Peter McAnena

Circulating Nucleosomes and Nucleosome Modifications as Biomarkers in Cancer

Traditionally the stratification of many cancers involves combining tumour and clinicopathological features (e.g., patient age; tumour size, grade, receptor status and location) to inform treatment options and predict recurrence risk and survival. However, current biomarkers often require invasive excision of the tumour for profiling, do not allow monitoring of the response to treatment and stratify patients into broad heterogeneous groups leading to inconsistent treatment responses. Here we explore and describe the benefits of using circulating biomarkers (nucleosomes and/or modifications to nucleosomes) as a non-invasive method for detecting cancer and monitoring response to treatment. Nucleosomes (DNA wound around eight core histone proteins) are responsible for compacting our genome and their composition and post-translational modifications are responsible for regulating gene expression. Here, we focus on breast and colorectal cancer as examples where utilizing circulating nucleosomes as biomarkers hold real potential as liquid biopsies. Utilizing circulating nucleosomes as biomarkers is an exciting new area of research that promises to allow both the early detection of cancer and monitoring of treatment response. Nucleosome-based biomarkers combine with current biomarkers, increasing both specificity and sensitivity of current tests and have the potential to provide individualised precision-medicine based treatments for patients.

Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options

BackgroundRecent studies have shown that breast cancer subtype can change from the primary tumour to the recurrence. Discordance between primary and recurrent breast cancer has implications for further treatment and ultimately prognosis. The aim of the study was to determine the rate of change between primary and recurrence of breast cancer and to assess the impact of these changes on survival and potential treatment options.MethodsPatient demographics were collected on those who underwent surgery for breast cancer between 2001 and 2014 and had a recurrence with biopsy results and pathology scoring of both the primary and recurrence.ResultsOne hundred thirty two consecutive patients were included. There were 31 (23.5%) changes in subtype. Discordance occurred most frequently in luminal A breast cancer (n = 20), followed by triple negative (n = 4), luminal B (n = 3) and HER2 (n = 3). Patients who changed from luminal A to triple negative (n = 18) had a significantly worse post-recurrence survival (p < 0.05) with overall survival approaching significance (p = 0.064) compared to concordant luminal A cases (n = 46). Overall receptor discordance rates were: estrogen receptor 20.4% (n = 27), progesterone receptor 37.7% (n = 50) and HER2 3% (n = 4). Loss of estrogen receptor and progesterone receptor was more common than gain (21 vs. 6 (p = 0.04) and 44 vs. 6 (p = 0.01) respectively). Nine patients (6.8%) gained receptor status potentially impacting treatment options.ConclusionDiscordance in subtype and receptor status occurs between primary and recurrent breast cancer, ultimately affecting survival and potentially impacting treatment options.

Correction to: Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options

It has been highlighted that the original manuscript [1] contains a typesetting error regarding the authorship.

Tu1814 What Is the Diameter of the Gastroesophageal Junction Produced During Nissen Fundoplication Surgery

Introduction It has been previously demonstrated that the gastroeseophgeal junction (GEJ) may be visualized during laparoscopic Nissen fundoplication (LNF) surgery using a standardized technique, EndoFLIP (Crospon, Galway, Ireland). We sought to determine if the dimensions of the wrap are associated with post-operative morbidity. Methods and Procedures An EndoFLIP model EF-325 catheter was used. This catheter has an 8cm long image field and provides 16 diameter measurements 5mm apart. The EndoFLIP system was used to inflate the balloon catheter with 30mL of a calibrated diluted saline solution. It was deployed transorally to the stomach, and then pulled back into the GEJ, to a point where the GEJ was observed to be located centrally within the balloon. The minimum diameter of the GEJ was noted from the EndoFLIP system (a) prior to commencement of the procedure once pneumoperitoneum had been established (b) after crural repair and (c) after completion of the wrap stitches. Patients were interviewed to determine if they had experienced any of the following symptoms in the first 90 days after surgery a) Dysphagia b) Inability to burp c) Nausea d) Excess flatulence. If they experienced any of these symptoms they were scored as having experienced post-operative morbidity. 3 patients who were lost to follow up were classed as not having post-operative morbidity. The diameters at each step were compared between the group of patients who experienced post-operative morbidity and those who did not experience post-operative morbidity. Results LNF operations were performed on 23 patients (15M). Mean age was 51 years (range 25-77). 11 patients (6 male) experienced symptoms (group A) and 12(9 male) did not (group B). The mean (SEM) age of group A was 56.9(4.0) years and for group B was 46.2(4.0) years. Table 1 shows the diameters (SEM) which were measured for both groups. Conclusion We observed that patients who experienced symptoms had a wrap diameter on average 1.1mm tighter than those that did not with a strong trend to statistical significance. Use of EndoFLIP to titrate wrap diameter to approximately 7 mm may offer the potential to reduce post-operative symptoms experienced after LNF. Further studies are planned to evaluate if the percentage of patients experiencing symptoms can be reduced by applying this intra-operative titration strategy. Diameter measurements for patients with and without post-operative symptoms

Tu1813 Is Post-Operative Morbidity Associated With Dimensions of the Wrap Created During Laparoscopic Nissen Fundoplication ?

Introduction It has been previously demonstrated that the gastroeseophgeal junction (GEJ) may be visualized during laparoscopic Nissen fundoplication (LNF) surgery using a standardized technique, EndoFLIP (Crospon, Galway, Ireland). We sought to determine if the dimensions of the wrap are associated with post-operative morbidity. Methods and Procedures An EndoFLIP model EF-325 catheter was used. This catheter has an 8cm long image field and provides 16 diameter measurements 5mm apart. The EndoFLIP system was used to inflate the balloon catheter with 30mL of a calibrated diluted saline solution. It was deployed transorally to the stomach, and then pulled back into the GEJ, to a point where the GEJ was observed to be located centrally within the balloon. The minimum diameter of the GEJ was noted from the EndoFLIP system (a) prior to commencement of the procedure once pneumoperitoneum had been established (b) after crural repair and (c) after completion of the wrap stitches. Patients were interviewed to determine if they had experienced any of the following symptoms in the first 90 days after surgery a) Dysphagia b) Inability to burp c) Nausea d) Excess flatulence. If they experienced any of these symptoms they were scored as having experienced post-operative morbidity. 3 patients who were lost to follow up were classed as not having post-operative morbidity. The diameters at each step were compared between the group of patients who experienced post-operative morbidity and those who did not experience post-operative morbidity. Results LNF operations were performed on 23 patients (15M). Mean age was 51 years (range 25-77). 11 patients (6 male) experienced symptoms (group A) and 12(9 male) did not (group B). The mean (SEM) age of group A was 56.9(4.0) years and for group B was 46.2(4.0) years. Table 1 shows the diameters (SEM) which were measured for both groups. Conclusion We observed that patients who experienced symptoms had a wrap diameter on average 1.1mm tighter than those that did not with a strong trend to statistical significance. Use of EndoFLIP to titrate wrap diameter to approximately 7 mm may offer the potential to reduce post-operative symptoms experienced after LNF. Further studies are planned to evaluate if the percentage of patients experiencing symptoms can be reduced by applying this intra-operative titration strategy. Diameter measurements for patients with and without post-operative symptoms