Low-grade Dysplasia Research Articles

Tissue factor (TF) and factor VII/TF ratio (fVIIa:TF) as potential indicators of malignancy in pancreatic cystic lesions.

669 Background: Premalignant pancreatic cellular genotype may remain stable for many years, but compounding conditions can produce rapid malignant cellular transformation. This onset is rarely spontaneous and is often associated with the presence of inflammation. One inflammatory modulator is “tissue factor (TF),” which usually acts in complex with “coagulation factor VIIa (fVIIa)” to initiate coagulation. The role of TF in malignancy and its impact beyond thrombosis on cell proliferation, angiogenesis, and metastasis is well established. This suggests that TF may be a diagnostic marker in the inflammatory microenvironment of the precursor lesions of pancreatic cancer. Aim: To examine the potential of TF concentrations and the fVII:TF ratio within pancreatic cyst fluid as indicators of malignant cellular transformation from benign to malignant. Methods: Cyst fluid was prospectively collected from 31 patients with pancreatic cystic lesions (REC 18/LO/0736) and analysed in a blinded fashion. The level of TF and fVIIa proteins were measured by ELISA, and the fVIIa:TF ratios calculated. A cut-off value for TF concentration was determined using a ROC curve and compared to the conventional assessment parameters, including radiological features, carcinoembryonic antigen (CEA) and amylase. Results: Patients were categorised into four groups based on histology. Significant histological stage-dependent increases in TF level were observed, which corresponded to the progression of the normal ductal epithelium to invasive adenocarcinoma. The mean TF concentration was significantly higher ( p= 0.006) in the high-risk group (high-grade dysplasia & malignant; 1.17 ng/ml, 95% CI 0.68, 1.67) vs the low-risk group (benign & low-grade dysplasia; 0.27 ng/ml, 95% CI 0.1, 0.44). A strong positive correlation between TF concentration and the high-risk group was observed (correlation coefficient 0.746, p < 0.001, the cut-off value for TF 0.75 ng/ml, AUC 0.877, p= 0.002). In addition, the fVIIa:TF ratio, was marginally lower ( p= 0.274) in the high-risk group (mean = 84.82 [95% CI 0, 185.04]) vs the low-risk group (mean = 437.46 [95% CI 0, 901.02]). TF concentrations performed consistently better as an indicator of malignant transformation when compared to the conventional parameters and will be presented at the meeting. Conclusions: Cyst-associated TF levels appear to correlate with the cytological progression to the malignant phenotype, while the fVIIa:TF ratio indicates a breakdown in the ability of the body to contain the disease. Such indicators may allow better presurgical discrimination of malignant potential of tumours and offer a more nuanced tool for monitoring indeterminate cystic lesions. Further work is needed with a larger cohort to confirm these findings.

Evaluation of Tofacitinib in Primary Sclerosing Cholangitis and Associated Colitis: A Multicenter, Retrospective Study

Evaluation of Tofacitinib in Primary Sclerosing Cholangitis and Associated Colitis: A Multicenter, Retrospective Study

P571 Frequency and risk factors of advanced neoplasia in Korean IBD patients with Low Grade Dysplasia in previous surveillance

Abstract Background There are insufficient studies on clinical outcome after surveillance of low grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD). We aimed to evaluate the clinical feature, frequency and risk factors of advanced neoplasia in IBD patients after diagnosis of LGD Methods From 2003 to 2020, medical records of 166 IBD patients from 6 university hospitals in Korea were reviewed retrospectively. All of the patients were diagnosed as LGD in surveillance. Patents’ baseline characteristics, disease status, polyp characteristics and treatment were evaluated. The frequency and risk factors of advanced neoplasia were also analyzed. Results Disease duration was 11.47 years (7.85-14.50), and follow-up duration was 3.74 years (1.95-7.58). Colitis associated LGD was noted in 56 cases (33.7%), Advanced neoplasia developed in 12 cases (6 large LGD, 3 tubulovillous adenoma, 3 high grade dysplasia) and all the cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo score and colitis-related dysplasia were more common than sporadic lesions (83.3% vs. 29.9%; P<0.001). In multivariate analysis, colitis-associated LGD significantly increased the risk of developing advanced neoplasia (Odds ratio [OR], 10.516; 95% confidence interval [CI], 2.064-53.577; P=0.005). Among patients with colitis-associated lesions, a significant risk factor for advanced neoplasia was a history of LGD (OR, 9.429; 95% CI, 1.330-66.863; P=0.025). Conclusion Advanced neoplasia developed in 7.2% of IBD patients with LGD. Because most of advanced neoplasia developed from colitis-associated lesions, more careful examination is suggested in patients with colitis -associated LGD, especially with previous history, in surveillance colonoscopy.

Incidence of Gastric Neoplasms Arising from Autoimmune Metaplastic Atrophic Gastritis: A Systematic Review and Case Reports.

Autoimmune metaplastic atrophic gastritis (AMAG) is associated with an increased risk of gastric neoplasms. This study aimed to systematically analyze the incidence rate of gastric cancer (GC), low-grade dysplasia (LGD) and type-1 gastric neuroendocrine tumor (gNETs) development in AMAG adults. Studies on AMAG patients reporting the incidence of gastric neoplasms was identified through a systematic search in PUBMED and EMBASE. Study quality was assessed using the Joanna Briggs Institute quality assessment tool. Incidence rates of GC, LGD and type-1 gNETs were examined by meta-analysis. Thirteen studies met eligibility criteria. Incidence rate of gastric cancer calculated from the pooled data was 0.14% per person-year in both single-center studies and national registration studies. Meta-analysis showed a relative risk of 11.05 (95% CI: 6.39-19.11) for gastric cancer development in AMAG patients. The calculated pooled gastric LGD and type-1 gNETs incidence rates were 0.52% and 0.83% per person-year, respectively. As for experience from our center, we presented three distinctive cases of gastric neoplasm arising from the background of AMAG. This study underscores the potential for malignant transformation of precancerous lesions and reiterates the importance of careful esophagogastroduodenoscopy screening.

P164 Dysplasia detection rates in a surveillance program real-world data from a tertiary referral center for inflammatory bowel diseases

Abstract Background Patients with inflammatory bowel diseases (IBD) with an increased risk of developing colorectal carcinoma should undergo periodic surveillance colonoscopies. There is no quality metric for dysplasia detection rate (DDR) in IBD surveillance. We evaluated DDR in a dedicated surveillance program at a tertiary IBD referral center. Methods This cross-sectional study assessed DDR among consecutive patients with quiescent colitis enrolled in our surveillance program. Patients underwent high-definition colonoscopy with dye chromoendoscopy (DCE). A single specialized operator performed the procedures. Advanced dysplasia (AD) was defined as low-grade dysplasia ≥ 10mm, high-grade dysplasia, or colorectal cancer. We evaluated risk factors for dysplasia detection. Results Overall, 119 patients [female: 39.5%; median age: 54 years (IQR 43-66); median disease duration: 20 years (IQR 14-29)] underwent 151 procedures that revealed 206 lesions, of which 40 were dysplastic, and seven were considered AD. Per-procedure and per-lesion DDR were: 20.5%, and 19.4%, respectively. Per-procedure AD detection rate (ADDR) was 4.6%. Per-procedure dysplasia detection was associated with increased age at diagnosis at the index colonoscopy and past dysplasia or indefinite dysplasia, however, on multivariable analysis, only past dysplasia or indefinite dysplasia maintained a significant association (AdjOR 4.84, 95% CI 1.52-15.45, p=0.008). A Kudo pit pattern of II-V had a sensitivity of 92.5% for per-lesion dysplasia detection but a false positive rate of 64.8% (p<0.001). Conclusion DDR in a dedicated surveillance program in a real-world setting reached 20%. DDR should be considered a quality measure while surveying high-risk patients with IBD.

P362 Systematic review: Oncological outcomes of patients with Inflammatory Bowel Disease undergoing segmental colonic resections for colorectal cancer and dysplasia

Abstract Background Current international guidelines recommend that patients with inflammatory bowel disease (IBD) diagnosed with high grade dysplasia (HGD), or colorectal cancer undergo a proctocolectomy, and that proctocolectomy is considered within a shared decision-making framework with the patient in cases of low grade (LGD) or indeterminate (IND) dysplasia. However, segmental colectomy (surgical resection leaving remaining colon or rectum) is considered by some as a valid alternative, with less physiological stress, stoma avoidance and thus acceptability to patients. This systematic review aims to assess oncological and post-operative outcomes in studies reporting on segmental colectomy or proctocolectomy for patients with IBD and colonic or rectal dysplasia and cancer. Methods This systematic review was prospectively registered with PROSPERO (CRD42021292891) and carried out in line with the PRISMA guidelines. Studies published between 1990 and 2022 reporting on oncological and surgical outcomes of adult patients undergoing segmental resection and/or proctocolectomy that included at least three cases of neoplasia were included. Descriptive statistics were used in the context of significant heterogeneity. A meta-analysis was performed for outcomes with at least three results. Results The search returned 2178 results, and after screening 12 studies were included in the final analysis. A total 12,701 patients were included reporting on outcomes of 10,386 segmental resections and 2,315 proctocolectomies. The pooled incidence of missed synchronous cancers (i.e. identified in remaining colon or rectum within 6 months of surgery) in the segmental resection group was 1.4%, and dysplasia 0.5%; metachronous cancer recurrence was 1.4% (1.1% in subtotal colectomy, 11.8% in any other segmental resection), and dysplasia recurrence 5.3% (4.7% in subtotal colectomy, 7.5% in any other segmental). Average time to recurrence for metachronous cancer was 6.5 years. Recurrence of metastatic cancer was 0.2% for proctocolectomy, and 0.1% for segmental resection (OR 1.28, 95% CI 0.19 - 8.65, p =ns). Conclusion Segmental colectomy does not disadvantage against metastatic cancer recurrence. The incidence of missed synchronous lesions is low. There is increased metachronous cancer risk, however this is mitigated by subtotal colectomy. These results may help to counsel patients regarding the risks and benefits of segmental resection for IBD-related dysplasia and cancer. The risk of metachronous cancer after segmental resection reiterates the need for enhanced high quality post-operative surveillance. The paucity of data in this field is also demonstrated here by the high inter-study heterogeneity, highlighting the need for prospective studies.

P327 Characteristics of esophago-gastro-duodenal Crohn’s disease in the biologic era: a nationwide study of the Young GETECCU Group

Abstract Background There is scarce information about Crohn’s disease (CD) affecting oesophagus, stomach and duodenum. The aim of the study was to describe phenotypic features, disease course and treatment response in these patients. Methods Patients with CD and upper involvement (oesophagus, stomach and/or duodenum) were included (upper CD=UCD). Extensive CD (ECD) was defined as concomitant distal involvement (jejunal, ileal and/or colonic). A multicentric, longitudinal and retrospective study was designed to evaluate disease characteristics at diagnosis and behaviour of UCD in patients >= 18 years between January 2000 and December 2019 with at least 1 year follow-up since diagnosis. All treatments for UCD diagnosis and reason to start them were recorded, as well as 14- and 52-week response. Incidence of malignancy was also evaluated. Descriptive statistics were applied for quantitative and qualitative variables. Exact Fisher test was used for comparison of proportions. Results 197 (0.9%) UCD among 21.670 patients with Crohn’s Disease (CD) from 28 Spanish centres were included with a median of 10.7 years follow-up (min 2.2– max 22.1). Nearly 55% were men: median age at CD diagnosis was 29 years whereas for UCD was 32 years, with a mean of 2 months between CD and UCD diagnosis (SD 0.4). Only 9 patients had isolated UCD, whereas the rest presented ECD. 97% were diagnosed by endoscopy, in 2/3 due to symptoms (epigastric pain and dyspepsia). Inflammatory phenotype was prevalent in UCD with aphthous ulcer as the main endoscopic lesion (42%). Isolated duodenal location was the most frequent, followed by the antrum. Systemic corticosteroids and thiopurines were the most used treatments after UCD diagnosis. Treatment response at 14- and 52-weeks is detailed in Figures 1 and 2. Treatment withdrawal due to UCD activity was seen in 2-11% of patients. Thiopurines was the most durable treatment (median 50 months, min 0–max 210) followed by infliximab and adalimumab. Ten patients presented phenotype change over time (90% from inflammatory to stricturing). 53% of patients underwent endoscopic control (44% due to symptoms). De novo metaplasia was detected in 3 patients, and low-grade visible dysplasia in one. Two patients developed neoplasia: 1 gastric MALT lymphoma and 1 oesophagus carcinoma 5.5 and 20 years after UCD diagnosis, respectively. Conclusion UCD in adult population is infrequent. Upper involvement does not have an impact on immunosuppressive treatment requirements, but extensive disease does, appreciating a similar response to treatments for proximal and distal disease, both in the short and medium term. Although rare, risk of malignancy in UCD exists.

P252 Solid organ transplant (with the exception of liver) in patients with inflammatory bowel disease: An ECCO CONFER Multicentre Case Series

Abstract Background There are limited data available on the course of IBD in patients with solid organ transplantation. The aim of this ECCO CONFER study was to evaluate the trend of IBD before and after solid organ transplantation but liver. Methods This was a retrospective observational multicentre study that collected cases through the CONFER project. Patients with an established IBD diagnosis who underwent a solid organ transplantation (with the exception of liver) were eligible candidates. Results 33 patients with solid organ transplantation (67% male; 55% CD) were collected from 12 referral centres in five different countries. Mean age was 53 ± 16 years. 34 organs were transplanted in 33 patients. Most of the patients underwent kidney transplantation (n=27, 82%). 4 (12%) received a heart and 1 (3%) underwent lung transplantation; 1 (3%) underwent a combined heart and kidney transplant. The mean duration of IBD was 18.4 ± 14.7 months. Clinical characteristics are summarized in Table 1. The median follow-up after transplantation was 4.3 years (IQR 3.25 – 10.7). 7/33 patients (21.2%) experienced organ rejection, with 1 kidney retransplant. Regarding immunosuppressive therapy, 29/33 patients (88%) were treated with tacrolimus, 25 (76%) with systemic steroids, 22 (67%) with mycophenolate mofetil, 11 (33%) with everolimus, 6 with cyclosporine (18%), 3 (9%) with thiopurines. Regarding biologics, 1 patient was treated with infliximab, 2 with adalimumab, 2 with vedolizumab, 1 with ustekinumab. Defining a severe IBD course the need for biologic therapy or bowel resection or hospitalization, 4 patients (11.7%) had a severe disease course after transplantation versus 3 patients (9.3%) in the first 51 months of disease before transplantation (p = 0.26). Univariate analysis is reported in Table 2. 1 case of low-grade dysplasia was found 10 years after the transplantation. 1 case of colorectal cancer was found in a patient affected by CD five years after kidney transplantation. The other cases of tumours after transplantation are reported in Table 3. The first serious infectious episode after transplantation is shown in Table 4: 17 of 33 patients (51.5%) reported at least 1 episode of serious infection. In total 29 different serious infectious episodes after transplantation were recorded, compared to 28 episodes in the pre-transplantation period. At the last follow-up visit, 6/33 (18.2%) patients had died: 1 due to cholangiocarcinoma, 1 amyloidosis, 1 heart failure, 1 myocardial infection (2 not available). Conclusion Solid organ transplantation appears to have a satisfactory course for both the transplanted organ and IBD, in terms of organ survival and IBD severity; furthermore, the use of biologics in these patients does not appear to be linked to a worse outcome.

Rectal Cancer following Local Excision of Rectal Adenomas with Low-Grade Dysplasia-A Multicenter Study.

Purpose: Rectal polyps with low-grade dysplasia (LGD) can be removed by local excision surgery (LE). It is unclear whether these lesions pose a higher risk for recurrence and cancer development and might warrant an early repeat rectal endoscopy. This study aims to assess the rectal cancer rate following local excision of LGD rectal lesions. Methods: A retrospective multicenter study including all patients that underwent LE for rectal polyps over a period of 11 years was conducted. Demographic, clinical, and surgical data of patients with LGD werecollected and analyzed. Results: Out of 274 patients that underwent LE of rectal lesions, 81 (30%) had a pathology of LGD. The mean patient age was 65 ± 11 years, and 52 (64%) were male. The mean distance from the anal verge was 7.2 ± 4.3 cm, and the average lesion was 3.2 ± 1.8 cm. Full thickness resection was achieved in 68 patients (84%), and four (5%) had involved margins for LGD. Nine patients (11%) had local recurrence and developed rectal cancer in an average time interval of 19.3 ± 14.5 months, with seven of them (78%) diagnosed less than two years after the initial LE. Seven of the nine patients were treated with another local excision, whilst one had a low anterior resection, and one was treated with radiation. The mean follow-up time was 25.3 ± 22.4 months. Conclusions: Locally resected rectal polyps with LGD may carry a significant risk of recurring and developing cancer within two years. This data suggests patients should have a closer surveillance protocol in place.

Intraductal papillary mucinous neoplasm of pancreas: Clinicopathological features and long-term survival after surgical resection

IntroductionIntraductal papillary mucinous neoplasm (IPMN) of the pancreas can progress from low-grade dysplasia to high-grade dysplasia and invasive carcinoma. MethodsIn this single-center retrospective series, we analyze the clinicopathological features and long-term follow up of patients who underwent pancreatic resection for IPMN, from January 2009 to December 2019. Results31 patients were diagnosed with IPMN: 9 males and 22 females. Mean age was 67 years. Twenty-seven patients (87%) were symptomatic. Seven patients had main duct IPMN, 11 branch-type IPMN and 13 mixed-type IPMN. High-risk stigmata were found in 20 patients (64.5%) and worrisome features in 10 patients (32.2%). Thirteen patients (41.9%) had an associated invasive carcinoma, 4 (12.9%) high-grade dysplasia and 14 (45.2%) low-grade dysplasia. The follow-up was from 2 to 12 years. Median survival for patients with IPMN and associated invasive carcinoma was 45.8 months, and disease-free survival was 40.8 months. ConclusionsIPMN had a higher prevalence in females, mostly symptomatic and high incidence of associated invasive carcinoma with branch type. The 5-year survival was good even with associated invasive carcinoma.

PENTOSAN POLYSULFATE-ASSOCIATED DYSPLASIA IN INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract BACKGROUND Pentosan polysulfate is used for symptomatic management of interstitial cystitis. At one institution we incidentally noted six patients who were on this agent and had a diagnosis of inflammatory bowel disease (IBD). Three of these patients stopped the drug and all three had clinical and/or endoscopic improvement. Three of the six patients developed multifocal dysplasia. This observation led us to evaluate the hypothesis that pentosan polysulfate is associated with dysplasia in patients with IBD. METHODS We searched the electronic medical records at two tertiary care centers to identify patients using pentosan polysulfate who had a diagnosis of Crohn’s disease or ulcerative colitis. RESULTS Thirty patients who met the search criteria were identified. Of these, 10 (33.3%) had colonic dysplasia: 8 (80%) with low-grade dysplasia and 2 (20%) with both low- and high-grade dysplasia. Of the patients with dysplasia, 6 (60%) required colectomy for endoscopically unresectable dysplasia. Following physician consultation, three patients (10%) discontinued the drug and subsequently demonstrated clinical benefit and/or achieved endoscopic healing. CONCLUSIONS Inflammatory bowel disease patients at two institutions who had taken pentosan polysulfate had high rates of colonic dysplasia leading to surgery. Patients in this cohort who stopped this agent showed improvement in their colitis. These findings raise questions about whether pentosan polysulfate may play a causal role in both the development of colitis and the observed high rate of dysplasia. If larger studies validate these findings, this would indicate a readily identifiable subset of patients who are at high risk of developing colitis-associated malignancy.

Tumor heterogeneity and carcinoma in resected specimens of gastric low-grade dysplasia: A retrospective single center study.

Lesions diagnosed as gastric low-grade dysplasia (LGD) may be pathologically upgraded to early gastric cancer (EGC) or high-grade dysplasia (HGD) after endoscopic resection (ER). In this study, we investigated the risk factors for pathological upgrades after ER and assessed the reason for these upgrades by retrospectively analyzing ER data between January 1999 and December 2019. We enrolled patients with LGD confirmed by forceps biopsy; the patients were classified into pathologically concordant (LGD) and upgraded (HGD and EGC) groups according to the pathology of their resected specimen. To determine the risk factors for upgrade, we compared the endoscopic findings of the concordant and upgraded groups via 1:1 matched case-control design. To find the reasons for discordance, all upgraded cases were pathologically re-evaluated. Among 1,643 cases of LGD, pathological upgrades were observed in 423 (25.7%) resected specimens and EGC was found in 111 (6.7%) lesions. After matching the upgraded and concordant cases, lesion sizes exceeding 1.5 cm (odds ratio (OR): 1.8; 95% CI: 1.1-3.0), mucosal nodularity (OR: 10.8; 95% CI: 5.6-21.0), heterogeneous color (OR: 3.0; 95% CI: 1.7-5.3), presence of erosion (OR: 2.7; 95% CI: 1.8-5.3), and open-type gastric atrophy (OR: 2.9; 95% CI: 1.7-4.9) were noted to be significantly associated with upgraded pathology to EGC. Among the EGC cases, 99 (89.2%) were found to have pre-existing dysplasia. In conclusion, endoscopic evaluations should be performed because of possible pathological upgrades and co-existence of carcinomas in LGDs, especially when they exhibit surface nodularity, erosion, heterogeneous color, and large size.

A model for predicting degree of malignancy in patients with intraductal papillary mucinous neoplasm.

There is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion. A retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a. Of the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model. This predictive model will help assess an individual's risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.

Current status in Barrett's esophagus

Barrett's esophagus has been an important issue in clinical medicine for many years. In the 70 s of the last century, the association between gastroesophageal reflux disease and BE was detected. Only ten years later, the association between BE and adenocarcinoma of the esophagus was reported. Starting in the 90s in Europe, endoscopic resection and ablation have seen an expanding role in the management of BE. In analogy with other diseases, patients are undergoing individualized surveillance and treatment strategies. In non-neoplastic Barrett's esophagus, surveillance intervals are clearly defined by national and European guidelines. Only in case of malignant transformation of BE which may range from low-grade dysplasia to high-grade dysplasia and early Barrett's cancer, endoscopic therapy is indicated. At present, there are emerging techniques of artificial intelligence. Due to these rapid developments in BE management, it is important to keep an eye on the current status of BE management.

Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus.

Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE). A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation. A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P=0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P=0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P=0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively. This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.

Simultaneous and sequential combination of genetic and epigenetic biomarkers for the presence of high-grade dysplasia in patients with pancreatic cyst: Discovery in cyst fluid and test in pancreatic juice

Background/ObjectivesScreening patients with intraductal papillary mucinous neoplasms (IPMN) has the primary goal of identifying potentially curable noninvasive precursors. We aimed to evaluate the diagnostic impact of genetic and epigenetic biomarkers in the presence of noninvasive precursors. MethodsMutated KRAS/GNAS and methylated SOX17/TBX15/BMP3/TFPI2 DNA were assessed by droplet digital PCR in a discovery cohort of 70 surgically aspirated cyst fluids, and diagnostic performances for differentiating high-grade dysplasia (HGD) from low-grade dysplasia (LGD) was evaluated. We then tested these markers using an independent test cohort consisting of 156 serially collected pancreatic juice samples from 30 patients with IPMN. ResultsMutated KRAS and GNAS are specific for IPMNs but are not helpful for the prediction of histological grades. Cyst fluids from IPMN with HGD showed higher methylation levels of SOX17 (median, 0.141 vs. 0.021; P = 0.086) and TBX15 (median, 0.030 vs. 0.003; P = 0.028) than those with LGD. The combination of all tested markers yielded a diagnostic performance with sensitivity of 69.6%, and specificity of 90.0%. Among the 30 pancreatic juice samples exhibiting the highest abundance of KRAS/GNAS mutations in each patient in the test cohort, patients with histologically proven HGD due to pancreatic resection had a significantly higher prevalence (100% vs. 31%, P = 0.018) and abundance (P = 0.037) of methylated TBX15 than those without cytohistological diagnosis undergoing surveillance. ConclusionsA simultaneous and sequential combination of mutated and methylated DNA markers in pancreatic cyst fluid and juice sample markers can help detect noninvasive pancreatic precursor neoplasms.

Dilatation of the main pancreatic duct of unknown origin: causes and risk factors of pre-malignancy or malignancy.

A dilatation of the main pancreatic duct (MPD) is mainly due to obstructive causes (pancreatic tumor, chronic pancreatitis) or intraductal papillary mucinous neoplasm (IPMN). This study aims to assess the risk of pre-malignancy or malignancy in case of MPD dilatation with no visible mass nor obstructive calcification on computed tomography scan (CT-scan) in a population operated for it. All patients operated on from November 2015 to December 2019 in our center for a significant dilatation of the MPD without visible obstructive cause on CT-scan were included. Preoperative work-up included at least CT-scan, magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). Primary endpoint was the final pathological diagnosis. Secondary endpoints were predictive factors of malignancy. 101 patients were included, mean age 68years-old. Final pathological data were pancreatic adenocarcinoma (n = 2), IPMN with high-grade dysplasia (n = 37), high-grade Pancreatic Intraepithelial Neoplasia (PanIN) (n = 2) (total of pre-malignant or malignant lesions: n = 41), neuroendocrine tumor (n = 6), IPMN with low-grade dysplasia (n = 45), low-grade PanIN (n = 5), chronic pancreatitis (n = 3), and benign stenosis (n = 1). On preoperative explorations, the median diameter of MPD was 7mm [3-35]. MRI and/or EUS showed intraductal material, nodule, or cyst in 22, 32, and 52 patients, respectively; 22 patients without nodule visible on MRI or EUS had still a pre-malignant or malignant lesion. In multivariate analysis, predictive factors forpre-malignancy or malignancy were symptoms before surgery (p = 0.01), MPD dilatation without downstream stenosis (p = 0.046), and the presence of nodule (p = 0.009). A dilatation of the MPD without detectable mass or obstructive calcification on CT-scan was associated with a pre-malignant or malignant lesion in 41 patients. Symptoms before surgery, MPD dilatation without duct narrowing, and the presence of nodules on MRI/EUS were associated with the risk of pre-malignancy ormalignancy.

Comparison of Clinical and Imaginal Features According to the Pathological Grades of Dysplasia in Branch-Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN) for Personalized Medicine.

Background: In patients with BD-IPMN, surgical indications have been focused on finding malignant lesions (HGD, high-grade dysplasia/IC, invasive carcinoma). The aim of this study was to compare the preoperative factors that distinguish HGD from LGD (low-grade dysplasia) and HGD from IC to find the optimal pathologic target for surgery according to individuals, considering surgical risks and outcomes. Methods: We retrospectively analyzed 232 patients with BD-IPMN diagnosed based on pathology after surgery and preoperative images. The primary outcome was identifying preoperative factors distinguishing HGD from LGD, and HGD from IC. Results: In patients with LGD/HGD, a solid component or an enhancing mural nodule ≥ 5 mm (OR = 9.29; 95% CI: 3.3-54.12; p &lt; 0.000) and thickened/enhancing cyst walls (OR = 6.95; 95% CI: 1.68-33.13; p = 0.008) were associated with HGD. In patients with malignant lesions (HGD/IC), increased serum CA 19-9 (OR = 12.59; 95% CI: 1.81-87.44; p = 0.006) was associated with IC. Conclusions: The predictive factors for HGD were the presence of a solid component or an enhancing mural nodule ≥ 5 mm and thickened/enhancing cyst walls compared with LGD, and if accompanied by increased CA 19-9, it might be necessary to urgently evaluate the lesion due to the possibility of progression to IC. Based on this finding, we need to find HGD as the optimal pathologic target for surgery to improve survival in low-surgical-risk patients, and IC could be assumed to be the optimal pathologic target for surgery in high-surgical-risk patients because of high morbidity and mortality associated with surgery.

Risk factors in the development of gastric adenocarcinoma in the general population: A cross-sectional study of the Wuwei Cohort.

Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income, Helicobacter pylori (H. pylori) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy, H. pylori infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis. H. Pylori eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.

Long-term (18 Years) Results of Patients With Long-segment Barrett Esophagus Submitted to Acid Suppression-duodenal Diversion Operation: Better Than Nissen Fundoplication?

To determine late results of AS-DD procedure in long-segment (LSBE) and extralong-segment BE (ELSBE) using subjective and objective measurements to ascertain the histological impact over intestinal metaplasia (IM) and progression to EAC. Barrett esophagus (BE) is a known precursor of esophageal adenocarcinoma (EAC), and Nissen fundoplication has proven to be unable to stop mixed reflux among them. Our group proposed a surgical procedure that handles pathophysiological changes responsible for BE. This prospective study included 127 LSBE and ELSBE subjects submitted to clinical and functional analyses. They were presented to selective vagotomy, fundoplication, partial gastrectomy with Roux-en-Y reconstruction. The changes in IM were determined in both groups. Follow-up was completed at a mean of 18 years in 81% of the cases. Visick I-II scores were seen in 88% of LSBE and 65% in ELSBE ( P < 0.01). There was significant healing of erosive esophagitis and esophageal peptic ulcers, and strictures were resolved in 71%. There was 38% of IM regression in LSBE. Two cases in each group progressed to EAC at a mean of 15 years. Pathologic acid reflux was abolished in 91% and duodenal in 100%. There was a regression of low-grade dysplasia to IM in 80%. AS-DD permanently eliminates pathologic refluxate to the esophagus. The progression to HGD/EAC is lower compared to medical treatment, with an 8-fold reduction in LSBE and 2.2-fold in ELSBE. AS-DD seems to influence IM behaviors, and it is a tool that could reduce and delay progression to EAC.