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Biomedical subjects

Ronan A Cahill

Publications and source records attributed to Ronan A Cahill.

8 recordsLinked to original sources

Preoperative profiling of symptomatic breast cancer by diagnostic core biopsy.

BACKGROUND: Precise preoperative profiling of breast tumors could facilitate fuller consideration of (neo)adjuvant therapies. METHODS: Diagnostic core biopsy (DCB) accuracy in profiling the primary tumor was prospectively studied in 95 patients with operable breast cancer. The histological type and grade (hematoxylin and eosin staining) and membrane receptor status (semiquantitative immunohistochemistry for estrogen [ER] and progesterone [PR] receptors, as well as Her-2 antigen expression) were assigned by the DCB before surgery. These measures were then compared with those of the definitive surgical specimen available after operation. RESULTS: DCB correctly ascribed tumor type and grade and ER, PR, and Her-2 receptor status in most cases (correlating exactly in 97.5%, 77%, 68%, 71%, and 60%, respectively) with at least moderate concordance (weighted kappa, >.41). When miscategorized, DCB consistently tended to upscore the receptor stain intensity compared with the surgical specimen (22%, 19%, and 27% had higher ER, PR, and Her-2 categorical scores, respectively). ER H-scores correlated best in specimens that stained strongly (224.4 +/- 3 vs. 215.5 +/- 5) and were significantly higher on DCB in those that stained either moderately (195.6 +/- 8.2 vs. 156.8 +/- 5.1; P < .0001) or weakly (157.1 +/- 24.8 vs. 81.4 +/- 4; P = .02). DCB accurately identified all tumors with clinically important ER and Her-2 expression. Furthermore, it promoted three patients into the therapeutically significant range of ER (n = 1) or Her-2 (n = 2) expression. ER negativity on DCB (n = 25) indicated a high-grade tumor (88%), although 11 (44%) patients also overexpressed Her-2. Significant Her-2 expression (n = 16) on DCB predicted the tumor as being poorly differentiated (80%) and both ER and PR negative (67%). CONCLUSIONS: DCB accurately profiles clinically relevant measures of primary tumor cell differentiation. It also reliably categorizes patients with regard to (neo)adjuvant therapy before radical surgery is attempted.

Adult↗

Parathormone response to thyroid surgery.

BACKGROUND: Confident determination of adequate residual parathyroid function early after thyroid surgery could facilitate the discharge of patients soon after their operation without the need for subsequent serum calcium monitoring and/or calcium and vitamin D supplementation. METHODS: Thirty-one patients who underwent 33 thyroid operations (22 unilateral lobectomies and 11 bilateral thyroid resections) were prospectively studied. Parathormone (PTH) levels were measured intraoperatively, and serum calcium was monitored before and after surgery to determine PTH and calcium homeostatic response to thyroid surgery. RESULTS: A significant decrease in circulating PTH occurred during 27 procedures, most markedly after specimen mobilization. Intraoperative PTH and postoperative calcium levels were lowest in those who underwent bilateral operations. Patients who underwent unilateral procedures experienced significant decreases in PTH but not postoperative calcium levels. A PTH level >50% of baseline predicted normocalcemia by postoperative day 3. However, PTH level did not accurately triage other patients' risk for postoperative hypocalcemia. CONCLUSIONS: A decrease in PTH levels intraoperatively is a common event during both unilateral and bilateral thyroid operations. Although normal PTH levels at the end of surgery ensure normocalcemia after surgery, patients with low final PTH measurements may not develop significant hypocalcemia after surgery.

Adult↗

Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.

BACKGROUND: Peritoneal injury sustained at laparotomy may evoke local inflammatory responses that result in adhesion formation. Peritoneal mast cells are likely to initiate this process, whereas vascular permeability/endothelial growth factor (VEGF) may facilitate the degree to which subsequent adhesion formation occurs. METHODS: Mast cell deficient mice (WBB6F1-/-), along with their mast cell sufficient counterparts (WBB6F1+/+), underwent a standardized adhesion-inducing operation (AIS) with subsequent sacrifice and adhesion assessment 14 days later in a blinded fashion. Additional CD-1 and WBB6F1+/+, and WBB6F1-/- mice were killed 2, 6, 12, and 24 hours after operation for measurement of VEGF by ELISA in systemic serum and peritoneal lavage fluid. Two further groups of CD-1 mice underwent AIS and received either a single perioperative dose of anti-VEGF monoclonal antibody (10 mug/mouse) or a similar volume of IgG isotypic antibody and adhesion formation 2 weeks later was evaluated. RESULTS: WBB6F1-/- mice had less adhesions then did their WBB6F1+/+ counterparts (median [interquartile range] adhesion score 3[3-3] vs 1.5[1-2] respectively; P < .003). Local VEGF release peaked 6 hours after AIS in both WBB6F1+/+ and CD-1 mice whereas levels remained at baseline in WBB6F1-/- mice. CD-1 mice treated with a single dose of anti-VEGF therapy during operation had less adhesions than controls (2[1.25-2] vs 3[2.25-3], P = .0002). CONCLUSIONS: Mast cells and VEGF are central to the formation of postoperative intra-abdominal adhesions with mast cells being responsible, either directly or indirectly, for VEGF release into the peritoneal cavity after operation. In tandem with the recent clinical success of anti-VEGF monoclonal antibodies in oncologic practice, our observations suggest an intriguing avenue for research and development of anti-adhesion strategy.

Abdomen↗

Trends in the incidence and significance of presentations to the emergency department due to acute pancreatitis.

INTRODUCTION: Acute pancreatitis is an important cause of abdominal pain that may be associated with significant morbidity for the patient and considerable workload for the hospital. Our impression has been that it is becoming increasingly common, perhaps in tandem with increased rates of other alcohol-related disease. METHODS: The medical records of all patients attending our emergency department with acute pancreatitis by Hospital Inpatient Enquiry coding over a 9-year period were examined to determine its incidence, aetiology and significance (Imrie severity of pancreatitis scoring, length of hospital stay and interventional workload). RESULTS: The incidence of acute pancreatitis (n=97, 40 male patients) increased approximately threefold over the study period (especially in the lattermost triennial period with 75 patients) in a fashion disproportionate to changes in our locality's population. Gallstone-related disease continues to be most prevalent although alcohol-related disease also became more common. Disease severity (length of hospital stay and Imrie score) was similar throughout with a mean length of hospital stay exceeding that of the majority of accident and emergency admissions. Seven acute complications of acute pancreatitis were noted while 34 chronic sequelae developed. Requirement for invasive intervention doubled (n=19 in first triennial period in the study vs 39 in the latter triennial period), although the relative need for endoscopic retrograde cholangiopancreaticography diminished with increased availability of magnetic resonance cholangiography imaging. Nine patients with gallstone-related acute pancreatitis suffered recurrent attacks while awaiting cholecystectomy. CONCLUSION: Acute pancreatitis is an increasingly frequent cause of hospital admission while the clinical significance of each incident remains high. The presentation of acute pancreatitis to the emergency department as an early declaration of symptomatic cholelithiasis is especially worrisome as it suggests a failing of recognition and/or effective referral of premonitory biliary complaints.

Adult↗

Duration of increased bleeding tendency after cessation of aspirin therapy.

BACKGROUND: Aspirin has a significant effect on hemostasis, so it is often recommended that patients taking aspirin discontinue treatment before elective surgery. While off aspirin, these patients may be at risk of thrombosis. The optimum period of time that aspirin should be withheld is controversial. The aim of this study was to establish the duration of the antihemostatic effect of prolonged aspirin therapy. STUDY DESIGN: In a prospective study, 51 healthy volunteers were randomly assigned into 3 groups, each receiving an identical tablet for 14 days. One group received a placebo tablet; individuals in the other two groups received either 75 mg or 300 mg of aspirin once a day. Template bleeding times and specific platelet function testing (using the PFA-100; Dade Behring) were carried out on subjects before therapy and again after its completion until they returned to baseline. RESULTS: Thirty-eight volunteers complied sufficiently with the protocol to provide useful results. All bleeding times normalized within 96 hours and all platelet function tests within 144 hours after stopping aspirin. There was no demonstrable hemostatic defect in any volunteer persisting by or beyond the sixth day after treatment cessation. There was no apparent difference in duration of effect between those taking either 75 mg or 300 mg of aspirin. CONCLUSIONS: This study uses sensitive measures of platelet function to demonstrate the duration of increased bleeding tendency after withdrawal of aspirin therapy. It supports discontinuation of aspirin therapy 5 days before elective surgery (with the operation being performed on the sixth day).

Adult↗

The effect of aspirin on blood loss and transfusion requirements in patients with femoral neck fractures.

Although it is widely accepted that aspirin will increase the risk of intra- and post-operative bleeding, clinical studies have not consistently supported this assumption. We aimed to assess the effect of pre-operative aspirin on blood loss and transfusion requirements in patients undergoing emergency fixation of femoral neck fractures. A prospective case-control study was undertaken in patients presenting with femoral neck fractures. Parameters recorded included intra-operative blood loss, post-operative blood loss, transfusion requirements and peri-operative reduction in haemoglobin concentration. Of 89 patients presenting with femoral neck fractures 32 were on long-term aspirin therapy. Pre-operative aspirin ingestion did not significantly affect peri-operative blood loss, or change in haemoglobin concentration or haematocrit. However those patients taking aspirin pre-operatively had a significantly lower haemoglobin concentration and haematocrit and were more likely to be anaemic at presentation than those who were not receiving aspirin. Patients taking aspirin were also more likely to receive blood transfusion post-operatively.

Aged↗