• Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.

      Dillon, J P; Laing, A J; Cahill, R A; O'Brien, G C; Street, J T; Wang, J H; Mc Guinness, A; Redmond, H P; Department of Academic Surgery and Orthopaedics, Cork University Hospital and, National University of Ireland, Cork, Ireland. dillionjp@o2.ie (2012-02-03)
      Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.
    • Co-immunotherapy with interleukin-2 and taurolidine for progressive metastatic melanoma.

      O'Brien, G C; Cahill, R A; Bouchier-Hayes, D J; Redmond, H P; Dept of Academic Surgery, Cork University Hospital and NUI. (2012-02-03)
      BACKGROUND: Recombinant interleukin-2(rIL-2) therapy in metastatic melanoma is limited by toxicities, particularly vascular leak syndrome(VLS). Taurolidine potentiates the anti-neoplastic effects of IL-2 while reducing its associated endothelial cell dysfunction in experimental settings. We hypothesized that co-administration of rIL-2 with taurolidine could enhance tolerability without weakening effectiveness. METHODS: Eleven patients with progressive metastatic melanoma received high-dose rIL-2 with co-infusion of taurolidine. Patients were monitored for the development of toxicities and evidence of response. RESULTS: Ten patients tolerated twenty-nine courses of high-dose rIL-2 without dose-reduction. Most toxicities were low-grade. No patient developed VLS. Seven patients died from disease progression. Two had complete clinical and radiological responses to treatment. Two patients remain alive despite evidence of disease progression a mean of 17.5 months after diagnosing metastatic disease. CONCLUSION: Co-administration of taurolidine with high-dose rIL-2 in stage IV melanoma patients appears to greatly enhance the tolerability of this regime without diminishing its therapeutic value.
    • The impact of bone marrow micrometastases on metastatic disease-free survival in patients with colorectal carcinoma.

      O'Connor, O J; Cahill, R A; Kirwan, W O; Redmond, H P; Department of Academic Surgery, Cork University Hospital, Wilton, Cork, Ireland. (2012-02-03)
      AIMS: The biological relevance of bone marrow micrometastases (BMM) in colorectal cancer remains unknown. Here, we investigate their nature by examining the impact of the presence of BMM on metastatic disease-free survival in a cohort of patients with this disease. METHODS: Sixty-three consecutive patients undergoing surgery for colorectal cancer of any stage were studied after approval of the study protocol by the local ethics committee and with full individual informed consent. All had bilateral iliac crest bone marrow aspirates prior to operation. Aspirates were then examined for the presence of aberrant cytokeratin-18-positive cells by a blinded observer using both flow cytometric and APAAP immunohistochemical techniques. RESULTS: Mean follow-up after surgery was 4.6 years (range 1.9-6.9) for those without hepatic metastases at diagnosis. Seven of 34 patients with Dukes' stage A or B developed metastatic disease after a mean interval of 4.7 years (range 3.8-6.8). However, only 2 of these patients demonstrated BMM at the time of surgery. Nine of 15 patients with Dukes' C carcinoma at the time of surgery subsequently developed metastases after a mean interval of 4.4 years (range 1.9-6.9). Again, only two of these patients had BMM detectable initially. In only three of the 14 patients known to have metastases at the time of operation (i.e. Dukes''D' disease) were BMM found. CONCLUSION: The presence of BMM as detected by this methodology was not predictive of tumour recurrence or metastasis. This study does not support the consideration of adjuvant therapy based on the presence of BMM at a single pre-operative time point in patients with colorectal cancer.
    • The incidence of postoperative venous thrombosis among patients with ulcerative colitis.

      O'Connor, O J; Cahill, R A; Kirwan, W O; Redmond, H P; Dept of Academic Surgery, Cork University Hospital, Wilton, Cork. (2012-02-03)
      BACKGROUND: Patients with Ulcerative Colitis (UC) have inherent prothrombotic tendencies. It is unknown whether this necessitates the use of additional perioperative anti-thrombotic prophylaxis when such patients require major surgery. METHODS: The postoperative courses of 79 patients with UC undergoing 180 major abdominal and pelvic operations were examined for clinical and radiological evidence of venous thrombosis. Eighteen patients with Familial Adenomatous Polyposis (FAP) having surgery (35 operations) of similar magnitude were also studied. Standard anti-thrombosis prophylaxis was utilised in all patients. RESULTS: Nine patients with UC were clinically suspected of developing postoperative venous thrombosis, but only three (3.8%) had their diagnosis confirmed radiologically (all had a pulmonary embolus). Therefore, the overall postoperative thrombosis rate, on an intention to treat basis, was 1.7% (3/180). No patient with FAP developed significant venous thrombosis. CONCLUSION: Standard perioperative antithrombotic modalities are sufficient to maintain any potential increase in postoperative thrombotic risk at an acceptable level in patients with UC undergoing operative intervention.
    • Influence of delays on perforation risk in adults with acute appendicitis.

      Kearney, D; Cahill, R A; O'Brien, E; Kirwan, W O; Redmond, H P; Department of Surgery, Cork University Hospital, Cork, Ireland. (2012-02-03)
      PURPOSE: This study analyzed whether prehospital or in-hospital delay was the more significant influence on perforation rates for acute appendicitis and whether any clinical feature designated patients requiring higher surgical priority. METHODS: A retrospective analysis was conducted over one year at a tertiary referral hospital without a dedicated emergency surgical theater. Admission notes, theater logbook, and the Hospital Inpatient Enquiry system were reviewed to identify the characteristics and clinical course of patients aged greater than 16 years who were operated upon for histologically confirmed acute appendicitis. RESULTS: One hundred and fifteen patients were studied. The overall perforation rate was 17 percent. The mean duration of symptoms prior to hospital presentation was 38.1 hours with the mean in-hospital waiting time prior to operation being 23.4 hours. Although body temperature on presentation was significantly greater in patients found to have perforated appendicitis (P < 0.05), only patient heart rate at presentation and overall duration of symptoms, but not in-hospital waiting time, independently predicted perforation by stepwise linear regression modeling. CONCLUSION: In-hospital delay was not an independent predictor of perforation in adults with acute appendicitis although delays may contribute if patients are left to wait unduly. Tachycardia at presentation may be a quantifiable feature of those more likely to have perforation and who should be given higher surgical priority.
    • The spectrum of urological disease in patients with spina bifida.

      Cahill, R A; Kiely, E A; Department of Urology, Cork University Hospital, Ireland. cahillronan@hotmail.com (2012-02-03)
      BACKGROUND: [corrected] Urological complications are the major cause of ill health during childhood and adult life of patients with spina bifida but the significance of urinary tract disease on the individual and the healthcare services is underemphasised. AIM: To assess the effects of spina bifida on the individual and the healthcare services. METHODS: A retrospective review was performed to assess the frequency and significance of urological conditions requiring hospital attendance in patients with spina bifida currently attending a specialised multidisciplinary clinic over a period of six months. RESULTS: Urinary sepsis accounted for the majority of admissions (62%), while 38 of 62 patients required 60 surgical procedures. Targeting the primary urological abnormality (the dysfunctional and usually poorly compliant bladder) allows implementation of effective treatments, including regular intermittent bladder catherisation (52%) in order to preserve upper renal tract function. Associated postural abnormalities complicated both conservative and interventional therapies. CONCLUSION: This study highlights the surgical commitment for units caring for patients with spina bifida, the important considerations for the future healthcare services, and the range and severity of urological diseases encountered by these patients.
    • Synchronous high-risk melanoma and lymphoid neoplasia.

      Cahill, R A; McGreal, G; Neary, P; Redmond, H P; Department of Surgery, N. U. I., Cork University Hospital, Wilton, Cork, Ireland. (2012-02-03)
      Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.