Relationship among eye and muzzle temperatures measured using digital infrared thermal imaging and vaginal and rectal temperatures in hair sheep and cattle.

Digital infrared thermal imaging (DITI) using a thermal camera has potential to be a useful tool for the production animal industry. Thermography has been used in both humans and a wide range of animal species to measure body temperature as a method to detect injury or inflammation. The objective of these experiments was to compare the temperature of the eye (EYE) or muzzle (MUZ) measured using DITI to vaginal (VT) and rectal temperature (RT) as measures of core body temperature in hair sheep and beef cattle. In Exp.1 EYE, VT and RT were measured in lactating, multiparous hair sheep ewes (St. Croix White, n = 10, and Dorper × St. Croix White, n = 10) in a non-febrile state 5 times over a 48-h period. Data loggers were used to measure VT and a digital veterinary thermometer was used to measure RT. There was a high correlation (P < 0.001) between VT and RT (r = 0.95), EYE and RT (r = 0.76) and EYE and VT (r = 0.77). In Exp. 2 EYE, MUZ, VT and RT were measured in multiparous, lactating ewes (St. Croix White, n = 2, and Barbados Blackbelly, n = 12) at -12, -1, 0, 1, 2, 3, 4, 6, 12, 24, 36, and 48 h after being administered lipopolysaccharide (LPS; n = 7; 0.2 µg/kg BW, i.v.) or saline (n = 7; 0.5 mL, i.v.). Data loggers were used to measure VT and a digital veterinary thermometer was used to measure RT. When data were combined across treatments (LPS and saline) there was a high correlation (P < 0.001) between VT and RT (r = 0.96), EYE and RT (r = 0.82), MUZ and RT (r = 0.72), and EYE and VT (r = 0.93). In Exp. 3 EYE, MUZ, VT and RT were measured in multiparous, non-lactating, pregnant Senepol cattle (n = 44) between 0900 and 1200 h on a single day. A digital veterinary thermometer was used to measure both VT and RT. There was a high correlation (P < 0.001) between VT and RT (r = 0.78), a moderate correlation (P < 0.001) between VT and EYE (r = 0.52), RT and EYE (r = 0.58) and EYE and MUZ (r = 0.48). There was no correlation (P > 0.10) between RT or VT and MUZ. The findings of these three studies indicate that temperature of the eye, measured using DITI, can be used as an indicator of core body temperature in hair sheep and beef cattle as an alternative to using vaginal or rectal temperature.

Ten-year follow-up of skin-sparing mastectomy followed by immediate breast reconstruction.

BACKGROUND: The oncological safety of skin-sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is debated owing to a presumed compromise in the completeness of mastectomy. Current evidence is poor as it is based mostly on short-term follow-up data from highly selected patients. METHODS: A prospectively maintained institutional database was searched to identify patients who underwent SSM and IBR between 1995 and 2000. A retrospective review of medical records was carried out, including only patients with ductal carcinoma in situ and invasive breast cancer. During this time all patients treated with mastectomy were offered IBR regardless of tumour stage. RESULTS: Follow-up data from 253 consecutive patients with IBR were reviewed. Patients with incomplete follow-up data and those undergoing SSM for recurrent disease following previous lumpectomy were disregarded, leaving 207 for analysis. Offering IBR to all women requiring mastectomy resulted in a large proportion of patients with advanced disease. During a median follow-up of 119 months, 17 (8·2 per cent) locoregional, six (2·9 per cent) local and 22 (10·6 per cent) distant recurrences were detected; the overall recurrence rate was 39 (18·8 per cent). Overall recurrence rate was associated with axillary lymph node metastasis (P = 0·009), higher stage (P < 0·001) and higher tumour grade (P = 0·031). The breast cancer-specific survival rate was 90·8 per cent (19 of 207 women died from recurrence). CONCLUSION: Based on these long-term follow-up data, SSM combined with IBR is an oncologically safe treatment option regardless of tumour stage.

Impact of national guidelines on family history breast cancer surveillance.

The breast cancer risk of women already under family history surveillance was accurately assessed according to national guidelines in an attempt to rationalize the service. Women attending two breast units in Glasgow between November 2003 and February 2005 were included. One thousand and five women under annual surveillance were assessed and had their relatives diagnoses verified. Four hundred and ninety-seven women were at significantly increased risk and eligible for follow-up. Five hundred and eight (50%) women attending were not eligible for family history surveillance, and 498 (98%) of these women accepted discharge. In conclusion, national guidelines have helped to more clearly define women who should undergo surveillance. This avoids unnecessary and potentially harmful routine investigations, and the service has been improved.

Pancreatic-derived pathfinder cells enable regeneration of critically damaged adult pancreatic tissue and completely reverse streptozotocin-induced diabetes.

We demonstrate that intravenous delivery of human, or rat, pancreas-derived pathfinder (PDP) cells can totally regenerate critically damaged adult tissue and restore normal function across a species barrier. We have used a mouse model of streptozotocin (STZ)-induced diabetes to demonstrate this. Normoglycemia was restored and maintained for up to 89 days following the induction of diabetes and subsequent intravenous delivery of PDP cells. Normal pancreatic histology also appeared to be restored, and treated diabetic animals gained body weight. Regenerated tissue was primarily of host origin, with few rat or human cells detectable by fluorescent in situ hybridization (FISH). Crucially, the insulin produced by these animals was overwhelmingly murine in origin and was both types I and II, indicative of a process of developmental recapitulation. These results demonstrate the feasibility of using intravenous administration of adult cells to regenerate damaged tissue. Critically, they enhance our understanding of the mechanisms relating to such repair and suggest a means for novel therapeutic intervention in loss of tissue and organ function with age.

A new pathological system for grading DCIS with improved prediction of local recurrence: results from the UKCCCR/ANZ DCIS trial.

BACKGROUND: There is no consensus agreement regarding optimal management of locally excised ductal carcinoma in situ (DCIS) or features of greatest assistance in predicting disease behaviour. Cases in the UKCCCR/ANZ DCIS trial have been histologically reviewed to determine the features of prognostic importance. METHOD: A total of 72% of 1694 cases entered into the UKCCCR/ANZ DCIS trial had full pathological review. A large number of histological features were assessed, blinded to outcome and compared regarding ability to predict ipsilateral recurrence, as either DCIS or progression to invasive carcinoma. RESULTS: Pathological features associated with ipsilateral recurrence in univariate analysis included high cytonuclear grade, larger lesion size, growth pattern, presence of necrosis or chronic inflammation, incompleteness (or uncertainty of completeness) of excision and smaller margin width. Receipt of post-operative radiotherapy was also a strong prognostic factor.We report a novel sub-division of the large group of high-grade lesions, which enables identification of a very poor prognosis sub-group; namely, DCIS that is of high cytonuclear grade, predominantly (>50%) solid architecture, bearing extensive comedo-type necrosis (>50% of ducts). In addition, we found little difference in ipsilateral recurrence rates between low- and intermediate-grade groups. Hazard ratios for low, intermediate, high and the new, very high, grade were 0.42, 0.33, 0.62 and 1.00, respectively, for ipsilateral in situ or invasive recurrence. CONCLUSION: We present a novel pathological classification for DCIS with substantially better prognostic discrimination for ipsilateral recurrence than the classical categorisation based on cytonuclear grade alone.

Comparison of breast cancer mortality rates with those of ovarian and colorectal carcinoma.

BACKGROUND: Traditional survival curves cannot easily be used to predict outcome for an individual patient on a year-to-year basis. This difficulty is partly overcome by yearly mortality analysis. This method was employed to analyse long-term follow-up of three cancers: colorectal, ovarian and breast cancer. METHODS: The study used prospectively collected cancer registry data from geographically defined regions in Scotland. Cohort sizes were 7196 patients with breast cancer, 3200 with colorectal cancer and 1866 with ovarian cancer. Follow-up extended to 23 years. RESULTS: Two distinct patterns of mortality emerged. Mortality rates for ovarian and colorectal cancer were initially high (41 and 21 per cent) but decreased rapidly; by 10 years patients had either died or were cured. The influence of stage diminished with follow-up. Breast cancer mortality was lower than that of colorectal or ovarian cancer, but remained raised in comparison to the general population throughout follow-up. The influence of breast cancer size reduced with follow-up, whereas that of nodal status persisted. CONCLUSION: Patients with breast cancer live at increased risk of death to the end of follow-up, supporting the concept of dormancy in breast cancer biology. This was not observed with colorectal or ovarian cancer.

Altered sirtuin expression is associated with node-positive breast cancer.

Sirtuins are genes implicated in cellular and organismal ageing. Consequently, they are speculated to be involved in diseases of ageing including cancer. Various cancers with widely differing prognosis have been shown to have differing and characteristic expression of these genes; however, the relationship between sirtuin expression and cancer progression is unclear. In order to correlate cancer progression and sirtuin expression, we have assessed sirtuin expression as a function of primary cell ageing and compared sirtuin expression in normal, 'nonmalignant' breast biopsies to breast cancer biopsies using real-time polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly increased in breast cancer (P<0.0001). Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (P<0.05 and P<0.0001, respectively). This study has demonstrated differential sirtuin expression between nonmalignant and malignant breast tissue, with consequent diagnostic and therapeutic implications.

The use of telomere biology to identify and develop superior nitrone based anti-oxidants.

We have employed a biological chemistry approach to dissect the mechanisms underpinning cellular responses to oxidant stress and to develop biologically relevant anti-oxidants. We have used telomere biology to define cellular stress responses and have observed telomere independent, p21- and p16-dependent stasis following oxidative insult in human fibroblasts. This was accompanied by a [corrected] reduction in XRCC5 expression and a reduction in [corrected] SIRT 1 expression. Using these markers in conjunction with senescence-associated beta-galactosidase expression, we have developed and screened novel nitrone based anti-oxidant compounds. We have identified functional compounds that are unsuitable for use in primary human cells. This has allowed subsequent identification of suitably structured compounds that act as superior biological anti-oxidants, which have potential for use in clinical interventions.

Axillary recurrence in breast cancer.

AIM: To determine whether axillary recurrence reflects inadequate axillary treatment or adverse pathological features. METHODS: The case-records were reviewed of 2122 women aged under 75 years, treated for invasive breast cancer during the time-period 1/1/86-31/12/91 in a geographically defined area. Data were abstracted on operations performed, pathological features, post-operative treatments and details of axillary recurrence. The risk of axillary recurrence was examined by pathological, treatment and patient factors. RESULTS: Axillary recurrence was more than twice as likely after inadequate compared to adequate treatment of the axilla (adequate staging or axillary radiotherapy or clearance). Delayed treatment of the axilla was not as successful as adequate primary treatment: multiple axillary recurrences were twice as common, one third of which were uncontrolled at time of death. Inadequate surgical treatment was associated with increased rates of recurrence despite endocrine therapy, chemotherapy or radiotherapy. Lymphoedema was twice as common if axillary radiotherapy was combined with any axillary surgical procedure. CONCLUSIONS: Axillary recurrence is more common in tumours with adverse pathology but may also result from inadequate axillary treatment. In order to minimise axillary recurrence, optimal treatment of the axilla entails adequate staging (sampling of four or more nodes) and treatment (axillary clearance or radiotherapy and endocrine therapy) in all women.

Does deprivation affect breast cancer management?

We evaluated whether social deprivation affected decision-making for breast cancer surgery. Of 3419 patients, 53.6% had mastectomy and this was predicted by deprivation, age, tumour size and hospital, all of which retained significance on multivariate analysis, except deprivation. Pathological characteristics and surgical decision-making determined choice of operation not deprivation.

Inadequate treatment of symptomatic breast cancer.

BACKGROUND: Early trials that compared breast and axillary treatments showed differing recurrence rates without significant differences in survival. Consequently, there was a wide range of opinion and practice in the management of breast cancer. The present study explored this variability in surgical management to determine the impact of breast and axillary treatment on recurrence and survival. METHODS: The records of 2776 women with histologically confirmed invasive breast cancer diagnosed between 1986 and 1991 were reviewed. The relationship between adequacy of breast and axillary treatment, recurrence and survival was examined in 2122 women who had surgery with curative intent. A Cox proportional hazards model that included tumour size, node status, grade, socioeconomic status and use of adjuvant therapy was used. RESULTS: Inadequate treatment was associated with a significantly higher risk of local recurrence after breast-conserving surgery (relative hazard ratio (RHR) 4.19 (95 per cent confidence interval (c.i.) 2.73 to 6.43); P < 0.001). Inadequate axillary treatment was associated with a significantly higher risk of regional recurrence (RHR 2.29 (95 per cent c.i. 1.65 to 3.16); P < 0.001). The risk of death from breast cancer was significantly higher if locoregional treatment was inadequate (RHR 1.29 (95 per cent c.i. 1.07 to 1.55); P = 0.008). CONCLUSION: Adequate surgery is fundamental to the optimal treatment of breast cancer. Inadequate surgery resulted in higher recurrence rates despite adjuvant treatments.

Immediate breast reconstruction does not lead to a delay in the delivery of adjuvant chemotherapy.

Immediate breast reconstruction (IBR) has been considered by some to lead to a delay in the delivery of adjuvant chemotherapy. Our aim was to determine whether IBR led to a delay when compared to conservation surgery and non-reconstructive mastectomy. Ninety-five cases of IBR receiving chemotherapy were reviewed. These were compared to 95 consecutively treated patients undergoing conservation surgery and 95 undergoing non-reconstructive mastectomy. Our data shows that IBR does not lead to a delay in the delivery of adjuvant chemotherapy when compared to standard non-reconstructive surgery and should not adversely affect breast cancer outcome.

Increased mortality from breast cancer and inadequate axillary treatment.

BACKGROUND: The assessment of axillary nodal status remains divisive: inaccurate staging may result in untreated axillary disease, and appropriate adjuvant therapy not being delivered. The impact of inadequate axillary treatment on survival remains controversial. We analyse the impact of failure to adequately assess the axillary nodal status on survival. METHODS: All women with confirmed breast cancer in a 15-year period were identified, and the original pathology reports examined, and details of radiotherapy obtained. The survival of women by axillary sample size was compared to a reference group of women and corrected for nodal status, tumour size, age, deprivation category and speciality of treating surgeon. FINDINGS: Sampling less than four nodes is associated with a significantly increased risk of death. This cannot be due to understaging the extent of axillary disease nor is fully explainable by differential prescription of adjuvant therapies. We conclude that the survival of the women studied may have been adversely effected by inadequate axillary treatment.

Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial.

BACKGROUND: As a consequence of mammographic breast screening programmes, ductal carcinoma in situ is diagnosed with increasing frequency. Mastectomy for localised ductal carcinoma in situ is thought to be an over-treatment by many physicians, but there is much controversy as to whether complete local excision alone is sufficient. We aimed to assess the effectiveness of adjuvant radiotherapy and tamoxifen. METHODS: We used a 2x2 factorial design in a randomised controlled trial. Between May, 1990, and August, 1998, 1701 patients recruited from screening programmes were randomised to both treatments in combination or singly, or to none, or to either one (eg, radiotherapy) with an elective decision to give or to withhold the other (ie, in this case tamoxifen). Patients had complete surgical excision of the lesion confirmed by specimen radiography and histology. Patients have been followed up at least once a year. Median follow-up was 52.6 (range 2.4-118.3) months. Our primary endpoint was the incidence of ipsilateral invasive disease. FINDINGS: Ipsilateral invasive disease was not reduced by tamoxifen but recurrence of overall ductal carcinoma in situ was decreased (hazard ratio 0.68 [0.49-0.96]; p=0.03). Radiotherapy reduced the incidence of ipsilateral invasive disease (0.45 [0.24-0.85]; p=0.01) and ipsilateral ductal carcinoma in situ (0.36 [0.19-0.66]; p=0.0004), but there was no effect on the occurrence of contralateral disease. There was no evidence of interaction between radiotherapy and tamoxifen. INTERPRETATION: Radiotherapy can be recommended for patients with ductal carcinoma in situ treated by complete local excision; however, there is little evidence for the use of tamoxifen in these women.

Pregnancy postponement and childlessness leads to chronic hypervascularity of the breasts and cancer risk.

Epidemiologists have established that women with small families, and particularly nulliparae, are prone to develop breast cancer later in life. We report that physiological mammary hypervascularity may be an intermediate reason against the background that breast-core vascularity is normal in pregnancy but pathological in the vascularisation of cancer. We examined breast 'core' vascularity in nulliparae during their potential reproductive life and in parous women after their last birth but before their menopause. Fifty clinically normal pre-menopausal non-pregnant women (100 breasts) were studied daily for one 'luteal positive' menstrual cycle. Their parity history varied from zero to five babies. Under controlled domestic conditions each wore a special electronic thermometric bra to automatically record breast 'core' temperature changes as a measure of mammary tissue blood flow. In the nulliparae there was a rise of breast vascularity throughout reproductive life. In the parous women, a year or so after each birth, breast vascularity was reset at a lower level than before the pregnancy; thereafter, as in nulliparae, there was progressive increase in mammary vascularity until the menopause.

A comparison of serum and plasma levels of vascular endothelial growth factor during the menstrual cycle in healthy female volunteers.

Angiogenesis is the formation of new blood vessels from the existing vasculature, and is essential for the growth and metastasis of most solid tumours. One of the most important growth factors involved in the angiogenesis process is vascular endothelial growth factor. Vascular endothelial growth factor expression has been shown to be regulated by female hormones in breast cancer cell lines, and two previous authors have reported on cyclical variations in serum vascular endothelial growth factor concentrations with conflicting results. No work has been performed on variations in plasma levels of vascular endothelial growth factor during the menstrual cycle. We therefore conducted the first prospective trial to compare serum and plasma levels of vascular endothelial growth factor in healthy pre-menopausal volunteers. Twenty healthy pre-menopausal women were recruited and had blood samples taken over one menstrual cycle with an average of eight samples taken per patient. Plasma and serum samples were then analysed for sex hormones and vascular endothelial growth factor 165. Serum vascular endothelial growth factor levels were found to be significantly higher than plasma vascular endothelial growth factor levels (P<0.005). We found no significant difference between serum and plasma vascular endothelial growth factor in the luteal and follicular phases of the cycle. The majority of the measurements for plasma levels of vascular endothelial growth factor at all phases of the cycle were under the limit of detection of the vascular endothelial growth factor ELISA kit. We found no significant correlation between plasma or serum levels of vascular endothelial growth factor and either FSH, LH, Oestradiol or Progesterone levels. This study has demonstrated no difference in serum concentrations of vascular endothelial growth factor during the different phases of the menstrual cycle in a group of healthy volunteers. We also demonstrated no obvious difference in plasma concentrations of vascular endothelial growth factor between the phases of the cycle, but most of the measurements were below the level of accuracy reported by the ELISA kit manufacturer. With the sensitivity of this ELISA test, therefore, we must still regard the question of whether there is a variation in plasma concentrations of vascular endothelial growth factor throughout the menstrual cycle as unanswered.

Randomized clinical trial of no wound drains and early discharge in the treatment of women with breast cancer.

BACKGROUND: Women undergoing surgery for primary breast cancer routinely have suction drains inserted deep to the wounds, which are removed approximately 6-8 days after operation, requiring a period of stay of that duration in hospital. The aim of this study was to perform a prospective randomized clinical trial to evaluate a new surgical technique of suturing flaps without wound drainage, combined with early discharge, in women undergoing surgery for breast cancer. METHODS: A total of 375 patients undergoing surgery for breast cancer were randomized to conventional surgery or suturing of flaps with no drain. The main outcome measures were length of hospital stay, surgical morbidity, psychological morbidity and health economics. RESULTS: Suturing of flaps and avoiding wound drainage in women undergoing surgery for breast cancer resulted in a significantly shorter hospital stay. Adopting this surgical technique with early discharge did not lead to any difference in surgical or psychological morbidity. Health economic benefits to the National Health Service resulted from saved bed days with no impact on community costs. CONCLUSION: Wound drainage following surgery for breast cancer can be avoided, thereby facilitating early discharge with no associated increase in surgical or psychological morbidity.

Breast reconstruction in the United Kingdom and Ireland.

BACKGROUND: Although it is becoming more common, previous surveys have identified concerns regarding the safety of immediate reconstruction following mastectomy. The aims of this study were to define current practice of breast reconstruction in the UK and Ireland, and to identify the characteristics of surgeons who use immediate breast reconstruction. METHODS: : A postal questionnaire survey of 498 consultant breast surgeons in the UK and Ireland was performed in January 2000. RESULTS: There were 376 responses (response rate 76 per cent). Eighty-eight per cent of surgeons 'always' or 'usually' discuss reconstruction with patients due to undergo mastectomy; clinicians with a heavy caseload were significantly more likely to discuss it (odds ratio (OR) 18.45 (95 per cent confidence interval 1.99 to 171.07)). The majority of respondents (57 per cent) preferred delayed to immediate breast reconstruction; 70 per cent believed that immediate reconstruction has disadvantages, most commonly that it interferes with adjuvant therapy (56 per cent). Older surgeons were significantly less likely to perform immediate reconstruction (OR 5.18 (2.21 to 12.11)), and were significantly more likely to believe that immediate breast reconstruction has disadvantages (OR 2.02 (1.01 to 4.05)). Surgeons from Ireland were less likely to discuss and perform breast reconstruction (OR 0.20 (0.10 to 0.43) and 0.27 (0.12 to 0.60) respectively), or to have access to a plastic surgeon (OR 0.22 (0.11 to 0.44)). CONCLUSION: : Significant variation exists in the delivery of breast reconstruction after mastectomy in the UK and Ireland. The age, workload and personal characteristics of the surgeon are important in determining reconstructive practice.