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Biomedical subjects

A D Purushotham

Publications and source records attributed to A D Purushotham.

At least 55 records · Page 3Linked to original sources
PubMed1999

Margin assessment by cavity shaving after breast-conserving surgery: analysis and follow-up of 543 patients.

AIMS: To analyse cavity shaving as a method of assessing completeness of surgical excision after breast-conserving surgery. METHODS: Shavings were taken from the wall of the cavity remaining in the breast after breast-conserving surgery in 543 women. Each shaving was extensively sectioned and the presence and type of microscopic disease recorded. Disease in cavity shavings (tumour bed positivity) was correlated with clinicopathological factors as well as overall survival. RESULTS: Tumour bed positivity (TBP) was found in 37% of patients (16% with invasive disease). Patients were selected for further surgery according to the extent of positivity, which varied widely. A total of 15% of patients underwent re-excision or mastectomy. TBP was significantly associated with high tumour grade, presence of an extensive intraduct component, young age and large tumour diameter. It was also associated with a significantly shorter overall survival when compared to patients who were tumour bed negative. CONCLUSIONS: Cavity shaving is a practical and sensitive method of assessing completeness of excision after breast-conserving surgery. In addition it may provide useful prognostic information.

Adult↗
PubMed1999

Verrucous carcinoma of the female breast.

Verrucous carcinoma is a rare skin malignancy of squamous cell origin. It is characterised by negligible cellular atypia and a low mitotic rate. These are reflected in slow locally invasive behaviour and very infrequent metastatic spread. The tumour is also recognised in oral and anogenital sites. Cutaneous lesions present most commonly on the sole of the foot. We report a unique case occurring in the female breast.

Aged↗
PubMed1998

Putative markers for the detection of breast carcinoma cells in blood.

The aim of this study was to investigate certain genes for their suitability as molecular markers for detection of breast carcinoma cells using the reverse transcriptase-polymerase chain reaction (RT-PCR). RNA was prepared from MCF-7 breast carcinoma cells and peripheral blood leucocytes of healthy female volunteers. This RNA was screened for mRNA of MUC1, cytokeratin 19 (CK19) and CD44 (exons 8-11) by RT-PCR and the results validated by Southern blots. Variable degrees of expression of MUC1 and CD44 (exons 8-11) were detected in normal peripheral blood, rendering these genes non-specific for epithelial cells and therefore unsuitable for use as markers to detect breast carcinoma cells. Although CK19 mRNA was apparently specific, it was deemed unsuitable for use as a marker of breast cancer cells in light of its limited sensitivity. Furthermore, an attempt at using nested primers to increase sensitivity resulted in CK19 mRNA being detected after two amplification rounds in blood from healthy volunteers.

Adenocarcinoma↗
PubMed1998

Lymphatic mapping and sentinel node biopsy in breast cancer.

BACKGROUND: Sentinel lymph node biopsy is a recently developed, minimally invasive technique for staging the axilla in patients with breast cancer. It has been suggested that this technique will avoid the morbidity associated with more extensive axillary dissection. A wide range of different methods and materials has been employed for lymphatic mapping, but there has been little consensus on the most reliable and reproducible technique. METHODS: This is a comprehensive review of all published literature on sentinel node biopsy in breast cancer, using the Medline and Embase databases and cross-referencing of major articles on the subject. RESULTS AND CONCLUSION: Sentinel node biopsy is a valid technique in breast cancer management, providing valuable axillary staging information. The optimal technique of lymphatic mapping utilizes a combination of vital blue dye and radiolabelled colloid. However, there remain controversial issues which require to be resolved before sentinel node biopsy becomes a widely accepted part of breast cancer care.

Axilla↗
PubMed1997

Tumour bed positivity predicts outcome after breast-conserving surgery.

BACKGROUND: Local recurrence after breast-conserving surgery is associated with a short distant disease-free survival, particularly if it occurs early. Early recurrence is caused by residual disease left at the time of surgery. Previous studies have demonstrated that disease in the tumour bed is a common finding after breast-conserving surgery. METHODS: The follow-up (mean 4.4 years) of 300 patients who had tumour bed analysis performed by the cavity shaving technique following breast-conserving surgery is presented. Postoperative radiotherapy was administered to all patients. RESULTS: The incidence of tumour bed positivity was 39.3 per cent. With a selective re-excision policy the local recurrence rate was 2.0 per cent and distant recurrence rate 10.4 per cent. Multivariate analysis identified lymphovascular invasion, oestrogen receptor status and tumour bed status as independent predictors of time to distant recurrence. CONCLUSION: A low rate of local recurrence can be achieved using this technique of margin assessment. Tumour bed status may be a useful prognostic factor following breast-conserving surgery.

Adult↗
PubMed1996

Hepatocyte growth factor/scatter factor expression and c-met in primary breast cancer.

Hepatocyte growth factor/scatter factor (HGF/SF) is a fibroblast-derived cytokine whose receptor is encoded by c-met. Activation of c-met promotes tumour cell proliferation, dissociation, invasiveness and angiogenesis. Aberrant expression of HGF/SF or c-met may play a role in tumour progression. HGF/SF and c-met were determined in 73 breast cancers (median follow up: 61 months) and 10 samples of tumour-free breast tissue. HGF/SF was detected at significantly higher concentrations in breast cancers (median 350, range 58-1604 ng per 100 mg total protein) when compared with normal breast tissue (median 108, range 66-213 ng per 100 mg total protein) (P < 0.001). C-met was detected in all 10 samples of tumour-free breast tissue and in 26 breast cancers. HGF/SF concentrations correlated with disease relapse (P < 0.001) and reduced overall survival (P < 0.001). Tumours with detectable c-met correlated significantly with disease-relapse (P = 0.012). Multivariate analysis demonstrated a significant interaction between HGF/SF and c-met in relation to disease-relapse (P = 0.014). These results suggest a biological interaction involving HGF/SF and c-met in promoting tumour progression in breast cancer.

Breast↗
PubMed1996

Local recurrence after breast-conserving surgery for breast cancer.

Local recurrence following breast-conserving surgery for breast cancer is a significant failure of local treatment. This article reviews the mechanisms, risk factors and overall significance of such local recurrence. The presence of disease at excision margins, an extensive intraduct component, lymphatic vessel invasion, tumour grade and tumour size are currently the best predictors of risk for local recurrence. Early local recurrence is due to residual disease and is associated with both decreased distant disease-free survival and overall survival; it appears to reflect aggressive biological characteristics of the primary tumour. The importance of adequate local treatment for breast cancer is discussed.

Breast Neoplasms↗
PubMed1995

Expression and loss of heterozygosity of c-met proto-oncogene in primary breast cancer.

The c-met proto-oncogene encodes the receptor to hepatocyte growth factor-scatter factor (HGF-SF), a mesenchyme-derived cytokine with cell-dissociating, invasion, and angiogenic properties. The expression of c-met in breast cancer is the subject of controversy; 111 primary breast cancers were examined for LOH of c-met by Southern blot electrophoresis. c-met expression was measured in a further 40 patients with breast cancer and in 8 patients with benign breast disease by flow cytometry. LOH of c-met was detected in only 4% of informative breast cancers. Expression of c-met was significantly greater in patients with breast cancer than in those with benign breast disease (P < 0.01, Mann-Whitney). There was no correlation however between increased c-met expression and clinicopathological prognostic variables. These results do not support the role of c-met as a tumour suppressor gene in breast cancer but suggest increased receptor expression in malignant breast disease. The significance of this increased expression in breast cancer is the subject of further investigation.

Blotting, Southern↗
PubMed1995

Detection of intraoperative tumor cell dissemination in patients with breast cancer by use of reverse transcription and polymerase chain reaction.

BACKGROUND: Animal studies have shown that malignant cells are shed into the blood stream during surgical resection of a primary tumor and that this may enhance the development of metastases. The evidence for tumor cell dissemination during surgical manipulation of human cancer is unclear. We have applied the technique of reverse transcription and polymerase chain reaction to detect circulating tumor cells in peripheral venous blood of patients with breast cancer perioperatively. METHODS: To target breast-specific gene transcription complementary DNA was prepared by reverse transcription of blood messenger RNA with oligonucleotide primers unique to CK18 and DF3 antigens. Preliminary assessment of specificity showed that the DF3 antigen was more suitable than CK18 for the purpose of this study. Assessment of sensitivity showed that as few as 10 tumor cells per 5 ml blood could be identified by this method. Peripheral blood samples were obtained by venepuncture from patients before, during, and 24 hours after breast surgery (nine malignant and three benign). RESULTS: In the group of patients with malignant disease, tumor cells were detected in one patient before operation and four patients during operation. No tumor cells were detected in the postoperative samples nor in any of the samples of patients with benign disease. CONCLUSIONS: These findings suggest that tumor manipulation during operation encourages tumor cell dissemination.

Breast Neoplasms↗
PubMed1995

Predicting local recurrence by correlating pre-operative mammographic findings with pathological risk factors in patients with breast cancer.

The pre-operative mammograms for 231 patients undergoing conservation surgery for breast cancer between March 1988 and September 1992 were analysed for features that may predict the presence of pathological risk factors of local recurrence (residual microscopic disease, extensive intraduct carcinoma (EIC) and lymphatic/vascular invasion). Residual microscopic disease was detected in 40% of patients and was associated with a DY mammographic pattern (p = 0.03), casting calcification (p = 0.0002) and absence of mammographic nidus (p = 0.0006). Residual microscopic disease was found in 75-88.9% of patients when two of these preoperative mammographic features were present in combination. The mean lumpectomy diameter was significantly smaller for patients with DY compared to N1 mammographic pattern on Wolfe grade (p = 0.039). Both residual disease and Wolfe grade were related to age (p = 0.0032 and p < 0.0001). EIC was found in 22% of patients and was associated with casting (p < 0.0001) and non-casting (p = 0.04) calcification, absence of mammographic nidus (p < 0.0001) and stellate mammographic nidus (p = 0.02). No significant association was found between mammographic features and lymphatic/vascular invasion. Pre-operative mammographic features can predict patients likely to have residual microscopic disease or EIC following conservation surgery for breast cancer. These patients should be selected for wider primary excision.

Adult↗
PubMed1994

Breast-conserving surgery and tumour bed positivity in patients with breast cancer.

Between March 1988 and April 1992, in 264 patients undergoing breast-conserving surgery for stage I and II cancer, the tumour bed was analysed for residual disease. After a conventional breast-conserving operation the entire wall of the cavity from which the lumpectomy specimen had been taken was excised. This was involved with disease in 38 per cent of patients. Additional random biopsies of the secondary cavity were performed in 130 patients and were involved with disease in 13 per cent. Residual disease was detected in the tumour bed of 37 per cent of patients with screen-detected tumours.

Adult↗
PubMed1994

Inhibition of pulmonary tumor seeding by antiplatelet and fibrinolytic therapy in an animal experimental model.

Fibrin and platelets contribute to the development of blood borne metastases by facilitating the arrest of tumor cell emboli in the microcirculation. We have previously demonstrated that the fibrinolytic agent streptokinase inhibits pulmonary tumor cell seeding in an animal model. To determine whether this effect was potentiated by antiplatelet therapy, a further study was performed to assess the effect of streptokinase in combination with aspirin in a similar model. The results demonstrated that aspirin did not significantly enhance the antimetastatic effect of streptokinase (median: streptokinase = 60, streptokinase + aspirin = 60.5, P = 0.79, Mann Whitney). In a second series of experiments, the antimetastatic effect of streptokinase was compared with another fibrinolytic agent, human recombinant tissue plasminogen activator (rt-PA). Fibrinolytic doses of streptokinase (30,000 units/kg) and rt-PA (5 mg/kg) significantly reduced pulmonary tumor seeding when compared with controls (median: control = 48, streptokinase = 23, P < 0.01, rt-PA = 29, P < 0.001). There was no significant difference in pulmonary tumor seeding between the groups treated with streptokinase and rt-PA (P = 0.56). The clinical implications of these findings are discussed.

Animals↗
PubMed1994

Streptokinase inhibits pulmonary tumor seeding in an animal experimental model.

One aspect of the metastatic process involves entrapment of tumor cells within the microcirculation of organs in a "fibrin-platelet mesh." We postulate that destruction of this mesh by fibrinolysis might discourage tumor seeding, thereby inhibiting metastasis. To study this hypothesis, the effect of intravenous streptokinase on pulmonary tumor seeding was examined in a rodent model. In vitro experiments demonstrated that streptokinase had no cytotoxic or cytostatic effect on the Mtln3 cell line. Pharmacokinetic studies showed that at 30,000 U/kg, streptokinase caused systemic fibrinolysis in the Fischer rat, as demonstrated by the thrombin time and fibrin plate lysis assay. Streptokinase administered at this dose, 30 min after tumor cell injection, caused a significant decrease in pulmonary tumor seeding (median 23.0 in the streptokinase-treated group vs. 67.5 in untreated controls, P < 0.0001, Mann-Whitney U-test). Analysis of fibrin degradation products in the streptokinase-treated group suggested that this effect might be secondary to fibrinolysis. The implications of these findings are discussed.

Adenocarcinoma↗
PubMed1991

Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacrifice at various intervals, measured lung radioactivity was significantly higher (20%) in animals administered cells with the factor complex than in the other two groups (P less than 0.001, ANOVA and Student's t-test). These results indicate increased entrapment of tumour cells in the pulmonary microcirculation. In a second experiment, rat factor complex II, IX, X was prepared, and Mtln3 cells were then injected in female Fisher 344 rats alone or in combination with either human factor complex or rat factor complex. Following sacrifice, the number of pulmonary nodules in animals receiving cells with rat factor complex was similar to that in animals receiving human factor complex, and significantly higher than that in the control (P less than 0.001, ANOVA and Mann-Whitney), indicating that the observed enhancement of pulmonary seeding is unrelated to the xenogeneic properties of the human factor complex.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Use of a collagen coated vicryl tube in reconstruction of the porcine esophagus.

This experimental study assessed the use of a collagen-coated vicryl mesh tube to reconstruct the esophagus in growing piglets. Initial experiments, in which a segment of thoracic esophagus was excised and replaced by this prosthetic tube, resulted in all the animals succumbing to mediastinitis within the first 3-4 days. This was shown, at post-mortem, to be due to leakage of the prosthesis, secondary to acid reflux, resulting in dissolution of the prosthesis. The collagen-coated vicryl mesh was thereafter treated with glutaraldehyde and in-vitro studies showed that the glutaraldehyde-treated material exhibited a higher resistance to 0.01 M HCl at pH 2.0, when compared with untreated material. In addition, the glutaraldehyde-treated material also showed an increased resistance to digestion by bacterial collagenase. Further experiments to reconstruct the cervical esophagus in growing piglets were performed using the revised glutaraldehyde cross-linked collagen coated vicryl mesh tube. All the animals survived the procedure and the prosthesis were leakproof immediately post-operatively. The animals, however, developed severe stenosis at a mean of 11 days post-operatively. Attempts at neo-epithelialization of the graft were seen histologically. There was considerable granulation tissue and scar tissue formation on the mediastinal aspect of the graft. It is suggested that collagen coated vicryl mesh tube may find applications in the treatment of esophageal atresia only if the problem of stenosis of the prosthesis can be solved.

Anastomosis, Surgical↗
PubMed1991

Prostaglandins in the treatment of reflux oesophagitis: double-blind placebo controlled clinical trial.

The efficacy of the prostaglandin analogue, rioprostil, in the treatment of reflux oesophagitis has been assessed in a double-blind, randomized, placebo-controlled trial of 25 patients with endoscopic and histological evidence of reflux oesophagitis. At the beginning and end of the study, endoscopic appearances were graded 0-4 (0 = no oesophagitis, 4 = severe oesophagitis) and the symptoms of heartburn, regurgitation, pain and dysphagia were each graded 0-3 (0 = none, 3 = severe). Fourteen patients received rioprostil, 300 micrograms twice daily, and 11 patients received identically marked placebo for a period of 12 weeks. At the end of the study there were no significant differences between the groups in mean (s.d.) endoscopic grading (rioprostil 2.4 (1.3); placebo 1.9 (0.9)) and mean (s.d.) cumulative symptom score (rioprostil 2.5 (3.1); placebo 2.6 (1.5)). Five patients in the rioprostil group reported diarrhoea. Rioprostil had no significant benefit over placebo in the treatment of reflux oesophagitis.

Double-Blind Method↗
PubMedDate not supplied

Acceptability of early discharge with drain in situ after breast surgery.

The aim of this study was to evaluate a policy of early discharge at 48 hours with suction drains in situ in a cohort of patients undergoing surgery for breast cancer and to compare this with a similar cohort of patients discharged 5 days postoperatively. This was an integrated qualitative/quantitative study using a questionnaire given to both groups providing comparable results by using averages and percentages to describe and synthesize the data. A questionnaire of open and closed questions was given to 19 patients who chose to be discharged at 48 hours with drains in situ, and 16 patients who opted to be discharged at 5 days after drain removal. The study demonstrated that patients regarded early discharge as being safe and were satisfied with their care when they were given a high level of support from hospital and community staff. The results also identified that it was important for patients to make their own decision about either early discharge or standard discharge in order to be satisfied with the outcome of their care.

Adult↗