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Biomedical subjects

A D Purushotham

Publications and source records attributed to A D Purushotham.

At least 19 recordsLinked to original sources

"Inflammatory" breast cancer.

BACKGROUND: "Inflammatory" breast cancer is a rare and very aggressive form of the disease characterised by rapid onset and dismal outcome. METHODS: This review describes the clinical and molecular aspects of inflammatory breast cancer. The relevant English language literature on of inflammatory breast cancer was searched via Medline and ISI Web of Knowledge Cross Search (1924-2005), cross-referencing with key articles on the subject. RESULTS AND CONCLUSION: An increasing body of evidence demonstrates that inflammatory breast cancer is a unique form of breast cancer. A prompt diagnosis and multidisciplinary approach (based on neoadjuvant chemotherapy, loco-regional treatment with surgery and/or radiotherapy, followed in some cases by adjuvant systemic therapy) are the two factors most likely to have an impact on survival. As the molecular basis of the disease is becoming increasingly more defined, new potential therapeutic targets may arise in the future.

Breast Neoplasms↗

The value of immunohistochemistry in sentinel lymph node histopathology in breast cancer.

The optimal protocol for the histopathological examination of sentinel lymph nodes (SLNs) in breast cancer has not been determined. The value of more detailed examination using immunohistochemistry (IHC) is controversial. A total of 476 SLNs from 216 patients were reviewed. Sentinel lymph nodes were sectioned at three levels at 100 mum intervals and stained with haematoxylin and eosin (H&E). If the H&E sections showed no evidence of metastasis, then the three serial sections were stained with a murine monoclonal anti-cytokeratin antibody (CAM 5.2). Metastatic deposits were classified as macrometastasis (> 2.0 mm), micrometastasis (0.2-2.0 mm) or isolated tumour cells (ITC, < 0.2 mm). Of the 216 patients, 56 (26%) had metastasis as identified by H&E. Immunohistochemistry detected metastatic deposits in a further nine patients (4%), of whom four (2%) had micrometastasis and five (2%) had ITC only. Those cases with micrometastases were all, on review, visible on the H&E sections. Immunohistochemistry detects only a small proportion of metastasis in SLNs. All metastatic deposits identified by IHC were either micrometastasis or ITC. Until the prognostic significance of these deposits has been determined, IHC may be of limited value in the histopathological examination of SLNs.

Axilla↗

Axillary vein abnormalities contribute to development of lymphoedema after surgery for breast cancer.

BACKGROUND: The aetiology of breast cancer-related lymphoedema (BCRL) is poorly understood and multifactorial. Previous work has suggested that acquired abnormalities of the axillary vein may contribute to arm swelling. This prospective study evaluated venous changes in patients with a new diagnosis of breast cancer who had surgery that included axillary lymph node clearance. METHODS: Patients underwent arm volume measurement and Doppler ultrasonographic assessment of the axillary vein before, and at 3 and 12 months after surgery. RESULTS: A complete data set was available for 70 patients. BCRL was observed in 16 per cent at 3 months and 11 per cent at 12 months. Significant alterations to venous flow patterns were observed in those with BCRL. Vein wall movement was significantly reduced after surgery for the group as a whole, but did not correlate with arm swelling. Venous stenosis with impaired flow was also observed in the absence of BCRL. CONCLUSION: Axillary clearance can cause altered flow within the axillary vein, which is associated with an increased risk of developing lymphoedema.

Arm↗

Neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Neoadjuvant chemotherapy for breast cancer was originally used in locally advanced inoperable disease in order to achieve surgical resection. It was then extended to operable breast cancer with a view to downstaging tumours to facilitate breast-conserving surgery. Increasingly, it is being considered as a treatment for earlier-stage disease. METHODS: A Medline literature search was performed to identify articles relating to neoadjuvant chemotherapy in breast cancer published in the English language between 1960 and 2004. Secondary references were obtained from key articles. Search words included 'neoadjuvant chemotherapy', 'breast cancer', 'tumour biology', 'tumour markers' and 'sentinel lymph node biopsy'. RESULTS: Long-term results from randomized studies have shown no difference in disease-free or overall survival between neoadjuvant and adjuvant chemotherapy. The main benefit of neoadjuvant chemotherapy is its ability to downstage large tumours with a view to treatment by breast-conserving surgery, although there is a non-significant increase in the local recurrence rate. Initial results of neoadjuvant chemotherapy trials using newer agents such as taxanes have demonstrated a greater pathological complete response. Whether this will translate into better long-term survival remains to be seen.

Antineoplastic Combined Chemotherapy Protocols↗

Can breast MRI help in the management of women with breast cancer treated by neoadjuvant chemotherapy?

Contrast-enhanced (CE) MRI was used to monitor breast cancer response to neoadjuvant chemotherapy. Patients underwent CE MRI before and after therapy, together with conventional assessment methods (CAM). CE MRI was carried out at 1.5 T in the coronal plain with 3D sequences before and after bolus injection. An expert panel determined chemotherapy response using both CE MRI and CAM. Histopathological response in the surgical specimen was then used to determine the sensitivity and specificity of CE MRI and CAM. In total, 67 patients with 69 breast cancers were studied (mean age of 46 years). Tumour characteristics showed a high-risk tumour population: median size 49 mm: histopathological grade 3 (55%): oestrogen receptor (ER) negative (48%). Histopathological response was as follows: - complete pathological response (pCR) 17%; partial response (pPR) 68%; no response (NR) 15%. Sensitivity of CAM for pCR or pPR was 98% (CI 91-100%) and specificity was 50% (CI 19-81%). CE MRI sensitivity was 100% (CI 94-100%), and specificity was 80% (CI 44-97%). The absolute agreement between assessment methods and histopathology was marginally higher for CE MRI than CAM (81 vs 68%; P=0.09). In 71%, CE MRI increased diagnostic knowledge, although in 20% it was judged confusing or incorrect. The 2nd MRI study significantly increased diagnostic confidence, and in 19% could have changed the treatment plan. CE MRI persistently underestimated minimal residual disease. In conclusion, CE MRI of breast cancer proved more reliable for predicting histopathological response to neoadjuvant chemotherapy than conventional assessment methods.

Adult↗

Tissue-to-blood transport of radiolabelled immunoglobulin injected into the web spaces of the hands of normal subjects and patients with breast cancer-related lymphoedema.

AIM: The ability to return interstitial protein to central blood is key to the defence against oedema. The aim of this study was to quantify this ability by measuring the rate at which radiolabelled human immunoglobulin (HIgG) accumulated in blood following injection into the subcutis of the hand in normal volunteers and in patients with breast cancer-related lymphoedema (BCRL). METHODS: A total of 37 control subjects (healthy normal volunteers or breast cancer patients prior to treatment) and 18 women with BCRL were studied with dual-isotope lymphoscintigraphy. Each received bilateral subcutaneous depot injection in the dorsal web space of HIgG labelled with Tc-99m on one side and In-111 on the other. Activities remaining at the depot and accumulating in blood were measured at regular intervals for 3 h. Clearance from the depot was exponential and expressed as the rate constant k(depot) (min(-1)). Accumulation in blood was essentially linear and, using an estimate of blood volume based on height and weight, was expressed as the linear constant b(blood) (% administered activity x min(-1)). The time axis intercept of this linear fit was recorded as an index of the minimum time to arrival of radioprotein in blood. The efficiency with which radioprotein that has left the depot (extra-depot activity) is transported into blood [tissue-to-blood (T-B) transport] was quantified (1) as the quotient b(blood)/k(depot), and (2) as a function of time after injection by comparing the total amount of radioprotein in blood at any time with the total amount of radioprotein that was no longer in the depot at the same time. RESULTS: Tc-99m-HIgG and In-111-HIgG behaved similarly and are interchangeable. At all times between 60 and 180 min in controls, about 50% of protein that had left the depot was present in blood. T-B transport was reduced to about 20% in BCRL arms in which the hand was involved in swelling (p < 0.001 versus controls), but remained unchanged in patients in whom the hand was spared. The minimum time to arrival of radioprotein in blood was not reduced in BCRL; on the contrary, there appeared to be a small proportion of injected activity that arrived rapidly in blood in BCRL patients but not in controls. CONCLUSION: We conclude that T-B transport is only impaired in BCRL when radioprotein is injected into swollen tissue. Significant quantities of radioprotein may escape from the arm via local access to blood. Individual variation in this capacity may explain the regional sparing observed in BCRL.

Breast Neoplasms↗

Variation in lymphatic function may predispose to development of breast cancer-related lymphoedema.

AIMS: Breast cancer-related lymphoedema (BCRL) remains a common complication of breast cancer treatment. Many features of this condition remain poorly understood, such as why only approximately 25% of women are affected after similar treatment, and the phenomenon of 'sparing', in which regions of an otherwise swollen arm, most commonly the hand, remain unaffected. This study uses dual-isotope lymphoscintigraphy, involving measurement of rate of clearance of radiolabelled protein from a subcutaneous depot and subsequent appearance in blood, to quantify alterations in lymphatic function in women with BCRL, and to further investigate differences between those in whom the hand is involved with swelling and those in whom it is spared. METHODS: Participants received a depot injection of human immunoglobulin G in the dorsum of both hands, labeled with technetium-99m on one side and indium-111 on the other. Rates of clearance from the depot and appearance in venous blood were measured at regular intervals over a 3 h period. RESULTS: A total of 18 women with a history of BCRL were studied. Significant reductions in both depot clearance and venous appearance were observed in the affected arm compared with the unaffected contralateral control. On sub-group analysis, significant differences were also observed between swollen and spared hand groups, both for the affected and unaffected contralateral arm. DISCUSSION: This study, as well as confirming impaired lymphatic function in arms affected by BCRL, also shows underlying variation in lymphatic function in the unaffected contralateral arm, between those with and without hand sparing. This raises the possibility that the risk of developing BCRL may be, in part, pre-determined.

Arm↗

Radioguided occult lesion localisation (ROLL) and sentinel node biopsy for impalpable invasive breast cancer.

AIM: The aim of this study was to simplify the technique of ROLL and sentinel node biopsy without compromising tumour excision and sentinel node biopsy. METHODS: Twenty patients with impalpable primary invasive breast carcinoma underwent an injection of 99mTc-nanocolloid mixed with radiographic contrast medium Iohexol into the centre of the lesion under ultrasound or stereotactic guidance pre-operatively. No guidewire localisation was performed. Under general anaesthesia, a periareolar intradermal/subcutaneous injection of patent blue-V dye was performed. The sentinel node was identified by blue-stained lymphatics and node and a hot spot on the gamma probe. Surgical excision of the primary tumour was then carried out using the gamma probe. RESULTS: In eight of 20 cases an immediate re-excision was carried out and on histological assessment, all 20 patients were clear of invasive disease at the margins. In two patients, in situ disease was present at the margins and a further re-excision was therefore performed. The sentinel node was identified in all cases. In all, five of 20 patients were node positive on routine HE staining. In a further two patients, tumour cells were identified by immunohistochemistry with CAM5.2 antibody. Completion axillary clearance in six patients confirmed that the sentinel node was the only positive node. CONCLUSIONS: This modification of the previously described ROLL technique is feasible and safe and does not compromise tumour excision or sentinel node detection.

Aged↗

A survey of breast cancer patients' views on entry into several clinical studies.

During the course of their treatment and follow-up, women with breast cancer are likely to be asked to join a number of different clinical studies. Some local research ethics committees have expressed concerns about entry of individual patients into multiple research studies. A survey was undertaken to improve understanding of patients' own perceptions of participation in several clinical studies. A total of 96 patients who had previously undergone surgery for breast cancer from January to June 2000 were sent a questionnaire 6-12 months after completion of primary treatment. Eighty four per cent of questionnaires were returned of which 62% were from patients who had been approached to enter at least one clinical study. Sixty-four per cent of patients believed that there should not be a limit on the number of clinical studies offered to patients. Furthermore, three quarters of all patients would have considered entering more than one study if adequate explanation and written information were provided. Most patients felt that their participation in a clinical study was worthwhile and no patients surveyed regretted their decision to take part in a study. Almost two-thirds of patients who returned questionnaires believed there should not be a maximum number of studies offered to them. This survey suggests that the majority of patients are prepared to participate in more than one clinical study when adequate information and explanation are provided.

Breast Neoplasms↗

Accidental Epipen injection into a digit - the value of a Google search.

Despite the lack of awareness by the clinicians consulted of the most suitable treatment for accidentally injected epinephrine, this patient was successfully treated due mainly to the ability of clinicians on-site to access the Internet in the A&E department. A broad search engine such as Google can be an invaluable tool in finding important clinical information rapidly.

Adrenergic alpha-Agonists↗

Malignant eccrine poroma in breast cancer-related lymphoedema.

We describe the first case of malignant eccrine poroma arising in a lymphoedematous site. The patient had long-standing lymphoedema of the upper limb following breast cancer treatment. Lymphoedema is a recognised complication of breast cancer treatment and a risk factor for the subsequent development of malignancy. Possible mechanisms for this are discussed.

Aged↗

Bone marrow micrometastasis in breast cancer.

BACKGROUND: Several studies have demonstrated that bone marrow micrometastasis in patients with breast cancer is an independent prognostic factor for systemic recurrence and poorer survival. METHODS: This review describes the detection and clinical significance of micrometastatic cells in bone marrow, and examines the correlation between such micrometastasis and established clinicopathological prognostic factors. The relevant English language literature on bone marrow micrometastasis in breast cancer was searched via Medline (1975-2002), cross-referencing with key articles on the subject. RESULTS AND CONCLUSION: The balance of evidence favours the hypothesis that bone marrow micrometastasis impacts on disease-free and overall survival. Further prospective studies are required to examine this in greater detail, with particular reference to early node-negative breast cancer and the value of adjuvant systemic therapy in patients with bone marrow micrometastasis.

Bone Marrow Examination↗

Is physical function a more appropriate measure than volume excess in the assessment of breast cancer-related lymphoedema (BCRL)?

The aim of this study was to objectively measure impairment of arm function in women with breast cancer-related lymphoedema (BCRL), and investigate possible associations between this, arm volume excess, and psychological morbidity as measured by the Medical Outcomes Study 36-item short form (SF-36) questionnaire. A total of 48 patients were recruited. Manual dexterity was significantly impaired in the affected arm, independent of dominant or non-dominant arm involvement, but was not associated with arm volume excess. Psychological morbidity was significantly impaired in the domains of 'physical function' and 'bodily pain' when compared with population controls. Degree of impairment in the 'physical function' domain correlated with the absolute level of objectively tested manual dexterity. Impairment of manual dexterity appears to have a greater impact than arm volume excess on the overall psychological morbidity associated with BCRL, suggesting that greater emphasis should be placed upon arm function in the assessment, treatment targeting, and monitoring of patients with this condition.

Adult↗

Pregnancy after breast cancer.

The issue of pregnancy in patients previously treated for breast cancer is controversial. This paper reviews the literature using Medline and Embase databases over the last 50 years to address the issue. Overall survival in patients treated for breast cancer who subsequently become pregnant compares favourably with controls. This paper also addresses the effects of adjuvant therapy (loco-regional and systemic) on subsequent pregnancy. Introduction of a national registry of these patients may help inform such patients in the future.

Antineoplastic Agents↗

Hormone receptor status in primary breast cancer--time for a consensus?

In a previous study, we demonstrated wide variability in the access to oestrogen receptor (ER) measurement, patient selection, choice of technique and the cut-off point for positivity. The aim of this study was to update information on the current use of ER and progesterone receptor (PR) measurement in the United Kingdom (UK). Questionnaires, asking about availability, use and technique of ER and PR measurement, were returned from 170 (74%) units in the UK. Where ER positivity was determined using the percentage of cells staining positive (33%), the absolute cut-off point for positivity varied widely from 5 to 80% of cells. Of the 170 responding units, 107 (63%) felt that PR measurement was important. This study confirms considerable variability in both the technique of ER measurement and the absolute cut-off point for positivity (5-80%). It is essential that a consensus be reached regarding the choice of technique, as well as the threshold for positivity.

Attitude of Health Personnel↗