The role of contrast-enhanced mammography in the preoperative evaluation of invasive lobular carcinoma of the breast.

AIM: To assess the performance of contrast-enhanced mammography (CEM) in the preoperative staging of invasive lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS: The present study was a multicentre, multivendor, multinational retrospective study of women with a histological diagnosis of ILC who had undergone CEM from December 2013 to December 2021. Index lesion size and multifocality were recorded for two-dimensional (2D) mammography, CEM, and when available magnetic resonance imaging (MRI). Comparison with histological data was undertaken for women treated by primary surgical excision. Pearson correlation coefficients and Bland-Altman's analysis of agreement were used to assess differences with a significance level of 0.05. RESULTS: One hundred and fifteen ILC lesions were included, 46 (40%) presented symptomatically and 69 were screening detected. CEM demonstrated superior sensitivity when compared to standard mammography. The correlation between the histological size measured on the surgical excision specimen size was greater than with standard mammography (r=0.626 and 0.295 respectively, p=0.001), with 19% of lobular carcinomas not visible without a contrast agent. The sensitivity of CEM for multifocal disease was greater than standard mammography (70% and 20% respectively, p<0.0001). CEM overestimated tumour size by an average of 1.5 times, with the size difference increasing for larger tumour. When MRI was performed (n=22), tumour size was also overestimated by an average of 1.3 times. The degree of size overestimation was similar for both techniques, with the tumour size on CEM being on average 0.5 cm larger than MRI. CONCLUSION: CEM is a useful tool for the local staging of lobular carcinomas and could be an alternative to breast MRI.

Pre-operative optimisation for chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease is a condition commonly present in older people undergoing surgery and confers an increased risk of postoperative complications and mortality. Although predominantly a respiratory disease, it frequently has extra-pulmonary manifestations and typically occurs in the context of other long-term conditions. Patients experience a range of symptoms that affect their quality of life, functional ability and clinical outcomes. In this review, we discuss the evidence for techniques to optimise the care of people with chronic obstructive pulmonary disease in the peri-operative period, and address potential new interventions to improve outcomes. The article centres on pulmonary rehabilitation, widely available for the treatment of stable chronic obstructive pulmonary disease, but less often used in a peri-operative setting. Current evidence is largely at high risk of bias, however. Before surgery it is important to ensure that what have been called the 'five fundamentals' of chronic obstructive pulmonary disease treatment are achieved: smoking cessation; pulmonary rehabilitation; vaccination; self-management; and identification and optimisation of co-morbidities. Pharmacological treatment should also be optimised, and some patients may benefit from lung volume reduction surgery. Psychological and behavioural factors are important, but are currently poorly understood in the peri-operative period. Considerations of the risk and benefits of delaying surgery to ensure the recommended measures are delivered depends on patient characteristics and the nature and urgency of the planned intervention.

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

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 B3 lesions. The guidelines reflect suggested practice as stated by the NHS Breast Screening Programme and approved by the Royal College of Radiologists.

Factors influencing local control in patients undergoing breast conservation surgery for ductal carcinoma in situ.

BACKGROUND: The aim of our study was to assess various predictors for local recurrence (LR) in patients undergoing breast conservation surgery (BCS) for ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: An audit was performed of 582 consecutive patients with DCIS between Jan 1975 to June 2008. In patients undergoing BCS, local guidelines reported a margin of ≥10 mm during the above period. Guideline with regard to margin of excision changes soon after this period. We retrospectively analysed clinical and pathological risk factors for local recurrence in patients undergoing BCS. Statistical analysis was carried out using SPSS version 19, and a cox regression model for multivariate analysis of local recurrence was used. RESULTS: Overall 239 women had BCS for DCIS during the above period. The actuarial 5-year recurrence rate was 9.6%. The overall LR rate was 17% (40/239. LR was more common in patients ≤50 years: (10/31 patients, 32%) compared to patients > 50 years (30/208, 14%, P = 0.02). Forty three per cent of patients (6/14) with <5 mm margin developed LR which was significantly higher compared to patients with 5-9 mm margin (12%, 3/25) and with ≥10 mm margin (14%, 27/188, P = 0.01). On multivariate analysis age ≤50 years, <5 mm pathological margin were independent prognostic factors for local recurrence. CONCLUSION: Our study shows that younger age (≤50 years) and a margin < 5 mm are poor prognostic factors for LR in patients undergoing breast conservation surgery for DCIS.

Plasma concentrations of coffee polyphenols and plasma biomarkers of diabetes risk in healthy Japanese women.

Coffee consumption has been reported to reduce the risk of type 2 diabetes in experimental and epidemiological studies. This anti-diabetic effect of coffee may be attributed to its high content in polyphenols especially caffeic acid and chlorogenic acid. However, the association between plasma coffee polyphenols and diabetic risks has never been investigated in the literature. In this study, fasting plasma samples were collected from 57 generally healthy females aged 38-73 (mean 52, s.d. 8) years recruited in Himeji, Japan. The concentrations of plasma coffee polyphenols were determined by liquid chromatography coupled with mass tandem spectrometer. Diabetes biomarkers in the plasma/serum samples were analysed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman's correlation coefficients. The results showed that plasma chlorogenic acid exhibited negative associations with fasting blood glucose, glycated hemoglobin and C-reactive protein, whereas plasma total coffee polyphenol and plasma caffeic acid were weakly associated with these biomarkers. Our preliminary data support previous findings that coffee polyphenols have anti-diabetic effects but further replications with large samples of both genders are recommended.

Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis.

Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungiCladophialophora bantiana,Rhinocladiella mackenziei, andExophiala dermatitidis.Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Ourin vitrostudies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the orderChaetothyriales Furtherin vivostudies and clinical investigations to elucidate and confirm these observations are warranted.

Soft tissue ossification and condylar cartilage degeneration following TMJ disc perforation in a rabbit pilot study.

OBJECTIVE: There are limited clinical treatments for temporomandibular joint (TMJ) pathologies, including degenerative disease, disc perforation and heterotopic ossification (HO). One barrier hindering the development of new therapies is that animal models recapitulating TMJ diseases are poorly established. The objective of this study was to develop an animal model for TMJ cartilage degeneration and disc pathology, including disc perforation and soft tissue HO. METHODS: New Zealand white rabbits (n = 9 rabbits) underwent unilateral TMJ disc perforation surgery and sham surgery on the contralateral side. A 2.5 mm defect was created using a punch biopsy in rabbit TMJ disc. The TMJ condyles and discs were evaluated macroscopically and histologically after 4, 8 and 12 weeks. Condyles were blindly scored by four independent observers using OARSI recommendations for macroscopic and histopathological scoring of osteoarthritis (OA) in rabbit tissues. RESULTS: Histological evidence of TMJ condylar cartilage degeneration was apparent in experimental condyles following disc perforation relative to sham controls after 4 and 8 weeks, including surface fissures and loss of Safranin O staining. At 12 weeks, OARSI scores indicated experimental condylar cartilage erosion into the subchondral bone. Most strikingly, HO occurred within the TMJ disc upon perforation injury in six rabbits after 8 and 12 weeks. CONCLUSION: We report for the first time a rabbit TMJ injury model that demonstrates condylar cartilage degeneration and disc ossification, which is indispensible for testing the efficacy of potential TMJ therapies.

Fruit and vegetable consumption and risk of esophageal cancer: a case-control study in north-west China.

The north-western region of China carries a big burden of esophageal cancer with incidence above the national average. This study ascertained the association between fruit and vegetable consumption and the risk of esophageal cancer in this remote part of China. A case-control study was undertaken in Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region of China, between 2008 and 2009. Participants were 359 incident esophageal cancer patients and 380 hospital-based controls. Information on habitual fruit and vegetable consumption was obtained by face-to-face interview using a validated semiquantitative food frequency questionnaire. Unconditional logistic regression analyses were performed to assess the strength of the associations. The esophageal cancer patients consumed significantly less fruits (mean 364.3, standard deviation [SD] 497.4 g) and vegetables (mean 711.4, SD 727.9 g) daily than their counterparts without the disease (mean 496.5, SD 634.4 g and mean 894.5, SD 746.1 g, respectively). The adjusted odds ratios were 0.48 (95% confidence interval 0.33-0.71) and 0.46 (95% confidence interval 0.32-0.68) for consuming at least 515 g of fruits and 940 g of vegetables per day, respectively, relative to at most 170 g and 520 g. With respect to nutrients contained in fruits and vegetables, intakes of vitamin C, vitamin E, ß-cryptoxanthin, potassium, and magnesium at high levels also reduced the esophageal cancer risk. In conclusion, inverse associations were evident between consumption of fruits and vegetables and the risk of esophageal cancer for adults residing in north-west China.

Uptake of carotid artery stenting in England and subsequent vascular admissions: an appropriate response to emerging evidence?

OBJECTIVE: We report the uptake, length of stay and vascular readmission rates of carotid endarterectomy (CEA) and CAS among patients with symptomatic or asymptomatic carotid artery disease in the English National Health Service (NHS). METHODS: Retrospective cohort study based on routinely collected Hospital Episode Statistics (HES) inpatient data. We identified individual admissions for CEA (n = 15996) or CAS (n = 632) between 2006 and 2009. Summary data were used to describe procedure volumes between 2009 and 2012. We analysed trends in procedure use over time and used ordinary least squares regression to evaluate patient, clinical and organisational characteristics associated with longer length of stay for revascularisation. RESULTS: CAS made up less than 5% of carotid revascularisation procedures; there was no trend for increasing use between 2006 and 2012. Patients treated with CAS were on average younger, lived in areas of higher deprivation and were more likely to have amaurosis fugax or a comorbidity of heart disease. CAS patients had a 19% (95% CI 14-24) shorter stay in hospital than CEA patients. CONCLUSION: Despite the early promise of CAS and numerous randomised controlled trials evaluating efficacy, it has not been rapidly adopted in England. Cautious adoption may be appropriate given the higher periprocedural risk of stroke or death after CAS, particularly in recently symptomatic patients.

Sustainability of a physical activity and nutrition program for seniors.

OBJECTIVE: This prospective cohort study aimed to determine the impact of a low cost, home-based physical activity and nutrition program for older adults at 6 months follow-up. DESIGN: A follow-up survey was conducted 6 months after program completion via computer-assisted telephone interviewing. The International Physical Activity Questionnaire and the Fat and Fibre Barometer were used to measure physical activity levels and dietary behaviours, respectively. Self-reported height, weight, waist and hip circumferences were obtained. Changes over three time points of data collection (baseline, post-program, follow-up) and differences between the intervention and control groups were assessed. The use of program materials was also evaluated. SETTING: Community and home-based. PARTICIPANTS: Insufficiently active 60 to 70 year olds (n = 176, intervention and n = 198, control) residing in suburbs within the Perth metropolitan area. RESULTS: A sustained improvement was observed for the intervention group in terms of fat avoidance behaviours (p interaction = .007). Significant improvements were found for strength exercises, fibre intake, body mass index and waist-to-hip ratio at either post-program or follow-up, however the overall effect was not significant. At post-program, the intervention group increased time spent participating in moderate activity by 50 minutes (p > .05), which was followed by a significant decline at follow-up (p < .05). Among intervention group participants, males and females differed with respect to strength exercises and moderate physical activity. CONCLUSION: This low-cost physical activity and nutrition intervention resulted in a sustained improvement in fat avoidance behaviours and overall short-term gains in physical activity. Future studies for older adults are recommended to investigate gender-specific behavioural barriers as well as booster interventions which focus on physical activity.

The prognostic significance of B lymphocytes in invasive carcinoma of the breast.

Although the favourable role of T lymphocyte populations in different tumour types is established, that of B cells is still a matter of debate and needs further clarification. The presence of tumour-infiltrating B cells may represent an antibody response against breast tumour antigens. We used immunohistochemistry to investigate the density and localisation of B lymphocytes infiltrating 1470 breast tumours and to identify any prognostic significance and relationship to various clinicopathological factors. Higher numbers of CD20(+) cells were found in the stroma away from the carcinoma (mean 12 cells) compared with either intratumoural or adjacent stromal compartments (mean 1 cell). The majority of tumours showed a diffuse pattern of B cells rather than aggregates. There was a positive correlation between higher numbers of total CD20(+) B cells and higher tumour grade (r (s) = 0.20, P < 0.001), ER and PgR negativity (P < 0.001), and basal phenotype (P < 0.001) subclass. In univariate survival analysis, higher total number of infiltrating CD20(+) cells, irrespective of location, was associated with significantly better BCSS (P = 0.037) and longer DFI (P = 0.001). In multivariate analysis, total CD20(+) B cell count (HR = 0.75, 95% CI = 0.58-0.96 for BCSS and HR = 0.72, 95% CI = 0.58-0.89, for DFI), tumour size, nodal stage, grade, vascular invasion, HER-2 status, and total CD8(+) T cell count were independently associated with outcome. This suggests that humoral immunity, in addition to the cell mediated immunity, may be important in breast cancer. This should be considered in breast cancer immunotherapy and vaccine strategies.

Tumour-infiltrating macrophages and clinical outcome in breast cancer.

BACKGROUND: Macrophages constitute a major component of the leucocytic infiltrate of tumours. Human studies show an association between tumour-associated macrophages and tumours with poor prognostic features. In breast cancer, the presence of macrophages has been correlated with increased angiogenesis and poor prognosis but little information is available about the independent prognostic role of macrophages infiltrating breast carcinomas. AIMS AND METHODS: This study used immunohistochemistry and tissue microarrays to assess the density and localisation of CD68 macrophages infiltrating 1322 breast tumours and to identify any relationship with clinicopathological factors and patient outcome. RESULTS: Tumour-infiltrating macrophages were present in the majority of tumours with a predominantly diffuse pattern. The density of distant stromal macrophages (infiltrating stroma away from the carcinoma, median count 14 cells) was higher than intratumoural (median zero cells) and adjacent stromal macrophages (median three cells). Higher total macrophage number was associated with higher tumour grade (r(s)=0.39, p<0.001), ER and PgR negativity, HER-2 positivity and basal phenotype (p<0.001). In univariate survival analysis, higher numbers of CD68 macrophages were significantly associated with worse breast cancer-specific survival (p<0.001) and shorter disease-free interval (p=0.004). However in multivariate model analysis, the CD68 macrophage count was not an independent prognostic marker. CONCLUSIONS: Macrophages are heterogeneous with different subsets having different functions. The present study suggests that overall macrophage numbers are not related to prognosis in breast cancer. However, further studies are needed to investigate the potential role of different subsets of macrophages.

Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma.

The purpose of these studies was to identify human leukocyte antigen (HLA)-A2(+) immunogenic peptides derived from XBP1 antigens to induce a multiple myeloma (MM)-specific immune response. Six native peptides from non-spliced XBP1 antigen and three native peptides from spliced XBP1 antigen were selected and evaluated for their HLA-A2 specificity. Among them, XBP1(184-192), XBP1 SP(196-204) and XBP1 SP(367-375) peptides showed the highest level of binding affinity, but not stability to HLA-A2 molecules. Novel heteroclitic XBP1 peptides, YISPWILAV or YLFPQLISV, demonstrated a significant improvement in HLA-A2 stability from their native XBP1(184-192) or XBP1 SP(367-375) peptide, respectively. Cytotoxic T lymphocytes generated by repeated stimulation of CD3(+) T cells with each HLA-A2-specific heteroclitic peptide showed an increased percentage of CD8(+) (cytotoxic) and CD69(+)/CD45RO(+) (activated memory) T cells and a lower percentage of CD4(+) (helper) and CD45RA(+)/CCR7(+) (naïve) T cells, which were distinct from the control T cells. Functionally, the cytotoxic T lymphocytes (CTL) demonstrated MM-specific and HLA-A2-restricted proliferation, interferon-γ secretion and cytotoxic activity in response to MM cell lines and importantly, cytotoxicity against primary MM cells. These data demonstrate the distinct immunogenic characteristics of unique heteroclitic XBP1 peptides, which induce MM-specific CTLs and highlights their potential application for immunotherapy to treat the patients with MM or its pre-malignant condition.

The prognostic significance of inflammation and medullary histological type in invasive carcinoma of the breast.

UNLABELLED: The new gene expression molecular taxonomy of breast cancer places medullary carcinoma in the basal group. The basal group is considered to have a poor prognosis, but medullary carcinoma is considered to have a better prognosis than other grade 3 carcinomas. The prognostic significance of tumour associated inflammation, an important feature of medullary carcinomas, remains controversial. The aim of this study was to assess the prognostic importance of medullary histological type and inflammation in breast cancer. One thousand five hundred and ninety-seven patients who received no systemic adjuvant treatment and who had a median follow up of 9.5 years were studied. RESULTS: Prominent inflammation was associated with high histological grade and with better survival [relative risk (RR) 0.57, 95% confidence intervals (CI) 0.44-0.74] on multivariate analysis. Typical and atypical medullary carcinomas (n=132) did not have significantly different survival and were grouped together. Medullary carcinoma did not have significantly different prognosis than grade 3 ductal carcinoma with prominent inflammation, but both had a better prognosis than grade 3 ductal carcinoma without prominent inflammation (P<0.0001 and P=0.03). These differences were independent of other prognostic factors. These results question the current separation of typical and atypical medullary carcinoma. Prominent inflammation is associated with a better prognosis, and may explain the better prognosis in medullary carcinoma compared with grade 3 ductal carcinoma without prominent inflammation. The good prognosis of medullary carcinoma emphasises the heterogeneity of basal-like breast carcinomas. Further studies are needed to investigate the difference in survival between medullary carcinoma and other forms of basal carcinomas and the role of inflammation in any such differences in behaviour.

Entamoeba invadens myositis in a common water monitor lizard (Varanus salvator).

Amoebiasis is one of the most common protozoal diseases of reptiles, but amoebic myositis has not been reported in any animal species. An 11-year-old, male common water monitor lizard (Varanus salvator) was found dead with several subacute ulcerated skin wounds. Gross examination revealed multiple discrete to coalescing, white-yellow to gray, caseous foci scattered in the skeletal muscles and liver. The mucosa of small intestine was thickened, red, and contained many variably sized, dark red ulcers, with depressed and hemorrhagic centers. Histopathologic examination revealed severe necrotizing and granulomatous myositis, hepatitis, and enteritis accompanied by large numbers of intralesional, 10-20-microm diameter, periodic acid-Schiff-positive, amoeboid protozoa. Gene sequence analysis of a 136-bp region of the 18S ribosomal RNA amplified by polymerase chain reaction revealed 98-100% similarity with Entamoeba invadens. Aside from intestinal and hepatic involvement, no other internal organs were affected. The muscular infection by E. invadens likely resulted from a combination of direct invasion of trophozoites via skin wounds and hematogenous spread.

Vascular invasion in breast cancer; an overview of recent prognostic developments and molecular pathophysiological mechanisms.

Vascular invasion (VI) is an essential step in breast cancer metastasis and the main cause of morbidity and mortality from the disease. Detection of VI in the primary tumour is a marker of metastatic potential. The prognostic value of VI in breast cancer has been known for more than four decades, but its application in clinical practice is still fraught with difficulties due to the limited number of studies conducted on large numbers of well-characterized patients with long-term follow-up. Detection of VI in the primary tumour is currently assessed using sections stained with haematoxylin and eosin, which has some disadvantages. A number of vascular markers have been used to improve detection of VI; however, their sensitivity and specificity, as endothelial markers, vary considerably. In this review we describe the evolution of the prognostic importance of VI and the recent pathomolecular mechanisms that contribute to the ability of breast cancers to invade through vessels, in addition to the types, locations and methods of detection of vascular invasion.

Predictive value of needle core biopsy diagnoses of lesions of uncertain malignant potential (B3) in abnormalities detected by mammographic screening.

AIMS: Breast needle core biopsy (NCB) is now a commonplace diagnostic procedure in breast cancer screening, providing accurate diagnoses of both benign and malignant lesions. However, NCB may result in the borderline diagnoses of lesion of uncertain malignant potential (B3) or suspicious of malignancy (B4). The aim was to study a large series of B3 cases from population-based screening subjects in order to evaluate positive predictive values (PPVs) for malignancy. METHODS AND RESULTS: The results of 523 NCBs of women screened over a 7-year period (1999-2006) in the East Midlands region, UK, with a B3 diagnosis who underwent surgical excision, were reviewed and compared with the final excision histology. Five percent of NCBs were reported as B3. The most frequent histological subtypes were atypical intraductal epithelial proliferation (AIDEP) and radial scar/complex sclerosing lesion (RS/CSL). Final excision histology was benign in 417 (80%) and malignant in 106 (20%) subjects (60 ductal carcinoma in situ and 46 invasive carcinoma). Lesion-specific PPVs were as follows: AIDEP 32%; lobular neoplasia (LN) 30%; RS/CSL with AIDEP or LN 24%; RS/CSL without atypia 9%; papillary lesion with AIDEP or LN 36%; and papillary lesion without atypia 4%. Five of the 32 fibroepithelial lesions with cellular stroma were phyllodes tumours (four benign and one borderline). None of the five mucinous lesions on NCB was malignant. CONCLUSIONS: Our results show that approximately one-fifth of NCB of screen-detected breast lesions classified as B3 are malignant on excision, and the likelihood of malignancy varies substantially between different histological subtypes.

Vacuum-assisted excision of breast lesions of uncertain malignant potential (B3) - an alternative to surgery in selected cases.

To assess whether vacuum-assisted excision (VAE) is a safe alternative to surgery in the treatment of breast lesions of uncertain malignant potential (B3) in which no atypia is present on needle core biopsy (NCB). Forty two VAE procedures were performed for B3 lesions. Twenty four (57%) were papillary lesions. Eighteen (43%) were radial scars. Two patients (4.7%) were upgraded to carcinoma at VAE. Two patients with papillary lesions went on to develop cancer in the same breast (at 24 and 41 months post VAE). No cancer developed in the radial scar group. Eight patients (19%) had surgery - four for carcinoma, two for radial scars missed at VAE excision and two for symptomatic papillomatosis. Follow-up mammography after VAE of radial scars often showed residual distortion. VAE can be a safe alternative to surgery in the treatment of B3 lesions without atypia, providing thorough multidisciplinary discussion has taken place.