Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

BACKGROUND: Endoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus. METHODS: We first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance. FINDINGS: The prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia. INTERPRETATION: Cytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways. FUNDING: Medical Research Council, Cancer Research UK, Innovate UK.

Pericardial tamponade after laparoscopic repair of a giant diaphragmatic hernia.

Laparoscopic intraperitoneal onlay mesh repair is favoured for diaphragmatic hernias due to better outcomes. However, fixation devices pose risks, including cardiac tamponade. A man underwent laparoscopic repair for a large diaphragmatic hernia. One week later, he presented with chest discomfort which was initially attributed to postoperative pain. Subsequently, patient represented with worsening of chest pain and tachycardia. CT requested to rule out pulmonary embolism revealed a large pericardial effusion. Urgent drainage via apical approach resolved tamponade. The case highlights the challenges in managing pericardial effusions post-laparoscopy in the presence of diaphragmatic mesh and stresses multidisciplinary collaboration. Literature review highlights risks associated with fixation devices. Suggestions include limiting their use near vital structures. Key learning point of this case report is to raise awareness of cardiac tamponade following diaphragmatic hernia repair. Limited evidence necessitates cautious use of fixation devices, emphasising patient safety.

A prospective comparison of quality of life measures for patients with esophageal cancer.

Among the most widely used instruments to assess quality of life (QOL) in patients with cancer are the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30) and the Functional Assessment of Chronic Illness Therapy, cancer instrument (FACT-G). This study compared these approaches in patients who had undergone esophagectomy for cancer. The EORTC core questionnaire and esophageal module and the FACT-G and esophageal scale were completed by 57 patients. Missing data, relationships between QOL scales and analyses of patients' preferences were examined. There were 14/2736 (0.5%) missing items from EORTC questionnaires and 45/2565 (1.8%) from FACT instruments (p < 0.01). Relationships between corresponding generic EORTC and FACT scales were average to good (r > 0.57) except for the social function scale (r = 0.01). EORTC symptom scores were moderately correlated with the FACT general scale, but poorly related to the FACT esophageal scale (r < 0.28). EORTC swallowing scores were moderately correlated with all FACT scales. The FACT-E and EORTC QLQ-C30 measure assess similar generic aspects of QOL (except social function). EORTC esophageal symptom scores relate poorly to FACT esophageal scales, except for swallowing. Choice of QOL measure after esophagectomy for cancer depends upon outcomes of interest. Future studies will determine which instruments are appropriate in each context.