• Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?

      Kavanagh, Dara O; Chambers, Gillian; O'Grady, Liam; Barry, Kevin M; Waldron, Ronan P; Bennani, Fadel; Eustace, Paul W; Tobbia, Iqdam; Department of Surgery, Mayo General Hospital, Castlebar, Co Mayo, Ireland., dara_kav@hotmail.com (2012-01-31)
      BACKGROUND: The development of novel chemotherapeutic agents in colorectal cancer has improved survival. Following initial response to chemotherapeutic strategies many patients develop refractory disease. This poses a significant challenge common to many cancer subtypes. Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer. Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer. This may play a role in colorectal cancer. We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer. METHODS: Clinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital. Twenty-six contained non-malignant disease. Her-2/neu protein overexpression was detected using immunohistochemistry (IHC). The HER-2 4B5 Ventana monoclonal antibody was used. Fluorescent insitu hybridisation (FISH) was performed using INFORM HER-2/Neu Plus. Results were correlated with established clinical and pathological predictors of outcome including TNM stage. Statistical analysis was performed using SPSS version 11.5. RESULTS: 114 were HER-2/Neu negative using IHC, 7 showed barely perceptible positivity (1+), 9 showed moderate staining (2+) and 2 were strongly positive (3+). There was no correlation with gender, age, grade, Dukes' stage, TNM stage, time to recurrence and 5-year survival (p > 0.05). FISH was applied to all 2+ and 3+ cases as well as some negative cases selected at random. Three were amplified (2 were 3+ and 1 was 2+). Similarly, HER-2 gene overexpression did not correlate with established prognostic indicators. CONCLUSION: HER-2 protein is over expressed in 11% of colorectal cancer patients. The gene encoding HER-2 is amplified in 3% of cases. Overexpression of HER-2 is not a predictor of outcome. However, patients who over express HER-2 may respond to Herceptin therapy.
    • Mortality in perforated duodenal ulcer depends upon pre-operative risk: a retrospective 10-year study.

      Larkin, J O; Bourke, M G; Muhammed, A; Waldron, R; Barry, K; Eustace, P W; Department of Surgery, Mayo General Hospital, Castlebar, Co., Mayo, Ireland., larkin.dundalk@gmail.com (2012-01-31)
      INTRODUCTION: Most patients presenting with acutely perforated duodenal ulcer undergo operation, but conservative treatment may be indicated when an ulcer has spontaneously sealed with minimal/localised peritoneal irritation or when the patient's premorbid performance status is poor. We retrospectively reviewed our experience with operative and conservative management of perforated duodenal ulcers over a 10-year period and analysed outcome according to American Society of Anesthesiologists (ASA) score. METHODS: The records of all patients presenting with perforated duodenal ulcer to the Department of Surgery, Mayo General Hospital, between January 1998 and December 2007 were reviewed. Age, gender, co-morbidity, ASA-score, clinical presentation, mode of management, operative procedures, morbidity and mortality were considered. RESULTS: Of 76 patients included, 48 (44 operative, 4 conservative) were ASA I-III, with no mortality irrespective of treatment. Amongst 28 patients with ASA-score IV/V, mortality was 54.5% (6/11) following operative management and 52.9% (9/17) with conservative management. CONCLUSION: In patients with a perforated duodenal ulcer and ASA-score I-III, postoperative outcome is uniformly favourable. We recommend these patients have repair with peritoneal lavage performed, routinely followed postoperatively by empirical triple therapy. Given that mortality is equivalent between ASA IV/V patients whether managed operatively or conservatively, we suggest that both management options are equally justifiable.
    • Recurrent sigmoid volvulus - early resection may obviate later emergency surgery and reduce morbidity and mortality.

      Larkin, J O; Thekiso, T B; Waldron, R; Barry, K; Eustace, P W; Department of Surgery, Mayo General Hospital, Castlebar, Co. Mayo, Ireland., larkin.dundalk@gmail.com (2012-01-31)
      INTRODUCTION: Acute sigmoid volvulus is a well recognised cause of acute large bowel obstruction. PATIENTS AND METHODS: We reviewed our unit's experience with non-operative and operative management of this condition. A total of 27 patients were treated for acute sigmoid volvulus between 1996 and 2006. In total, there were 62 separate hospital admissions. RESULTS: Eleven patients were managed with colonoscopic decompression alone. The overall mortality rate for non-operative management was 36.4% (4 of 11 patients). Fifteen patients had operative management (five semi-elective following decompression, 10 emergency). There was no mortality in the semi-elective cohort and one in the emergency surgery group. The overall mortality for surgery was 6% (1 of 15). Five of the seven patients managed with colonoscopic decompression alone who survived were subsequently re-admitted with sigmoid volvulus (a 71.4% recurrence rate). The six deaths in our overall series each occurred in patients with established gangrene of the bowel. With early surgical intervention before the onset of gangrene, however, good outcomes may be achieved, even in patients apparently unsuitable for elective surgery. Eight of the 15 operatively managed patients were considered to be ASA (American Society of Anesthesiologists) grade 4. There was no postoperative mortality in this group. CONCLUSIONS: Given the high rate of recurrence of sigmoid volvulus after initial successful non-operative management and the attendant risks of mortality from gangrenous bowel developing with a subsequent volvulus, it is our contention that all patients should be considered for definitive surgery after initial colonoscopic decompression, irrespective of the ASA score.
    • Squamous cell carcinoma of the anal canal.

      Martin, F T; Kavanagh, D; Waldron, R; Department of Colorectal Surgery, Mayo General Hospital, Castlebar, Co. Mayo,, Ireland. fiachra1978@yahoo.com (2012-01-31)
      Squamous cell carcinoma ofthe anal canal represents 1.5% of all malignancies affectingthe gastrointestinal tract. Over the past 20 years dramatic changes have been seen in both the epidemiological distribution of the disease and in the therapeutic modalities utilised to manage it. CLINICAL MANAGEMENT: Historically abdominoperineal resection had been the treatment of choice with local resection reserved for early stage disease. Work by Nigro et al. has revolutionised how we currently manage carcinoma of the anal canal, demonstrating combined modality chemoradiotherapy as an appropriate alternative to surgical resection with the benefit of preserving sphincter function. Surgery is then reserved for recurrent disease with salvage abdominoperineal resection. This article reviews current literature and highlights the changing therapeutic modalities with selected clinical cases