Management of Barrett's oesophagus

Barrett's oesophagus, which is thought to be a consequence of gastro-oesophageal reflux disease (GORD), is a well-recognized precursor of oesophageal adenocarcinoma. Medical therapies and anti-reflux surgeries for GORD have shown conflicting results regarding the progression of Barrett's metaplasia to neoplasia. After high-grade dysplasia or intramucosal cancer is identified, it has been standard practice to conduct an oesophagectomy, despite this having an associated risk of morbidity and mortality. In recent years however, endoscopic therapy has become a viable alternative to oesophagectomy in treating early neoplasia

Optimising the performance and interpretation of small bowel capsule endoscopy

Small bowel capsule endoscopy has become a commonly used tool in the investigation of gastrointestinal symptoms and is now widely available in clinical practice. In contrast to conventional endoscopy, there is a lack of clear consensus on when competency is achieved or the way in which capsule endoscopy should be performed in order to maintain quality and clinical accuracy. Here we explore the evidence on the key factors that influence the quality of small bowel capsule endoscopy services

Diagnosing dysplasia in Barrett’s oesophagus still requires Seattle protocol biopsy in the era of modern video endoscopy: results from a tertiary centre Barrett’s dysplasia database.

Objectives: The role of random, four-quadrant biopsy (i.e. systematic biopsy) in Barrett’s oesophagus surveillance has been questioned given its drawbacks and the emergence of high-resolution endoscopy and advanced imaging modalities. Our study aims to assess whether neoplastic pathology is typically diagnosed in routine clinical practice by random, four-quadrant or targeted biopsy whilst using high-resolution endoscopy. Methods: The Nottingham University Hospital Barrett’s oesophagus dysplasia database was retrospectively analysed. Endoscopic and histopathologic data pertaining to the initial endoscopy in which pathology was diagnosed was extracted from the medical records. The most advanced histopathologic abnormality at initial diagnosis and within twelve months were noted. The corresponding endoscopic impression at initial diagnosis was used to group cases per type of biopsy – random, four-quadrant or targeted. Pearson’s chi-squared test of independence was used to analyse the relationship between the type of biopsy and diagnosis, indication for endoscopy, endoscopist level and advanced techniques used. Results: Of the 222 patients involved in the study - a higher proportion were diagnosed through random, four-quadrant biopsy (72.97%) than targeted biopsy (27.03%). 90.91% of low-grade dysplasia, 71.43% of high-grade dysplasia and 50% of intramucosal adenocarcinoma cases were diagnosed by random, four-quadrant biopsy. Across all grades of clinicians, patients were typically diagnosed through random, four-quadrant biopsy. However, amongst specialist consultant endoscopists (n=10) the proportion was equal. Conclusions: Our findings strongly emphasize the importance of random, four-quadrant biopsy in the detection of not only low-grade dysplasia, but also high-grade dysplasia and early invasive carcinoma as part of Barrett’s oesophagus surveillance

Upper GI biopsies for adenocarcinoma: how many biopsies should endoscopists take?

Aims: There is evidence that 4 or 5 gastric cancer biopsies are required for accurate HER2 interpretation. However, the number of biopsies that need to be taken to reach this number of viable cancer biopsies is without evidence. This study aimed to address this gap by assessing the number of biopsies required to get at least 4 viable biopsies containing cancerMethods and results: 105 consecutive biopsy cases of gastric and oesophageal adenocarcinoma were retrieved from file. Only definite cancer diagnoses were included; missed cancers or unproven cases were not considered. The cases were reviewed and the number of biopsies taken, and the number containing viable tumour was recorded. In total, 667 biopsies were taken of which 471 had viable tumour (70.6%) 70/105 cases (67%) had 4 viable tumour biopsies but only 47/105 (45%) had 5 viable tumour biopsies. In order to have a >90% chance of having 4 viable tumour biopsies, 7 biopsies needed to be taken, while 10 or more biopsies were required for a >90% chance of 5 viable tumour biopsies. Mathematically, using a 0.7 probability for a single biopsy, 8 biopsies would be required for a 94% chance of at least 4 viable tumour biopsies.Conclusion: In our large upper GI cancer centre, many biopsy cases do not contain sufficient material for adequate HER2 assessment. In order to meet the 4 biopsy requirement for adequate HER2 assessment in >90% of cases, at least 8 biopsies need to be taken, while 10 biopsies would be required for the 5 cancer biopsy threshold

Study to investigate the prevalence of human papillomavirus in Barrett's oesophagus using a novel screening methodology

Introduction Human papillomavirus (HPV) is strongly associated with Barrett's dysplasia and oesophageal cancer suggesting a role in carcinogenesis. HPV persistence predicts treatment failure after endotherapy for Barrett's dysplasia. This pilot study applies a novel HPV screening tool (previously only used in the oropharynx) to detect HPV DNA directly and determine the prevalence rates in Barrett's oesophagus (BO). Method DNA was extracted from 20 formalin-fixed BO samples. HPV DNA was detected using real-time PCR and gel electrophoresis. Results 5 out of 20 patients were identified as positive for HPV. Prevalence was 25% in patients with BO. Conclusion This method can be used in BO's tissue to determine HPV infection. Adoption of this as a screening test could potentially revolutionise future research in this area. If a clear link between HPV and Barrett's dysplasia can be confirmed, this qPCR method has the potential to aid in monitoring and/or dysplasia detection by stratifying those most at risk and aid in the development of new therapies

Diagnosis of Barrett’s esophagus and Esophageal Varices using a Magnetically Assisted Capsule Endoscopy system

Background and AimsMagnetically assisted capsule endoscopy (MACE) potentially offers a comfortable, patient friendly, and community-based alternative to gastroscopy (EGD). This pilot study aims to explore whether this approach can be used to accurately diagnose Barrett’s esophagus and esophageal varices.MethodsThe MiroCam Navi capsule system was used to examine the upper GI tract in patients due to undergo a clinically indicated EGD. A total of 50 participants were enrolled, of which 34 had known pathology, 17 Barrett’s esophagus (BE), 17 esophageal varices (EV), with 16 controls. Patients underwent the MACE procedure, with the operator blinded to the indication and any previous endoscopic diagnoses. The subsequent EGD was performed by an endoscopist blinded to the MACE findings. Diagnostic yield, comfort and patient preference between the 2 modalities were compared.ResultsParticipants had a mean age of 61 years old, a M:F ratio of 2.1:1, a mean body mass index (BMI) of 29.5, with an average chest measurement of 105.3 cm. Forty-seven patients undertook both procedures; 3 patients were unable to swallow the capsule. With the use of the magnet, it was possible to hold the capsule within the esophagus for a mean duration of 190 seconds and up to a maximum of 634 seconds. A correct real-time MACE diagnosis was made in 11 of 15 patients with EV (sensitivity 73.3% [95% CI, 44.9% - 92.2%] and specificity 100% [95% CI, 89.1% - 100%]) and 15 of 16 patients with BE (sensitivity 93.8% [95% CI, 69.8% - 99.8%] and a specificity of 100% [95% CI, 88.8% - 100%]). MACE was considered more comfortable than conventional endoscopy (p [less than] 0.0001) with a mean score of 9.2 with MACE compared with 6.7 with EGD, when assessed on a 10-point scale. No MACE or EGD -elated adverse events occurred.ConclusionThis pilot study demonstrates that MACE is both safe and well tolerated by patients. Accuracy for the diagnosis of BE was high and may therefore have a role in screening for this condition

Factors influencing participation in randomised clinical trials among patients with early Barrett's neoplasia: a multicentre interview study

OBJECTIVES: Strong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett's neoplasia. This paper aims to identify factors influencing patients' participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy. DESIGN: A semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes. SETTING: Interview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted. PARTICIPANTS: We interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined. RESULTS: Four themes were identified centred around interviewees' decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant-recruiter relationship; (2) participants' views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants' perceptions of surgical risks versus less invasive treatments. CONCLUSION: We identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett's-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials

Comparison of the reverse bevel versus Franseen type endoscopic ultrasound needle

BACKGROUNDReverse bevel (RB) needle is widely used for endoscopic ultrasound fine needle biopsy (EUS-FNB). A 3-plane symmetrical needle with Franseen geometry (FG) has recently become available. AIMTo compare the clinical efficacy of FG to that of RB needle.METHODSA retrospective cohort study of all adult patients who underwent EUS-FNB for solid and mixed lesions either with 22G RB needle or 22G FG needle between January 2016 and February 2019 was undertaken. All cytology slides were reviewed by an independent gastrointestinal cytopathologist blinded to the needle used and the initial cytology report. The primary and secondary outcomes were to assess the sample adequacy using Euro-cytology criteria and the number of cell clusters, respectively.RESULTSTwo hundred and twenty six procedures were included in the study. RB needle was used in 128 procedures and FG needle in 98 procedures. The baseline characteristics of both groups were comparable. On multivariable analysis, FG needle (P = 0.02) and location of the lesion (P < 0.01) were independently associated with adequate tissue. Further, the use of FG needle (P = 0.04) and the size of the lesion (P = 0.02) were independently associated with acquisition of increased number of cell clusters.CONCLUSIONFG needle is superior to RB needle in acquiring adequate tissue and attaining higher number of cell clusters for solid and mixed lesions

Standard versus simplified radiofrequency ablation protocol for Barrett's esophagus: comparative analysis of the whole treatment pathway.

Background and study aims  The standard radiofrequency ablation (RFA) protocol for Barrett's esophagus (BE) encompasses an intermediary cleaning phase between two ablation sessions. A simplified protocol omitting the cleaning phase is less labor-intensive but equally effective in studies based on single ablation procedures. The aim of this study was to compare efficacy and safety of the standard and simplified RFA protocols for the whole treatment pathway for BE, including both circumferential and focal devices. Patients and methods  We performed a retrospective analysis of prospectively collected data on patients receiving RFA between January 2007 and August 2017 at two institutions. Outcomes assessed were: 1) complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM) at 18 months; and 2) rate of esophageal strictures. Results  One hundred forty-five patients were included of whom 73 patients received the standard and 72 patients received the simplified protocol. CR-D was achieved in 94.5 % and 95.8 % of patients receiving the standard and simplified protocol, respectively ( P  = 0.71). CR-IM was achieved in 84.9 % and 77.8 % of patients treated with the standard and simplified protocol, respectively ( P  = 0.27). Strictures were significantly more common among patients who received the simplified protocol (12.5 %) compared to the standard protocol (1.4 %; P  = 0.008). The median number of esophageal dilations was one. Conclusion  The simplified RFA protocol is as effective as the standard protocol in eradicating BE but carries a higher risk of strictures. This needs to be taken into account, particularly in patients with higher pretreatment risk of strictures, such as those with esophageal narrowing from previous endoscopic mucosal resection (EMR)

Image enhanced endoscopy and molecular biomarkers vs Seattle protocol to diagnose dysplasia in Barrett's esophagus

BACKGROUND: Dysplasia in Barrett's esophagus (BE) is often invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers versus HRWLE with Seattle protocol biopsies. METHODS: BE patients with no dysplastic lesions were block randomized to standard endoscopy (HRWLE with Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6-12 weeks. Histological endpoint was diagnosis from all study biopsies (trial histology). Sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. Primary outcome was diagnostic accuracy for dysplasia by real-time pCLE versus HRWLE biopsies. RESULTS: Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared to standard endoscopy [74.3% (95%CI, 56.7-87.5) vs 80.0% (95%CI 63.1-91.6), p=0.48]. Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53 and aneuploidy had strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than Seattle protocol (81.5% vs 51.9%, p<0.001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; p=0.16) with an area under receiver operating curve of 0.83. CONCLUSIONS: Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. Addition of molecular biomarkers could improve diagnostic accuracy