Faculty Bibliography

Mucinous colorectal cancer is a unique histological subtype that is known to respond poorly to cytotoxic chemotherapy and radiotherapy. There are a number of genes known to be associated with resistance to 5-fluorouracil (5-FU), oxaliplatin, and irinotecan. The aim of this study was to compare the somatic mutation frequency and copy number variation (CNV) in these genes between mucinous and non-mucinous colorectal cancer. A systematic search of PubMed was performed to identify papers investigating drug resistance in colorectal cancer. From this review, a list of 26 drug-resistance-associated genes was compiled. Using patient data from The Cancer Genome Atlas (TCGA), the somatic mutation rate and CNV was compared between patients with mucinous and non-mucinous colorectal cancer. Statistical analysis was carried out using GraphPad PRISM® version 5.00. Data were available on 531 patients (464 non-mucinous, 67 mucinous). A statistically significant difference in the somatic mutation rate between the two cohorts was identified in the TYMP (p = 0.0179), ATP7B (p = 0.0465), SRPK1 (p = 0.0135), ABCB1 (p = 0.0423), and ABCG2 (p = 0.0102) genes. A statistically significant difference in CNV was identified between the two cohorts in the GSTP1 (p = 0.0405), CCS (p = 0.0063), and TOP1 (p = 0.0048) genes. Differences in somatic mutation rate and CNV in genes associated with resistance to 5-FU, oxaliplatin, and irinotecan may partly account for the pattern of resistance observed in mucinous colorectal cancers. These genetic alterations may prove useful when deciding on a personalized approach to chemotherapy and may also represent potential therapeutic targets going forward.

Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Morphologic changes such as fibrosis, inflammatory infiltrates, and the formation of extracellular mucin pools can be identified in the resection specimen after neoadjuvant CRT. The association of mucin pool formation with clinicopathologic variables and outcomes is unclear. The aim of this study was to meta-analyze all available evidence with regard to mucin pool formation and clinicopathologic outcomes following neoadjuvant CRT for rectal cancer. A comprehensive search for published studies analyzing outcomes between patients who formed mucin pools and patients who did not following neoadjuvant CRT for rectal cancer was performed. A random-effects model was used to combine the data. This study adhered to the recommendations of the MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. Data from 11 studies describing 1947 patients were included. Mucin pool formation was not associated with sex, T stage, N stage, tumor regression, pathologic complete response rate, lymphovascular invasion, perineural invasion, differentiation, margin status, local or distant recurrence, and disease-free or overall survival. Mucin pool formation is not associated with tumor response or downstaging; furthermore, on the basis of these data, it is not associated with local or systemic recurrence rate or survival.

INTRODUCTION/BACKGROUND:Mucinous adenocarcinoma of the rectum is an infrequently encountered histological subtype that is associated with an impaired response to chemoradiotherapy and a worse overall prognosis. A genomic profile analysis of mucinous rectal tumors has not yet been performed. The aim of this study was to comprehensively describe the burden of somatic mutations and copy number variation as well as perform mutational signature and microbial analysis of an in-house collected cohort of mucinous adenocarcinoma of the rectum. METHODS:Genomic DNA was extracted from 10 cases of mucinous rectal cancer and matched normal tissue. Whole genome sequencing (WGS) was carried out on these 10 cases and a comprehensive bioinformatic analysis was undertaken. RESULTS:in tumor samples compared to normal tissue. CONCLUSION/CONCLUSIONS:This study provides a detailed WGS analysis of 10 cases of mucinous rectal cancer. It demonstrates an important lesson in tumor biology in that histologically similar tumors can have extensive differences at the genomic level. This study is relevant as it raises important questions about the relationship between bacteria and malignancy.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Mucinous adenocarcinoma is a distinct subtype of colorectal cancer (CRC) with a worse prognosis when compared with non-mucinous adenocarcinoma. The aim of this study was to compare somatic mutations and copy number alteration (CNA) between mucinous and non-mucinous CRC. METHODS:Data from The Cancer Genome Atlas-colon adenocarcinoma and rectum adenocarcinoma projects were utilized. Mucinous and non-mucinous CRC were compared with regard to microsatellite status, overall mutation rate, the most frequently mutated genes, mutations in genes coding for mismatch repair (MMR) proteins and genes coding for mucin glycoproteins. CNA analysis and pathway analysis was undertaken. RESULTS:Mucinous CRC was more likely to be microsatellite instability-high (MSI-H) and hypermutated. When corrected for microsatellite status the single-nucleotide variation and insertion-deletion rate was similar between the two cohorts. Mucinous adenocarcinoma was more likely to have mutations in genes coding for MMR proteins and mucin glycoproteins. Pathway analysis revealed further differences between the two histological subtypes in the cell cycle, RTK-RAS, transforming growth factor-β, and TP53 pathways. CONCLUSIONS:Mucinous CRC has some distinct genomic aberrations when compared with non-mucinous adenocarcinoma, many of which are driven by the increased frequency of MSI-H tumors. These genomic aberrations may play an important part in the difference seen in response to treatment and prognosis in mucinous adenocarcinoma.

BACKGROUND:Unplanned readmission after surgery negatively impacts surgical recovery. Few studies have sought to define predictors of readmission in a rectal cancer cohort alone. Readmission following rectal cancer surgery may be reduced by the identification and modification of factors associated with readmission. OBJECTIVES:This study seeks to characterize the predictors of 30-day readmission following proctectomy for rectal cancer. DESIGN:This study is a retrospective analysis of prospectively gathered cohort data. Outcomes were compared between readmitted and nonreadmitted patients. Multivariate analysis of factors association with readmission was performed by using binary logistic regression. SETTINGS:This study was conducted at Beaumont Hospital, a nationally designated, publicly funded cancer center. PATIENTS:Two hundred forty-six consecutive patients who underwent proctectomy for rectal cancer between January 2012 and December 2015 were selected. MAIN OUTCOME MEASURES:The primary outcomes measured were readmission within 30 days of discharge and the variables associated with readmission, categorized into patient factors, perioperative factors, and postoperative factors. RESULTS:Thirty-one (12.6%) patients were readmitted within 30 days of discharge following index rectal resection. The occurrence of anastomotic leaks, high-output stoma, and surgical site infections was significantly associated with readmission within 30 days (anastomotic leak OR 3.60, p = 0.02; high-output stoma OR 11.04, p = 0.003; surgical site infections OR 13.39, p = 0.01). Surgical site infections and high-output stoma maintained significant association on multivariate analysis (surgical site infections OR 10.02, p = 0.001; high-output stoma OR 9.40, p = 0.02). No significant difference was noted in the median length of stay or frequency of prolonged admissions (greater than 24 days) between readmitted and nonreadmitted patients. LIMITATIONS:The institutional database omits a number of socioeconomic factors and comorbidities that may influence readmission, limiting our capacity to analyze the relative contribution of these factors to our findings. CONCLUSIONS:An early postoperative care bundle to detect postoperative complications could prevent some unnecessary inpatient admissions following proctectomy. Key constituents should include early identification and management of stoma-related complications and surgical site infection. See Video Abstract at http://links.lww.com/DCR/A912.

BACKGROUND:Appendectomy has for many years been the accepted treatment of appendicitis. In recent years, non-operative management of appendicitis (NOTA) has been reported as an effective treatment option. AIMS/OBJECTIVE:We aimed to assess the perspectives of public hospital attendees regarding the diagnosis and treatment options for appendicitis. METHODS:We conducted a cross-sectional survey of outpatients over a 10-week period (December 2016-March 2017). The questionnaire contained an information sheet and consent form and included open, closed and multiple-choice questions. RESULTS:Two hundred forty-four participants (159 female, 85 male) were surveyed. A high level of awareness of appendicitis as a surgical emergency existed amongst the participants. The primary reason participants were reluctant to receive non-operative treatment was a fear of their appendix "bursting" if not removed. CONCLUSIONS:Participant knowledge levels were variable with many concerned that non-operated appendicitis would always perforate. Perceptions of treatment were variable with some believing surgery was an absolute requirement and others preferring antibiotics due to the belief that NOTA is complication-free.

BACKGROUND:Peri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised. METHODS:We conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence. RESULTS:A total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo (p = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group (p = 0.27). Surgical site infection was reduced in the Taurolidine treated group (p = 0.09). CONCLUSION/CONCLUSIONS:Peri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer. TRIAL REGISTRATION/BACKGROUND:The trial was registered with EudraCT (year = 2008, registration number =  005570-12 ) and ISRCTN (year = 2008, registration number =  77,829,558 ).

BACKGROUND:The treatment paradigm for acute diverticulitis is changing. There is an increasing trend towards managing patients with uncomplicated diverticulitis in the community. AIMS/OBJECTIVE:The aim of this study was to analyse how acute diverticulitis is managed in our institution and also to analyse national data pertaining to treatment of acute diverticulitis. METHODS:A prospective database of all patients admitted to our institution over a 2-year period (2014-2016) with acute diverticulitis was maintained. Severity of disease, treatment received and average length of stay (LOS) were analysed for all patients. Contemporaneous hospital inpatient enquiry (HIPE) data was interrogated to analyse current management for acute diverticulitis at a national level. RESULTS:One hundred twenty-six patients were admitted to our institution with acute diverticulitis during the study period (inpatient stay = €1277/night). Of patients, 59.5% had uncomplicated diverticulitis while 40.5% had complicated disease. The median LOS was 4 (range 1-34) days and 8 (range 2-51) days in the uncomplicated and complicated group, respectively. Based on HIPE data, there were 11,357 patients with uncomplicated diverticulitis and 526 patients with complicated diverticulitis admitted to Irish hospitals in the year 2015. Nationally, the median LOS for those with uncomplicated diverticulitis was 3 (range 1-142) days and for those with complicated diverticulitis the median LOS was 7 (range 1-308) days. Projected total cost for hospital stay nationally for uncomplicated diverticulitis amounted to €43.5 million for the year 2015. CONCLUSIONS:At present, uncomplicated diverticulitis in Ireland is not being managed as per evidence-based guidelines. Changing practice could result in significant cost savings for surgical departments.

OBJECTIVE:To construct and pilot an educational tool to improve the quality of postoperative documentation at Mayo University Hospital. DESIGN:Retrospective data were collected from 100 consecutive patients treated surgically during October to November 2016. The first written ward based note following surgery was analyzed against RCS quality standards outlined in "Good Surgical Practice." An educational tool was then constructed to improve postoperative documentation. The mnemonic created was POST-OP-physiotherapy/mobilization, operative diagnosis, sepsis, thromboprophylaxis, oral intake/fluid balance, and pain. A second audit cycle involving 103 patients was carried out prospectively in March 2017. SETTING:Mayo University Hospital, a 330 bed teaching hospital affiliated with the National University of Ireland, Galway. PARTICIPANTS:All patients who had undergone either an elective or an emergency general surgery procedure over two 5-week periods. RESULTS:Comparing the 2 study periods, significant improvements in the quality of postoperative surgical documentation was observed. All standards improved including patient identification (17.8% vs 78.1%, p < 0.001) and name of note maker (54.7% vs 86.2%, p < 0.001). There was also improvement in the documentation of antibiotic use (23.8% vs 75.8%, p > 0.001), thromboprophylaxis (7.1% vs 75.8%, p < 0.001), analgesia (36.9% vs 74.7%, p < 0.001), operative diagnosis (66.6% vs 91.9%, p < 0.001), and mobilization (23.6% vs 78.1%, p < 0.001) following the introduction of the POST-OP tool. CONCLUSION:The design and introduction of the POST-OP education tool helped to significantly improve documentation and educate surgical residents on the essential components of postoperative care. The above data suggest that this effective mnemonic can improve the quality of postoperative documentation for surgical patients.