Paul McCormick

A systematic review of laparoscopic versus open abdominal incisional hernia repair, with meta-analysis of randomized controlled trials.

INTRODUCTION Development of an incisional hernia after abdominal surgery is a common complication following laparotomy. Following recent advancements in laparoscopic and open repair a literature review has demonstrated no difference in the short term outcomes between open and laparoscopic repair, concluding there was no favourable method of repair over the other and that both techniques are appropriate methods of surgical repair. However, long term outcomes in the available literature between these two approaches were not clearly analysed or described. The objective of this study is to assess the effectiveness and safety of laparoscopic versus open abdominal incisional hernia repair, and to evaluate the short and long term outcomes in regards to hernia recurrence using meta-analysis of all randomised controlled trials from 2008 to end of 2013. STUDY AIMS AND OBJECTIVES POPULATION Patients who developed an abdominal hernia or abdominal incisional hernia following a laparotomy. INTERVENTION Two methods of surgical repair, laparoscopic and open abdominal wall hernia repair. Comparison: To compare between laparoscopic and open repair in abdominal wall incisional hernia. OUTCOME length of hospital stay, operation time, wound infection and hernia recurrence rate. METHODS This study is a systematic review on all randomized controlled trials of laparoscopic versus open abdominal wall and incisional hernia repair. Medline, Pubmed, Cochrane library, Cinahl and Embase were the databases interrogated. Inclusion & exclusion criteria had been defined. The relevant studies identified from January 2008 to December 2013, are included in the analysis. The primary end point can be described as hernia recurrence, and secondary outcomes can be described as length of hospital stay post operatively, operation time and wound infection. RESULTS Five randomized controlled trials (RCTs) were identified and included in the final analysis with a total number of 611 patients randomized. Three hundreds and six patients were in the laparoscopic group and 305 patients in the open repair group. The range of follow up in the studies was two months to 35 months. The recurrence rate was similar (P = 0.30), wound infection was higher in the open repair group (P < 0.001), length of hospital stay was not statistically different (P = 0.92), and finally the operation time was longer in the laparoscopic group but did not reach statistical significance (P = 0.05) CONCLUSION: The short and long-term outcomes of laparoscopic and open abdominal wall hernia repairs are equivalent; both techniques are safe and credible and the outcomes are very comparable.

Fast-track protocols in colorectal surgery

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.

Current targeted therapies in the treatment of advanced colorectal cancer: a review

Treatment strategies for metastatic colorectal cancer (mCRC) patients have undergone dramatic changes in the past decade and despite improved patient outcomes, there still exist areas for continued development. The introduction of targeted agents has provided clinicians with additional treatment options in mCRC, however, results have been mixed at best. These novel therapies were designed to interfere with specific molecules involved in the cellular carcinogenesis pathway and ultimately deliver a more focused treatment. Currently, their use in mCRC has been limited primarily as an adjunct to conventional chemotherapy regimens. This review explores the relevant cell-signaling networks in colorectal cancer, provides focus on the current targeted agent armamentarium approved for use in mCRC and explores the usefulness of predictive mCRC biomarkers.

Development and progress of Ireland's biobank network: Ethical, legal, and social implications (ELSI), standardized documentation, sample and data release, and international perspective.

Biobank Ireland Trust (BIT) was established in 2004 to promote and develop an Irish biobank network to benefit patients, researchers, industry, and the economy. The network commenced in 2008 with two hospital biobanks and currently consists of biobanks in the four main cancer hospitals in Ireland. The St. Jamess Hospital (SJH) Biobank coordinates the network. Procedures, based on ISBER and NCI guidelines, are standardized across the network. Policies and documents-Patient Consent Policy, Patient Information Sheet, Biobank Consent Form, Sample and Data Access Policy (SAP), and Sample Application Form have been agreed upon (after robust discussion) for use in each hospital. An optimum sequence for document preparation and submission for review is outlined. Once consensus is reached among the participating biobanks, the SJH biobank liaises with the Research and Ethics Committees, the Office of the Data Protection Commissioner, The National Cancer Registry (NCR), patient advocate groups, researchers, and other stakeholders. The NCR provides de-identified data from its database for researchers via unique biobank codes. ELSI issues discussed include the introduction of prospective consent across the network and the return of significant research results to patients. Only 4 of 363 patients opted to be re-contacted and re-consented on each occasion that their samples are included in a new project. It was decided, after multidisciplinary discussion, that results will not be returned to patients. The SAP is modeled on those of several international networks. Biobank Ireland is affiliated with international biobanking groups-Marble Arch International Working Group, ISBER, and ESBB. The Irish government continues to deliberate on how to fund and implement biobanking nationally. Meanwhile BIT uses every opportunity to promote awareness of the benefits of biobanking in events and in the media.

Re-laparoscopy in the diagnosis and treatment of postoperative complications following laparoscopic colorectal surgery

BACKGROUND Laparoscopic colorectal surgery has increasingly become the standard of care in the management of both benign and malignant colorectal disease. We herein describe our experience with laparoscopy in the management of complications following laparoscopic colorectal surgery. METHODS Between November 2010 and July 2012, data were prospectively collected for all patients requiring surgical intervention for colorectal cancer. This was performed by a full-time colorectal cancer data manager. RESULTS A total of 203 patients had surgery for colorectal cancer during this period, 154 (75.9%) of which were performed laparoscopically and 49 (24.1%) performed by open surgery. Ten patients (4.9%) underwent surgery for complications of which 7 were following laparoscopic surgery. Two of these 7 patients had an exploratory laparotomy due to abdominal distension and haemodynamic instability. Laparoscopic surgical intervention was successful in diagnosing and treating the remaining 5 patients. Three of these patients developed small bowel obstruction which was managed by re-laparoscopy while in 2 patients there was a significant suspicion of an anastomotic leakage despite appropriate diagnostic imaging which was out ruled at laparoscopy. CONCLUSIONS Laparoscopy can frequently be used to diagnose and treat complications following laparoscopic colorectal surgery. This is another benefit associated with laparoscopic colorectal surgery which is rarely described and allows the benefits associated with the laparoscopic approach to be maintained.

Protein kinase C beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival

Despite extensive efforts, cancer therapies directed at the Protein Kinase C (PKC) family of serine/threonine kinases have failed in clinical trials. These therapies have been directed at inhibiting PKC and have, in some cases, worsened disease outcome. Here we examine colon cancer patients and show not only that PKC Beta II is a tumour suppressor, but patients with low levels of this isozyme have significantly decreased disease free survival. Specifically, analysis of gene expression levels of all PKC genes in matched normal and cancer tissue samples from colon cancer patients revealed a striking down-regulation of the gene coding PKC Beta in the cancer tissue (n = 21). Tissue microarray analysis revealed a dramatic down-regulation of PKC Beta II protein levels in both the epithelial and stromal diseased tissue (n = 166). Of clinical significance, low levels of the protein in the normal tissue of patients is associated with a low (10%) 10 year survival compared with a much higher (60%) survival in patients with relatively high levels of the protein. Consistent with PKC Beta II levels protecting against colon cancer, overexpression of PKC Beta II in colon cancer cell lines reveals that PKC Beta II reverses transformation in cell based assays. Further to this, activation of PKC Beta II results in a dramatic downregulation of IGF-I-induced AKT, indicating a role for PKCs in regulating IGF-1 mediated cell survival. Thus, PKC Beta II is a tumour suppressor in colon cancer and low levels serve as a predictor for poor survival outcome.

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

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.

Six-Year Experience of a Nurse-Led Colorectal Cancer Follow-Up Clinic

Aims and Objectives. To review the experience of a nurse-led colorectal cancer follow-up clinic in a tertiary referral colorectal cancer centre. Methodology. Data from the nurse-led colorectal cancer follow-up clinic in our unit was prospectively maintained in a colorectal cancer database. Data was analysed from January 1, 2006 until the December 31, 2011. Results. 1125 patients were diagnosed with colorectal cancer, and referred to our unit as a tertiary centre for specialised colorectal cancer. Nine hundred and four patients had surgical resection of their colorectal cancer. Four hundred and seven patients were referred to the nurse-led colorectal cancer clinic for surveillance. The mean age of the patient cohort was 67 years (range 32–88) and 56% of patients were male. One hundred and seventeen patients were discharged to their general practitioner having been disease free after 5 years of followup. Fifty-four patients were diagnosed with either local or distant recurrence. Conclusion. A nurse-led colorectal cancer follow-up clinic is running according to strict follow-up protocols. This type of clinic significantly reduces the number of routine follow-up patients that have to be seen by the colorectal surgical consultant.

Partial Herniation Through the Peritoneal Defect of a Pfannenstiel Incision: A Rare Complication of Non-Closure

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.

Expression of protein kinase C gamma promotes cell migration in colon cancer

Despite extensive efforts, Protein Kinase Cs (PKCs) have proven to be an intractable target in cancer therapies. Traditionally it was accepted that PKCs act as tumour promoters, however new research suggests that PKCs may play an important role in the suppression of cancer. A challenge in targeting PKCs is the limited data available in patient samples. One of the PKC isozymes, PKC gamma, is thought to be present only in the brain and has been largely neglected in the context of cancer. Analysis of gene expression levels of PKC gamma in patient matched normal and colon cancer tissue samples revealed an up-regulation of the gene in the cancer tissue of 54% of the patients examined. Mechanistically we demonstrate that a reduction in the levels of PKC gamma in the colon cancer cells inhibits cell migration and foci formation. Further to this, we observe an increase in cell adhesion and proliferation following the reduction of PKC gamma levels in the cell. Thus, PKC gamma plays a key role in colon cancer; making it an important isozyme that needs to be reconsidered in the context of cancer therapies.Despite extensive efforts, Protein Kinase Cs (PKCs) have proven to be an intractable target in cancer therapies. Traditionally it was accepted that PKCs act as tumour promoters, however new research suggests that PKCs may play an important role in the suppression of cancer. A challenge in targeting PKCs is the limited data available in patient samples. One of the PKC isozymes, PKC gamma, is thought to be present only in the brain and has been largely neglected in the context of cancer. Analysis of gene expression levels of PKC gamma in patient matched normal and colon cancer tissue samples revealed an up-regulation of the gene in the cancer tissue of 54% of the patients examined. Mechanistically we demonstrate that a reduction in the levels of PKC gamma in the colon cancer cells inhibits cell migration and foci formation. Further to this, we observe an increase in cell adhesion and proliferation following the reduction of PKC gamma levels in the cell. Thus, PKC gamma plays a key role in colon cancer; making it an important isozyme that needs to be reconsidered in the context of cancer therapies.