, men and women), BE prevalence 1.6%; and (iii) GERD-independent, BE prevalence 5%. The simulation compared multiple screening strategies with no screening: sedated endoscopy (sEGD), transnasal endoscopy, swallowable esophageal cell collection devices with biomarkers, and exhaled volatile organic compounds. A hypothetical cohort of 500,000 individuals followed for 40 years using a willingness to pay threshold of $100,000 per quality-adjusted life year (QALY) was simulated. Incremental cost-effectiveness ratios (ICERs) comparing each strategy with no screening and comparing screening strategies with each other were calculated.

Results: In both GERD-independent scenarios, most non-sEGD BE screening tests were cost effective. Swallowable esophageal cell collection devices with biomarkers were cost effective (<$35,000/QALY) and were the optimal screening tests in all scenarios. Exhaled volatile organic compounds had the highest ICERs in all scenarios. ICERs were low (<$25,000/QALY) for all tests in the GERD-based scenario, and all non-sEGD tests dominated no screening. ICERs were sensitive to BE prevalence and test costs.

Discussion: Minimally invasive nonendoscopic tests may make GERD-independent BE screening cost effective. Participation rates for these strategies need to be studied.
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http://dx.doi.org/10.14309/ajg.0000000000001336DOI Listing
June 2021

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

Surg Obes Relat Dis 2021 Aug 28;17(8):1457-1464. Epub 2021 Apr 28.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: 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.

Objectives: To study endoscopic surveillance and endoscopic eradication therapy (EET) outcomes of BE in post-RYGB patients versus controls with obesity.

Setting: Academic referral centers, a retrospective cohort study.

Methods: 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/m) by the initial BE stage at diagnosis. Surveillance and EET outcomes were compared.

Results: 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).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.soard.2021.04.018DOI Listing
August 2021

Validation of a methylated DNA marker panel for the nonendoscopic detection of Barrett's esophagus in a multisite case-control study.

Gastrointest Endosc 2021 Apr 20. Epub 2021 Apr 20.

Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background And Aims: We previously identified a 5 methylated DNA marker (MDM) panel for the detection of nonendoscopic Barrett's esophagus (BE). In this study, we aimed to recalibrate the performance of the 5 MDM panel using a simplified assay in a training cohort, validate the panel in an independent test cohort, and explore the accuracy of an MDM panel with only 3 markers.

Methods: Participants were recruited from 3 medical centers. The sponge on a string device (EsophaCap; CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and control subjects. A 5 MDM panel was blindly assayed using a simplified assay. Random forest modeling analysis was performed, in silico cross-validated in the training set, and then locked down, before test set analysis.

Results: The training set had 199 patients: 110 BE cases and 89 control subjects, and the test set had 89 patients: 60 BE cases and 29 control subjects. Sensitivity of the 5 MDM panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under the receiver operating characteristic curves were .96 and .97 in the training and test sets, respectively. Model accuracy was not influenced by age, sex, or smoking history. Multiple 3 MDM panels achieved similar accuracy.

Conclusions: A 5 MDM panel for BE is highly accurate in training and test sets in a blinded multisite case-control analysis using a simplified assay. This panel may be reduced to only 3 MDMs in the future. (Clinical trial registration number: NCT02560623.).
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http://dx.doi.org/10.1016/j.gie.2021.03.937DOI Listing
April 2021

Endoscopic submucosal dissection and potential cancer dissemination.

Authors:
Kenneth K Wang

Gut 2021 Mar 23. Epub 2021 Mar 23.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA

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http://dx.doi.org/10.1136/gutjnl-2020-323925DOI Listing
March 2021

Esophageal Epidermoid Metaplasia: Clinical Characteristics and Risk of Esophageal Squamous Neoplasia.

Am J Gastroenterol 2021 Jul;116(7):1533-1536

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: Esophageal epidermoid metaplasia (EEM) is a rare disease.

Methods: Patients with EEM diagnosed between 2014 and 2020 were reviewed.

Results: Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy.

Discussion: EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.
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http://dx.doi.org/10.14309/ajg.0000000000001225DOI Listing
July 2021

EUS-guided verteporfin photodynamic therapy for pancreatic cancer.

Gastrointest Endosc 2021 07 26;94(1):179-186. Epub 2021 Feb 26.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background And Aims: Locally advanced pancreatic cancer (LAPC) often causes obstruction. Verteporfin photodynamic therapy (PDT) can feasibly "debulk" the tumor more safely than noncurative surgery and has multiple advantages over older PDT agents. We aimed to assess the feasibility of EUS-guided verteporfin PDT in ablating nonresectable LAPC.

Methods: Adults with LAPC with adequate biliary drainage were prospectively enrolled. Exclusion criteria were significant metastatic disease burden, disease involving >50% duodenal or major artery circumference, and recent treatment with curative intent. CT was obtained between days -28 to 0. On day 0, verteporfin .4 mg/kg was infused 60 to 90 minutes before EUS, during which a diffuser was positioned in the tumor and delivered light at 50 J/cm for 333 seconds. CT was obtained on day 2, with adverse event monitoring occurring on days 1, 2, and 14. The primary outcome was presence of necrosis.

Results: Of 8 patients (62.5% men, mean age 65 ± 7.9 years) included in the study, 5 were staged at T3, 2 at T2, and 1 at T1. Most (n = 4) had primary lesions in the pancreatic head. Mean pretrial tumor diameter was 33.3 ± 13.4 mm. On day 2 CT, 5 lesions demonstrated a zone of necrosis measuring a mean diameter of 15.7 ± 5.5 mm; 3 cases did not develop necrosis. No adverse events were noted during the procedure or postprocedure observation period (days 1-3), and no changes in patient-reported outcomes were noted.

Conclusions: In this pilot study, EUS-guided verteporfin PDT is feasible and shows promise as a minimally invasive ablative therapy for LAPC in select patients. Tumor necrosis is visible within 48 hours after treatment. Patient enrollment and data collection are ongoing. (Clinical trial registration number: NCT03033225.).
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http://dx.doi.org/10.1016/j.gie.2021.02.027DOI Listing
July 2021

Longitudinal and Circumferential Distributions of Dysplasia and Early Neoplasia in Barrett's Esophagus: A Pooled Analysis of Three Prospective Studies.

Clin Transl Gastroenterol 2021 02 22;12(2):e00311. Epub 2021 Feb 22.

Division of Gastroenterology, Long Island Jewish Medical Center, Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, New Hyde Park, New York, USA.

Introduction: Studies have shown that dysplasia in Barrett's esophagus (BE) has a predilection for the right hemisphere. There is limited information on the longitudinal distribution. The aim was to determine both the longitudinal and circumferential distributions of dysplasia and early neoplasia from 3 prospective studies.

Methods: This is a pooled analysis from 3 prospective studies of patients with treatment-naive BE. Both circumferential and longitudinal locations (for BE segments greater than 1 cm) of dysplastic and early neoplastic lesions were recorded.

Results: A total of 177 dysplastic and early neoplastic lesions from 91 patients were included in the pooled analysis; of which 59.3% (n = 105) were seen on high-definition white light endoscopy, 29.4% (n = 52) on advanced imaging, and 11.2% (n = 20) with random biopsies. The average Prague score was C3M5. Of 157 lesions within BE segments greater than 1 cm, 49 (34.8%) lesions were in the proximal half, whereas 92 lesions (65.2%) were in the distal half (P < 0.001). The right hemisphere of the esophagus contained 55% (86/157) of the total lesions compared with 45% (71/157) for the left hemisphere (P = 0.02). This was because of the presence of high-grade dysplasia being concentrated in the right hemisphere compared with the left hemisphere (60% vs 40%, P = 0.002).

Discussion: In this pooled analysis of prospective studies, both low-grade dysplasia and high-grade dysplasia are more frequently found in the distal half of the Barrett's segment. This study confirms that the right hemisphere is a hot spot for high-grade dysplasia. Careful attention to these locations is important during surveillance endoscopy.
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http://dx.doi.org/10.14309/ctg.0000000000000311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901801PMC
February 2021

Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett's Esophagus in a Multi-Center Study.

Clin Gastroenterol Hepatol 2021 Feb 4. Epub 2021 Feb 4.

Columbia University Irving Medical Center, New York, New York.

Background & Aims: Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett's esophagus (BE) in a multi-center (5-site) clinical study.

Methods: Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-μm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE.

Results: 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ± 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ± 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE.

Conclusions: The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.
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http://dx.doi.org/10.1016/j.cgh.2021.02.008DOI Listing
February 2021

Gene expression profiles of esophageal squamous cell cancers in Hodgkin lymphoma survivors versus sporadic cases.

PLoS One 2020 21;15(12):e0243178. Epub 2020 Dec 21.

Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Hodgkin lymphoma (HL) survivors are at increased risk of developing second primary esophageal squamous cell cancer (ESCC). We aimed to gain insight in the driving events of ESCC in HL survivors (hESCC) by using RNA sequencing and NanoString profiling. Objectives were to investigate differences in RNA signaling between hESCC and sporadic ESCC (sESCC), and to look for early malignant changes in non-neoplastic esophageal tissue of HL survivors (hNN-tissue). We analyzed material of 26 hESCC cases, identified via the Dutch pathology registry (PALGA) and 17 sESCC cases from one academic institute and RNA sequencing data of 44 sESCC cases from TCGA. Gene expression profiles for the NanoString panel PanCancer IO 360 were obtained from 16/26 hESCC and four hNN-tissue, while non-neoplastic squamous tissue of four sporadic cases (sNN-tissue) served as reference profile. Hierarchical clustering, differential expression and pathway analyses were performed. Overall, the molecular profiles of hESCC and sESCC were similar. There was increased immune, HMGB1 and ILK signaling compared to sNN-tissue. The profiles of hNN-tissue were distinct from sNN-tissue, indicating early field effects in the esophagus of HL survivors. The BRCA1 pathway was upregulated in hESCC tissue, compared to hNN tissue. Analysis of expression profiles reveals overlap between hESCC and sESCC, and differences between hESCC and its surrounding hNN-tissue. Further research is required to validate our results and to investigate whether the changes observed in hNN-tissue are already detectable before development of hESCC. In the future, our findings could be used to improve hESCC patient management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243178PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751872PMC
January 2021

Epidemiology and Outcomes of Young-Onset Esophageal Adenocarcinoma: An Analysis from a Population-Based Database.

Cancer Epidemiol Biomarkers Prev 2021 01 11;30(1):142-149. Epub 2020 Dec 11.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Esophageal adenocarcinoma is a lethal cancer with rising incidence. There are limited data in younger (<50 years) patients with esophageal adenocarcinoma. We aimed to assess time trends in the incidence and outcomes of "young-onset" esophageal adenocarcinoma using a population-based database.

Methods: We queried the Surveillance, Epidemiology, and End Results 9 database to identify patients with esophageal adenocarcinoma between 1975 and 2015. Patients were stratified into three age strata: <50, 50 to 69, and ≥70 years. Staging was stratified as localized, regional, and distant. Trends in incidence, disease stage, and survival were assessed in three periods (1975-89, 1990-99, and 2000-2015). Univariate and multivariate models were created to identify predictors of mortality.

Results: Esophageal adenocarcinoma incidence has increased in patients <50 years of age, with an annual percentage change of 2.9% (95% confidence interval, 1.4%-4.4%) from 1975 to 2015. Young-onset esophageal adenocarcinoma presented at more advanced stages (regional + distant) compared with older patients (84.9% vs. 67.3%; < 0.01), with increasing proportion of advanced stages over the study period. These patients also experienced poorer 5-year esophageal adenocarcinoma-free survival compared with older patients (22.9%% vs. 29.6%; < 0.01), although this finding was attenuated on stage-stratified analysis.

Conclusions: Young-onset esophageal adenocarcinoma, while uncommon, is rising in incidence. Concerningly, the proportion of advanced disease continues to increase. Young-onset esophageal adenocarcinoma also presents at more advanced stages, resulting in poorer esophageal adenocarcinoma-free survival.

Impact: Patients with esophageal adenocarcinoma younger than 50 years present at more advanced stages with higher esophageal adenocarcinoma-specific mortality compared with older peers. Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855414PMC
January 2021

Finding Barrett's oesophagus: is there a machine learning approach in our future?

Lancet Digit Health 2020 01 23;2(1):e6-e7. Epub 2019 Dec 23.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.

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http://dx.doi.org/10.1016/S2589-7500(19)30226-2DOI Listing
January 2020

Response.

Gastrointest Endosc 2020 12;92(6):1276

Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1016/j.gie.2020.09.031DOI Listing
December 2020

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

Clin Gastroenterol Hepatol 2020 Nov 18. Epub 2020 Nov 18.

Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Rochester, Minnesota. Electronic address:

Background & Aims: 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.

Methods: 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.

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1016/j.cgh.2020.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128933PMC
November 2020

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

Gastrointest Endosc 2021 06 2;93(6):1250-1257.e3. Epub 2020 Nov 2.

Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA. Electronic address:

Background And Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.gie.2020.10.027DOI Listing
June 2021

Risk Factor Profiles Can Distinguish Esophageal Adenocarcinoma From Barrett's Esophagus.

Am J Gastroenterol 2021 01;116(1):198-201

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: It is assumed that screening risk factors for Barrett's esophagus (BE) and prevalent esophageal adenocarcinoma (EAC) are the same.

Methods: A matched case-control study comparing risk factors between EAC and BE was performed.

Results: In 1,356 patients (678 with EAC and 678 with BE), heartburn (52.7%), diabetes, hyperlipidemia, hypertension, nonalcoholic steatohepatitis, and metabolic syndrome were less common in EAC (52.7, 29.2, 45.7, 48.2, 12, and 28.5%, resp.) compared with BE (84.5, 37.6, 82.2, 64.6, 18.4, and 44.1%, P < 0.01). Mean alanine aminotransferase and HgA1c levels were also significantly lower in EAC compared with BE.

Discussion: Optimal strategies for screening for prevalent EAC may be different than that for BE.
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http://dx.doi.org/10.14309/ajg.0000000000001001DOI Listing
January 2021

Application of artificial intelligence using a novel EUS-based convolutional neural network model to identify and distinguish benign and malignant hepatic masses.

Gastrointest Endosc 2021 05 28;93(5):1121-1130.e1. Epub 2020 Aug 28.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background And Aims: Detection and characterization of focal liver lesions (FLLs) is key for optimizing treatment for patients who may have a primary hepatic cancer or metastatic disease to the liver. This is the first study to develop an EUS-based convolutional neural network (CNN) model for the purpose of identifying and classifying FLLs.

Methods: A prospective EUS database comprising cases of FLLs visualized and sampled via EUS was reviewed. Relevant still images and videos of liver parenchyma and FLLs were extracted. Patient data were then randomly distributed for the purpose of CNN model training and testing. Once a final model was created, occlusion heatmap analysis was performed to assess the ability of the EUS-CNN model to autonomously identify FLLs. The performance of the EUS-CNN for differentiating benign and malignant FLLs was also analyzed.

Results: A total of 210,685 unique EUS images from 256 patients were used to train, validate, and test the CNN model. Occlusion heatmap analyses demonstrated that the EUS-CNN model was successful in autonomously locating FLLs in 92.0% of EUS video assets. When evaluating any random still image extracted from videos or physician-captured images, the CNN model was 90% sensitive and 71% specific (area under the receiver operating characteristic [AUROC], 0.861) for classifying malignant FLLs. When evaluating full-length video assets, the EUS-CNN model was 100% sensitive and 80% specific (AUROC, 0.904) for classifying malignant FLLs.

Conclusions: This study demonstrated the capability of an EUS-CNN model to autonomously identify FLLs and to accurately classify them as either malignant or benign lesions.
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http://dx.doi.org/10.1016/j.gie.2020.08.024DOI Listing
May 2021

Outcomes of radiofrequency ablation by manual versus self-sizing circumferential balloon catheters for the treatment of dysplastic Barrett's esophagus: a multicenter comparative cohort study.

Gastrointest Endosc 2021 04 31;93(4):880-887.e1. Epub 2020 Jul 31.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background And Aims: Radiofrequency ablation (RFA) is the preferred ablative modality for treating dysplastic Barrett's esophagus. The recently introduced self-sizing circumferential ablation catheter eliminates the need for a sizing balloon. Although it enhances efficiency, outcomes have not been compared with the previous manual-sizing catheter. We evaluated the comparative safety and efficacy of these 2 ablation systems in a large, multicenter cohort.

Methods: Patients undergoing RFA at 3 tertiary care centers from 2005 to 2018 were included. Circumferential RFA was performed in a standard fashion, followed by focal RFA as needed. Outcomes were compared between the self-sizing and manual-sizing groups. The primary outcome was the rate of adverse events, including strictures, perforation, and bleeding. Secondary outcomes were procedure time and treatment efficacy, as assessed by rates and time to complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM).

Results: Three hundred eighteen patients were included, 90 (28.3%) treated with the self-sizing catheter and 228 (71.7%) with the manual-sizing catheter. Twenty-one patients (6.6%) developed strictures (8 [8.9%] in the self-sizing group and 13 [5.7%] in the manual-sizing group, P = .32). Of the self-sizing strictures, 75% occurred at the 12J dose before widespread adoption of the current 10J treatment standard. One patient developed bleeding, and no perforations were encountered. Procedure time was significantly shorter in the self-sizing group. No significant differences were observed in rates of and time to CE-D and CE-IM.

Conclusions: These findings suggest that both systems are comparable in safety and efficacy. The use of the self-sizing system may enhance the efficiency of RFA for treating dysplastic Barrett's esophagus.
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http://dx.doi.org/10.1016/j.gie.2020.07.056DOI Listing
April 2021

Screening for Barrett's oesophagus: is now the time?

Lancet 2020 08;396(10247):292-293

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)31531-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392563PMC
August 2020

Safety and feasibility of same-day discharge after esophageal endoscopic submucosal dissection.

Gastrointest Endosc 2021 04 25;93(4):853-860. Epub 2020 Jul 25.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background And Aims: Endoscopic submucosal dissection (ESD) is used for treating early luminal GI cancers. ESD is the standard of care in Asia, where it results in multiday admissions for observation. The goal of our study was to evaluate the safety and feasibility of same-day discharge (SDD) after ESD.

Methods: This is a retrospective cohort study of adults who underwent similar esophageal ESD with a Clutch Cutter device (DP2618DT; Fujifilm) at the Mayo Clinic (Rochester, Minn, USA) from 2017 to 2019 with a single endoscopist. The primary end point was postprocedural adverse events within 7 days of ESD.

Results: Of 96 patients (75% male, mean age, 70 ± 10.3 years) undergoing a total of 140 ESDs, 85 were SDD versus 55 admissions. Of the 55 admits, 53 were discharged within 24 hours, whereas 2 were admitted for 2 to 3 days for reasons unrelated to the ESD procedure. Admissions were more likely to have a history of antiplatelet/anticoagulant use (56.4% vs 34.1%; P = .01) and higher mean American Society of Anesthesiologists (ASA) score (3.2 vs 2.9; P = .007). Admissions had larger resections (28.6 vs 20.1 mm; P < .0001) with longer procedural durations (103.4 vs 62 minutes; P < .0001). Among SDDs, no intraprocedural or postprocedural adverse events were seen. Among admissions, 1 (1.8% vs 0%; P = .39) experienced intraprocedural bleeding requiring endoscopic intervention, 1 required transfusion before discharge within 24 hours of ESD (1.8% vs 0%; P = .39), and 1 required rehospitalization and endoscopic intervention within 7 days to address an active bleed along the resection margin (1.8% vs 0%; P = .39).

Conclusions: SDD after esophageal ESD is safe and feasible. An experienced endoscopist can determine if SDD can be considered in patients with ASA physical classification status ≤2 who undergo resections off antiplatelet/anticoagulant therapy and do not experience intraprocedural adverse events.
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http://dx.doi.org/10.1016/j.gie.2020.07.037DOI Listing
April 2021

Neoplasia Detection Rate in Barrett's Esophagus and Its Impact on Missed Dysplasia: Results from a Large Population-Based Database.

Clin Gastroenterol Hepatol 2021 May 21;19(5):922-929.e1. Epub 2020 Jul 21.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background & Aims: It is a challenge to detect dysplasia in Barrett's esophagus (BE) and esophageal adenocarcinomas (EACs) are missed in 25%-33% of cases. The neoplasia detection rate (NDR), defined as the rate of high-grade dysplasia (HGD) or EAC detection during initial surveillance endoscopy, has been proposed as a quality metric for endoscopic evaluation of patients with BE. However, current estimates are from referral center cohorts, which might overestimate NDR. Effects on rates of missed dysplasia are also unknown. We analyzed data from a large cohort of patients with BE to estimate the NDR and factors associated with it, and assess the effects of the NDR on the rate of missed dysplasia.

Methods: We analyzed data from 1066 patients in the Rochester Epidemiology Project-linked medical record system, a population-based cohort of patients with BE (confirmed by review of the endoscopic and histologic reports) from 11 southeastern Minnesota counties from 1991 through 2019. Biopsies reported to contain dysplasia were confirmed by expert gastrointestinal pathologists. The NDR was calculated as the rate of HGD or EAC detected by histologic analyses of biopsies collected during the first surveillance endoscopy. Patients without HGD or EAC at their initial endoscopy (n = 391) underwent repeat endoscopy within 12 months; HGD or EAC detected at the repeat endoscopy were considered to be missed on index endoscopy. Factors associated with NDR and missed dysplasia were identified using univariate and multivariate logistic regression models.

Results: The NDR was 4.9% (95% CI, 3.8-6.4); 3.1% of patients had HGD, 1.8% had EAC, and 10.6% had low-grade dysplasia. Factors associated with higher rates of detection of neoplasia included older age, male sex, smoking, increasing length of BE, and surveillance endoscopies by gastroenterologists. This NDR was associated with a substantially lower rate of missed dysplasia (13%).

Conclusions: In an analysis of 1066 patients with BE in a population-based cohort, we found a lower NDR and lower rate of missed dysplasia than previously reported. NDR may have value as a quality metric in BE surveillance if validated in other cohorts.
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http://dx.doi.org/10.1016/j.cgh.2020.07.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854811PMC
May 2021

Accurate Nonendoscopic Detection of Barrett's Esophagus by Methylated DNA Markers: A Multisite Case Control Study.

Am J Gastroenterol 2020 08;115(8):1201-1209

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester Minnesota, USA.

Introduction: Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay.

Methods: BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation.

Results: Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4-9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%-96%) and 94% (95% confidence interval 87%-98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median [interquartile range] tolerability 2 [0, 4] on 10 scale grading), and 95% preferred SOS over endoscopy.

Discussion: Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.
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http://dx.doi.org/10.14309/ajg.0000000000000656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415629PMC
August 2020

Notch Signaling Mediates Differentiation in Barrett's Esophagus and Promotes Progression to Adenocarcinoma.

Gastroenterology 2020 08 20;159(2):575-590. Epub 2020 Apr 20.

Department of Medicine, Columbia University Irving Medical Center, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York.

Background & Aims: Studies are needed to determine the mechanism by which Barrett's esophagus (BE) progresses to esophageal adenocarcinoma (EAC). Notch signaling maintains stem cells in the gastrointestinal tract and is dysregulated during carcinogenesis. We explored the relationship between Notch signaling and goblet cell maturation, a feature of BE, during EAC pathogenesis.

Methods: We measured goblet cell density and levels of Notch messenger RNAs in BE tissues from 164 patients, with and without dysplasia or EAC, enrolled in a multicenter study. We analyzed the effects of conditional expression of an activated form of NOTCH2 (pL2.Lgr5.N2IC), conditional deletion of NOTCH2 (pL2.Lgr5.N2fl/fl), or loss of nuclear factor κB (NF-κB) (pL2.Lgr5.p65fl/fl), in Lgr5 (progenitor) cells in L2-IL1B mice (which overexpress interleukin 1 beta in esophagus and squamous forestomach and are used as a model of BE). We collected esophageal and stomach tissues and performed histology, immunohistochemistry, flow cytometry, transcriptome, and real-time polymerase chain reaction analyses. Cardia and forestomach tissues from mice were cultured as organoids and incubated with inhibitors of Notch or NF-kB.

Results: Progression of BE to EAC was associated with a significant reduction in goblet cell density comparing nondysplastic regions of tissues from patients; there was an inverse correlation between goblet cell density and levels of NOTCH3 and JAG2 messenger RNA. In mice, expression of the activated intracellular form of NOTCH2 in Lgr5 cells reduced goblet-like cell maturation, increased crypt fission, and accelerated the development of tumors in the squamocolumnar junction. Mice with deletion of NOTCH2 from Lgr5 cells had increased maturation of goblet-like cells, reduced crypt fission, and developed fewer tumors. Esophageal tissues from in pL2.Lgr5.N2IC mice had increased levels of RelA (which encodes the p65 unit of NF-κB) compared to tissues from L2-IL1B mice, and we found evidence of increased NF-κB activity in Lgr5 cells. Esophageal tissues from pL2.Lgr5.p65fl/fl mice had lower inflammation and metaplasia scores than pL2.Lgr5.N2IC mice. In organoids derived from pL2-IL1B mice, the NF-κB inhibitor JSH-23 reduced cell survival and proliferation.

Conclusions: Notch signaling contributes to activation of NF-κB and regulates differentiation of gastric cardia progenitor cells in a mouse model of BE. In human esophageal tissues, progression of BE to EAC was associated with reduced goblet cell density and increased levels of Notch expression. Strategies to block this pathway might be developed to prevent EAC in patients with BE.
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http://dx.doi.org/10.1053/j.gastro.2020.04.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484392PMC
August 2020

Risk factors for serious adverse events associated with multiband mucosectomy in Barrett's esophagus: an international multicenter analysis of 3827 endoscopic resection procedures.

Gastrointest Endosc 2020 08 30;92(2):259-268.e2. Epub 2020 Mar 30.

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Background And Aims: Multiband mucosectomy (MBM) is a widely used technique for the treatment of Barrett's esophagus (BE). However, large multicenter studies enabling a generalizable estimation of the risk of serious adverse events, such as perforation and postprocedural bleeding, are lacking. The aim of this study was to estimate the rate of, and risk factors for, serious adverse events associated with MBM.

Methods: In this retrospective analysis, consecutive patients who underwent MBM for treatment of BE in 14 tertiary referral centers in Europe, the United States, Canada, and Australia were included. Primary outcomes were perforation and postprocedural bleeding rate. Potential risk factors were identified by logistic regression.

Results: Between 2001 and 2016, a total of 3827 MBM procedures were performed in 2447 patients (84% male, mean age 66 years, median BE length C2M4). Perforation occurred in 17 procedures (0.4%; 95% confidence interval [CI], 0.3-0.7), of which 15 could be treated endoscopically or conservatively. Female gender was an independent risk factor for perforation (odds ratio [OR], 2.77; 95% CI, 1.02-7.57; P = .05). Postprocedural bleeding occurred after 35 procedures (0.9%; 95% CI, 0.6-1.3). The number of resections (OR, 1.15; 95% CI, 1.06-1.25; P < .001) was significantly associated with postprocedural bleeding.

Conclusion: The results of this study show that MBM for BE is safe with a low risk of serious adverse events. In addition, most of the adverse events could be managed endoscopically or conservatively. The number of resections was an independent risk factor for postprocedural bleeding.
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http://dx.doi.org/10.1016/j.gie.2020.03.3842DOI Listing
August 2020

Development and Pilot Testing of Decision Aid for Shared Decision Making in Barrett's Esophagus With Low-Grade Dysplasia.

J Clin Gastroenterol 2021 01;55(1):36-42

Division of Gastroenterology and Hepatology.

Goals: To develop an encounter decision aid [Barrett's esophagus Choice (BE-Choice)] for patients and clinicians to engage in shared decision making (SDM) for management of BE with low-grade dysplasia (BE-LGD) and assess its impact on patient-important outcomes.

Background: Currently, there are 2 strategies for management of BE-LGD-endoscopic surveillance and ablation. SDM can help patients decide on their preferred management option.

Study: Phase-I: Patients and clinicians were engaged in a user-centered design approach to develop BE-Choice. Phase-I included review of evidence on BE-LGD management, observation of usual care (UC), creation, field-testing, and iterative development of BE-Choice in clinical settings. Phase-II: Impact of BE-Choice on patient-important outcomes (patient knowledge, decisional conflict, and patient involvement in decision making) was assessed using a controlled before-after study design (UC vs. BE-Choice).

Results: Phase-I: Initial prototype was designed with observation of 8 clinical encounters. With field-testing, 3 successive iterations were made before finalizing BE-Choice. BE-Choice was paper based and fulfilled the qualifying criteria of International patient decision aid standards. Phase II: 29 patients were enrolled, 8 to UC and 21 to BE-Choice. Compared with UC, use of BE-Choice improved patient knowledge (90.4% vs. 70.5%; P=0.03), decisional comfort (89.6 vs. 71.9; P=0.01), and patient involvement (OPTION score: 27.1 vs. 19.2; P=0.01).

Conclusions: BE-Choice is a feasible and effective decision aid to promote SDM in the management of BE-LGD. On pilot testing, BE-Choice had promising impact on patient-important outcomes. A larger multicenter trial is needed to confirm our results and promote widespread use of BE-Choice.
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http://dx.doi.org/10.1097/MCG.0000000000001319DOI Listing
January 2021

How I Treat Patients With Barrett Esophagus When Endoscopic Ablation Fails.

Authors:
Kenneth K Wang

Gastroenterol Hepatol (N Y) 2020 Feb;16(2):82-87

Director, Esophageal Neoplasia Clinic Director, Barrett's Esophagus Unit Russ and Kathy Van Cleve Professor of Gastroenterology Research Mayo Clinic Rochester, Minnesota.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132674PMC
February 2020

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

Gastrointest Endosc 2020 07 15;92(1):31-39.e1. Epub 2020 Jan 15.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background And Aims: The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival.

Methods: Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival.

Results: One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival.

Conclusions: In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.
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http://dx.doi.org/10.1016/j.gie.2020.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321863PMC
July 2020

Photodynamic Therapy for Gastrointestinal Cancer.

Photochem Photobiol 2020 05 17;96(3):517-523. Epub 2020 Mar 17.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.

The clinical application of photodynamic therapy (PDT) for gastrointestinal (GI) neoplastic lesions has been developed with appreciation for the great efforts and kind support of Dr. Tom Dougherty and his followers' contributions. There are several published studies on clinical PDT in the field of GI oncology. Esophageal cancer was one of the first clinical indications for PDT that was approved as an endoscopic procedure in both the United States and Japan. PDT was initially used as a palliative local treatment for patients with obstructive esophageal cancer. PDT is also indicated for eradicative therapy for dysplastic Barret's esophagus, which is the precursor state of esophageal adenocarcinoma, with the support of level one evidence. In Japan, PDT was approved as a curative treatment for superficial esophageal carcinoma lesions, which are difficult to treat with endoscopic resection. Further, PDT using second-generation photosensitizers is approved for early local failure after radiotherapy, for which treatment with other modalities is difficult. PDT has also been assessed in other GI cancers, including gastric cancer, biliary cancer and pancreatic cancer. In this review, we overview the history and state of PDT for GI cancer.
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http://dx.doi.org/10.1111/php.13206DOI Listing
May 2020

Safety and histologic outcomes of endoscopic submucosal dissection with a novel articulating knife for esophageal neoplasia.

Gastrointest Endosc 2020 04 20;91(4):797-805. Epub 2019 Dec 20.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Background And Aims: Treatment of large esophageal neoplasia is gradually evolving from piecemeal to en bloc resections. Endoscopic submucosal dissection (ESD) is known to achieve more complete resections than piecemeal EMR for large lesions, yet it remains underused in the West because of technical and safety concerns with traditional electrosurgical knives. We aimed to evaluate a novel endoscopic articulating knife used with ESD (ESD-AR) to determine its safety and efficacy for large esophageal neoplasms in comparison with EMR.

Methods: We retrospectively studied clinically indicated cases of ESD-AR and EMR for esophageal lesions that were 15 mm or greater. All EMR cases had at least 3 simultaneous EMRs to adequately compare resection area. Rates of perforation, GI bleeding, technical performance, and pre- and postendoscopic resection diagnoses were evaluated.

Results: Seventy-two ESD-AR and 72 widespread EMR cases were evaluated for Barrett's esophagus (56%), adenocarcinoma (36%), squamous nodularity (2%), and squamous cell carcinoma (6%). There were no statistical differences in age, sex, Barrett's esophagus length, and lesion or resection size between the 2 groups. No perforations occurred. Two adverse events were recorded with ESD-AR and none with EMR (3% vs 0%, P = .50); these were associated with anticoagulation use (P = .04) and greater resection area (P = .02). There were more upgraded diagnoses post-ESD versus EMR (27% vs 12%, P = .05).

Conclusions: ESD-AR by an experienced endoscopist has a comparable safety profile with widespread EMR for large esophageal neoplasia and may have advantages for diagnostic staging.
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http://dx.doi.org/10.1016/j.gie.2019.12.016DOI Listing
April 2020

Clinical impact of celiac ganglia metastasis upon pancreatic ductal adenocarcinoma.

Pancreatology 2020 Jan 14;20(1):110-115. Epub 2019 Nov 14.

Division of Gastroenterology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Electronic address:

Background: Pre-operative staging of pancreatic adenocarcinoma guides clinical decision making. Limited data indicate that metastasis to celiac ganglia (CG) correlates with poor prognosis. We investigated feasibility and safety of endoscopic ultrasound fine needle aspiration (EUS-FNA) detection of CG metastasis and its impact upon tumor stage, resectability, and survival in pancreatic ductal adenocarcinoma (PDAC).

Patients: We reviewed our prospectively maintained EUS and cytopathology databases to identify patients with FNA proven CG metastasis in patients with PDAC from 2004 to 2017. Clinical demographics, EUS, CT, MRI, cytopathology, cancer stage, and resectability data were analyzed. Survival of PDAC patients with CG metastasis was compared to the expected survival of PDAC patients of similar stage as reported by the United States National Cancer Database.

Results: Twenty-one patients with PDAC [median age 73 (IQR63-78); 14 (67%) female)], had CG metastasis confirmed by cytopathologic assessment. CG metastasis resulted in tumor upstaging relative to other EUS findings and cross sectional imaging findings in 12 (57%) and 15 (71%) patients, and converted cancers from resectable to unresectable relative to EUS and cross sectional imaging in 7 (37%) and 7 (37%) patients, respectively. In patients with PDAC, the survival of patients with CG metastasis was not significantly different from the overall survival (hazard ratio 0.71; 95% confidence interval 0.44, 1.13; p = 0.15).

Conclusions: EUS-FNA may safely identify CG metastases. While CG metastasis upstaged and altered the resectability status among this cohort of patients with PDAC, the survival data with regard to PDAC suggest that this may be misguided.
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http://dx.doi.org/10.1016/j.pan.2019.11.003DOI Listing
January 2020