PubMed Health⌕ Search

Biomedical subjects

P F Ridgway

Publications and source records attributed to P F Ridgway.

16 recordsLinked to original sources
PubMed2006

A surgically induced hypoxic environment causes changes in the metastatic behaviour of tumours in vitro.

The use of laparoscopic techniques for curative resections of malignant tumours has been under scrutiny. The potential benefits to the patient in the form of earlier recovery and less immune paresis are countered by the reports of increased tumour recurrence. The biological sequelae of the hypoxic laparoscopic environment on tumour cells is unknown. Components of the metastatic cascade were evaluated under in vitro laparoscopic conditions using a human colonic adenocarcinoma cell line (SW1222). Exposure to the laparoscopic gases carbon dioxide and helium for 4 h, comparable to the duration of a laparoscopic colorectal resection, had no effect on cell viability. A cellular hypoxic insult was demonstrated by the induction of hypoxia inducible factor 1alpha (HIF-1alpha). Exposure also resulted in significant reduction in homotypic adhesion as well as to a variety of extracellular matrix components. These effects were recoverable under re-oxygenation. The changes were reflected at the molecular level by significant down regulation of adhesion molecules known to be involved in tumour progression (E-cadherin, CD44 and beta1 sub-unit). Modulation of adherence has significant implications for laparoscopic oncological surgery, demonstrating that tumours become potentially more friable and easier to disseminate in surgeons who are less experienced or where instrumentation is sub-optimal.

Adenocarcinoma↗
PubMed2006

Construct validation of a novel hybrid surgical simulator.

BACKGROUND: Simulated minimal access surgery has improved recently as both a learning and assessment tool. The construct validation of a novel simulator, ProMis, is described for use by residents in training. METHODS: ProMis is a surgical simulator that can design tasks in both virtual and actual reality. A pilot group of surgical residents ranging from novice to expert completed three standardized tasks: orientation, dissection, and basic suturing. The tasks were tested for construct validity. Two experienced surgeons examined the recorded tasks in a blinded fashion using an objective structured assessment of technical skills format (OSATS: task-specific checklist and global rating score) as well as metrics delivered by the simulator. RESULTS: The findings showed excellent interrater reliability (Cronbach's alpha of 0.88 for the checklist and 0.93 for the global rating). The median scores in the experience groups were statistically different in both the global rating and the task-specific checklists (p < 0.05). The scores for the orientation task alone did not reach significance (p = 0.1), suggesting that modification is required before ProMis could be used in isolation as an assessment tool. CONCLUSIONS: The three simulated tasks in combination are construct valid for differentiating experience levels among surgeons in training. This hybrid simulator has potential added benefits of marrying the virtual with actual, and of combining simple box traits and advanced virtual reality simulation.

Computer Simulation↗
PubMed2006

Optimising preoperative diagnosis in phyllodes tumour of the breast.

The role of the pathologist in the preoperative diagnosis of phyllodes tumours of the breast is critical to appropriate surgical planning. However, reliable differentiation of phyllodes tumour from cellular fibroadenoma remains difficult. Preoperative diagnostic accuracy allows correct surgical treatment, avoiding the pitfalls of reoperation because of inadequate excision, or surgical overtreatment. Specific clinical indices may arouse diagnostic suspicion but are unreliable for confirmation, as with current imaging modes. Fine needle aspiration cytology has a high false negative rate. Few studies have evaluated the role of core needle biopsy, but it may prove a useful adjunct. Both diagnostic and prognostic information may in future be gained from application of immunohistochemical and other techniques assessing the expression of proliferative markers including p53, Ki-67, and others.

Adult↗
PubMed2006

Proton pump inhibition is a feasible primary alternative to surgery and balloon dilatation in adult peptic pyloric stenosis (APS): report of six consecutive cases.

INTRODUCTION: Surgery has been the gold standard in the treatment of adult pyloric stenosis (APS). The introduction of proton pump inhibitors (PPIs) in 1989 revolutionised the treatment of peptic ulcer disease and its complications. PATIENTS AND METHODS: We carried out a prospective study to evaluate the effectiveness of PPIs as an alternative to surgery for treatment of APS. Six consecutive patients admitted with a diagnosis of adult peptic pyloric stenosis between November 1999 and August 2002 were studied. The diagnosis was confirmed with endoscopy. All patients were commenced on a twice-daily dose of intravenous PPI. This was changed to oral treatment after 2 days. Main outcome measures evaluated were resolution of symptoms on PPIs and failure of medical therapy. RESULTS: There were five females and one male. Median age at diagnosis was 72 years (range, 30-90 years). Median duration of symptoms was 2 weeks (range, 1-5 weeks). Of the patients, five had a history of peptic ulcer disease. Complete resolution was achieved in 5 patients (83%). Median duration for resolution of symptoms was 9 days (range, 5-14 days). All patients were changed to oral PPIs after 2 days. One patient did not respond to oral therapy and required surgical intervention (pyloroplasty). Median follow-up was 26 months (range, 6-48 months). There was no recurrence of symptoms. All patients were discharged on low-dose PPI. CONCLUSIONS: This study supports the view that proton pump inhibitors are a safe and feasible alternative to surgery in adult pyloric stenosis secondary to peptic ulcer disease.

Adult↗
PubMed2005

Peritoneal nebulizer: a novel technique for delivering intraperitoneal therapeutics in laparoscopic surgery to prevent locoregional recurrence.

BACKGROUND: Peritoneal involvement is a significant issue in the treatment of gastrointestinal malignancies. Current statistics indicate that after surgical intervention, up to 20% of patients will present with locoregional metastasis. The ability to inhibit initial tumor adhesion to the mesothelial lining of the peritoneum may be considered critical in the inhibition of tumor development. This article describes, the use of a novel nebulizer system capable of delivering high-concentration, low-dose therapeutics to the peritoneal cavity. METHODS: For this study, 30 male WAG rats were inoculated with CC531 colorectal tumor cells. The rats were randomized into three groups: control group (n = 10), heparin-treated group (n = 10), and high-molecular-weight hyaluronan-treated group (n = 10). A peritoneal cancer index was used to determine tumor burden at 15 days. Analysis of variance (ANOVA) was used to compare multiple group means. RESULTS: Nebulization therapy was performed without any complication in the cohort. Heparin inhibited macroscopic intraperitoneal tumor growth completely (p = 0.0001) without affecting tumor cell viability. The introduction of hyaluronan attenuated both tumor size and distribution, was compared with the control group (p = 0.002). CONCLUSION: Nebulized heparin and hyaluronic acid using a novel nebulization technique attenuates peritoneal tumor growth after laparoscopic surgery. The technique itself is easy to use and safe.

Animals↗
PubMed2005

Attitudes towards skills examinations for basic surgical trainees.

Objective measures of surgical skill and cognition are becoming available. A questionnaire study examining surgeons' beliefs towards a skills-based examination, current standards and possible benefits was devised. Three hundred pairs of standardised anonymous questionnaires were sent to consultants and their basic surgical trainees (BSTs) irrespective of surgical specialty. Responses were requested using a Likert scale (1-5, 3=neutral response). Two-hundred and two replies were received (including 54 pairs). BST experience ranged from 6 to 60 months (mean 24 months). When questioned regarding current training in basic surgical skills, only 34% believed that they were given adequate training at present. Sixty-four per cent of respondents believed the introduction of a skills examination would raise standards and 66% believed it necessary. Eighty-three per cent of respondents believed that they or their BST would practice these skills, if an examination were introduced and 85% wanted or would provide dedicated teaching time for this. However, 68% had no access to a dedicated skills facility, and uptake of these, where available, was variable. When questioned about their ability to perform the six appropriate tasks, there was a poor correlation of scoring between the groups. Consultants and their BSTs do not believe that they are given adequate training in basic skills. The introduction of an examination would lead to practice of these skills and is seen as a positive move.

Attitude of Health Personnel↗
PubMed2004

Dislocation of the mandible.

We report the first case of bilateral temporomandibular joint (TMJ) dislocation in a woman after endoscopy. We go on to discuss the case reports published in the literature, with particular focus on potential factors that may predispose to this complication, and we offer some suggestions on dealing with this significant complication.

Adult↗
PubMed2004

Perioperative diagnosis of cystosarcoma phyllodes of the breast may be enhanced by MIB-1 index.

BACKGROUND: The recurring theme in cystosarcoma phyllodes (CSP) is one of underdiagnosis by pathologists and undertreatment by surgeons. Major areas of investigation relating to the diagnosis of CSP center on accurate preoperative diagnosis, elucidating the relevance of histological classification with respect to outcome, and identifying novel markers to reliably differentiate CSP from fibroadenoma (FA). MATERIALS AND METHODS: Fifteen CSP and 7 cellular FA controls (where the preoperative diagnosis was unclear) were retrospectively investigated. Preoperative histological and radiological investigations were reviewed for efficacy. The ability of MIB-1 antibody to differentiate the two fibroepithelial lesions was investigated using immunohistochemical estimation of the MIB-1 index. RESULTS AND DISCUSSION: Preoperative core biopsy had a sensitivity of 75% but was carried out in only 23% of cases. Fine needle aspiration cytology and radiological assessment were not efficacious in preoperative diagnosis. Proliferative activity (MIB-1 indices) was significantly higher in CSP than in a selected population of FA where there was preoperative diagnostic uncertainty (P < 0.0001). Indices were also able to determine CSP subclassification. This suggests MIB-1 as a constructive adjunctive investigation when evaluating histological features to differentiate CSP from FA in difficult cases. CONCLUSIONS: The use of MIB-1 may increase the sensitivity of preoperative core biopsy diagnosis, offering more effective surgical planning and decreasing immediate reoperation rates.

Adolescent↗
PubMed2003

Laparoscopic enhancement of tumour cell binding to the peritoneum is inhibited by anti-intercellular adhesion molecule-1 monoclonal antibody.

BACKGROUND: There still remain some concerns over the phenomenon of port-site metastases (PSM) after laparoscopic surgery. The aim of this study was to investigate the effect of the pneumoperitoneum on tumor-mesothelial cell interactions. METHODS: The adhesion of a colon carcinoma cell line to a mesothelial cell monolayer exposed to carbon dioxide, helium, or air was assessed using an in vitro adhesion assay. Changes in adherence were correlated with alterations in cell surface molecule expression by the mesothelial cells using flow cytometry after exposure to the different environments. RESULTS: Exposure of the mesothelial cells to an in vitro pneumoperitoneum significantly enhanced tumor cell binding to the mesothelial cell monolayer. No differences in cell viability were observed between the groups. This was associated with increased expression of mesothelial intercellular adhesion molecule-1 (ICAM-1) mediated by nuclear factor kappa-B. The enhanced adhesion was abolished by ICAM-1 inhibition. CONCLUSIONS: This study demonstrated that the laparoscopic environment increases the susceptibility of the mesothelium to tumor cell adherence, and this may be explained by changes in ICAM-1 expression.

Adenocarcinoma↗
PubMed2003

Objective measurement of breast cancer oestrogen receptor status through digital image analysis.

AIMS: The authors have previously described quantitative, computer-assisted analysis of oestrogen receptor status in immuno-histochemically stained sections in patients with primary breast cancer. The aim of this study was to validate the aforementioned system against the commonly used methods of assessing oestrogen receptor status. METHODS: Paraffin embedded sections from 156 patients with primary breast carcinoma were stained with anti-alpha-oestrogen receptor monoclonal antibody (1D5) using a standard immunohistochemical protocol. Images from 10 high-powered fields were captured from each section using a digital camera mounted on a microscope and analyzed using Adobe Photoshop image analysis software. A nuclear mask was obtained by digitally selecting the nuclear area. Staining intensity in the nuclear mask was then analyzed using red-scale absorption characteristics. Manual assessment of oestrogen receptor status was performed through counting the percentages of cells that are positive from 200 randomly sampled nuclei from ten high powered fields HPF. Cut off value for positivity was taken as 10%. Cytosolic oestrogen receptor concentration was measured through enzyme immunisation. Cut off value for ER positivity was taken as 200 fmol/g (wet tissue). RESULTS: One hundred and fifty-six sections were studied of which 41 were ER negative. Median percentage positivity in the remainder was 90% (17-100) by manual assessment. The median red scale value was 108 (58-156). A close correlation was observed between median optical density of the nuclear mask and percentage positivity assessed manually (P<0.0001). There was a significant correlation between the optical density of the nuclear mask and cytosolic oestrogen receptor concentration (P<0.001). CONCLUSION: Oestrogen receptor positivity can be accurately assessed through digital image analysis. This process offers objective data regarding the amount of oestrogen receptors within the nuclei as well as the percentage of nuclei, which express oestrogen receptors.

Adult↗
PubMed2002

Laparoscopic staging of pancreatic tumors induces increased invasive capacity in vitro.

INTRODUCTION: Laparoscopy and laparoscopic ultrasound have a well-defined role in staging patients with pancreatic malignancy. The effect of the hypoxic pneumoperitoneum induction on tumor biology is unknown. The authors investigated whether an in vitro pneumoperitoneum augments the invasive capacity of pancreatic tumors and elucidate a mechanism by which this may occur. METHODS: A pancreatic (PSN-1) adenocarcinoma cell line was exposed to an in vitro pneumoperitoneum (carbon dioxide (CO2) or helium) for a maximum of 2 h or left in normal growth conditions (control). Cells were nonenzymatically harvested and placed in invasion assays. These were performed over 72 h using Matrigel coated 8-mm Transwell filters and analyzed using MTS colorimetric assay. Gelatin zymography was employed to assess the level of matrix metalloproteases (MMP) 2 and 9 (gelatinase A and B) secretion. Expression of tissue inhibitor of metalloproteases 1 (TIMP-1) was assessed using ELISA (Biotrak). Inhibition of invasion assays was performed using a specific gelatinase inhibitor (MMPI; Calbiochem). RESULTS: The invasive capacity of pancreatic tumour cells is augmented versus control in both helium (p <0.05) and CO2 (p <0.001) groups. Concomitant significant upregulation of the gelatinase activity was demonstrated with both insufflants (p <0.05; 0.001, respectively). Enhanced invasion was attenuated by the addition of a specific gelatinase inhibitor (p <0.05). CONCLUSIONS: These results indicate the invasive capacity of pancreatic tumor cells is augmented by laparoscopic staging in vitro. This is in part mediated by increased gelatinase activity and may be attenuated by the addition of specific inhibitors.

Adenocarcinoma↗
PubMed2001

Pneumoperitoneum augmented tumor invasiveness is abolished by matrix metalloproteinase blockade.

BACKGROUND: Certain surgical strategies, including Helium (He) and carbon dioxide (CO2) insufflation in laparoscopy, have been shown to induce a hypoxic environment. This may have a significant effect on the invasive capacity of tumor cells and may be a factor in the incidence of port-site metastases seen in patients following laparoscopic resection for malignancy. METHODS: A colon adenocarcinoma cell line (SW1222) was exposed to an in vitro pneumoperitoneum of CO2 or He at 3 mmHg or left in normal growth conditions (control). After a 4-hour exposure to an in vitro pneumoperitoneum, the ability of the cells to invade through 8.0-microm Transwell filters coated with Matrigel was analyzed by colorimetric MTS assay and by direct staining of the filters. The effect of the addition of a known blocker of matrix metalloproteinases (MMPs), 1,10-phenanthroline (1,10-P), was investigated. RESULTS: Cells exposed to an in vitro pneumoperitoneum demonstrate significantly increased invasive capacity compared to the control set, without loss of viability (He vs control, p <0.001; CO2 vs control, p <0.001). This augmented capacity is abolished by the addition of 1,10-P (p <0.01). CONCLUSION: Exposure of a colonic adenocarcinoma cell line to either a CO2 or He pneumoperitoneum causes an increase in tumor cell invasiveness, which is abolished by the presence of a known inhibitor of MMPs. This suggests that MMPs have an important role in the metastatic potential of tumors exposed to a hypoxic operative environment.

Adenocarcinoma↗
PubMed1999

Unfractionated heparin, time for a change?

BACKGROUND: In Ireland physician transfer to utilisation of Low Molecular Weight Heparin for Venous Thromboembolism has been slow, despite evidence of efficacy and concern about the level of anticoagulation achieved with Unfractionated Heparin. OBJECTIVE: To examine the effectiveness of Unfractionated Heparin administration in a teaching hospital in Ireland. Primary outcomes measured were time to therapeutic APTT and length of hospital stay. METHODS: We identified 50 consecutive eligible patients treated with continuous intravenous unfractionated heparin for Venous Thromboembolism from the period August 1994 to December 1996 at Beaumont Hospital, Dublin, Ireland. Data analysed included length of hospital stay, costing data and anticoagulation parameters (time to therapeutic APTT, percentage of time within therapeutic range, number of diagnostic tests, heparin dosages). RESULTS: A significant number of patients (22%) never achieved therapeutic APTT levels. Of those who did achieve therapeutic APTT levels at some time during their therapy, therapeutic range APTT was maintained only 28% of the time on heparin. 57% of the time results were below therapeutic while 15% of the time results were above therapeutic. Also 26% of the patients were discharged with INR results outside the therapeutic range despite an average length of stay of 13.3 days (over twice the ideal of 6 days). Ineffective anticoagulation influenced hospital length of stay in 60% of cases in our evaluation. Average cost of treatment with Unfractionated Heparin was 5897.86 Pounds versus the projected cost of Low Molecular Weight Heparin at 2562.78 Pounds for 6 days of in-patient therapy or 60.78 Pounds for outpatient therapy (excluding physician visit costs). CONCLUSIONS: Unfractionated Heparin therapy as reviewed in our study is sub-optimal with inadequate anti coagulation and prolonged hospitalisation. Low Molecular Weight heparin, with comparable therapeutic effect documented elsewhere, overall may cost less.

Anticoagulants↗
PubMedDate not supplied

Splenic preserving distal pancreatectomy of a solid pseudopapillary pancreatic tumour.

BACKGROUND: Solid pseudopapillary tumours are rare primary lesions of the pancreas. They occur most commonly in young female patients. They are traditionally regarded as benign tumours with malignant potential. AIM: We describe the incidental finding of this rare pancreatic lesion in a healthy 37-year-old female which was treated with splenic preserving distal pancreatectomy. RESULTS: The patient underwent curative resection with an uncomplicated postoperative course. Histology revealed the tumour origin with clear resection margins. The patient did not require adjunct therapy. Follow-up computed tomography (CT) scanning has demonstrated no evidence of local recurrence. CONCLUSION: The authors conclude that splenic preservation is safe and desirable where no compromise in oncological principles exists. Despite improvements in histological characteristics of solid pseudopapillary tumours, no prognostic features exist and each case must be followed-up on an individual basis.

Adult↗
PubMedDate not supplied

Laparoscopic environmental changes during surgery enhance the invasive potential of tumours.

OBJECTIVE: The use of laparoscopic techniques in resection of malignant tumours has been proposed to offer potential benefit to the patient in the form of earlier recovery and less immune paresis; however, reported tumour seeding, both peritoneal and at port site, has put this approach into question. The biological effects of the introduction of carbon dioxide or helium to form a pneumoperitoneum on tumour invasion and dissemination are unknown. METHODS: A human colonic adenocarcinoma cell line (SW1222) was exposed to in vitro laparoscopic environment of either carbon dioxide or helium for 4 h, mimicking the duration of a laparoscopic colorectal resection. Alteration in production of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator (uPA) due to exposure to a laparoscopic environment was determined by zymography and correlated to invasive capacity by a standard Matrigel-based invasion assay. Incorporation of specific gelatinase inhibitors or antibodies directed at the uPA receptor was utilized to determine the relative importance of proteases. RESULTS: Exposure to the laparoscopic environment significantly enhanced production of the proteases MMP-2, MMP-9 and uPA. A concomitant enhancement of invasive capacity was also observed, being blocked by specific protease inhibitors. Changes in both protease production and aggression were observable for at least 24 h following the removal of the operative environment, indicating the possible long-term effects of the initial insult. CONCLUSION: Exposure to the laparoscopic environment enhances the invasive capacity of colonic adenocarcinomas via a well-defined protease-determined pathway. It therefore appears likely that tumour cells released into the operative field can be made increasingly aggressive by a laparoscopic operative environment and can thus contribute to disease dissemination.

Adenocarcinoma↗