Diagnosis Of High-grade Dysplasia Research Articles

Prevalence and Natural History of Barrett’s Esophagus in Lung Transplant: A Single-Center Experience

Barrett's esophagus (BE)-intestinal metaplasia in the esophagus-may progress to low-grade dysplasia (LGD), high-grade dysplasia (HGD), and ultimately, invasive esophageal adenocarcinoma (EAC). The course of BE in immunosuppressed lung transplant recipients is unknown. This study retrospectively reviewed the records of patients who underwent lung transplant at asingle center, Norton Thoracic Institutein Phoenix, Arizona, between January 1, 2010 andOctober 31, 2016. Pretransplant esophagram, esophagogastroduodenoscopy, 24-hour pH monitoring, high-resolution manometry, and gastric emptying studies were analyzed. Of the 466 patients who underwent lung transplant during the study period, 54 (11.59%) had BEon pretransplant esophagogastroduodenoscopy. Of these, 1 patient had HGD before lung transplant. The median age of patients was 64 years (interquartile range, 58.25 to 68.75 years); 66.7% were men. Median follow-up duration was 29.48 months (interquartile range, 19.69 to 37.98 months). Sixteen of 54 patients (29.62%) underwent antireflux surgery after lung transplant. LGD or EAC developed in 3 patients during posttransplant surveillance. One patient had a diagnosis of HGD 24 months after retransplant. Sheunderwent complete endoscopic ablation and was dysplasia-free for 5 months, but ultimately the condition recurred, and she underwent esophagectomy for invasive cancer. Two patients had a diagnosis of LGD 7 and 13 months after lung transplant and were successfully treated with radiofrequency ablation. The rate of progression to dysplasia or EAC was 2.3% per patient-year. BE seems to be more prevalent in lung transplant recipients than in the general population. The study findings suggest that patients with BE have a higher risk of BE-to-EAC progression after lung transplant and that HGD may progress rapidly in immunosuppressed patients. More intensive surveillance endoscopy may be required in patients with BE after lung transplant.

Increasing prevalence of high-grade dysplasia and adenocarcinoma on index endoscopy in Barrett’s esophagus over the past 2 decades: data from a multicenter U.S. consortium

Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE-associated dysplasia on index endoscopy over the past 25 years. The Barrett's Esophagus Study is a multicenter outcome project of a large cohort of patients with BE. Proportions of patients with index endoscopy findings of no dysplasia (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC were extracted per year of index endoscopy, and 5-yearly patient cohorts were tabulated over years 1990 to 2010+ (2010-current). Prevalent dysplasia and endoscopic findings were trended over the past 25 years using percentage dysplasia (LGD, HGD, EAC, and HGD/EAC) to assess changes in detection of BE-associated dysplasia over the last 25 years. Statistical analysis was done using SAS version 9.4 software (SAS, Cary, NC). A total of 3643 patients were included in the analysis with index endoscopy showing NDBE in 2513 (70.1%), LGD in 412 (11.5%), HGD in 193 (5.4%), and EAC in 181 (5.1%). Over time, there was an increase in the mean age of patients with BE (51.7 ± 29 years vs 62.6 ± 11.3 years) and the proportion of males (84% vs 92.6%) diagnosed with BE but a decrease in the mean BE length (4.4±4.3 cm vs 2.9±3.0 cm) as time progressed (1990-1994 to 2010-2016 time periods). The presence of LGD on index endoscopy remained stable over 1990 to2016. However, a significant increase (148% in HGD and 112% in EAC) in the diagnosis of HGD, EAC, and HGD/EAC was noted on index endoscopy over the last 25 years (P< .001). There was also a significant increase in the detection of visible lesions on index endoscopy (1990-1994, 5.1%; to 2005-2009, 6.3%; and 2010+, 16.3%) during the same period. Our results suggest that the prevalence of HGD and EAC has significantly increased over the past 25 years despite a decrease in BE length during the same period. This increase parallels an increase in the detection of visible lesions, suggesting that a careful examination at the index examination is crucial.

FA02.05: PROGRESSION RATE OF BARRETT’S ESOPHAGUS FROM NATIONAL REGISTRY OF EXPERT CENTERS IS MUCH GREATER THAN ANTICIPATED FROM POPULATION STUDIES

Abstract Background Barrett's Esophagus (BE) is well established as the main pathological precursor for esophageal adenocarcinoma (EAC). Progression to high grade dysplasia (HGD) or EAC varies widely between population based studies and specialized BE registries from high volume centers. No such data existed from the Republic of Ireland until 2011 when a multicenter registry was established involving three centers to more accurately determine the risk of progression to EAC in the Irish population. Methods A detailed clinical, endoscopic and pathological database includes 3397 patients from January 2008 to July 2017, with BE defined by the presence of specialized intestinal metaplasia (SIM). A prospective web based database was used to gather information from three designated esophageal centers with initial and follow up data abstracted by a data manager and overseen by a project manager. Results 325 were excluded following a diagnosis of HGD or EAC at index biopsy, or being a tertiary referral, leaving 3072 with a median age of 61 and a 2.1:1 male to female ratio and a median follow up of 3 years, and 5024 person years. 127 (4%) cases progressed to HGD/EAC, 65 after one year of follow up. 55 (2%) developed EAC were identified, 30 of those within one year. The overall incidence HGD/EAC was 2.53% per year, 1.3% if the first year is excluded. The risk of progression to EAC alone was 1.09% per year, 0.5% excluding the first year. Low grade dysplasia (LGD) on index biopsy was associated with a progression rate of 11.7% per year, 4.2% with the first year excluded. Conclusion With strict data entry and pathologic quality assurance, progression rates for non-dysplastic BE was several fold higher than population studies, highlighting caution in abstracting from population data. True LGD, as evidenced in a recent report by Kestens et al.1 represent high risk disease, with most of the risk evident within the first year. Reference: 1. Kestens C, Offerhaus G, van Baal J, Siersema PD. Patients wtih Barrett's esophagus and persistent low-grade dysplasia have an increased risk for high- grade dysplasia and cancer. Clin Gastroenterol Hepatol. 2016;14:956–962 Disclosure All authors have declared no conflicts of interest.

Impact of the development of an endoscopic eradication program for Barrett's esophagus with high grade dysplasia or early adenocarcinoma on the frequency of surgery.

Background and aims The impact of the advent of an institutional endoscopic eradication therapy (EET) program on surgical practice for Barrett’s esophagus (BE)-associated high grade dysplasia (HGD) or suspected T1a esophageal adenocarcinoma (EAC) is unknown. The aims of this study are to evaluate the different endoscopic modalities used during development of our EET program and factors associated with the use of EET or surgery for these patients after its development. Methods Patients who underwent primary endoscopic or surgical treatment for BE-HGD or early EAC at our hospital between January 1992 and December 2014 were retrospectively identified. They were categorized by their initial modality of treatment during the first year, and the impact over time for choice of therapy was assessed by multivariable logistic regression. Results We identified 386 patients and 80 patients who underwent EET and surgery, respectively. EET included single modality therapy in 254 (66 %) patients and multimodal therapy in 132 (34 %) patients. Multivariable logistic regression showed that, for each subsequent study year, EET was more likely to be performed in patients who were older ( P = 0.0009), with shorter BE lengths ( P < 0.0001), and with a pretreatment diagnosis of HGD ( P = 0.0054) compared to surgical patients. The diagnosis of EAC did not increase the utilization of EET compared to surgery as time progressed ( P = 0.8165). Conclusion The introduction of an EET program at our hospital increased the odds of utilizing EET versus surgery over time for initial treatment of patients who were older, had shorter BE lengths or the diagnosis of BE-HGD, but not in patients with EAC.

Low proportion of unreported cervical treatments in the cancer registry of Norway between 1998 and 2013

Background: Accurate information about treatment is needed to evaluate cervical cancer prevention efforts. We studied completeness and validity of reporting cervical treatments in the Cancer Registry of Norway (CRN).Material and methods: We identified 47,423 (92%) high-grade cervical dysplasia patients with and 3983 (8%) without recorded treatment in the CRN in 1998–2013. We linked the latter group to the nationwide registry of hospital discharges in 1998–2015. Of patients still without treatment records, we randomly selected 375 for review of their medical history. Factors predicting incomplete treatment records were assessed by multiple imputation and logistic regression.Results: Registry linkage revealed that 10% (401/3983) of patients received treatment, usually conization, within one year of their initial high-grade dysplasia diagnosis. Of those, 11% (n = 44) were missing due to unreporting and 89% (n = 357) due to misclassification at the CRN. Of all cases in medical review, patients under active surveillance contributed almost 60% (223/375). Other reasons of being without recorded treatment were uncertain dysplasia diagnosis, invasive cancer or death. Coding error occurred in 19% (73/375) of randomly selected cases. CRN undercounted receipt of treatment by 38% (n = 1526) among patients without recorded treatment which translates into 97% overall completeness of treatment data. Incomplete treatment records were particularly associated with public laboratories, patients aged 40–54 years, and the latest study years.Conclusions: CRN holds accurate information on cervical treatments. Completeness and particularly validity can be further improved through the establishment of new internal routines and regular linkage to hospital discharges.

Excess Cost of Cervical Cancer Screening Beyond Recommended Screening Ages or After Hysterectomy in a Single Institution.

The aim of the study was to estimate the excess cost of guideline nonadherent cervical cancer screening in women beyond the recommended screening ages or posthysterectomy in a single healthcare system. All Pap tests performed between September 1, 2012, and August 31, 2014, in women younger than 21 years, older than 65 years, or after hysterectomy, were coded as guideline adherent or nonadherent per the 2012 America Society of Colposcopy and Clinical Pathology guidelines. We assumed management of abnormal results per the 2013 America Society of Colposcopy and Clinical Pathology management guidelines. Costs were obtained from a literature review and Center for Medicare and Medicaid Services data and applied to nonadherent screening and subsequent diagnostic tests. During this period, 1,398 guideline nonadherent Pap tests were performed (257 in women <21 years, 536 in women >65 years, and 605 after hysterectomy), with 88 abnormal results: 35 (13.5%) in women younger than 21 years, 14 (2.6%) in women older than 65 years, and 39 (6.5%) in women after hysterectomy. The excess cost for initial screening, diagnostic tests, and follow-up was US $35,337 for 2 years in women younger than 21 years, US $54,378 for 5 years in women older than 65 years, and US $77,340 for 5 years in women after hysterectomy, resulting in a total excess cost of US $166,100 for 5 years. Of the 1,398 women who underwent guideline nonadherent screening, there were only 2 (0.1%) diagnoses of high-grade dysplasia (VaIN3). Guideline nonadherent cervical cancer screening in women beyond the recommended screening ages and posthysterectomy resulted in costs exceeding US $160,000 for screening, diagnostic tests, and follow-up with minimal improvement in detection of high-grade dysplasia.

The Role of Wide Area Transepithelial Sampling in Screening for Esophageal Adenocarcinoma

Barrett's esophagus (BE) requires surveillance to monitor for dysplasia and esophageal adenocarcinoma. New methods have been developed to detect dysplasia and esophageal adenocarcinoma. One of these methods called the wide area trans epithelial sampling 3D brush biopsy (WATS 3D) is a computer-assisted brush-biopsy technique which uses an abrasive sampling instrument to detect dysplasia or esophageal adenocarcinoma. The aim of our case is to demonstrate the clinical utility of this tool in Barrett's surveillance. Patient is a 66 year old with a past medical history of lifelong heartburn and regurgitation. He was on Esomeprazole 20mg daily and denied family history of colon or esophageal cancer. The patient had a screening endoscopy for surveillance of BE three months ago, which showed a 3-5 cm area of full circumferential salmon colored mucosa suspicious for BE. Biopsies revealed squamocolumnar mucosa with intestinal metaplasia and focal high-grade glandular dysplasia without malignancy. Repeat endoscopy confirmed a Prague C5M5 lesion (Fig. 1). Repeat biopsies read by 2 different pathologists confirmed the diagnosis of high grade dysplasia (Fig. 2). Wide area trans epithelial sampling 3D brush biopsy was also performed at that time. The WATS pathology report stated that patient has at least high-grade dysplasia in his cytopathology and was suggestive of esophageal adenocarcinoma. Patient was successfully managed with 2 RFA ablation sessions with obliteration of the BE and replacement of the Barrett's mucosa with a neosquamous epithelium. Esophageal adenocarcinoma has a high mortality rate and a poor prognosis. As such screening for BE is critical in preventing progression. As illustrated in our case, the WATS brush biopsy addresses the sampling error inherent in random forceps biopsy testing of the esophagus. In just a few minutes, gastroenterologists can easily obtain a wide area, full-thickness transepithelial tissue sample for computer-assisted 3D laboratory analysis. The case was discussed with experts in BE and felt there was a small foci of adenocarcinoma in the setting of high grade dysplasia. Without evidence of invasion, lesion was safe to be treated with RFA. This foci of esophageal adenocarcinoma is likely missed with the traditional sampling methods. Overall, institutions should consider either adding WATS 3D as an adjunct to standard forceps biopsy or using it as primary tool for detecting dysplasia.Figure: Narrow band image of a C5M5 area of Barrett's seen on endoscopy.Figure: Few foci of highly dysplastic epithelium, seen singly and within apparent small vascular spaces, strongly suggestive of adenocarcinoma, in a background of Barrett's metaplasia.

Cytological study of DNA content and nuclear morphometric analysis for aid in the diagnosis of high-grade dysplasia within oral leukoplakia

To quantitatively examine the DNA content and nuclear morphometric status of oral leukoplakia (OL) and investigate its association with the degree of dysplasia in a cytologic study. Oral cytobrush biopsy was carried out to obtain exfoliative epithelial cells from lesions before scalpel biopsy at the same location in a blinded series of 70 patients with OL. Analysis of nuclear morphometry and DNA content status using image cytometry was performed with oral smears stained with the Feulgen-thionin method. Nuclear morphometric analysis revealed significant differences in DNA content amount, DNA index, nuclear area, nuclear radius, nuclear intensity, sphericity, entropy, and fractal dimension (all P<.01) between low-grade and high-grade dysplasia. DNA content analysis identified 34 patients with OL (48.6%) with DNA content abnormality. Nonhomogeneous lesion (P=.018) and high-grade dysplasia (P=.008) were significantly associated with abnormal DNA content. Importantly, the positive correlation between the degree of oral dysplasia and DNA content status was significant (P=.004, correlation coefficient=0.342). Cytology analysis of DNA content and nuclear morphometric status using image cytometry may support their use as a screening and monitoring tool for OL progression.

Coding of Barrett’s oesophagus with high-grade dysplasia in national administrative databases: a population-based cohort study

ObjectivesThe International Classification of Diseases 10th Revision (ICD-10) system used in the English hospital administrative database (Hospital Episode Statistics (HES)) does not contain a specific code for oesophageal high-grade dysplasia...

Pancreaticoduodenectomy for nonampullary duodenal lesions: indications and results

Pancreaticoduodenectomy (PD) is a complex procedure, associated with a definite risk of mortality and 30-50% risk of complications. For nonampullary duodenal lesions, PD can carry a higher morbidity as they are more commonly associated with a soft pancreas and narrow-calibre main pancreatic ducts. It is therefore paramount that the risks and benefits of surgery are considered carefully in this group of patients. A preoperative histological diagnosis for duodenal lesions is normally achieved by endoscopic biopsy. In this study, we aim to assess the outcome of PD in patients with nonampullary duodenal lesions and correlate the preoperative endoscopic histology work-up with the definitive postoperative pathology. We reviewed a prospectively collected PD database from January 2007 to December 2013. Demographic and clinical data were included. Preoperative endoscopic histology was compared with final specimen histology to assess concordance. Forty patients (55% women, mean age 69.4 years, range 45-83 years) underwent PD for duodenal lesions over a 7-year time period. The most common presenting symptom was epigastric pain (32.5%), followed by anaemia (20%). Overall, the complication rate was 55%, with the most frequent adverse event being pancreatic fistula in 13/40 (32.5%). The perioperative mortality was 2/40 (5%). Duodenal adenocarcinoma (65%) was the most common postoperative histological diagnosis. The mean tumour size was 36 mm (range 5-103 mm) and a median of 13 nodes were harvested. The median length of stay was 15 days (range 7-66 days). Overall, 12/40 patients (30%) had a preoperative diagnosis of high-grade dysplasia. The postoperative specimen in this subgroup of patients was reviewed carefully and only 3/12 (25%) patients had high-grade dysplasia in the resection specimen. In the remaining patients, 3/12 (25%) had adenocarcinoma in the resection specimen and 6/12 patients (50%) had low-grade dysplasia. PD carries a high mortality and morbidity, especially for duodenal lesions. We recommend a careful endoscopic review after the index case with a high-definition optical evaluation of duodenal lesions. This, in addition to an experienced histological assessment of the index biopsy material, forms an essential prerequisite in aiding the multidisciplinary team in the decision-making process with respect to triage of these lesions to conservative management, surveillance, endoscopic resection or finally surgical resection.

Pancreatico-duodenectomy for non-ampullary duodenal lesions: Indications and results

Aims: Pancreaticodudenectomy (PD) is a complex procedure, associated with a definitive risk of mortality and 30–50% risk of complications. For non-ampullary duodenal lesions, PD can carry a higher morbidity as they are more commonly associated with soft pancreas and small main pancreatic ducts. The pre-operative histology is essential in assisting the surgeon and the multidisciplinary team in decision-making with regard to the best management of such lesions. We aim to assess the outcome of PD in patients with non-ampullary duodenal lesions and also correlate pre-operative histologies to post-operative histologies. Methods: We reviewed a prosspectively collected PD database from Jan 2007 to Dec 2013. Demographic and clinical data was included. Pre-operative endoscopic histology was compared with final specimen histology to assess concordance. Results: Forty patients (female 55%, mean age 69.4 years, age range 45–83 years) underwent PD for duodenal lesions. The commonest presenting symptom was epigastric pain (32.5%). Overall complication rate was 55% and the most common complication was pancreatic fistula in 13/40 (32.5%) and the peri-operative mortality was in 2/40 (5%). Duodenal adenocarcinoma (62.5%) was the commonest post-operative diagnosis. Mean tumour size was 36 mm (range 5–103 mm) and a median of 13 nodes were harvested. The median length of stay was 15 days (range 7–66 days).13/40 patients (32.5%) had a pre-operative diagnosis of high grade dysplasia. The post-op specimen in this group of patients was reviewed carefully and only 3/13 patients (23.1%) had high grade dysplasia in the resection specimen. In the remaining 3/13 patients (23.1%) the resection specimen showed adenocarcinoma, and in 7/13 patients (53.8%) the resection specimen showed low grade dysplasia Conclusions: PD for duodenal lesions is associated with high mortality and morbidity compared with PD for adenocarcinoma and hence there should be minimal discordance between pre-operative diagnosis and post-operative histology for duodenal lesions.

High-resolution microendoscopy: a point-of-care diagnostic for cervical dysplasia in low-resource settings.

Cervical cancer is the third leading cause of cancer-related death among women in low-to-middle income countries. Pap testing and pathological services are difficult to implement under these settings. Alternative techniques for the diagnosis of cervical precancer in these settings are needed to reduce the burden of the disease. The objective of this study was to evaluate the diagnostic accuracy of a low-cost, high-resolution microendoscope imaging system in identifying precancerous lesions of the cervix in vivo. A retrospective study of 59 patients undergoing colposcopy for an abnormal Pap test was performed at Hospital de Câncer de Barretos in Brazil. All patients underwent colposcopy as per standard of care, and acetowhite lesions were recorded. High-resolution microendoscopy (HRME) images were obtained from one colposcopically normal region and from all lesions observed on colposcopy. Biopsies of abnormal areas were obtained and reviewed by three independent, blinded pathologists and compared with HRME findings. The mean nuclear area and the median nuclear eccentricity were calculated from HRME images acquired from each site. A diagnostic algorithm to distinguish histopathologically diagnosed cervical intraepithelial neoplasias of grade 2 or more severe lesions (high grade) from less severe lesions (low grade) was developed using these parameters. A test of trend was used to analyze the relationship between HRME positivity and severity of histopathogical diagnosis. Fisher's exact test was used to analyze differences in HRME positivity between high-grade and low-grade lesions. Evaluable images were obtained from 108 of 143 discrete sites. Of these, 71 sites were colposcopically normal or low grade according to histopathology and 37 were diagnosed as high grade on the basis of histopathology. Using the mean nuclear area and the median nuclear eccentricity, HRME images from 59 colposcopically abnormal sites were classified as high grade or low grade with 92% sensitivity and 77% specificity compared with histopathological findings. Increasing HRME positivity showed a significant trend with increasing severity of diagnosis (Ptrend<0.001). We found a strong association (P<0.001) between HRME positivity and a histopathological diagnosis of cervical intraepithelial neoplasia of grade 2 or higher. HRME demonstrated an accurate in-situ diagnosis of high-grade dysplasia. In low-resource settings in which colposcopy and histopathology services are severely limited or unavailable, HRME may provide a low-cost, accurate method for diagnosis of cervical precancer without the need for biopsy, allowing for a single 'screen-and-treat' approach.

Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists.

AIMTo evaluate annual incidence of low grade dysplasia (LGD) progression to high grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC) when diagnosis was made by two or more expert pathologists.METHODSStudies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic.RESULTSInitial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies (n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate (AIR) of progression to HGD and or EAC was 10.35% (95%CI: 7.56-13.13) and progression to EAC was 5.18% (95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett’s esophagus, the AIR of progression to HGD and EAC was 0.65% (95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42% (95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63% (95%CI: 13.98-43.27).CONCLUSIONWhen LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett’s esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.

Evaluation of Mutational Testing of Preneoplastic Barrett's Mucosa by Next-Generation Sequencing of Formalin-Fixed, Paraffin-Embedded Endoscopic Samples for Detection of Concurrent Dysplasia and Adenocarcinoma in Barrett's Esophagus

Barrett's intestinal metaplasia (BIM) may harbor genomic mutations before the histologic appearance of dysplasia and cancer and requires frequent surveillance. We explored next-generation sequencing to detect mutations with the analytical sensitivity required to predict concurrent high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus by testing nonneoplastic BIM. Formalin-fixed, paraffin-embedded (FFPE) routine biopsy or endoscopic mucosal resection samples from 32 patients were tested: nonprogressors to HGD or EAC (BIM-NP) with BIM, who never had a diagnosis of dysplasia or EAC (N = 13); progressors to HGD or EAC (BIM-P) with BIM and a worse diagnosis of HGD or EAC (N = 15); and four BIM-negative samples. No mutations were detected in the BIM-NP (0 of 13) or BIM-negative samples, whereas the BIM-P samples had mutations in 6 (75%) of 8 cases in TP53, APC, and CDKN2A (P=0.0005), detected in samples with as low as 20% BIM. We found that next-generation sequencing from routine FFPE nonneoplastic Barrett's esophagus samples can detect multiple mutations in minute areas of BIM with high analytical sensitivity. Next-generation sequencing panels for detection of TP53 and possibly combined mutations in other genes, such as APC and CDKN2A, may be useful in the clinical setting to improve dysplasia and cancer surveillance in patients with Barrett's esophagus.

Can we really continue to diagnose high grade dysplasia in Barrett’s esophagus in Europe without magnified virtual chromo-endoscopy?

Can we really continue to diagnose high grade dysplasia in Barrett’s esophagus in Europe without magnified virtual chromo-endoscopy?

Utility of liquid-based cytologic examination of distal esophageal brushings in the management of Barrett esophagus: a prospective study of 45 cases

The goal of Barrett esophagus surveillance is to identify high-grade dysplasia (HGD) for eradication. Surveillance programs currently rely on limited histologic sampling; however, the role of cytology in this setting is not well studied. From December 1, 2011 to March 30, 2014, 45 patients underwent 4 circumferential brushings of the distal tubular esophagus followed by standard 4-quadrant biopsies. One ThinPrep slide and 1 Cellient cellblock (Hologic, Boxborough, Mass) were prepared. Six cytopathologists evaluated each for adequacy, intestinal metaplasia (IM) and dysplasia. Findings were classified using the traditional 5-tier system used for biopsies. A prospectively modified 3-tier cytologic classification was also tested: negative for HGD, indeterminate for HGD, and HGD. Sensitivity, specificity, and kappa values (interobserver agreement) for cytology were calculated. Ten of 45 patients had nondiagnostic cytologies; none of whom had dysplasia on biopsy. Cytology had good sensitivity (82%) and specificity (88%) for identifying IM compared with biopsy with moderate interobserver agreement (pairwise average of Fleiss and Krippendorf kappa value = 0.589, 79% agreement). One case had IM on cytology not detected on histology. Six of 45 patients had dysplasia on biopsy including 1 intramucosal adenocarcinoma, 1 indeterminate for dysplasia, 2 high-grade dysplasias, and 2 low-grade dysplasias. A non-negative adequate cytology sample had a sensitivity of 100% and a specificity of 88% and 94% for the 5-tier and the 3-tier classification, respectively. Cytology appears to have good sensitivity and specificity for diagnosis of HGD, and cytology may be poised to synergize with advances in other techniques for management of patients with Barrett esophagus. Improvements in brushing devices may help to decrease the nondiagnostic rate.

Prevalence and Outcomes of Cystic Neoplasm of the Pancreas in Immunosuppressed Patients With Solid Organ Transplantation

Introduction: To determine the prevalence of incidental pancreatic cystic neoplasms (PCNs) in solid organ transplant (SOT) recipients and describe the clinical course of these lesions in patients on chronic immunosuppressive therapy after transplantation. Methods: Using organ transplant databases at Mayo Clinic Florida, we retrospectively reviewed medical records of all patients who received a SOT between 2000 and 2013. Records of cross-sectional abdominal imaging were searched for the diagnosis of pancreatic cyst(s). We also reviewed radiographic imaging to confirm the presence of PCNs. The “worrisome features” were defined as: main pancreatic duct (MPD) involvement (dilation >6 mm), mural nodule, abrupt change in the MPD caliber with distal pancreatic atrophy. The characteristics of the PCN at the initial and follow-up imaging were compared. Cyst size was considered to have changed if there was a difference of ≥5 mm. Results: Of 3,188 patients, 11.4% (n=356) had at least 1 incidental PCN detected on imaging. The prevalence of PCN increased with age; was more common in females (14.7%) than in males (9.7%); and more common in liver transplant recipients (14.9%) as compared to kidney (5%), lung (3%), and heart (6%) transplant patients. The median diameter of the largest pancreatic cyst was 7.0 mm (range: 1-31) and in 6.8% of patients, the cysts were ≥2 cm. Two patients (0.5%) had worrisome features at the time of pancreatic cyst diagnosis. One patient who had a mural nodule at the time of cyst diagnosis had no evidence of malignant transformation after 71 months of follow-up. One patient with branch duct intraductal papillary mucinous neoplasms (IPMN) and MPD involvement died of a non-pancreatic related cause 2 months after the cyst diagnosis. In a cohort of 155 patients with follow-up examination (median follow-up of 39 months), only 2 patients (1.3%) developed worrisome features on follow-up imaging. One case with a newly developed mural nodule underwent pancreatic surgery, with a pathologic diagnosis of high-grade dysplasia. One case with progressive MPD dilatation noted during the follow-up did not undergo surgical resection due to multiple comorbidities. The majority (83%) of pancreatic cysts evaluated at follow-up were either unchanged or smaller in size. Although 16% of patients had increased cyst size during follow-up, none of them developed malignancy or had pancreatic-related morbidity. Conclusion: PCNs are common in SOT recipients. In PCN without high-risk features, the development of features worrisome for cancer is a rare event. Therefore, PCNs can be managed conservatively and their presence should not affect patients’ eligibility for transplant.

Interobserver variability in assessing dysplasia and architecture in colorectal adenomas: a multicentre Canadian study

AimsFollowing the introduction of colorectal cancer screening programmes throughout Canada, it became necessary to standardise the diagnosis of colorectal adenomas. Canadian guidelines for standardised reporting of adenomas were developed in...

Consistency of a high-grade dysplasia diagnosis in Barrett's oesophagus: A Dutch nationwide cohort study

Consistency of high-grade dysplasia in Barrett's oesophagus is incompletely known and the clinical course may vary between patients. To evaluate the consistency of high-grade dysplasia diagnosis in a Dutch nationwide cohort and to identify predictors for (re-)detecting high-grade dysplasia or oesophageal adenocarcinoma when ≥ 1 follow-up evaluations after an initial high-grade dysplasia diagnosis were scored with a lower histological grade. In this retrospective cohort study, all patients diagnosed with high-grade dysplasia in Barrett's oesophagus between 1999 and 2008 in the Netherlands were selected using the nationwide histopathology registry. Multivariate analysis was performed to identify predictors for (re-)detecting high-grade dysplasia or oesophageal adenocarcinoma in patients with ≥ 1 follow-up evaluations scored with a lower grade. In total, 512 high-grade dysplasia patients were included, of whom 53% had ≥ 1 follow-up evaluations scored with a lower grade. The (re-)detection risk was increased when follow-up was performed in a university hospital and when endoscopic/surgical resection was performed and decreased with an increasing number of follow-up evaluations scored with a lower grade. High-grade dysplasia diagnosis was inconsistent in more than half of patients. (Endoscopic) resection in an expert centre is recommended to (re-)detect high-grade dysplasia or oesophageal adenocarcinoma when an endoscopic follow-up protocol with biopsies repeatedly shows a lower histological grade.

Gender-based Differences in the Risk for High-Grade Dysplasia (HGD) or Cancer in Barrettʼs Esophagus (BE) Patients with Low-Grade Dysplasia (LGD)

Purpose: Regression of LGD has been observed in majority of patients with BE and LGD. A few patients progress to HGD/ adenocarcinoma. Ongoing surveillance is the standard of care with endoscopic ablation offered in select patients. Identifying patients at higher risk for progression will help in tailoring the optimal intervention. The factors which predict this progression are not clearly known. Our aim was to assess the natural history of LGD and evaluate the risk factors for progression to HGD/adenocarcinoma. Methods: BE Patients with a diagnosis of LGD with no prior diagnosis of HGD / adenocarcinoma with atleast one follow up endoscopy were included in the study. Demographic features such as age, gender and race, diabetes, hypertension, fundoplication, number of endoscopies, BE length, hiatal hernia, and biopsy results were recorded. Prevalent cases were those diagnosed at the time of or within one year of the first endoscopy. The rest were incident cases. Persistent cases were those with LGD on 2 or more consecutive endoscopies. Follow-up (F/U) is from the time of detection of LGD to last endoscopy or the end points of HGD/ adenocarcinoma. Results: Cleveland Clinic Barrett's registry included 2,370 patients. Of these, 313 met the study criteria. Table 1 details the results of this group. On competing risk analysis (Table 2), men have almost 3 fold higher risk of progression than women. Prevalent LGD were 3.5 times more likely to have progression of disease than those with incident LGD. For every 5 year increase in the age at time of diagnosis of LGD, chance of regression increased by 7%. Also for every 1 cm increase in the BE length, the chance of regression decreased by 6%.Table 1: Demographic and clinical characteristicsTable 2: Competing risks analysisConclusion: Only a minority of patients with LGD progress to HGD/adenocarcinoma. Men and patients with prevalent LGD are at higher risk for progression. Older age at the diagnosis of LGD and shorter BE segment length are associated with regression. These novel findings are useful in the risk stratification and intervention in BE patients with LGD.