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Biomedical subjects

P J Crowe

Publications and source records attributed to P J Crowe.

At least 19 recordsLinked to original sources
PubMed2006

Expression of HER1/EGFR protein in human soft tissue sarcomas.

AIM: To measure epidermal growth factor receptor (HER1/EGFR) expression in a range of soft tissue sarcoma (STS) patient samples. METHOD: HER1/EGFR expression was examined by immunohistochemistry in archival tissues of 46 STS patients. RESULTS: HER1/EGFR was positively expressed in 36/46 of STS samples distributed among different histological types. The levels of HER1/EGFR in STS tumour tissues in positive samples were higher compared to those in nearby normal tissues. CONCLUSION: HER1/EGFR is significantly expressed in soft tissue sarcomas, which is a finding reflected in other series. The significance of this finding for targeted therapy is as yet unknown.

Adolescent↗
PubMed2001

Genetic markers of survival and liver recurrence after resection of liver metastases from colorectal cancer.

A significant number of patients with liver metastases from colorectal cancer (CRC) achieve 5-year survival after liver resection. Increased expression of genetic markers in the primary tumor are known to predict outcome after colonic resection, but the predictive value of such markers after resection of hepatic metastases is unknown. The objective of this study was to evaluate whether DNA content and multiple genetic markers, separately or expressed together, can predict patient outcome (liver recurrence and survival) after resection of hepatic metastases. We studied the paraffin-embedded liver tissue of 71 consecutive patients who had undergone a potentially curative resection of hepatic metastases from CRC. Using DNA flow cytometry and immunohistochemical staining techniques we determined the DNA content and the level of co-expression of seven tumor-associated proteins: proliferating cellular nuclear antigen (PCNA), epidermal growth factor receptor (EGFr), p53, c-erbB-2, H-ras, c-myc, and nm23. Three endpoints (liver recurrence, cancer specific, overall survival) were correlated with these tumor markers. The 5-year overall survival of the group was 31.2%. There was no correlation detected between the DNA aneuploidy and overall or cancer-specific survival. Similarly, expression of the individual tumor-associated proteins did not predict survival. Patients whose tumors co-expressed multiple markers had survivals similar to those whose tumors expressed fewer markers. However, a significant difference in hepatic recurrence was found between the p53-positive and p53-negative patients (p = 0.007), with marker-negative tumors having decreased recurrence. In conclusion, this study demonstrates that the DNA content and genetic markers c-myc, c-erbB-2, EGFr, H-ras, p53, PCNA, and nm23 do not predict survival after potentially curative resection of hepatic metastases from CRC. However, the immunoreactivity of p53 may be an important marker of local recurrence in the liver, which may be useful if re-resection of metastatic liver tumors is considered a viable management option in this disease.

Adult↗
PubMed2000

Urokinase-type plasminogen activator and its receptor in colorectal cancer: independent prognostic factors of metastasis and cancer-specific survival and potential therapeutic targets.

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plasminogen (Plg), and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) have been observed in many cancers and may contribute to progression and metastasis. In our study, we examined the expression of the 5 proteins by immunohistochemistry in 59 consecutive primary colorectal cancers (CRC) and correlated the protein expression with patient outcome. In addition, we determined the effect of down-regulation of uPAR on the invasive/metastatic capability of CRC cells, by measuring antisense-uPAR transfected HCT116 and control cell lines, in terms of uPAR expression, uPA-binding activity, invasiveness through Matrigel in vitro and metastasis after cecal orthotopic implantation in nude mice in vivo. We found that higher expression of uPA or uPAR in primary tumor tissues was positively correlated with distant metastasis of CRC (Mann-Whitney, p < 0.02) and negatively correlated with both patient overall survival (OS) and cancer-specific survival (CSS; Cox model, p < 0.04). The prognostic value of uPA and uPAR for both OS and CSS was independent of other variables (multivariate Cox model, p < 0. 007). Antisense-uPAR transfected HCT116 cells, which expressed significantly lower levels of total cellular and cell surface uPAR proteins and uPA-binding activity compared with either wild-type or cells transfected with vector alone (Bonferroni, p < 0.05/3), consistently showed decreased invasiveness through Matrigel (Bonferroni, p < 0.05/3) and decreased metastasis formation in nude mice (Fisher, p < 0.05). Our data suggest that uPAR and uPA are independent prognostic factors in CRC; anti-uPAR treatment, which affects both uPAR and uPA levels, may have potential for new treatment of the disease.

Adult↗
PubMed2000

Genomic alterations (LOH, MI) on chromosome 17q21-23 and prognosis of sporadic colorectal cancer.

Genomic alterations at the long arm of chromosome 17, and in particular at the nm23 locus, are still controversial in colorectal cancer (CRC). Our aim was to investigate the possible relationship of loss of heterozygosity (LOH) and microsatellite instability (MI), at 4 microsatellite loci spanning the 17q21-23 region, to the risk of liver metastasis and nm23 protein expression. Genomic DNA extracted from 58 primary and 54 liver secondary formalin-fixed and paraffin-embedded CRCs was obtained from 82 patients. A fluorescent PCR coupled with an automated DNA sequencer was applied. Increasing fraction of loci showing LOH was positively associated with risk of liver metastases (logrank test for trend, p = 0.005); this remained independent after adjusting to T-stage (Cox regression, p = 0.022), N-stage (p = 0.007), or Dukes' stage (p = 0.012). Conversely, increasing frequency of MI was associated with a reduced risk of liver metastases in Dukes' B tumours (logrank test for trend, p = 0.032). When comparing 30 primary and matched liver secondary lesions, we found concordant genomic alteration in 72% (NME1) to 43% (D17S579). Finally, we observed a trend in association between the proportion of loci with LOH and nm23 positivity (chi2 test for trend, p = 0.024). Our findings suggest that genomic alterations in the 17q21-23 region may affect prognosis of CRC as well as regulation of the nm23 protein expression via an unknown underlying mechanism.

Adult↗
PubMed2000

Evidence for post-transcriptional down-regulation of the apoptosis-related gene bcl-2 in human colorectal cancer.

This retrospective study was undertaken to investigate the expression of bcl-2 protein and messenger RNA in colorectal cancer (CRC). Immunohistochemical analysis using a monoclonal mouse antibody to the bcl-2 protein and in situ hybridization using a digoxigenin-labelled bcl-2 cRNA probe were carried out on formalin-fixed and paraffin-embedded specimens from 53 colorectal adenocarcinomas, 27 liver secondaries, and 60 adenomas with various degrees of dysplasia. Normal human tonsil sections were used as positive controls. Expression of bcl-2 protein and of messenger RNA was evaluated semiquantitatively. The expression of bcl-2 protein was gradually and significantly lost during the progression from moderately dysplastic adenoma to primary CRC (moderate/severe dysplasia: Mann-Whitney U-test, p=0.0001; severe dysplasia/primary CRC: p=0.027), whereas the cellular expression of bcl-2 mRNA was gradually increased during the dysplasia/adenoma-carcinoma neoplastic sequence. These observations suggest that in a proportion of colorectal cancer cases, the bcl-2 proto-oncogene expression may be down-regulated at a post-transcriptional level.

Adenoma↗
PubMed2000

Hypomagnesemia and hypocalcemia after thyroidectomy: prospective study.

Hypomagnesemia after total thyroidectomy has not been studied extensively. Our anecdotal experience suggests that it may be important in some patients after thyroid excision. The hypomagnesemic hypocalcemic syndrome has been described in other disease states in which a state of functional hypoparathyroidism exists. This study was designed to determine the incidence of hypomagnesemia after total thyroidectomy and relate it to hypocalcemia and symptoms during the postoperative period. A prospective study of all patients undergoing total thyroidectomy between September 1994 and July 1996 was performed. Patient data, thyroid function, retrosternal extension, initial versus reoperative surgery, operative details, parathyroid resection, and pathology were recorded. Calcium, magnesium, electrolytes, blood count, liver function tests, and albumin were measured prior to surgery and twice daily during the postoperative period. Fifty patients underwent total thyroidectomy: 68% were hypocalcemic, 72% were hypomagnesemic, and 36% were symptomatic during the postoperative period. Hypomagnesemia and gender were associated with hypocalcemia. Volume of fluid and neck dissection were associated with low magnesium levels. Hypomagnesemia and parathyroid resection were risk factors for symptoms after thyroidectomy. No patients developed permanent hypoparathyroidism. Transient hypocalcemia and hypomagnesemia occur frequently after total thyroidectomy. The etiology of this phenomenon is probably multifactorial. Patients are more likely to be symptomatic when both cations are low, and attempting to correct only hypocalcemia may prolong symptoms. It is important to monitor both calcium and magnesium levels after total thyroidectomy and to correct deficiencies to facilitate prompt resolution of symptoms.

Adult↗
PubMed1999

Australia's breast surgery workload is changing: comparison of a metropolitan and a rural hospital.

BACKGROUND: Breast cancer is a common disease in our community and its incidence is increasing. As a result of the improvements in community awareness and introduction of screening, patients are being diagnosed with earlier breast cancer and with a higher incidence of pre-invasive disease. Improvements in radiology, often coupled with minimally invasive diagnostic modalities, have lessened the requirement for open diagnostic biopsies and also reduced the number of operations for benign breast disease. METHODS: An audit of the surgical workload at Prince of Wales/Prince Henry Hospitals and Tamworth Base Hospital was conducted to document and compare the above changes in the metropolitan and rural settings. This study was conducted between 1987 and 1996 to assess the effect of screening and improved technology over a 10-year period. RESULTS: The study found that a high percentage of malignant lesions are being diagnosed by fine-needle aspiration biopsy (FNAB) with a corresponding reduction in open biopsy rate at the Prince of Wales Hospital. There is a smaller percentage of benign operations in both settings with a reduction of equal proportion. The reporting of the pathology specimens has markedly improved at both institutions. There has been a reduction in the number of patients having modified radical mastectomy and there has been a corresponding increase in breast conservation surgery especially at the Prince of Wales/Prince Henry Hospitals, although there was an unexpectedly high incidence of breast conservation surgery at Tamworth Base Hospital in 1987. In 1996 the rates of breast conservation surgery were the same in both hospitals. CONCLUSIONS: There are minimal differences in the quality of surgical care being offered to patients at the Tamworth Base Hospital compared with the Prince of Wales Hospital and both institutions are within reach of the accepted best management practices available.

Australia↗
PubMed1999

Extremity soft tissue sarcoma: factors predictive of local recurrence and survival.

BACKGROUND: To identify risk factors for local recurrence and overall survival in patients with extremity soft tissue sarcoma. METHODS: A retrospective study was performed of all patients with extremity soft tissue sarcoma treated at the Combined Surgical Oncology Clinic in the Institute of Oncology at Prince of Wales Hospital between 1972 and 1992. Variables analysed included clinical presentation, patient characteristics, tumour characteristics, treatment factors and outcome. RESULTS: One hundred and nineteen patients were eligible for the study. The most common type of presentation was with a painless mass, usually in the thigh. Local control rates at 5 and 10 years were 75% and 73%. Local control was higher in patients who had more radical surgery and in those who received adjuvant radiotherapy. Tumour size and high grade were independent risk factors for poorer survival. Patients over 50 had poorer survival than younger patients and those who presented with recurrent tumours also tended to have poor survival compared to patients presenting de novo. The respective 5- and 10-year survival rates were 65% and 62%. CONCLUSION: This study suggests that local control of extremity soft tissue sarcoma is improved by radical surgery and by the addition of radiotherapy when more conservative procedures are used. Overall survival appeared to be largely determined by patient (age, recurrent presentation) and tumour characteristics (grade, size).

Amputation, Surgical↗
PubMed1999

Voice changes and thyroid surgery: is pre-operative indirect laryngoscopy necessary?

BACKGROUND: Indirect laryngoscopy (IDL) is often performed prior to thyroid surgery to detect pre-existing vocal cord pathology. METHODS: A retrospective chart review of 201 patients undergoing thyroid surgery at the Prince of Wales Hospital was undertaken in order to study the patterns of pre-operative and postoperative voice changes and IDL findings. RESULTS: A total of 9% of patients had pre-operative voice symptoms, and 22% of this group had abnormalities detected on pre-operative IDL. Of 160 documented IDL, 4% revealed vocal cord pathology in asymptomatic patients, including an asymptomatic recurrent laryngeal nerve palsy. CONCLUSIONS: Indirect laryngoscopy remains a useful but flawed pre-operative screening tool for patients with voice symptoms, but the literature suggests that more advanced phoniatric tests will provide superior diagnostic sensitivity. The role of routine pre-operative laryngoscopy for asymptomatic patients is of debatable value.

Hoarseness↗
PubMed1999

Protein markers in colorectal cancer: predictors of liver metastasis.

OBJECTIVE: To assess the significance of the expression of five protein markers (nm23, p53, c-erbB-2, u-PA, and VEGF) to the development of metastasis in colorectal cancer. SUMMARY BACKGROUND DATA: The metastatic cascade is a complex multistep process involving several genetic alterations, angiogenesis activation, and tissue proteolysis. Although the prognosis of colorectal cancer depends on the stage of the tumor, the development of metastasis is difficult to predict. METHODS: Paraffin-embedded specimens of 58 patients who underwent surgery for colorectal cancer were retrospectively analyzed by immunohistochemistry, and the coexpression of these protein markers was related to patient outcome. RESULTS: The risk of developing liver secondaries was correlated with the expression of nm23 protein (p < 0.0001); this was also the case in those patients with Dukes' stage B showing positive nm23 immunostaining (p = 0.006). The determination of the number of positive markers or the cumulative intensity score did not improve the predictive value over and above that of nm23 protein alone. CONCLUSION: Expression of nm23 protein is correlated with the risk of developing liver metastasis. Its evaluation alone may help to determine which patients who have undergone apparently curative resection of a colorectal cancer have an increased risk of liver recurrence, especially those with Dukes' stage B tumors who might be considered for adjuvant chemotherapy.

Adult↗
PubMed1998

Re-engineering the elective surgical service of a tertiary hospital: a historical controlled trial.

OBJECTIVE: To study the clinical effects of re-engineering the processes associated with elective surgery. DESIGN: A prospective, historical controlled trial. Control patients were enrolled from March 1995 to January 1996, and postintervention patients from February 1996 to October 1996. SETTING: A major teaching, tertiary care hospital (Prince of Wales Hospital, Sydney). PATIENTS: 224 patients (123 before and 101 after the intervention) undergoing elective herniorrhaphy of laparoscopic cholecystectomy who lived in the local area. INTERVENTION: Introduction of a re-engineered surgical service consisting of preadmission assessment and education, admission on day of surgery, and postacute care after discharge. There were no changes to the operative methods or infection control procedures. MAIN OUTCOME MEASURES: Length of stay, operative complications, pain scores and patient satisfaction. RESULTS: The risk of a patient suffering one or more complications was reduced in the postintervention group (postintervention v. control patients: 25.7% v. 38.2%; relative risk [RR], 0.66; 95% confidence interval [CI], 0.44-0.98; P = 0.035) because of a reduced risk of wound infections (5.0% v. 16.3%; RR, 0.30; 95% CI, 0.12-0.78; P = 0.0075). Other complications (perioperative or postoperative) and pain scores were unchanged. Patients treated by the re-engineered service had a significantly shorter length of stay, reported a higher level of satisfaction with the preoperative and postdischarge care, and were more likely to say that they would have the same treatment again (92.9% v 82.6%; P = 0.037). CONCLUSIONS: Re-engineering surgical services, with an associated reduction in length of stay, does not lead to a deterioration in care and may decrease postoperative complications and increase patient satisfaction.

Australia↗
PubMed1998

Overexpression of nm23 protein assessed by color video image analysis in metastatic colorectal cancer: correlation with reduced patient survival.

The function and prognostic significance of the nm23 gene is controversial in colorectal cancer (CRC). The aim of this study was to determine if nm23 protein expression correlated with the subsequent development of liver metastasis. Paraffin-embedded sections of 30 metastasizing CRC primaries and their subsequently resected liver secondaries were compared with those of 28 nonmetastasizing CRCs, 20 adenomas, and 20 cases of normal colonic mucosa. Expression of nm23 protein, assayed by immunohistochemistry, was measured using a standard semiquantitative scaling system and compared with a microcomputerbased color video image analysis (VIA). There was good correlation between color VIA and semiquantitative evaluation of nm23 immunoreactivity, confirming the validity of quantitative analysis (Pearson's r = 0.88; p < 0.001). Metastasizing CRC primaries and secondaries overexpressed nm23 protein when compared with the other clinical groups, particularly nonmetastasizing CRC (Student's t-test, p < 0.001). Furthermore, more nm23 immunoreactivity was associated with a higher risk of death from CRC (log-rank test, p = 0.002). These results suggest that overexpression of nm23 is highly associated with liver metastases from CRC and reduced survival.

Antigens, Neoplasm↗
PubMed1998

The role of the journal club in surgical training.

BACKGROUND: The development of skills in critical appraisal of the medical literature is an important aspect of surgical training. METHODS: At the Prince of Wales Hospital a journal club has been conducted for more than 5 years to improve the registrars' training in this area. A questionnaire was circulated regarding the success of the journal club at achieving adequate review of the important current literature, development of critical appraisal skills by registrars and providing a convivial social gathering. RESULTS: A total of 28 out of 39 current or previous journal club members responded to the questionnaire. Twenty-three of the respondents felt that the journal club provided a good to excellent review of current literature, 26 felt that the journal club facilitated development of critical appraisal skills and all 28 said that the journal club was a convivial social forum. Eight research projects developed from journal club reviews, 19 of the respondents reported that their clinical practice had changed, and 19 had been stimulated to further review a topic as a result of the journal club. Many of the respondents had specific criticisms of the journal club, and these have been used to improve the journal club format. CONCLUSIONS: The present study has highlighted the strengths and weaknesses of our journal club. The journal club is a valuable component of surgical education.

Clinical Competence↗
PubMed1998

Correlates of urokinase-type plasminogen activator in colorectal cancer: positive relationship with nm23 and c-erbB-2 protein expression.

We undertook a study to analyze the expression of urokinase-type plasminogen activator (u-PA) protein in colorectal cancer (CRC) and to compare it with c-erbB-2 (HER2/neu) and nm23 protein expression. Paraffin-embedded specimens from 58 patients with CRC were retrospectively collected. Immunohistochemical staining of u-PA, c-erbB-2, and nm23 was quantitatively evaluated using a color video image analysis (color VIA) technique. No correlation was found between u-PA expression and tumor stage, age, sex, or tumor site. Although there was no evidence from our data that the level of u-PA in the primary tumors could predict risk of liver metastasis or survival duration, CRC showing overexpression of u-PA (above 85 pixels) had a worse prognosis (P = 0.013). There were significant positive correlations among all three u-PA, c-erbB-2, and nm23 proteins (u-PA vs. c-erbB-2, P = 0.003; u-PA vs. nm23, P < 0.001; c-erbB-2 vs. nm23, P = 0.001), suggesting that, in vivo, all proteins interact or are similarly regulated.

Biomarkers, Tumor↗
PubMed1996

Higher expression of oncoproteins c-myc, c-erb B-2/neu, PCNA, and p53 in metastasizing colorectal cancer than in nonmetastasizing tumors.

BACKGROUND: Expression of individual oncogenes may predict outcome in patients with metastatic colorectal cancer (CRC). We studied the oncogene profile in the tumors of patients with CRC and assessed their value as predictors of liver metastases. METHODS: The oncoproteins c-myc, c-erbB-2/neu (c-neu), PCNA and p53, were measured by immunohistochemistry in sections of metastasizing human CRC (n = 34) and their liver secondaries as well as in sections of nonmetastasizing human CRC (n = 25). RESULTS: The metastasizing primary CRC expressed proliferating-cell nuclear antigen (PCNA), c-neu, and c-myc at significantly higher levels than the nonmetastasizing primary cancer, p53 was also overexpressed in the metastatic group compared with the nonmetastasizing CRC, but this difference was not significant. The frequency of expression of all these markers was similar in the metastasizing primary CRC and the liver secondaries from the same patients. There was no correlation between the expression of the individual markers and histological grade, DNA ploidy, and subsequent local recurrence and lung metastasis and survival. However, when both groups were assessed together, positive expression of c-myc was more likely to occur in poorly differentiated tumors, whereas PCNA expression increased with more advanced Dukes stages. CONCLUSION: These results suggest that the overexpression of c-myc, c-neu, PCNA, and p53 may occur in CRC that are likely to metastasis to the liver.

Colorectal Neoplasms↗
PubMed1996

DNA flow-cytometric analysis in colorectal cancer: a comparison of metastasizing and non-metastasizing tumours.

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n = 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n = 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P = 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes' classification for identifying metastasizing tumours (Logistic Regression; P = 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.

Cell Cycle↗
PubMed1995

Laparoscopic repair of a traumatic diaphragmatic hernia.

The laparoscopic diagnosis and repair of an unusual diaphragmatic hernia are described. Extensive radiological assessment failed to demonstrate the injury, which was diagnosed by laparoscopy 5 weeks after the initial presentation. The diaphragmatic tear was adjacent to the costal margin and was repaired using a novel percutaneous technique. The place of laparoscopy in blunt abdominal trauma is discussed.

Abdominal Injuries↗