Oliver J. McAnena

Differential miRNA Expression in Omental Adipose Tissue and in the Circulation of Obese Patients Identifies Novel Metabolic Biomarkers

BACKGROUND Omental fat accumulation is associated with development of the metabolic syndrome, although its molecular characteristics are poorly understood. Mi(cro)RNAs (miRNAs), a class of small noncoding RNAs, are known to regulate various metabolic processes, although their role in obesity and the metabolic syndrome is not clearly defined. This study sought to characterize the miRNA expression in omentum, sc fat and in the circulation of obese and nonobese individuals. Their potential as noninvasive metabolic biomarkers was also explored. METHODS miRNA was extracted from paired omentum and sc fat tissues, and blood samples, from a total of 50 obese and nonobese patients. A miRNA microarray was performed and a panel of differentially expressed miRNAs validated using RQ-PCR. RESULTS The miRNA expression profiles were unique for omentum and paired sc fat; no correlation in miRNA expression was observed between these two fat depots. Expression of two miRNAs (miR-17-5p and miR-132) differed significantly between obese and nonobese omental fat (P = 0.048 and P = 0.016). This expression pattern was reflected in the circulation in which these same two miRNAs were also significantly dysregulated in blood from obese subjects. The miRNA expression in omental fat and blood from obese patients correlated significantly with body mass index, fasting blood glucose, and glycosylated hemoglobin. CONCLUSION This study demonstrates that candidate metabolic miRNAs are altered in adipose tissue and circulation of the obese. Omental fat tissue and systemic miRNA levels reflect components of the metabolic syndrome, highlighting their potential as novel biomarkers for this complex syndrome.

MicroRNA signature analysis in colorectal cancer: identification of expression profiles in stage II tumors associated with aggressive disease

PurposeColorectal cancer (CRC) is a clinically diverse disease whose molecular etiology remains poorly understood. The purpose of this study was to identify miRNA expression patterns predictive of CRC tumor status and to investigate associations between microRNA (miRNA) expression and clinicopathological parameters.MethodsExpression profiling of 380 miRNAs was performed on 20 paired stage II tumor and normal tissues. Artificial neural network (ANN) analysis was applied to identify miRNAs predictive of tumor status. The validation of specific miRNAs was performed on 102 tissue specimens of varying stages.ResultsThirty-three miRNAs were identified as differentially expressed in tumor versus normal tissues. ANN analysis identified three miRNAs (miR-139-5p, miR-31, and miR-17-92 cluster) predictive of tumor status in stage II disease. Elevated expression of miR-31 (p = 0.004) and miR-139-5p (p < 0.001) and reduced expression of miR-143 (p = 0.016) were associated with aggressive mucinous phenotype. Increased expression of miR-10b was also associated with mucinous tumors (p = 0.004). Furthermore, progressively increasing levels of miR-10b expression were observed from T1 to T4 lesions and from stage I to IV disease.ConclusionAssociation of specific miRNAs with clinicopathological features indicates their biological relevance and highlights the power of ANN to reliably predict clinically relevant miRNA biomarkers, which it is hoped will better stratify patients to guide adjuvant therapy.

Acta from the EndoFLIP® Symposium.

Laparoscopic fundoplication (LF) is a surgical treatment for gastroesophageal reflux disease (GERD) that has been performed for more than 20 years. High-volume centers of excellence report long-term success rates greater than 90% with LF. On the other hand, general population-based outcomes are reported to be markedly worse, leading to a nihilistic perception of the procedure on the part of the medical referral population. The lack of standardization of the technique and the lack of tools to calibrate objectively the repairs are probably among the causes of variability in the outcomes and may explain the decline in the number of LF procedures in recent years. The functional lumen imaging probe (EndoFLIP®) device is essentially a “smart bougie” in the form of a balloon catheter that measures shape and compliance of the gastroesophageal junction (GEJ) during surgery using impedance planimetry. With approximately 3 years of international experience gained with this tool, a symposium was convened in October 2012 in Strasbourg, France, with the aim of determining if intraoperative EndoFLIP use could provide standardization of surgical treatment of GERD through the understanding of physiological changes occurring to the GEJ during fundoplication. This article provides a brief history of the EndoFLIP system and reviews data previously published on the use of EndoFLIP to characterize the GEJ in normal subjects. It then summarizes the data from the 5 high-volume international sites with expert surgeons performing LF presented in Strasbourg to objectively profile the characteristics of a normal postoperative GEJ.

Increased use of multidisciplinary treatment modalities adds little to the outcome of rectal cancer treated by optimal total mesorectal excision.

PurposeTotal mesorectal excision (TME) is the standard surgical treatment for rectal cancer. The roles of chemotherapy and radiotherapy have become more defined, accompanied by improvements in preoperative staging and histopathological assessment. We analyse our ongoing results in the light of changing patterns of treatment over consecutive time periods.MethodsIn total, 151 consecutive patients underwent potentially curative rectal excision for cancer in a single institution. Management and outcomes were compared between 1993–1999 and 2000–2007 which corresponded with the restructuring of the regional oncological services.ResultsWe found an increase in patients treated with neoadjuvant chemoradiotherapy after 1999 (20/89 vs 1/62, p < 0.001). There was an increase in the mean number of lymph nodes examined (11.9 vs 9.4, p = 0.037). The locoregional recurrence rate was 5.3%. The rates were not significantly different between the two study periods [4/89 (4.5%) 1999–2007 vs 4/62 (6.5%) 1993–1999, p = 0.597]. There was no statistical difference in overall or disease-free survival in the time periods examined.ConclusionsIncreasing use of neoadjuvant therapy and concomitant improvement in lymph node assessment did not translate into a concurrent reduction in the local recurrence, disease-free and overall survival rates. Our results demonstrate the enduring benefit of specialist training in TME in the outcome of rectal cancer surgery. This observational study suggests that low local recurrence rates are surrogate markers for improved overall and disease-free survival. Multidisciplinary team practice should be examined and made cost effective according to the individual unit’s local recurrence rate in the light of this and other reports.

Primary splenic lymphoma presenting with ascites

An 84 year-old gentleman presented with abdominal distension, anorexia and occasional epigastric pain over a four-week period. Blood parameters revealed a hypochromic microcytic anaemia. Both CT and US scan identified ascites and a mass in the left upper quadrant. An ascitic tap was performed identifying bloody ascites and the presence of reactive mesothelial cells on cytology. A subsequent laparotomy and splenectomy was performed. Histology of the resected spleen revealed a Grade 2 follicular lymphoma (Figure 2). The patient had an uneventful postoperative recovery and was well at 6 months follow up. The spleen is an organ with an important immunological function. Primary splenic involvement occurs in less than 1% of non-hodgkin’s lymphoma. Symptoms of primary splenic lymphoma (PSL) include pyrexia, weight-loss, night sweats, generalised weakness and left upper quadrant pain secondary to spleno - megaly. Ascites is a rare presenting feature of PSL. This report illustrates a case of primary splenic lymphoma which poses diagnostic challenges for the pathologist and clinician and ultimately requires definitive splenectomy to confirm a diagnosis. Figure 2 Photograph of histology slide displaying the lymphoma at 10× magnification.

Awareness and Uptake of Family Screening in Patients Diagnosed with Colorectal Cancer at a Young Age

Background. One-fifth of people who develop colorectal cancer (CRC) have a first-degree relative (FDR) also affected. There is a large disparity in guidelines for screening of relatives of patients with CRC. Herein we address awareness and uptake of family screening amongst patients diagnosed with CRC under age 60 and compare guidelines for screening. Study Design. Patients under age 60 who received surgical management for CRC between June 2009 and May 2012 were identified using pathology records and theatre logbooks. A telephone questionnaire was carried out to investigate family history and screening uptake among FDRs. Results. Of 317 patients surgically managed for CRC over the study period, 65 were under age 60 at diagnosis (8 deceased). The mean age was 51 (30–59). 66% had node positive disease. 25% had a family history of colorectal cancer in a FDR. While American and Canadian guidelines identified 100% of these patients as requiring screening, British guidelines advocated screening for only 40%. Of 324 FDRs, only 40.9% had been screened as a result of patients diagnosis. Conclusions. Uptake of screening in FDRs of young patients with CRC is low. Increased education and uniformity of guidelines may improve screening uptake in this high-risk population.

Surgery for oesophageal cancer at Galway University Hospital 1993–2008

BackgroundSurgical volume and outcome remain controversial in the management of oesophageal cancer.AimsTo assess the outcome of oesophagectomy for cancer at Galway University Hospital (GUH).MethodsBetween 1994 and 2008, patients who underwent oesophagectomy were analysed.ResultsDuring the study period, 126 oesophagectomies were performed for cancer. The average surgeon volume was 9 cases per year. The 30-day and overall in-hospital mortality rates were 6.3 and 7.9%, respectively. Restructuring of our critical care services has led to a reduction in 30-day mortality from 8.2 to 5.1%. The use of neoadjuvant chemoradiotherapy has increased from 17 to 35% during the study period. In patients who underwent resection, the 3 and 5-year overall survival rates were 45 and 29%, respectively.ConclusionsOperative morbidity and mortality at GUH are comparable with worldwide outcomes. Improved resources and national restructuring of cancer services have significantly improved the quality of care and outcomes of patients.

Sustained weight loss and improvement of quality of life after laparoscopic adjustable gastric banding for morbid obesity: a single surgeon experience in Ireland

BackgroundAlthough substantial weight loss is the primary outcome following bariatric surgery, changes in obesity-related morbidity and quality of life (QoL) are equally important. This study reports on weight loss, QoL and health outcomes following laparoscopic adjustable gastric banding (LAGB).MethodsBariatric analysis and reporting outcome system questionnaire survey was carried out on patients who had LAGB. Patients’ body weight, body mass index, QoL and co-morbidities were recorded.ResultsTwenty-three of 26 patients answered the questionnaire (response rate of 92%). Fifteen patients (60%) achieved over 50% excess weight loss. Twenty-two patients (84.6%) reported improvement in QoL. Co-morbidities in 18 patients (75%) resolved or improved. One patient had postoperative aspiration pneumonia and no other morbidity was recorded.ConclusionsLaparoscopic adjustable gastric banding is a safe and feasible method of bariatric surgery. It can achieve satisfactory weight loss with significant improvement in QoL and co-morbidity provided patients undergo thorough preoperative preparation and rigorous postoperative follow-up.

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