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.

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.

Acute Neurological Illness in a Kidney Transplant Recipient Following Infection With Enterovirus-D68: An Emerging Infection?

We report the first case of enterovirus-D68 infection in an adult living-donor kidney transplant recipient who developed rapidly progressive bulbar weakness and acute flaccid limb paralysis following an upper respiratory infection. We present a 45-year-old gentleman who underwent pre-emptive living-donor kidney transplantation for IgA nephropathy. Eight weeks following transplantation, he developed an acute respiratory illness from enterovirus/rhinovirus that was detectable in nasopharyngeal (NP) swabs. Within 24 h of onset of respiratory symptoms, the patient developed binocular diplopia which rapidly progressed to multiple cranial nerve dysfunctions (acute bulbar syndrome) over the next 24 h. Within the next 48 h, asymmetric flaccid paralysis of the left arm and urinary retention developed. While his neurological symptoms were evolving, the Centers for Disease Control reported that the enterovirus strain from the NP swabs was, in fact, Enterovirus-D68 (EV-D68). Magnetic resonance imaging of the brain demonstrated unique gray matter and anterior horn cell changes in the midbrain and spinal cord, respectively. Constellation of these neurological symptoms and signs was suggestive for postinfectious encephalomyelitis (acute disseminated encephalomyelitis [ADEM]) from EV-D68. Treatment based on the principles of ADEM included intensive physical therapy and other supportive measures, which resulted in a steady albeit slow improvement in his left arm and bulbar weakness, while maintaining stable allograft function.

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.

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.

Long-term outcome of primary non-surgical root canal treatment.

AIM: The aim of this study is to examine the survival distributions of primary root canal treatment using interval-censored data and to assess the factors affecting the outcome of primary root canal treatment, in terms of periapical healing and tooth survival. MATERIALS AND METHODS: About one tenth of primary root canal treatment performed between January 1981 and December 1994 in a dental teaching hospital were systematically sampled for inclusion in this study. Information about the patients' personal particulars, medical history, pre-operative status, treatment details, and previous review status of the treated teeth, were obtained from dental records. Patients were recalled for examination clinically and radiographically. Treatment outcomes were categorized according to the status for periapical healing and tooth survival. The event time was interval-censored and subjected to survival analysis using the Weibull accelerated failure time model. RESULTS: A total of 889 teeth were suitable for analysis. Survival curves of both outcome measures (periapical healing and tooth survival) declined in a non-linear fashion with time. Median survival of the treated teeth was 119 months (periapical healing) and 252 months (tooth survival). Age, tooth type, pre-operative periapical status, occlusion, type of final restoration, and condition of the tooth/restoration margin were significant factors affecting both periapical healing and tooth survival. Apical extent and homogeneity of root canal fillings had a significant impact towards periapical healing (p < 0.05), but not tooth survival. CONCLUSION: The longevity of treated teeth based on tooth survival was considerably greater than that of periapical healing. Both outcome measures were affected by a number of socio-demographic, pre-, intra-, and post-operative factors. CLINICAL RELEVANCE: Root canal-treated teeth may continue to function for a considerable period of time even though there may be radiographic periapical lesion present. Decision for extraction may be due to reasons other than a failure of the periapical tissues to heal.

Comparison between a moving bed bioreactor and a fixed bed bioreactor for biological phosphate removal and denitrification.

Moving bed bioreactors (MBBR) and fixed bed bioreactors (FBBR) were compared for biological phosphorus removal and denitrification. The sorption denitrification P-elimination (S-DN-P) process was selected for this study. Results indicated that all nutrients were removed by the FBBR process compared with the MBBR process: 19.8% (total COD), 35.5% (filtered COD), 27.6% (BOD(5)), 62.2% (acetate), 78.5% (PO(4)-P), and 54.2% (NO(3)-N) in MBBR; 49.7% (total COD), 54.0% (filtered COD), 63.2% (BOD(5)), 99.6% (acetate), 98.6% (PO(4)-P), and 75.9% (NO(3)-N) in FBBR. The phosphate uptake and NO(3)-N decomposition in the FBBR process during the denitrification phase were much higher than for the MBBR process despite being of shorter duration. Results obtained from this study are helpful in elucidating the practical implications of using MBBR and FBBR for the removal of bio-P and denitrification from wastewater.

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.

High incidence of respiratory infections in 'nil by mouth' tube-fed acute ischemic stroke patients.

BACKGROUND: Respiratory infections are common in acute stroke. Previous studies have found dysphagia is associated with respiratory infections. Of interest is whether patients who are 'Nil by Mouth' (NBM) and tube fed have higher risk of developing infections due to aspiration of bacteria-laden saliva or refluxed material than stroke patients who are fed orally. METHODS: Prospective cohort of 330 ischemic stroke survivors were followed for 30 days and infections recorded. RESULTS: 115 infections were treated with antibiotics; these included 51 respiratory infections. Incidence of infection in NBM tube-fed stroke patients (n = 74) was 69%, with 30 respiratory infections occurring in 74 patients who received enteral feeding after stroke. Logistic regression analysis showed tube feeding during admission was a significant risk for respiratory infection. We also saw a significant time-to-event effect with 73% (22/30) respiratory infections in tube-fed survivors diagnosed on days 2-4 after stroke, and 76% (39/51) of infections in all tube-fed survivors occurring by day 7 after stroke. Relevance to a theory of critical period of susceptibility to infection in acute stroke is discussed. CONCLUSIONS: NBM tube-fed survivors were unlikely to have aspirated anything other than saliva/secretions or reflux, yet experienced significantly higher rates of respiratory infections than survivors fed orally. Stringent oral care and measures to prevent reflux are potentially modifiable aspects of stroke management.

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.

Reduced colonic smooth muscle cholinergic responsiveness is associated with impaired bowel motility after chronic experimental high-level spinal cord injury.

The mechanisms underlying bowel dysfunction after high-level spinal cord injury (SCI) are poorly understood. However, impaired supraspinal sympathetic and parasympathetic control is likely a major contributing factor. Disruption of the descending autonomic pathways traversing the spinal cord was achieved by a T3 complete spinal cord transection, and colonic function was examined in vivo and ex vivo four weeks post-injury. Total gastrointestinal transit time (TGTT) was reduced and contractility of the proximal and distal colon was impaired due to reduced M3 receptor sensitivity. These data describe a clinically relevant model of bowel dysfunction after SCI.

Recent developments in the histological diagnosis of spindle cell carcinoma, fibromatosis and phyllodes tumour of the breast.

This article reviews recent advances in the diagnosis of these three unusual tumours of the breast. Spindle cell carcinoma needs to be considered in the differential diagnosis of many mammary spindle cell lesions: it is important to be aware of the wide range of appearances, including the recently described fibromatosis-like variant. Immunohistochemistry using a broad panel of cytokeratin antibodies is needed to exclude spindle cell carcinoma; there is frequent expression of basal cytokeratins and p63. CD34 is often expressed by the stroma of phyllodes tumours, but does not appear to be expressed by spindle cell carcinoma or fibromatosis. Nuclear beta-catenin is found in about 80% of fibromatoses, but can also be seen in spindle cell carcinomas and phyllodes tumours. Two recent studies have described features useful in the distinction of phyllodes tumour and fibroadenoma on core biopsy, including increased cellularity, mitoses and overgrowth of the stroma, adipose tissue in the stroma and fragmentation of the biopsy specimen. Periductal stromal tumour is a recently described biphasic tumour composed of spindle cells around open tubules or ducts (but no leaf-like architecture) with frequent CD34 expression. The overlap of morphology with phyllodes tumour suggests that it may be best regarded as a variant of phyllodes tumour.

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.

The significance of lobular neoplasia on needle core biopsy of the breast.

The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological-pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological-pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy, raising the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia.