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ABSTRACT: HTS significantly enhances neutrophil-mediated intracellular killing of bacteria. This provides further evidence of the beneficial
effects of hypertonic resuscitation in the critically ill patient.
Irish Journal of Medical Science 04/2012; 171:10-10. · 0.58 Impact Factor
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ABSTRACT: These findings demonstrate for the first time that taurolidine can inhibit angiogenesis in a dose-dependent manner. Taurolidine
may prevent VEGF-mediated angiogenesis and thus it may potentially inhibit the growth of dormant micrometastases following
surgical removal of a primary tumour.
Irish Journal of Medical Science 04/2012; 171:10-11. · 0.58 Impact Factor
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Irish Journal of Medical Science 04/2012; 171:11-11. · 0.58 Impact Factor
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ABSTRACT: Paediatric foreign body (FB) ingestion is a common problem and while most can be managed conservatively, a sub-population require intervention.
To establish clear guidelines for management of paediatric FB ingestion.
A retrospective chart review analysing all paediatric admissions with FB ingestion over a 10-year period from 1990 to 1999.
Of 339 patients presenting to the accident and emergency department with FB ingestion, 59 required admission. Ingestion was accidental in 93.0% of patients. The reasons for admission were as follows: large FBs; dangerous FBs; and living far from the hospital. Nineteen patients (32.2%) were discharged without intervention. Thirty-seven (62.7%) required endoscopic retrieval. In two, the FB was not identified at endoscopy. Only three (5%) required surgery.
Conservative management of FB ingestion in the paediatric population is possible in the majority of cases. However, a minority require intervention. While guidelines for intervention are ill-defined, definitive indications include symptomatic patients, or dangerous objects.
Irish Journal of Medical Science 04/2012; 170(2):100-2. · 0.58 Impact Factor
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ABSTRACT: BackgroundPatients 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.
MethodsThe 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.
ResultsNine 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.
ConclusionStandard 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.
Irish Journal of Medical Science 04/2012; 174(3):20-22. · 0.58 Impact Factor
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ABSTRACT: PurposeThis 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.
MethodsA 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 16years who were operated upon for histologically confirmed acute appendicitis.
ResultsOne 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.
ConclusionIn-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.
Diseases of the Colon & Rectum 04/2012; 51(12):1823-1827. · 3.13 Impact Factor
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M J Smith,
A C Culhane,
M Donovan,
J C Coffey,
B D Barry,
M A Kelly,
D G Higgins,
J H Wang, W O Kirwan,
T G Cotter,
H P Redmond
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ABSTRACT: Tumour stroma gene expression in biopsy specimens may obscure the expression of tumour parenchyma, hampering the predictive power of microarrays. We aimed to assess the utility of fluorescence-activated cell sorting (FACS) for generating cell populations for gene expression analysis and to compare the gene expression of FACS-purified tumour parenchyma to that of whole tumour biopsies. Single cell suspensions were generated from colorectal tumour biopsies and tumour parenchyma was separated using FACS. Fluorescence-activated cell sorting allowed reliable estimation and purification of cell populations, generating parenchymal purity above 90%. RNA from FACS-purified and corresponding whole tumour biopsies was hybridised to Affymetrix oligonucleotide microarrays. Whole tumour and parenchymal samples demonstrated differential gene expression, with 289 genes significantly overexpressed in the whole tumour, many of which were consistent with stromal gene expression (e.g., COL6A3, COL1A2, POSTN, TIMP2). Genes characteristic of colorectal carcinoma were overexpressed in the FACS-purified cells (e.g., HOX2D and RHOB). We found FACS to be a robust method for generating samples for gene expression analysis, allowing simultaneous assessment of parenchymal and stromal compartments. Gross stromal contamination may affect the interpretation of cancer gene expression microarray experiments, with implications for hypotheses generation and the stability of expression signatures used for predicting clinical outcomes.
British Journal of Cancer 06/2009; 100(9):1452-64. · 5.04 Impact Factor
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ABSTRACT: Aims: Acute hepatobiliary pathology is a common general surgical emergency, and diagnosis requires imaging of the biliary tree by ultrasound. Herein, we examine the accuracy and impact of surgeon-performed ultrasound (SUS) on the diagnosis of emergent hepatobiliary pathology.Methods: This prospective study, over a 6-month period, enrolled all patients with symptoms or signs of acute hepatobiliary pathology. Patients provided informed consent and underwent both SUS and standard radiology-performed ultrasound (RUS). SUS was performed using a 2–5 MHz broadband portable ultrasound probe by two surgeons trained in ultrasound and RUS using a 2–5 MHz fixed unit. SUS results were correlated with RUS and pathological diagnoses.Results: Fifty-three consecutive patients received a total of 106 ultrasound investigations. SUS agreed with RUS in 50 of the 53 patients (94.3 per cent). SUS accurately detected cholilithiasis in all but two cases and no patients were inaccurately diagnosed to have cholilithiasis at SUS (95 per cent sensitivity and 100 per cent specificity). As an overall complimentary diagnostic tool, SUS provided the correct diagnosis in 94 per cent of the patients. Time to scan was significantly shorter following SUS (3.07 h versus 12 h, P < 0.05).Conclusions: SUS offers excellent alacrity in the diagnosis of emergency hepatobiliary pathology. SUS may be a useful adjuvant in the emergency management of hepatobiliary disease.
British Journal of Surgery 01/2009; 89(S1):60 - 60. · 4.61 Impact Factor
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International Journal of Colorectal Disease 04/2008; 23(3):329-30. · 2.38 Impact Factor
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International Journal of Colorectal Disease 06/2007; 22(5):561-2. · 2.38 Impact Factor
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ABSTRACT: Endothelial progenitor cells (EPCs) derived from bone marrow incorporate into foci of neovascularization to propagate tumor growth. These cells are mobilized in response to surgical injury. Laparoscopic surgery may protect against the oncologic adverse effects of open surgical tumor excision, and this may be related to attenuated mobilization of EPCs.
For this study, 132 C57BL/6 mice were randomized to standardized laparotomy, laparoscopy, or control groups. The animals were killed at 6, 24, 48, and 72 h. Femur bone marrow and peripheral blood were harvested. Bone marrow EPCs were detected by flow cytometric dual staining for the stem cell antigen-1/cKit phenotype. Circulating EPCs were characterized in blood by vascular endothelial growth factor receptor 2 positive/macrophage activating complement-1 negative staining. Separately, 12 C57/bl6 mice bearing 3LL Lewis lung tumors 12 days after laparotomy or laparoscopy had their tumors excised and examined for endothelial cell expression (marker P1H12).
Laparoscopy decreased circulating EPCs and bone-marrow EPC levels, as compared with laparotomy, at all time points. Bone marrow EPC levels were 2.95% +/- 0.32% after laparotomy, as compared with 0.65 +/- 0.21 in the laparoscopy group (p < 0.05). The circulating EPC level in the laparotomy group was 35.2% +/- 6% of cells, as compared with 3.1% +/- 0.2% in the laparoscopy group (p < 0.05). In homogenized tumors, the percentage of P1H12 expression among laparoscopy-treated animals was 22.1% +/- 4.2%, as compared with 39% +/- 8% in the laparotomy group (p < 0.05).
Laparoscopy decreased EPC levels in both bone marrow and circulation, resulting in decreased tumor endothelial cell burden. This may represent a novel mechanism by which laparoscopy protects against the oncologic adverse effects of open surgical tumor excision.
Surgical Endoscopy 01/2007; 21(1):87-90. · 4.01 Impact Factor
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ABSTRACT: The resolution of pouchitis with metronidazole points to an anaerobic aetiology. Pouchitis is mainly seen in patients with ulcerative colitis pouches (UCP). We have recently found that sulphate reducing bacteria (SRB), a species of strict anaerobe, colonize UCP exclusively. Herein, we aimed to correlate levels of different bacterial species (including SRB) with mucosal inflammation and morphology.
Following ethical approval, fresh faecal samples and mucosal biopsies were taken from 9 patients with UCP and 5 patients with familial adenomatous polyposis pouches (FAPP). For the purposes of comparison, faecal samples and mucosal biopsies were also taken from the stomas of 7 of the 9 patients with UC (UCS). Colonization by four types of strict anaerobes (SRB, Clostridium perfringens, Bifidobacteria and Bacteroides) as well as by three types of facultative anaerobes (Enterococci, Coliforms and Lactobacilli) was evaluated. Inflammatory scores and mucosal morphology were assessed histologically in a blinded fashion by a pathologist.
In general, strict anaerobes predominated over facultative in the UCP (P = 0.041). SRB were present in UCP exclusively. Even after exclusion of SRB from total bacterial counts, strict anaerobes still predominated. In the UCS, facultative anaerobes predominated. Strict and facultative anaerobes were present at similar levels in the FAPP. Enterococci were present at significantly reduced levels in the UCP when compared with the UCS (P = 0.031). When levels of SRB and other anaerobic species were individually correlated with mucosal inflammation and morphology, no trends were observed.
We have previously identified that SRB exclusively colonize UCP. In addition we have now identified a novel increase in the strict/facultative anaerobic ratio within the UCP compared to UCS. These stark differences in bacterial colonization, however, appear to have limited impact on mucosal inflammation or morphology.
Colorectal Disease 12/2005; 7(6):563-70. · 2.93 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Colorectal Disease 08/2005; 7(4):406-9. · 2.93 Impact Factor
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ABSTRACT: Oncological procedures may have better outcomes if performed by high-volume providers.
A review of the English language literature incorporating searches of the Medline, Embase and Cochrane collaboration databases was performed. Studies were included if they involved a patient cohort from 1984 onwards, were community or population based, and assessed health outcome as a dependent variable and volume as an independent variable. The studies were also scored quantifiably to assess generalizability with respect to any observed volume-outcome relationship and analysed according to organ system; numbers needed to treat were estimated where possible.
Sixty-eight relevant studies were identified and a total of 41 were included, of which 13 were based on clinical data. All showed either an inverse relationship, of variable magnitude, between provider volume and mortality, or no volume-outcome effect. All but two clinical reports revealed a statistically significant positive relationship between volume and outcome; none demonstrated the opposite.
High-volume providers have a significantly better outcome for complex cancer surgery, specifically for pancreatectomy, oesphagectomy, gastrectomy and rectal resection.
British Journal of Surgery 05/2005; 92(4):389-402. · 4.61 Impact Factor
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ABSTRACT: Both the expressions of the inducible form of cyclooxygenase-2 and the presence of bone marrow micrometastases are poor prognostic markers in patients with colorectal carcinoma.
As cyclooxygenase-2 expression in these tumours is associated with increased metastatic potential in vitro, our objectives were to determine the relationship between cyclooxygenase-2 and haematogenous spread to bone marrow.
Thirty-two patients with resection of colorectal carcinoma were evaluated (median age: 69.5 years). Bone marrow was obtained from all patients from both iliac crests before manipulation of the primary tumour. The tumours were of varying stages at diagnosis (5 Dukes' A, 14 Dukes' B, 11 Dukes' C and 2 Dukes' D). Tumour sections were stained for cyclooxygenase-2 using the avidin-biotin immunohistochemical technique. Extent of staining was graded depending on the percentage of epithelial cells staining positive for cyclooxygenase-2. Micrometastases were detected by staining contaminant cytokeratin-18 positive cells in the bone marrow aspirates by either immunohistochemical (ARAAP) or immunological (flow cytometry) methods. Fisher's exact probability test was used to calculate statistical significance.
Cyclooxygenase-2 expression in the primary tumour was detected in 72% of the patients. Twelve (38%) patients had bone marrow micrometastases detected by either immunohistochemistry or flow cytometry. Of the 12 patients who had bone marrow micrometastases, 8 tumours demonstrated increased expression of cyclooxygenase-2 protein (66.6%). In contrast, 9 out of the 20 (45%) patients in whom micrometastases were not detected expressed increased levels of cyclooxygenase-2 (P = 0.29). When dividing the patients into subgroups of localised (Dukes' A and B) versus disseminated (Dukes' C and D) disease, there was no further association between cyclooxygenase-2 expression and bone marrow micrometastases (P = 0.179 and 1.0).
In this pilot study, there was no association between cyclooxygenase-2 expression and bone marrow micrometastases in patients with otherwise localised or disseminated disease.
Digestive and Liver Disease 07/2004; 36(6):392-7. · 3.05 Impact Factor
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ABSTRACT: The use of transanal stapling devices may impair continence because of digital dilatation and/or instrumentation. This study assessed the effect of pharmacological dilatation of the sphincter prior to stapler insertion.
A randomized, placebo-controlled, double-blinded study of 60 patients undergoing transanal stapled anastomosis was undertaken. Consenting patients were randomly assigned to receive a single intraoperative dose of topical 0.2 percent nitroglycerin (glyceryl trinitrate) ointment or nitroglycerin-free placebo. All patients were assessed preoperatively and postoperatively by clinical methods (Wexner incontinence scores and examination), anorectal manometry by a station pull-through technique, and endoanal ultrasonography.
Intraoperative mean (+/-SEM) resting pressures (mmHg) were significantly reduced by nitroglycerin compared with prenitroglycerin levels (9.9 +/- 0.9 vs. 50.5 +/- 2.7; P = 0.002) or controls (56.0 +/- 3.2; P = 0.001). Twenty-one of the 28 controls (75 percent) but only 4 of the 32 patients in the nitroglycerin group (12.5 percent) required digital dilatation to insert the stapling instrument ( P = 0.003). Squeeze pressures were unaltered by the intervention but mean resting pressures were higher in the nitroglycerin group postoperatively (52.9 +/- 3.2 - 31.6 +/- 1.3 = 21.3 mmHg; 95 percent confidence interval, 14-27). Incontinence scores were lower in the nitroglycerin group at the 3-month (1.1 +/- 0.2 vs. 4.6 +/- 0.3; P = 0.003) and 12-month (0.9 +/- 0.1 vs. 4.4 +/- 0.3; P = 0.002) clinic visits.
Preoperative nitroglycerin dilatation protects sphincter function in patients undergoing transanal stapled anastomoses.
Diseases of the Colon & Rectum 06/2004; 47(5):697-703. · 3.13 Impact Factor
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British Journal of Surgery 10/2003; 90(9):1166. · 4.61 Impact Factor
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ABSTRACT: Background
Postoperative intra-abdominal adhesion formation remains a significant cause of complications in surgical patients. To date, no agent has been shown consistently to block adhesion formation; preliminary evidence has shown that intra-abdominal adhesion formation is angiogenesis dependent. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and promotes vascular leakage. This study determined whether a specific VEGF monoclonal antibody (mAb) could prevent postoperative adhesion formation without affecting wound and anastomotic integrity.Methods
After developing a standardized peritoneal injury which resulted in a reproducible adhesion model, 40 CD-1 mice were randomized and treated intraperitoneally with either VEGF mAb (n = 20) or immunoglobulin (Ig) G isotype control mAb (n = 20) at the time of abdominal closure. Animals (n = 10 per group) were killed on postoperative day 14, and the development of intra-abdominal adhesions was determined and graded blindly using well established criteria. Animals (n = 10 per group) were also killed 10 days after operation, and laparotomy wounds and gastrointestinal anastomoses were assessed by tensiometry. Statistical analyses were performed using the Mann–Whitney and Fisher's exact tests.ResultsTreatment with VEGF mAb resulted in a significantly lower incidence of adhesion formation compared with control animals (P < 0·001). Furthermore, intergroup analysis for the presence of marked adhesions (grade 2 or 3) demonstrated that mice treated with VEGF mAb had a significantly lower incidence of advanced adhesions compared with controls (10 versus 90 per cent). Laparotomy wound and gastrointestinal anastomotic strength were similar between groups. Adhesion scoreWound breaking strength (N)Values are mean(s.d.)0123Laparotomy woundGastrointestinal anastomosisVEGF mAb81100·89(0·18)0·68(0·12)lgG mAb01360·92(0·25)0·71(0·14)Conclusion
This study demonstrates that the formation of postoperative intra-abdominal adhesions is attenuated following the administration of VEGF mAb without adversely affecting wound strength or anastomotic integrity. © 2000 British Journal of Surgery Society Ltd
British Journal of Surgery 12/2002; 87(7):950 - 951. · 4.61 Impact Factor
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ABSTRACT: Acute hepatobiliary pathology is a common general surgical emergency referral. Diagnosis requires imaging of the biliary tree by ultrasonography. The accuracy and impact of surgeon-performed ultrasonography (SUS) on the diagnosis of emergent hepatobiliary pathology was examined.
A prospective study, over a 6-month period, enrolled all patients with symptoms or signs of acute hepatobiliary pathology. Patients provided informed consent and underwent both SUS and standard radiology-performed ultrasonography (RUS). SUS was performed using a 2-5-MHz broadband portable ultrasound probe by two surgeons trained in ultrasonography, and RUS using a 2-5-MHz fixed unit. SUS results were correlated with those of RUS and pathological diagnoses.
Fifty-three consecutive patients underwent 106 ultrasonographic investigations. SUS agreed with RUS in 50 (94.3 per cent) of 53 patients. SUS accurately detected cholelithiasis in all but two cases and no patient was inaccurately diagnosed as having cholelithiasis at SUS (95.2 per cent sensitivity and 100 per cent specificity). As an overall complementary diagnostic tool SUS provided the correct diagnosis in 96.2 per cent of patients. Time to scan was significantly shorter following SUS (3.1 versus 12.0 h, P < 0.05).
SUS provides a rapid and accurate diagnosis of emergency hepatobiliary pathology and may contribute to the emergency management of hepatobiliary disease.
British Journal of Surgery 11/2002; 89(11):1402-4. · 4.61 Impact Factor
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ABSTRACT: We report a case of a twin pregnancy which was complicated by a twin-twin transfusion in which the recipient twin was noted to have an intra-abdominal echogenic mass. This twin died at two days of age of hepatic infarction. The donor twin was healthy at birth, at thirty weeks' gestation, and did not have any subsequent problems. Fetal intra-abdominal echogenicity may be a marker of hepatic infarction.
Prenatal Diagnosis 06/2002; 22(5):430-2. · 2.11 Impact Factor
