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J R Monson

Publications and source records attributed to J R Monson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Isolation of human colorectal tumour reactive antibodies using phage display technology.

Few highly specific anti-colorectal tumour antibodies exist. Here, we describe the isolation of a panel of colorectal tumour reactive antibodies, using bacteriophage-antibody display technology. A whole-cell based panning protocol has been used to isolate antibodies. panning against a cell type related to the colorectal tumour cells was used to remove antibodies reacting with common antigens. The 11 antibodies studied possess different levels of specificity, all bound to protein or glycoprotein molecules, and 2 of them recognised tunicamycin-sensitive epitopes. None of the antibodies recognise the commonly expressed colorectal-markers CEA or EP-CAM. Our work demonstrates the potential of this technology for the development of new anti-tumour reagents.

Antibodies, Neoplasm↗
PubMed2000

Improving the view in the rectal clinic: a randomised control trial.

BACKGROUND: Rigid sigmoidoscopy forms an integral part of the out-patient assessment of patients with colorectal symptoms. However, the value of this of this examination is often diminished by faecal loading of the rectum. This trial aimed to determine the ability of a single self-administered glycerine suppository to clear the rectum in preparation for rigid sigmoidoscopy, and considered patient acceptability of this practice. METHODS: Consecutive patients were randomly allocated to receive suppository or no suppository prior to out-patient rigid sigmoidoscopy. Assessment was made of patient compliance, the effectiveness of rectal examination, and the depth to which the sigmoidoscope was inserted. RESULTS: 131 patients were randomised into suppository (n = 66) or control groups (n = 65). The number of patients deemed to have good views of the rectum (> 75% of rectal mucosa seen) was significantly greater in suppository than control groups (79% versus 26.2%, P < 0.05 Chi square test), whilst that of poor examinations (< 50% of rectal mucosa seen) was significantly greater in control than suppository groups (44.6% versus 4%, P < 0.05). The depth of insertion of the sigmoidoscope was significantly greater in those receiving suppositories (54.5% versus 21.5% undergoing evaluation to 18 cm or more, P < 0.05). Compliance amongst those who received suppositories was high with only 3 of 53 (4.5%) patients in the suppository group evaluated by questionnaire reporting difficulty or concerns over their use. CONCLUSION: Self-administered suppositories are acceptable to patients and significantly improve the efficiency of outpatient rigid sigmoidoscopy. Their usage should become routine.

Adult↗
PubMed1999

Genetic changes associated with telomerase activity in breast cancer.

Telomerase, the enzyme responsible for maintenance of the telomeres, is absent from the vast majority of somatic cells but is present in most tumours. Little is known about how telomerase is activated in cancer, although it is thought vital for immortalisation to occur. The aim of our study was to identify genetic changes associated with telomerase activity. Thirty-three breast carcinomas were assessed for telomerase activity using the PCR based TRAP assay, and genetic changes by comparative genomic hybridisation (CGH). Seventy-five percent of the tumours were telomerase positive, and these were further divided into low or high level telomerase activity groups. A large number of genetic aberrations were identified but 4 chromosomal regions were identified that correlated with the telomerase status of the tumour. Gain of 1q correlated with telomerase negative tumours, gain of 3q correlated with high level telomerase activity. Gain of 8q correlated with telomerase positive tumours and furthermore with high level telomerase activity; deletion of 17p also correlated with high level telomerase activity. CGH analysis of breast tumours in conjunction with telomerase status has supported early results suggesting the involvement of the telomerase hTR, c-myc and p53 genes in the control of telomerase activity. These genes are located on chromosomes 3q, 8q and 17p. Most importantly, our results have identified the involvement of gene(s) located on chromosome 1q in telomerase expression.

Breast Neoplasms↗
PubMed1999

Genetic analysis of head and neck squamous cell carcinoma and surrounding mucosa.

OBJECTIVE: Comparative genomic hybridization was performed on head and neck squamous cell carcinoma and surrounding mucosa to determine whether common chromosomal aberrations could be detected that would predispose an individual to developing a second primary tumor. DESIGN: Biopsy specimens were taken from 19 patients with squamous cell carcinoma of the head and neck, 3 samples from each person: 1 specimen from the tumor site and 1 each from 1 and 5 cm from the macroscopic tumor margin. Samples were snap frozen in liquid nitrogen. A portion of each distant sample and tissue taken from immediately adjacent to the site of the tumor specimen were sectioned and stained with hematoxylin-eosin, either to search by light microscopy for tumor cells or signs of dysplasia in the distant samples, or to determine whether the tumor specimen had substantial non-tumor cell content. Tissue adjacent to the tumor biopsy site was used because the biopsy specimens were relatively small. Comparative genomic hybridization was performed on all samples. SUBJECTS: Nineteen patients with newly diagnosed carcinomas of the head and neck. RESULTS: The tumor biopsy specimens showed no substantial nontumor cell content, and the distant specimens were all histologically normal. The tumors showed multiple mutations: mean (SD) number of deletions, 5.4 (4.3); amplifications, 5.2 (4.6). Deletion of chromosome 3p was seen in 13 of 19 cases and was associated with amplification of 3q in 10 cases. No mutations were seen in the distant biopsy specimens. CONCLUSIONS: Frequently occurring chromosomal aberrations were seen in the tumor cells, suggesting a key role for these mutations in tumor development. Screening histologically normal upper aerodigestive tract mucosa with comparative genomic hybridization does not provide information on early genetic events that predispose a patient to developing a second primary tumor.

Aged↗
PubMed1999

The role of monocytes and natural killer cells in mediating antibody-dependent lysis of colorectal tumour cells.

Monocytes and natural killer (NK) cells are known to be important effector cell populations in mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Purified monocyte and NK effector cell populations, from normal and colorectal cancer (CRC) patients, together with a number of murine (17-1A and 323/A3) and their chimaeric (c17-1A) or humanised (3622W94) equivalents, and chimaeric (c) SF25 were compared for their ability to mediate ADCC of colorectal tumour cells. The chimaeric and humanised antibodies were significantly better at mediating tumour lysis than their murine equivalents with all-effector populations. When effector cells from CRC patients were used the cSF25 antibody was significantly better than 3622W94 (P < 0.02) which, in turn, was significantly better than c17-1A (P < 0.03). Depletion of NK cells produced a decrease in specific tumour lysis with all antibodies. In addition a higher rate of NK cell death was observed in CRC patients during the assay than in normal controls. The chimaeric and humanised antibodies stained a similar percentage of the HT-29 target cells (>80%), but 3622W94 bound to significantly more cells from primary tumour biopsies than cSF-25 (P = 0.001). Together, the results suggest that NK cells are the most important effector cell type mediating ADCC in vitro, that there is some impairment of NK function in CRC patients, and that cSF25 is the most potent antibody. For use in vivo the anti-Ep-CAM antibody 3622W94 would appear to be the most suitable reagent for further study.

Adenocarcinoma↗
PubMed1999

Dynamic contrast enhanced magnetic resonance imaging of the breast is superior to triple assessment for the pre-operative detection of multifocal breast cancer.

BACKGROUND: Inadequately treated multifocal and multicentric disease results in increased local recurrence following breast-conserving surgery. The accurate preoperative diagnosis of multifocal/ centric breast cancer would facilitate the planning of appropriate surgery and prevent reoperation for residual disease. While triple assessment remains the established diagnostic technique, its sensitivity for the diagnosis of multifocal disease remains poor. Dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) of the breast represents an alternative emerging diagnostic modality that has been shown to be highly sensitive for the delineation of primary breast cancer. The aim of this study was to prospectively compare the diagnostic accuracy of DCE-MRI of the breast with conventional triple assessment for the preoperative diagnosis of multifocal/centric breast cancer. METHODS: Patients were recruited from the symptomatic breast clinics. All patients underwent standard triple assessment and DCE-MRI. The MRI scans were reported by a single radiologist blinded to the results of the triple assessment. Surgery was then planned accordingly to all available scan results and the specimens examined by a single pathologist. All patients who did not undergo surgery have been followed up for a minimum of 18 months. RESULTS: A total of 334 women were recruited. There were 178 (52%) cancers that were histologically confirmed and multifocal/centric breast cancer was diagnosed provisionally by the preoperative investigations in 68 (38%); multifocal n = 33, multicentric n = 35, of these patients. In this group, subsequent histology confirmed multifocal/centric disease in 50 (73.5%): multifocal n = 15, multicentric n = 35. Unifocal cancer was found in 15 (22%) and benign disease in 3 (4.4%). The resultant sensitivity, specificity, positive, and negative predictive values were 18%, 100%, 100%, and 76% for triple assessment and 100%, 86%, 73%, and 100% for DCE-MRI. CONCLUSION: DCE-MRI identified a subgroup of breast cancer patients with multifocal/centric disease not evident on standard triple assessment. MRI of the breast should be considered for the preoperative planning of surgery for primary breast cancer.

Aged↗
PubMed1999

Neoadjuvant therapy in the treatment of high risk rectal carcinoma.

The management of rectal cancer remains a challenging and controversial area of surgical oncology. The spectre of local recurrence, with its' poor prognostic and palliative outcomes, is known to be highly dependent on operative technique and to vary widely between surgeons. The roles of radiotherapy and chemotherapy have been the subject of trials for 30 years and yet no consensus on treatment exists. In this review article we will summarise the evolution of radiotherapy and chemoradiation in the treatment of rectal cancer and evaluate the evidence available for the use of "neoadjuvant" chemoradiation. In particular, the role of adjuvant therapies in the setting of total mesorectal excision will be discussed.

Chemotherapy, Adjuvant↗
PubMed1999

Preoperative magnetic resonance staging of rectal cancer with an endorectal coil and dynamic gadolinium enhancement.

BACKGROUND: The aim of the study was to assess the value of endorectal coil magnetic resonance imaging (MRI) with gadolinium enhancement in the preoperative staging of rectal cancer. METHODS: In addition to standard evaluation, patients with rectal lesions were assessed by MRI obtained with a pelvic phased-array coil in combination with an endorectal coil. RESULTS: The study group comprised 29 patients with rectal cancer staged with an endorectal coil who had surgery without preoperative adjuvant therapy. In addition to standard T1- and T2-weighted images, dynamic contrast-enhanced images were acquired in all patients. Considerable interobserver variation was noted, particularly for pathological tumour stage pT1 or pT2 (kappa = 0.36). Compared with pathological findings, endorectal MRI correctly staged nine patients, overstaged 16 and understaged four. Whilst lymph node metastases were accurately detected in 70 per cent of patients, the positive predictive value was only 58 per cent. CONCLUSION: MR staging of rectal cancer with an endorectal coil and gadolinium enhancement is inaccurate for early tumours (stage T1 or T2) and is associated with a considerable degree of interobserver variation for individual scan sequences.

Gadolinium DTPA↗
PubMed1999

Prospective comparison of standard triple assessment and dynamic magnetic resonance imaging of the breast for the evaluation of symptomatic breast lesions.

OBJECTIVE: To compare the sensitivity and specificity of the traditional triple assessment of symptomatic breast lesions with contrast-enhanced dynamic magnetic resonance imaging. BACKGROUND: Although triple assessment is currently the gold standard for the assessment of symptomatic breast disease, its specificity is such that open biopsies are still required in many cases to be confident of the diagnosis. Contrast-enhanced dynamic magnetic resonance imaging of the breast represents an alternative diagnostic modality. METHODS: Patients were recruited from the symptomatic breast clinics. If any of the diagnostic modalities suggested malignancy, the lesion was excised. The remaining patients were followed clinically and radiologically. RESULTS: Two hundred eighty-five patients with a mean age of 43 years (range 21 to 77) were recruited. Malignant lesions were excised in 131 patients and benign lesions in 55 patients. The 99 patients who did not undergo surgery were followed clinically and radiologically for a median of 20 months. The sensitivity of each modality was as follows: clinical examination 84%, mammography 87.6%, fine-needle aspiration cytology 79.1%, triple assessment 99.2%, and magnetic resonance imaging 99.2%. In addition, histologically confirmed multifocal disease was detected in 40 patients on magnetic resonance imaging but in only 9 (22.5%) on mammography. The specificity for the diagnosis of benign disease was as follows: clinical examination 83.1%, ultrasound 88.9%, mammography 86.4%, fine-needle aspiration cytology 97%, triple assessment 59.1%, and magnetic resonance imaging 90.9%. CONCLUSION: Contrast-enhanced dynamic magnetic resonance imaging of the breast is as sensitive and more specific than the combined traditional triple assessment for the diagnosis of malignant breast lesions.

Adult↗
PubMed1999

Optimal education techniques for basic surgical trainees: lessons from education theory.

"Calmanisation" of surgical training and the introduction of the "New Deal" on doctor's hours has led to a reduction in "in service" training and a proliferation of training courses. Little research has been done into the optimum design of these courses. Education theory has shown that individuals have optimal learning styles and that these styles tend to be generalised across professional groups. It was decided, therefore, to investigate the optimal learning styles of basic surgical trainees. A learning style inventory was used to assess the preferred learning style of 52 basic surgical trainees. The predominant learning styles (86.5%) were convergent (n = 31) or accommodative (n = 14) whilst only 5 (9.6%) assimilative and 2 (3.9%) divergent styles were detected. Convergent and accommodative learners rely principally on hands on experience and problem solving as their optimal learning technique. Given the shorter hours and duration of Basic Surgical Training, in service practical training and surgical courses should be structured accordingly.

Adult↗
PubMed1999

Laparoscopic colorectal resection for cancer: clearance, complications prevention.

The first description of the laparoscopic approach to colorectal cancer resection was in 1991. Today, the exact role of laparoscopic colorectal cancer surgery remains undefined and awaits the results of multicenter randomized controlled trials. Most authors agree that pending these results, such surgery should be performed only in specialist centers and on study populations. This hesitant adoption of the laparoscopic modality in colorectal cancer surgery is in stark contrast to the speed and enthusiasm with which laparoscopic cholecystectomy was adopted without a randomized controlled trial. Adapting laparoscopic techniques to malignant disease requires confirmation that the laparoscopic approach conforms to the principles of surgical oncology: adequacy of resection margins, wide clearance of lymph nodes fields, and the avoidance of iatrogenic tumor dissemination.

Journal Article↗
PubMed1998

Endosonographic evidence of injury to the internal anal sphincter after low anterior resection: long-term follow-up.

PURPOSE: Transanal stapled anastomosis has been associated with continence disturbances and reduced postoperative anal sphincter function. The aim of the present work was to study the effect of transanal stapling on anal sphincter morphology by endoanal ultrasound. METHODS: Thirty-nine consecutive patients undergoing stapled low anterior resection for rectal carcinoma were assessed. Each patient was assessed by endoluminal ultrasound before surgery, immediately after surgery, and at 3, 6, 9, 12, and 24 months after surgery. RESULTS: There were no preoperative internal anal sphincter defects observed. Three female patients were observed to have preoperative evidence of external anal sphincter defects. After low anterior resection, seven patients were found to have internal anal sphincter defects, which persisted after the two-year follow-up. There were no additional external anal sphincter injuries. Three patients with internal anal sphincter injuries required the use of pads for poor bowel function. CONCLUSIONS: Up to 18 percent of patients who underwent stapled low anterior resection had long-term evidence of internal anal sphincter injury. The external sphincter does not appear to be affected by the procedure.

Anal Canal↗
PubMed1998

Impaired interleukin-12 production is associated with a defective anti-tumor response in colorectal cancer.

INTRODUCTION: Despite development of many chemotherapeutic regimens, colorectal cancer continues to have a high mortality. One of the major new potential therapies is interleukin-12, a heterodimeric cytokine produced by antigen presenting cells. In vitro and in vivo studies have demonstrated the role of interleukin-12 in stimulating a cell-mediated anti-tumor response against a number of colon adenocarcinoma tumor models. However, it is unknown whether patients with colorectal cancer have impaired interleukin-12 production. A study was performed to investigate production of interleukin-12 preoperatively and the relationship between these levels and disease stage at surgery. METHODS: Preoperative peripheral blood mononuclear cells from colorectal cancer patients and age-matched controls were stimulated by Staphylococcus aureus Cowan's Strain 1 (0.0075 percent wt/vol) in vitro for 24 hours. Expression of interleukin-12 was then assessed by enzyme-linked immunosorbent assay. A single pathologist assessed the tumors for stage according to TNM and Dukes classifications. RESULTS: Twenty-eight patients with colorectal cancer and 14 controls were recruited for the study. Interleukin-12 production was significantly impaired in patients with colorectal cancer compared with controls (P = 0.014), especially those with advanced disease: Dukes C, P = 0.001 and T4, P < 0.05. CONCLUSION: Interleukin-12 production is impaired in patients with colorectal cancer, especially those with advanced disease, suggesting a defective Thl-mediated anti-tumor response. These patients may well benefit from exogenous interleukin-12 treatment.

Adenocarcinoma↗
PubMed1998

Interactive multimedia information program for use by breast-care nurses--a patient acceptability study.

AIMS: To design an interactive multimedia program for use by breast-care nurses and evaluate the acceptability of this technology to patients in the clinical setting. METHODS: In order to ensure that the clarity of the information was maintained the multimedia program was developed by a multidisciplinary team, including non-medical personnel and patients. A prospective analysis of the subjective impressions of patients with symptomatic breast disorders and breast-care nurses to a multimedia patient information system was then performed using a standard questionnaire and semi-structured interviews. RESULTS: Fifty women were recruited for the study. Thirty-six (72%) considered the multimedia counselling to be superior to the traditional modalities. Forty-nine (98%) graded the system as good or better. No patient regarded the technology as anxiety-provoking or inferior to the traditional leaflet-based approach. Women over 55 years old found the system as acceptable and easy to use as the younger women. CONCLUSIONS: The multimedia breast counselling programme was acceptable to patients and was considered superior to the traditional leaflet-based approach by the majority. The inherent advantages of this technology will lead to its increasing utilization in the clinical setting.

Adult↗
PubMed1998

Vascular endothelial growth factor in premenopausal women--indicator of the best time for breast cancer surgery?

Timing of surgery in premenopausal patients with breast cancer remains controversial. Angiogenesis is essential for tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. We aimed to determine whether the study of VEGF in relation to the menstrual cycle could help further the understanding of this issue of surgical intervention. Fourteen premenopausal women were recruited, along with three post-menopausal women, a woman on an oral contraceptive pill and a single male subject. Between eight and 11 samples were taken per person, over one menstrual cycle (over 1 month in the five controls) and analysed for sex hormones and VEGF165. Serum VEGF was significantly lower in the luteal phase and showed a significant negative correlation with progesterone in all 14 premenopausal women. No inter-sample variations of VEGF were noted in the controls. Serum from both phases of the cycle from one subject was added to MCF-7 breast cancer cells; VEGF expression in the supernatant was lower in the cells to which the luteal phase serum was added. The lowering of a potent angiogenic cytokine in the luteal phase suggests a possible decreased potential for micrometastasis establishment in that phase. This fall in VEGF may be an effect of progesterone and should be the focus of future studies.

Analysis of Variance↗
PubMed1998

Transcatheter coil embolotherapy: a safe and effective option for major colonic haemorrhage.

BACKGROUND: The management of major colonic bleeding is problematic. A proportion of patients require emergency surgery which is associated with high morbidity and mortality. Percutaneous embolotherapy, previously considered a high risk procedure in the colon, may provide an alternative treatment in this group of patients. AIMS: To assess the safety and efficacy of embolotherapy in the treatment of life threatening colonic haemorrhage. PATIENTS AND METHODS: Thirty eight patients with fresh haemorrhage per rectum were referred for surgery because of failed conservative treatment. All underwent angiography; in 14 a bleeding site or vascular abnormality was detected. A coaxial catheter was directed to the most distal bleeding artery and this was embolised with platinum coils. RESULTS: Detection of a bleeding site correlated with haemodynamic stability at the time of angiography (r = 1 for a systolic blood pressure less than 100 mm Hg). Bleeding sites or vascular abnormalities were detected and embolised in 14 patients (37%). In 12/14 there was immediate and sustained haemodynamic improvement; two continued to bleed and required emergency hemicolectomy (14%). Three developed ischaemic complications (21.4%); these were managed conservatively and required no intervention. The 30 day mortality was 7.1% in the embolotherapy group and 10.5% in the overall group of 38 patients. CONCLUSION: Colonic embolotherapy for life threatening haemorrhage is an effective, relatively safe procedure with a low incidence of major complications. Its use depends on the identification of a focal bleeding point or vascular abnormality, which in turn depends on the haemodynamic stability of the patient at the time of angiography.

Aged↗