An International Multicenter Review of the Malignancy Rate of Excised Papillomatous Breast Lesions.

BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.

The utility of the radionuclide probe in parathyroidectomy for primary hyperparathyroidism.

INTRODUCTION Parathyroidectomy is the definitive treatment for primary hyperparathyroidism but the intraoperative identification of adenomas is challenging. The aim of this study was to evaluate the utility of a radionuclide probe (RNP) in addition to intraoperative parathyroid hormone ( IOPTH) measurement as an intraoperative diagnostic adjunct in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS This was a retrospective cohort study of patients treated between 2004 and 2015 in a university affiliated teaching hospital. Patients were grouped into those with RNP use (RNP+) and those without (RNP-). The primary outcome measure was rate of operative failure, which included false positives. The diagnostic sensitivity and positive predictive value of both RNP and IOPTH were also evaluated. RESULTS A total of 298 patients were included in the study, 127 (42.6%) being in the RNP+ group and 171 (57.4%) in the RNP- group. The false positive rate for the RNP+ patients was 1.6% compared with 9.4% for RNP- patients (p=0.006, hazard ratio [HR]: 6.45). The rates of operative failure were 6.3% and 11.7% respectively (p=0.159, HR: 1.97). RNP use had a sensitivity of 92.0% and a positive predictive value of 98.3% compared with 78.6% and 95.2% respectively for IOPTH monitoring. CONCLUSIONS RNP use is associated with fewer false positives and reduced operative failure than IOPTH measurement. It also has a higher sensitivity and positive predictive value. RNP use is recommended in centres that have the required facilities.

PATI: Patient accessed tailored information: A pilot study to evaluate the effect on preoperative breast cancer patients of information delivered via a mobile application.

OBJECTIVES: The information needs of cancer patients are highly variable. Literature suggests an improved ability to modulate personalised stress, increased patient involvement with decision making, greater satisfaction with treatment choices and reduced anxiety levels in cancer patients who have access to information. The aim of this project was to evaluate the effects of a mobile information application on anxiety levels of patients undergoing surgery for breast cancer. MATERIALS AND METHODS: An application was developed for use with Apple iPad containing information on basic breast cancer biology, different treatments used and surgical techniques. Content and face validity studies were performed. A randomized control trial was designed, with a 1:2 allocation. Data collected include basic demographics and type of surgery. Questionnaires used included: the HADS, Mini-MAC, information technology familiarity and information satisfaction. RESULTS: A total of 39 women participated. 13 women had access to an iPad containing additional information and 26 women acted as controls. The mean age was 54 and technology familiarity was similar among both groups. Anxiety and depression scores at seven days were significantly lower in control patients without access to the additional information provided by the mobile application (p = 0.022 and 0.029 respectively). CONCLUSION: Anxiety and depression in breast cancer patients is both multifactorial and significant, with anxiety levels directly correlating with reduced quality of life. Intuitively, information should improve anxiety levels, however, we have demonstrated that surgical patients with less information reported significantly lower anxiety. We advise the thorough testing and auditing of information initiatives before deployment.

Tuberculosis and AIDS: is the white plague up and coming?

We have studied the effect of the HIV epidemic on the incidence of tuberculosis in an inner city area of London which has a high incidence of acquired immunodeficiency syndrome (AIDS). During the period 1985-1991, there was a steady increase in the number of new AIDS cases, whilst the numbers of notifications and laboratory isolates of Mycobacterium tuberculosis remained largely unchanged. Before 1990 there were few cases of tuberculosis in HIV-infected individuals but in the past 2 years there has been a marked increase. In 44% of patients, the site of infection was pulmonary, in 39% extrapulmonary and in 17% pulmonary and extrapulmonary. There were no previous manifestations of immunodeficiency in 58% of patients. This is the first study to show an association between tuberculosis and HIV in the U.K. and supports the suggestion that there is an increased incidence of tuberculosis in patients with HIV infection who are not intravenous drug users.

Pyrexia of undetermined origin in patients with human immunodeficiency virus infection and AIDS.

The case records of consecutive patients admitted to a specialist HIV/AIDS inpatient unit between 1989 and 1993 with pyrexia of undetermined origin (PUO) were reviewed in order to determine the eventual diagnosis. Seventy-nine episodes occurred in 75 patients; 52 patients had a prior AIDS defining diagnosis. CD4+ lymphocyte counts ranged widely, 0-0.79 (median = 0.04) x 10(9)/l. Infections were found in 63 episodes (79%), including mycobacterial infection in 41 episodes (53%) and bacterial infection in 12 episodes (15%). Tumours were found in 6 episodes (8%), 5 of these were lymphoma. Factitious fever accounted for 2 episodes (3%) and connective-tissue disease for 1 episode (1%); no definite diagnosis was reached in 7 episodes (9%). PUO in HIV positive patients is commonly due to infection or tumour. Unexplained fever in this patient group should not be ascribed to HIV infection itself and should be vigorously investigated to find a cause.

Chronic obstructive pulmonary disease.

COPD is the most common chronic condition in the UK and it varies in severity from mild through to disabling and severe disease with respiratory failure. The treatment of the disease is tailored to the severity of the symptoms and the cornerstones are stopping smoking, inhaled bronchodilator and inhaled corticosteroid therapy. Preoperative assessment of patients with COPD needs to be thorough; remember that these patients may have concomitant ischaemic heart disease. Patients with severe COPD are at particularly high risk when given intravenous sedatives, opiates or general anaesthetics.

Histologically atypical Pneumocystis carinii pneumonia.

BACKGROUND: Infection with Pneumocystis carinii typically results in a pneumonia which histologically is seen to consist of an eosinophilic foamy alveolar exudate associated with a mild plasma cell interstitial infiltrate. Special stains show that cysts of P carinii lie within the alveolar exudate. Atypical histological appearances may occasionally be seen, including a granulomatous pneumonia and diffuse alveolar damage. In these patients the clinical presentation may be atypical and results of investigations negative unless lung biopsies are performed and tissue obtained for histological examination. METHODS: The incidence and mode of presentation of histologically atypical pneumocystis pneumonia was studied in a cohort of HIV-I antibody positive patients. RESULTS: Over a 30 month period 138 patients had pneumocystis pneumonia, of whom eight (6%) had atypical histological appearances which were diagnosed (after negative bronchoalveolar lavage) by open lung biopsy in five, percutaneous biopsy in one, and at post mortem examination in two. Atypical appearances included granulomatous inflammation in four patients, "pneumocystoma" in two (one also had extrapulmonary pneumocystosis), bronchiolitis obliterans organising pneumonia in one patient, diffuse alveolar damage and subpleural cysts in one (who also had intrapulmonary cytomegalovirus infection), and extrapulmonary pneumocystosis in two patients. CONCLUSIONS: Various atypical histological appearances may be seen in pneumocystis pneumonia. Lung biopsy (either percutaneous or open) should be considered when bronchoalveolar lavage is repeatedly negative and evidence of P carinii should be sought, by use of special stains, in all lung biopsy material from HIV-I antibody positive patients.

Inter-relationship between tumour necrosis factor-alpha (TNF-alpha) and TNF soluble receptors in pulmonary sarcoidosis.

BACKGROUND: The importance of tumour necrosis factor-alpha (TNF-alpha) in the pathogenesis of pulmonary sarcoidosis has remained uncertain because of the paucity of clinical features associated with excessive levels of this cytokine. Increased levels of soluble TNF receptors (TNF-R), which are known to inhibit TNF-alpha activity, were recently described in the lungs of subjects with sarcoidosis. We hypothesised that TNF-alpha bioactivity may be inhibited in sarcoidosis by the presence of TNF-R. A study was therefore undertaken to investigate for the first time the relationship between soluble receptors and TNF-alpha bioactivity in the lungs of subjects with sarcoidosis. METHODS: Alveolar macrophages (AMs) from 16 subjects with histologically proven sarcoidosis and 13 healthy controls were cultured in the presence and absence of lipopolysaccharide (LPS). The subjects with sarcoidosis were grouped by radiological assessment into stage I (n = 6) and stage II/III (n = 10). The cell culture supernatants and bronchoalveolar lavage (BAL) fluid were assayed for TNF bioactivity using the WEHI 164 clone 13 assay. Immunoreactive (bound and free) TNF-alpha and free TNF-Rs (p55 and p75) were determined by ELISA. RESULTS: Bioactive TNF-alpha was undetectable in the BAL fluid of all the subjects with sarcoidosis and most of the healthy controls. However, there was significantly more immunoreactive TNF-alpha in the BAL fluid from subjects with sarcoidosis than from the controls (median values 0.304 ng/ml and 0.004 ng/ml, respectively, 95% CI 0. 076 to 0.455, p<0.001). The levels of both p55 and p75 in the BAL fluid were higher in both sarcoidosis groups than in the controls (p<0.0005 and p<0.001, respectively). In LPS stimulated AM supernatants reduced TNF-alpha bioactivity was seen in subjects with stage I sarcoidosis compared with those with stage II/III disease and healthy controls (median 0.333 ng/ml vs 1.362 ng/ml and 2.385 ng/ml, respectively, p<0.01). This contrasted with increased p55 levels in the AM supernatants derived from subjects with stage I sarcoidosis compared with those with stage II/III disease and healthy controls (median 0.449 ng/ml vs 0.058 ng/ml and 0.078 ng/ml, respectively, p<0.01). The levels of p75 were increased in unstimulated AM cultures in subjects with stage II/III disease compared with those with stage I disease and healthy controls (median 0.326 ng/ml vs 0.064 ng/ml and 0.102 ng/ml, p<0.05). CONCLUSIONS: These results indicate that TNF-alpha bioactivity may be inhibited by increased soluble TNF-R in the lungs of subjects with sarcoidosis, and this inhibition may be greater in patients with stage I sarcoidosis than in those with stage II/III disease. This may represent a homeostatic mechanism which protects the lung from excessive TNF production characteristic of chronic inflammation.

Changing patterns of respiratory disease in HIV positive patients in a referral centre in the United Kingdom between 1986-7 and 1990-1.

BACKGROUND: Respiratory illness is a significant contributor to morbidity and mortality in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). It has been suggested that Pneumocystis carinii pneumonia is no longer the most frequent cause of respiratory disease in this group because of widespread use of prophylaxis and anti-retroviral drugs. METHODS: A retrospective comparison of the diagnoses in HIV 1 antibody positive patients with respiratory illness admitted to a major UK centre in 1986-7 and 1990-1 was carried out to identify changes in patterns of respiratory disease. RESULTS: In the 1986-7 period there were 73 patients, of whom none received zidovudine or prophylaxis for pneumocystis pneumonia while in the 1990-1 period there were 122 patients. One hundred and ninety patients (98%) were male homosexuals. Pneumocystis pneumonia remained the commonest respiratory disease, comprising 68% of all diagnoses in the 1986-7 period and 48% in the 1990-1 period. Bacterial infections (bronchitis and pneumonia) were seen more commonly in the 1990-1 period (23%) than in the 1986-7 period (14%), as was pulmonary Kaposi's sarcoma (12% in 1990-1 and 4% in 1986-7). Mycobacterial infection remained uncommon (4% in 1986-7 and 6.5% in 1990-1). CONCLUSION: Despite widespread use of zidovudine and prophylaxis, pneumocystis pneumonia remains the commonest respiratory disease in homosexual men.

Tumour necrosis factor production by alveolar macrophages in pulmonary sarcoidosis and tuberculosis.

Tumour Necrosis Factor alpha (TNF/Cachectin) is a cytokine produced mainly by macrophages, which has been shown to cause endothelial cell damage, pyrexia and weight loss, clinical features of tuberculosis, but not of sarcoidosis which is in many other respects a similar disease. 1,25 di-hydroxy Vitamin D and gamma interferon, factors which are present in vivo in both tuberculosis and sarcoidosis, enhance the ability of macrophages to release TNF in vitro. We have studied the ability of pulmonary alveolar macrophages (PAM) harvested by broncho-alveolar lavage (BAL) to produce TNF in response to stimulation with E. coli endotoxin lipopolysaccharide (LPS). 25 patients undergoing bronchoscopy and BAL were studied: 9 with sarcoidosis, 7 with tuberculosis (TB) and 9 (non-neoplastic) disease controls. TNF was assayed by Enzyme Linked Immunosorbent Assay (ELISA) in lavage fluid and cell culture supernatants. No TNF was detected in lavage fluid from any of the groups. PAMs from control patients released no detectable TNF spontaneously, but released 59 +/- 31 units after LPS stimulation. Cells from patients with sarcoidosis and tuberculosis released TNF spontaneously in vitro (TB 226 +/- 106 units; Sarcoidosis 293 +/- 176). TNF release by these cells was not increased further by addition of an optimal concentration of LPS. Thus, the pulmonary macrophages of patients with sarcoidosis and tuberculosis released significantly more TNF than those of controls.

Community acquired lobar pneumonia in patients with HIV infection and AIDS.

BACKGROUND: Community acquired bacterial pneumonia is increasingly encountered in HIV infected individuals and some patients have a radiographic lobar pneumonia. METHODS: A retrospective review of clinical features, microbiological diagnosis, and outcome of community acquired lobar pneumonia was carried out in HIV positive patients admitted to a specialist unit from 1987 to 1993. RESULTS: Forty nine episodes occurred in 45 patients, all of whom were men. CD4 counts ranged widely. A bacteriological diagnosis was made in 25 episodes (51%), seven patients had more than one infective cause. The commonest pathogens were Streptococcus pneumoniae (11 episodes), Staphylococcus aureus (six), Pneumocystis carinii (three), Haemophilus influenzae (three), and Pseudomonas aeruginosa (two). Four patients died. Other complications included intrapulmonary cavitation or abscess formation (11 episodes), empyema (three), and pleural effusion (10 episodes). CONCLUSIONS: Many different infections cause community acquired lobar pneumonia in HIV positive men. Some patients have co-infections and there is a high complication rate.

Bronchoalveolar lavage cell counts as a predictor of short term outcome in pulmonary sarcoidosis.

Sixty seven patients with biopsy proven pulmonary sarcoidosis were prospectively studied to determine whether single point bronchoalveolar lavage cell counts were a useful indicator of functional outcome and whether repeated lavage helped in management. The mean follow up period was 25 (range 13-37) months. No patient was having corticosteroid treatment at the time of initial bronchoalveolar lavage. "High intensity alveolitis" (lymphocyte count greater than or equal to 28%) was present at the initial lavage in 42 patients. These patients showed a significant improvement in their pulmonary function and chest radiographs over the follow up period whereas patients with "low intensity alveolitis" did not. Of the 42 patients with high intensity alveolitis, 31 had chronic sarcoidosis (duration over two years, mean 80 months). These patients showed a significant improvement in FVC but not in TLCO. Corticosteroids resulted in greater functional and radiological improvement in the patients with high intensity alveolitis than in those with low intensity alveolitis. Repeat bronchoalveolar lavage in 34 patients, mean 8.4 months after the original lavage, showed a weak inverse relation between a reduced lymphocyte count and change in forced vital capacity and isotope uptake on a gallium scan. These correlations were too weak to make repeated cell counts useful in management. Our results suggest that high intensity alveolitis may be a favourable prognostic factor for lung function in pulmonary sarcoidosis, even in patients with chronic disease, but that repeat lavage adds little to the management of the individual patient.

Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease.

Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumour necrosis factor in bronchopulmonary secretions of patients with adult respiratory distress syndrome.

Tumour necrosis factor (TNF) concentrations were measured in the bronchopulmonary secretions of 5 patients with the adult respiratory distress syndrome. Each patient underwent fibreoptic bronchoscopy and bronchopulmonary aspiration, and control samples were obtained in an identical manner from 24 patients who underwent bronchoscopy for other reasons (8 had tuberculosis, 6 had sarcoidosis, and 10 had haemoptysis but no abnormal findings). Aspirated fluid was assayed for the presence of TNF by use of an enzyme-linked immunosorbent assay. In the 5 patients with adult respiratory distress syndrome, TNF concentrations exceeded 500 U/ml (12.5 ng/ml), whereas in the control samples no TNF was detected.