Nisha Sharma

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Radiological audit of interval breast cancers: Estimation of tumour growth rates

The Breast, 2020

Introduction: This multicentre, retrospective study aimed to establish correlation between estima... more Introduction: This multicentre, retrospective study aimed to establish correlation between estimated tumour volume doubling times (TVDT) from a series of interval breast cancers with their clinicopathological features. The potential impact of delayed diagnosis on prognosis was also explored. Materials and methods: Interval cancers, where screening mammograms demonstrated changes that were retrospectively classified as either uncertain or suspicious, were reviewed from five screening units within the UK NHS Breast Screening Programme (NHSBSP). Data collected included the time interval between screening mammogram and cancer diagnosis, the size of the initial mammographic abnormality and of the subsequent cancer, demographics, mammographic density and tumour biology. We estimated volume doubling times and the estimated change in size and node status, which would have followed if these cancers had been detected at the previous screen. Results: 306 interval cancers meeting the inclusion criteria were identified. Average time from screening to diagnosis was 644 days (SD 276 days). 19% were diagnosed in the first twelve months, 42% in the subsequent twelve months and 39% thereafter. Overall average estimated TVDT was 167 days (95% CI 151 e186). Significant differences were noted with age (p ¼ 0.01), grade (p < 0.001) and ER status (p < 0.001) with women under 60, grade 3 cancers and ER negative cancers having shorter TVDTs. HER2 positive tumours had shorter doubling times than HER2 negative, but this difference was not statistically significant. It was estimated that diagnosing these cancers at the previous screen would have increased tenyear survival from 82% to 86%. Conclusion: High grade, ER negativity and younger age were associated with shorter durations of TVDT. The role of HER2 status on interval cancer growth rate requires further assessment. It is likely that the delayed diagnosis of interval cancers confers a 4% reduction in ten-year survival.

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NHS Breast Screening multidisciplinary working group guidelines for the diagnosis and management of breast lesions of uncertain malignant potential on core biopsy (B3 lesions)

Clinical Radiology, 2018

Needle core biopsy is considered the histological diagnostic method of choice for screen detected... more Needle core biopsy is considered the histological diagnostic method of choice for screen detected breast lesions. Although the majority are definitively diagnosed as normal, benign or malignant, approximately 7% are categorised as B3, of uncertain malignant potential. These include a wide range of lesions with different risks of associated malignancy from <2% to approaching 40% from literature review in UK practice. Historically these have typically been surgically excised as a diagnostic procedure but the majority are then proven to be benign. An alternative approach, for many of these lesions, is thorough sampling/excision by vacuum-assisted biopsy techniques to exclude the presence of co-existing carcinoma. This would potentially reduce the benign open biopsy rate whilst maintaining accuracy of cancer diagnosis. A group from the Radiology, Surgery and Pathology NHS Breast Screening Programme Co-ordinating Committees and an additional co-opted expert were charged with review and development of guidelines for the clinical management of the B3 lesions. The guidelines reflect suggested practice as stated by the NHS Breast Screening Programme and approved by the RCR.

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A functional form for a representative individual arterial input function measured from a population using high temporal resolution DCE MRI

Magnetic resonance in medicine, Jan 26, 2018

To measure the arterial input function (AIF), an essential component of tracer kinetic analysis, ... more To measure the arterial input function (AIF), an essential component of tracer kinetic analysis, in a population of patients using an optimized dynamic contrast-enhanced (DCE) imaging sequence and to estimate inter- and intrapatient variability. From these data, a representative AIF that may be used for realistic simulation studies can be extracted. Thirty-nine female patients were imaged on multiple visits before and during a course of neoadjuvant chemotherapy for breast cancer. A total of 97 T -weighted DCE studies were analyzed including bookend estimates of T and model-fitting to each individual AIF. Area under the curve and cardiac output were estimated from each first pass peak, and these data were used to assess inter- and intrapatient variability of the AIF. Interpatient variability exceeded intrapatient variability of the AIF. There was no change in cardiac output as a function of MR visit (mean value 5.6 ± 1.1 L/min) but baseline blood T increased significantly following t...

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The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy

Oncotarget, Jan 15, 2016

The calpains are a family of intracellular cysteine proteases that function in a variety of impor... more The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy. Information on treatment and prognostic variables together with long-term clinical follow-up was available for these patients. Diagnostic pre-chemotherapy core biopsy samples and surgically excised specimens were available for analysis.Expression of calpastatin, calpain-1 or calpain-2 in the core biopsies was not associated with breast cancer specific survival in the total pat...

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Screen‐detected pleomorphic lobular carcinoma in situ (PLCIS): risk of concurrent invasive malignancy following a core biopsy diagnosis

Histopathology, 2010

Carder PJ, Shaaban A, Alizadeh Y, Kumarasuwamy V, Liston JC & Sharma N (2010) Histopathology 57, ... more Carder PJ, Shaaban A, Alizadeh Y, Kumarasuwamy V, Liston JC & Sharma N (2010) Histopathology 57, 472–478 Screen‐detected pleomorphic lobular carcinoma in situ (PLCIS): risk of concurrent invasive malignancy following a core biopsy diagnosisAims: Pleomorphic lobular carcinoma in situ (PLCIS) is an uncommon, recently recognized variant of lobular carcinoma in situ (LCIS). Its natural history, biological behaviour and clinical characteristics are uncertain. The aim was to review the radiological and pathological findings in a series of screen‐detected PLCIS diagnosed on needle core biopsy with a view to determining the diagnostic features, immunohistological profile and risk of concurrent invasive malignancy.Methods and results: Ten cases of core biopsy‐diagnosed, screen‐detected PLCIS were identified. Core biopsy findings were compared with pathological findings at subsequent surgery. Two cases were associated with possible microinvasion on the core. Two of 10 had invasive lobular c...

Large-volume Mammotome biopsy may reduce the need for surgery in screen-detected papillary lesions

Breast Cancer Research, 2008

The emphasis of mammographic breast screening is to detect small invasive breast cancers at a tim... more The emphasis of mammographic breast screening is to detect small invasive breast cancers at a time in their natural history when early detection and treatment will reduce significantly the risk of death. However, breast screening cannot be absolutely specific in its approach and detects a wide spectrum of breast cancer, ranging from microfocal low-grade ductal carcinoma in situ to large highgrade invasive cancer. It is well recognized that many of the lowgrade, special invasive cancers identified at screening have an excellent prognosis but may be so indolent that they would never have presented clinically or have threatened the life of the patients. It has been proposed alternatively that a proportion of these low-grade invasive tumours might, if not detected, de-differentiate over time into more aggressive, less well-differentiated tumours. Identification and removal of such cancers when they are at a low grade would avoid such progression. Detection of high-grade invasive cancers when they are small is clearly a means by which screening could reduce breast cancer mortality; for example, the Two-County Trial in Sweden has shown that histological grade 3 invasive cancers detected when <10 mm have an excellent prognosis, while it is widely recognized that large high-grade invasive cancers have a poor prognosis. In addition, the presence of vascular invasion and lymph node metastasis, which are associated with development of metastatic disease, are rare in grade 3 tumours <10 mm, grade 2 tumours <10 mm and grade 1 tumours <20 mm, indicating that detecting tumours under a certain size should be beneficial.

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Immune responses following experimental infection with Ascaridia galli and necrotic enteritis in broiler chickens

Avian pathology : journal of the W.V.P.A, Jan 20, 2017

Broilers commonly suffer from necrotic enteritis (NE). Other gastrointestinal infectious diseases... more Broilers commonly suffer from necrotic enteritis (NE). Other gastrointestinal infectious diseases affect poultry, including nematode infections which are considered a re-emerging disease in barn and free-range systems. The aim of this study was to characterize the immune response of broilers after artificial infection with NE and contrast these with responses to the nematode Ascaridia galli and determine whether immune parameters measured during the course of infection can be used to distinguish infected from uninfected birds. A total of 96 one-day-old male Ross 308 broiler chickens were used in this study. At 10 days of age, broilers were randomly assigned to one of the following treatment groups: control birds (n = 32), A. galli infected birds (n = 32), or NE infected birds (n = 32) and inoculated with the appropriate infective agents. The immune response of birds was monitored through evaluation of haematology parameters, acute phase protein production, and intraepithelial intest...

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Synthesis and Characterization of Sterculia Gum Based pH Responsive Drug Delivery System for Use in Colon Cancer

Journal of Macromolecular Science, Part A, 2009

... Xin, X., Borzacchiello, A., Netti, PA, Ambrosio, L. and Nicolais, L. 2004. J. Biomater. Sci. ... more

Cytomorphological studies and HPTLC fingerprinting in different plant parts of three wild morphotypes of Datura metel L. "Thorn Apple" from North India

International Journal of Green Pharmacy, 2009

Datura metel L. (Solanaceae) with its trade name "Thorn Apple" is a herb that exists in tropical,... more Datura metel L. (Solanaceae) with its trade name "Thorn Apple" is a herb that exists in tropical, warm temperate regions of the old world, throughout the hills of India, up to an altitude of 8000 ft. The objective of the present study is to investigate the morphological and phytochemical variabilities in the wild taxa of D. metel. On the basis of 17 phenotypic traits three morphotypes I, II and III were identified, and highly significant variations were seen among them. The three morphotypes of the species, with quite distinct flower colours, that is, purple, yellow and white, had the same diploid chromosome number n=12. The pharmacological activities of D. metel are mainly attributed to the presence of two tropane alkaloids, namely hyoscyamine and scopolamine. For the systematic quantification of hyoscyamine and scopolamine in different plant parts such as, leaves, roots and seeds of these three wild morphotypes (I, II and III) of D. metel, the high performance thin layer chromatography (HPTLC) technique was employed. Better resolution was achieved by using chloroform:acetone:diethyl amine (50: 40: 10 v/v/v) as a mobile phase. Quantitative, densitometric evaluation of the plate was performed in the absorbance/reflectance mode at 530 nm. The average recovery of hyoscyamine and scopolamine was 97.4 and 96.8%, respectively, showing the excellent reproducibility of the method. The calibration curves were linear in the range of 1000-4000 ng for hyoscyamine and 500-2000 ng for scopolamine, respectively. The method was simple, precise, specific, sensitive, accurate and could be used for routine analysis as well as quality control of raw materials and herbal formulations. The present study has established a link between cytomorphological variations and chemical characterization for the first time and was also helpful in discovering the best genotype with richer active constituents for future herbal formulations.

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The influence of feeding crimped kernel maize silage on broiler production, nutrient digestibility and meat quality

British Poultry Science, 2016

Abstract Two experiments were carried out in parallel with male Ross 308 broilers over 37 d. An e... more Abstract Two experiments were carried out in parallel with male Ross 308 broilers over 37 d. An experiment with a total of 736 broilers was performed to study the effect of dietary inclusion of crimped kernel maize silage (CKMS) on broiler production and meat quality. Another study with 32 broilers was carried out from 21 to 25 d to investigate the inclusion of CKMS on nutrient digestibility. In both trials, 4 dietary treatments were used: wheat-based feed (WBF), maize-based feed (MBF), maize-based feed supplemented with 15% CKMS (CKMS-15) and maize-based feed supplemented with 30% CKMS (CKMS-30). Compared with MBF, the dry matter (DM) intakes of broilers receiving CKMS-15 and CKMS-30, respectively, were numerically 7.5 and 6.2% higher and feed conversion ratio 6 and 12% poorer (significant for 30% CKMS), although there were no significant differences in AME content between the three diets. At 37 d, the body weight of birds receiving 15% CKMS was similar to birds fed with MBF. However, the inclusion of 30% CKMS decreased broiler growth. Dietary supplementation with CKMS significantly reduced the apparent digestibility of phosphorus. The fat digestibility was significantly lower for CKMS-30 than for the other three diets. Broiler mortality decreased significantly when CKMS was added to the diet. The consumption of drinking water was significantly lower in all maize-based diets as compared to WBF and was lowest in broilers fed with CKMS-30. An improved litter quality in terms of DM content and a lower frequency of foot pad lesions was observed with broilers supplemented with both dietary levels of CKMS. The addition of CKMS to maize-based diets increased juiciness, tenderness and crumbliness of the meat. In conclusion, the dietary supplementation of 15% CKMS had no negative effect on broiler growth and positively influenced bird welfare in terms of mortality and foot pad health. Therefore, the addition of 15% CKMS to maize-based diets is considered an advantageous feeding strategy in broiler production.

Nisha Sharma

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