Publications by authors named "Brian J Mehigan"

9 Publications

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Sigmoid volvulus: definitive surgery is safe and should be considered in all instances.

Ir J Med Sci 2021 Jul 29. Epub 2021 Jul 29.

Department of Colorectal Surgery, St James's Hospital, Dublin 8, Ireland.

Background: Acute sigmoid volvulus (ASV) represents a small but significant portion of cases of large bowel obstruction, especially in the elderly and co-morbid. Given the characteristics of the patient cohort most commonly affected, a non-operative/conservative approach is often undertaken but is associated with a high rate of recurrence.

Objective: We sought to evaluate outcomes for those patients who underwent non-operative management, emergency surgery or staged, semi-elective surgery following decompression for ASV at our institution.

Methods: Hospital in-patient enquiry (HIPE) data were used to identify all patients who presented with sigmoid volvulus between January 2005 and June 2020 inclusive. Patient notes were interrogated, including surgical and endoscopic procedures performed. Patient demographics and co-morbidities were recorded.

Results: Thirty-nine patients were treated over a 15-year period with a mean age of 73 years at first presentation (range 36-93). Twenty-two patients (56%) had just a single admission for ASV with three deaths in this group. Seventeen patients (44%) had more than one admission with volvulus due to recurrence after a decompression-only strategy on the index admission. Of these, three succumbed to complications of their subsequent episodes of volvulus. Twenty-five patients underwent surgical intervention (fifteen on, or shortly following, their first admission and ten following at least two admissions for ASV). The overall mortality in the operative group was 2/25 (8%) with both deaths in those undergoing emergency surgeries. Five patients were treated successfully with endoscopic measures alone and had required no further interventions at the time of compiling data.

Conclusion: There is a high recurrence rate following non-operative management of acute sigmoid volvulus and consequently, a cumulative increase in the attendant significant morbidity and mortality with subsequent episodes. Given the relatively low complication rate of definitive surgery, even in those patients perceived to be high risk, we contend that all patients should be considered for early surgery to prevent the likely recurrence of sigmoid volvulus.
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http://dx.doi.org/10.1007/s11845-021-02713-0DOI Listing
July 2021

Obesity and anastomotic leak rates in colorectal cancer: a meta-analysis.

Int J Colorectal Dis 2021 Sep 1;36(9):1819-1829. Epub 2021 Apr 1.

Department of Colorectal Surgery, St James's Hospital, Dublin, Ireland.

Purpose: Anastomotic leak (AL) following colorectal cancer resection is associated with considerable morbidity and mortality with an impact on recurrence rates and survival. The impact of obesity on AL rates is debated. This meta-analysis aims to investigate the relationship between obesity and AL.

Methods: A search was conducted of the PubMed/MEDLINE, and Web of Science databases and included studies were split into Western and Asian groups based on population-specific body mass index (BMI) ranges for obesity. A meta-analysis was performed to assess the impact of obesity on AL rate following colorectal cancer resection.

Results: Two thousand three hundred and four articles were initially screened. Thirty-one studies totaling 32,953 patients were included. Patients with obesity had a statistically significant increase in AL rate in all Western and Asian study groups. However, this increase was only clinically significant in the rectal anastomotic subgroups-Western: 10.8% vs 8.4%, OR 1.57 (1.01-2.44) and Asian: 9.4% vs 7.4%, OR 1.58 (1.07-2.32).

Conclusions: The findings of this analysis confirm that obesity is a significant risk factor for anastomotic leak, particularly in rectal anastomoses. This effect is thought to be primarily mediated via technical difficulties of surgery although metabolic and immunological factors may also play a role. Obesity in patients undergoing restorative CRC resection should be discussed and considered as part of the pre-operative counselling.
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http://dx.doi.org/10.1007/s00384-021-03909-7DOI Listing
September 2021

Combining 1,4-dihydroxy quininib with Bevacizumab/FOLFOX alters angiogenic and inflammatory secretions in ex vivo colorectal tumors.

BMC Cancer 2020 Oct 2;20(1):952. Epub 2020 Oct 2.

Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland.

Background: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality worldwide with one in every five patients diagnosed with metastatic CRC (mCRC). In mCRC cases, the 5-year survival rate remains at approximately 14%, reflecting the lack of effectiveness of currently available treatments such as the anti-VEGF targeting antibody Bevacizumab combined with the chemotherapy folinic acid, fluorouracil and oxaliplatin (FOLFOX). Approximately 60% of patients do not respond to this combined treatment. Furthermore, Bevacizumab inhibits dendritic cell (DC) maturation in poor responders, a key process for tumor eradication.

Method: Following drug treatment, secreted expression levels of angiogenic and inflammatory markers in tumor conditioned media generated from human ex vivo colorectal tumors were measured by ELISA. Dendritic cell phenotypic and maturation markers were assessed by flow cytometry.

Results: Our novel compound, 1,4-dihydroxy quininib, acts in an alternative pathway compared to the approved therapy Bevacizumab. 1,4-dihydroxy quininib alone, and in combination with Bevacizumab or FOLFOX significantly reduced TIE-2 expression which is involved in the promotion of tumor vascularization. Combination treatment with 1,4-dihydroxy quininib significantly increased the expression level of DC phenotypic and maturation markers.

Conclusion: Our results indicate the anti-angiogenic small molecule 1,4-dihydroxy quininib could be an alternative novel treatment in combination therapy for CRC patients.
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http://dx.doi.org/10.1186/s12885-020-07430-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532092PMC
October 2020

Prophylactic negative pressure wound therapy for closed laparotomy wounds: a systematic review and meta-analysis of randomised controlled trials.

Ir J Med Sci 2021 Feb 25;190(1):261-267. Epub 2020 Jun 25.

Department of Colorectal Surgery, St James's Hospital, Dublin, 8, Ireland.

Surgical site infections are a common source of post-operative morbidity and contribute significantly to healthcare costs. Patients undergoing emergency laparotomy and/or bowel surgery are particularly at risk. Prophylactic negative pressure wound therapy (NPWT) has been shown to reduce wound infection. However, to date, there has been a lack of consensus around its use for closed laparotomy wounds. We conducted a systematic review of randomised controlled trials comparing the use of prophylactic negative pressure wound therapy with standard dressings for closed laparotomy incisions. The primary outcome was incidence of incisional surgical site infection (SSI) at 30 days post-operatively. Secondary outcomes included superficial and deep SSI, skin dehiscence, fascial dehiscence and length of stay. A total of 2182 publications were identified, of which, following review of titles, abstracts and full texts, five studies met the criteria for inclusion. Across these studies, 467 patients were randomised to NPWT and 464 to standard dressings. Overall SSI rate was 18.6% (n = 87/467) versus 23.9% (n = 111/464) in the NPWT and standard dressing groups, respectively (Odds ratio 0.71, 95% CI 0.52-0.99, p = 0.04*). Deep SSI incidence was the same in both groups (2.6%). Both skin dehiscence and fascial dehiscence were slightly higher in the standard dressing group ((4.2%, n = 11/263 versus 3.1% (n = 8/261) and (0.9% (n = 3/324) versus 0.6% (n = 2/323)), respectively. This study observed that NPWT reduces the overall SSI for closed laparotomy wounds. It supports data recommending the use of prophylactic NPWT dressings, especially in high-risk patients in both emergency and elective circumstances.
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http://dx.doi.org/10.1007/s11845-020-02283-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315908PMC
February 2021

Screening for mismatch repair deficiency in colorectal cancer: data from three academic medical centers.

Cancer Med 2017 Jun 3;6(6):1465-1472. Epub 2017 May 3.

St. James's Hospital, Dublin 8, Ireland.

Reflex immunohistochemistry (rIHC) for mismatch repair (MMR) protein expression can be used as a screening tool to detect Lynch Syndrome (LS). Increasingly the mismatch repair-deficient (dMMR) phenotype has therapeutic implications. We investigated the pattern and consequence of testing for dMMR in three Irish Cancer Centres (CCs). CRC databases were analyzed from January 2005-December 2013. CC1 performs IHC upon physician request, CC2 implemented rIHC in November 2008, and CC3 has been performing rIHC since 2004. The number of eligible patients referred to clinical genetic services (CGS), and the number of LS patients per center was determined. 3906 patients were included over a 9-year period. dMMR CRCs were found in 32/153 (21%) of patients at CC1 and 55/536 (10%) at CC2, accounting for 3% and 5% of the CRC population, respectively. At CC3, 182/1737 patients (10%) had dMMR CRCs (P < 0.001). Additional testing for the BRAF V600E mutation, was performed in 49 patients at CC3 prior to CGS referral, of which 29 were positive and considered sporadic CRC. Referrals to CGS were made in 66%, 33%, and 30% of eligible patients at CC1, CC2, and CC3, respectively. LS accounted for CRC in eight patients (0.8%) at CC1, eight patients (0.7%) at CC2, and 20 patients (1.2%) at CC3. Cascade testing of patients with dMMR CRC was not completed in 56%. Universal screening increases the detection of dMMR tumors and LS kindreds. Successful implementation of this approach requires adequate resources for appropriate downstream management of these patients.
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http://dx.doi.org/10.1002/cam4.1025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463076PMC
June 2017

Activated systemic inflammatory response at diagnosis reduces lymph node count in colonic carcinoma.

World J Gastrointest Oncol 2016 Aug;8(8):623-8

Rory P Kennelly, Brenda Murphy, John O Larkin, Brian J Mehigan, Paul H McCormick, Department of Colorectal Surgery, St James Hospital, Dublin 8, Ireland.

Aim: To investigate a link between lymph node yield and systemic inflammatory response in colon cancer.

Methods: A prospectively maintained database was interrogated. All patients undergoing curative colonic resection were included. Neutrophil lymphocyte ratio (NLR) and albumin were used as markers of SIR. In keeping with previously studies, NLR ≥ 4, albumin < 35 was used as cut off points for SIR. Statistical analysis was performed using 2 sample t-test and χ(2) tests where appropriate.

Results: Three hundred and two patients were included for analysis. One hundred and ninety-five patients had NLR < 4 and 107 had NLR ≥ 4. There was no difference in age or sex between groups. Patients with NLR of ≥ 4 had lower mean lymph node yields than patients with NLR < 4 [17.6 ± 7.1 vs 19.2 ± 7.9 (P = 0.036)]. More patients with an elevated NLR had node positive disease and an increased lymph node ratio (≥ 0.25, P = 0.044).

Conclusion: Prognosis in colon cancer is intimately linked to the patient's immune response. Assuming standardised surgical technique and sub specialty pathology, lymph node count is reduced when systemic inflammatory response is activated.
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http://dx.doi.org/10.4251/wjgo.v8.i8.623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980653PMC
August 2016

Partial herniation through the peritoneal defect of a pfannenstiel incision: a rare complication of non-closure.

J Obstet Gynaecol Can 2011 Jun;33(6):625-627

Department of Colorectal Surgery, St James's Hospital, Dublin, Ireland.

Background: The Pfannenstiel incision is used almost invariably in Caesarean section. With Caesarean section rates increasing, the Pfannenstiel is a commonly performed incision. The prevailing recommendation is not to close the peritoneum when closing a Pfannenstiel incision, and peritoneal non-closure does not appear to statistically influence postoperative complication rates.

Case: A 33-year-old woman presented with severe, intermittent lower abdominal pain one year after a Caesarean section. Laparoscopy showed a hernial defect at the Pfannenstiel incision, between the left rectus abdominis muscle and the anterior rectus sheath. Mesh repair was performed with uncomplicated postoperative outcome.

Conclusion: The current case illustrates that complications specific to non-closure of the peritoneum do arise. We advocate that laparoscopy should be considered for any patient with persistent, severe, or atypical pain following a Pfannenstiel incision.
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http://dx.doi.org/10.1016/S1701-2163(16)34912-XDOI Listing
June 2011

Fast-track protocols in colorectal surgery.

Surgeon 2011 Apr;9(2):95-103

Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin/St James' Hospital, Dublin 8, Ireland.

Fast-track surgery (FTS) is a set of protocols aimed to reduce the physiological burden of surgery thus improving outcomes. FTS aims to use evidence-based practice to reduce complications, improve post-operative quality of life and decrease hospital length of stay. This review seeks to examine the evidence base for protocols employed in colorectal surgery in the areas of pre-operative preparation, anaesthetic management, intraoperative and surgical factors and post-operative care. Despite the evidence that recovery after colorectal surgery can be enhanced by using these approaches, implementation of FTS protocols has been slow. Acceptance of FTS protocols by all members of the multi-disciplinary team and a change in organisational structure to accommodate structured peri-operative care, are imperative to implementation.
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http://dx.doi.org/10.1016/j.surge.2010.07.013DOI Listing
April 2011

Mismatch repair, p53 and chromosomal aberrations in primary colorectal carcinomas.

Acta Oncol 2006 ;45(1):61-6

Postgraduate Medical Institute of the University of Hull and Hull York Medical School, University of Hull, UK.

Colorectal carcinoma progresses via at least two genetic pathways. Microsatellite instability, due to defective mismatch repair genes, characterizes one pathway and gross chromosomal instability another. The involvement of p53 and mismatch repair gene abnormalities within these pathways has not been fully explored. We aimed to investigate the relationships of p53 and mismatch repair gene defects on gross chromosomal aberrations detected by comparative genomic hybridization in 49 colorectal carcinomas. Tumours demonstrating loss of expression for hMLH1 or hMSH2 proteins demonstrated a highly significant attenuation in the number of gross chromosomal aberrations (p = 0.007) and were less likely to show p53 overexpression (p = 0.02). Within the mismatch repair normal tumours, p53 status did not affect the total number of chromosomal aberrations but p53 overexpression was significantly associated with a higher frequency of amplifications at 8q22-ter and at 13q21-22. Colorectal cancer demonstrates distinct molecular phenotypes and should be sub-classified accordingly.
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http://dx.doi.org/10.1080/02841860500374463DOI Listing
July 2006
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