Benign breast papilloma: Is surgical excision necessary?

In many centers internationally, current standard of care is to excise all papillomas of the breast, despite recently reported low rates of upgrade to malignancy on final excision. The objective of this study was to determine the upgrade rate to malignancy in patients with papilloma without atypia. A retrospective review of a prospectively maintained database of all cases of benign intraductal papilloma in a tertiary referral symptomatic breast unit between July 2008 and July 2018 was performed. Patients with evidence of malignancy or atypia on core biopsy and those with a history of breast cancer or genetic mutations predisposing to breast cancer were excluded. One hundred and seventy-three cases of benign papilloma diagnosed on core biopsy were identified. Following exclusions, the final cohort comprised of 138 patients. Mean age at presentation was 51. Mean follow-up time was 9.6 months. The most common symptom was a lump (40%). Of the 124 patients who underwent excision, three had ductal carcinoma in situ and there were no cases of invasive disease, giving an upgrade rate to malignancy of 2.4%. Upgrade to other high-risk lesions (atypical lobular and ductal hyperplasia and lobular carcinoma in situ) was demonstrated in 15 cases (12.1%). Benign papilloma was confirmed in 100 cases (81.5%), and 6 (4.8%) had no residual papilloma found on final excision. Twelve patients (8.7%) were managed conservatively. Of those, one later went on to develop malignancy. Patients with a diagnosis of benign papilloma without atypia on core biopsy have a low risk of upgrade to malignancy on final pathology, suggesting that observation may be a safe alternative to surgical excision. Further research is warranted to determine which patients can be safely managed conservatively.

B7-H3 participates in the development of experimental pneumococcal meningitis by augmentation of the inflammatory response via a TLR2-dependent mechanism.

In addition to a well-documented role in regulating T cell-mediated immune responses, B7-H3, a newly discovered member of the B7 superfamily, has been recently identified as a costimulator in the innate immunity-mediated inflammatory response. In this study, we further report that B7-H3 participates in the development of pneumococcal meningitis in a murine model. Exogenous administration of B7-H3 strongly amplified the inflammatory response, exacerbated blood-brain barrier disruption, and aggravated the clinical disease status in Streptococcus pneumoniae-infected C3H/HeN wild-type mice. Consistent with the in vivo findings, B7-H3 substantially augmented proinflammatory cytokine and chemokine production, upregulated NF-κB p65 and MAPK p38 phosphorylation, and enhanced the nuclear transactivation of NF-κB p65 at both TNF-α and IL-6 promoters in S. pneumoniae-stimulated primary murine microglia cells. These B7-H3-associated in vitro and in vivo effects appeared to be dependent on TLR2 signaling, as B7-H3 almost completely lost its amplifying actions in both TLR2-deficient microglial cells and TLR2-deficient mice. Furthermore, administration of the anti-B7-H3 mAb (MIH35) attenuated the inflammatory response and ameliorated blood-brain barrier disruption in S. pneumoniae-infected wild-type mice. Collectively, our results indicate that B7-H3 plays a contributory role in the development of S. pneumoniae infection-induced bacterial meningitis.

The impact of routine open nonsuction drainage on fluid accumulation after thyroid surgery: a prospective randomised clinical trial.

BACKGROUND: Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours. METHODS: We conducted a prospective randomised clinical trial on patients undergoing thyroid surgery. Patients were randomly assigned to a drain group (n = 49) or a no-drain group (n = 44) immediately prior to wound closure. Patients underwent a neck ultrasound on day 1 and day 2 postoperatively. After surgery, we evaluated visual analogue scale pain scores, postoperative analgesic requirements, self-reported scar satisfaction at 6 weeks and complications. RESULTS: There was significantly less mean fluid accumulated in the drain group on both day 1, 16.4 versus 25.1 ml (P-value = 0.005), and day 2, 18.4 versus 25.7 ml (P-value = 0.026), following surgery. We found no significant differences between the groups with regard to length of stay, scar satisfaction, visual analogue scale pain score and analgesic requirements. There were four versus one wound infections in the drain versus no-drain groups. This finding was not statistically significant (P = 0.154). No life-threatening bleeds occurred in either group. CONCLUSIONS: Fluid accumulation after thyroid surgery was significantly lessened by drainage. However, this study did not show any clinical benefit associated with this finding in the nonemergent setting. Drains themselves showed a trend indicating that they may augment infection rates. The results of this study suggest that the frequency of acute life-threatening bleeds remains extremely low following abandoning drains. We advocate abandoning routine use of thyroid drains. TRIAL REGISTRATION: ISRCTN94715414.

Upgrade rates and outcomes of screen-detected atypical intraductal epithelial proliferation (AIDEP) diagnosed on core needle biopsy.

INTRODUCTION: Atypical intraductal epithelial proliferation (AIDEP) is a breast lesion categorised as "indeterminate" if identified on core needle biopsy (CNB). The rate at which these lesions are upgraded following diagnostic excision varies in the literature. Women diagnosed with AIDEP are thought to be at increased risk of breast cancer. Our aim was to identify the rate of upgrade to invasive or in situ carcinoma in a group of patients diagnosed with AIDEP on screening mammography and to quantify their risk of subsequent breast cancer. METHODS: We conducted a retrospective review of a prospectively maintained database containing all patients diagnosed with AIDEP on CNB between 2005 and 2012 in an Irish breast screening centre. Basic demographic data was collected along with details of the original CNB result, rate of upgrade to carcinoma and details of any subsequent cancer diagnoses. RESULTS: In total 113 patients were diagnosed with AIDEP on CNB during the study period. The upgrade rate on diagnostic excision was 28.3% (n = 32). 6.2% (n = 7) were upgraded to invasive cancer and 22.1% (n = 25) to DCIS. 81 patients were not upgraded on diagnostic excision and were offered 5 years of annual mammographic surveillance. 9.88% (8/81) of these patients went on to receive a subsequent diagnosis of malignancy. The mean time to diagnosis of these subsequent cancers was 65.41 months (range 20.18-145.21). CONCLUSION: Our data showing an upgrade rate of 28% to carcinoma reflects recently published data and we believe it supports the continued practice of excising AIDEP to exclude co-existing carcinoma.

Correction of iron-deficiency anaemia in colorectal surgery reduces perioperative transfusion rates: A before and after study.

BACKGROUND: Preoperative anaemia is a risk factor for poorer postoperative outcomes and many colorectal cancer patients have iron-deficiency anaemia. The aim of this study was to assess if a preoperative iron-deficiency anaemia management protocol for elective colorectal surgery patients helps improve detection and treatment of iron-deficiency, and improve patient outcomes. MATERIALS AND METHODS: Retrospective data was collected from 95 consecutive patients undergoing colorectal cancer surgery to establish baseline anaemia correction rates and perioperative transfusion rates. A new pathway for early detection of iron-deficiency anaemia, and treatment with intravenous iron replacement, for colorectal cancer patients was then developed and implemented. Data from 81 patients was collected prospectively post-implementation to assess the impact of the pathway. RESULTS: Pre-intervention data showed anaemic patients were seventeen times more likely to require perioperative transfusion than non-anaemic patients (95% CI 1.9-151.0, p = 0.011). Post-intervention, fifteen patients with iron-deficiency were treated with either intravenous (n = 8) or oral iron (n = 7). Mean Day 3 postoperative haemoglobin levels were significantly lower in patients with uncorrected anaemia (9.5 g/dL, p = 0.004); those patients whose anaemia was corrected by iron replacement therapy preoperatively had similar postoperative results to non-anaemic patients (10.93 g/dL vs 11.4 g/dL, p = 0.781). Postoperative transfusion rates remained high at 38% in patients with uncorrected anaemia, compared to 0% in corrected anaemia and 3.5% in non-anaemic patients. CONCLUSIONS: Introduction of an iron-deficiency anaemia management pathway has resulted in improved perioperative haemoglobin levels, with a reduction in perioperative transfusion, in elective colorectal patients. Implementation of this pathway could result in similar outcomes across other categories of surgical patients.

Is there a role for locoregional surgery in stage IV breast cancer?

Current guidelines do not recommend locoregional surgery for Stage IV breast cancer at presentation despite some studies suggesting a survival benefit. We aimed to assess outcomes in patients with Stage IV breast cancer who underwent surgery. In a cohort study of all Stage IV breast cancers diagnosed at our tertiary-referral specialist centre between 2006 and 2012, we assessed patient survival in the context of demographics, histopathology, metastatic burden, and type of surgery performed. One hundred and nine patients were included; 52 underwent surgery. Patients in the surgery group had longer 5-year-survival (p = 0.003). Survival was also significantly longer in those with just one site of metastatic disease (p < 0.001). Patients with axillary cytology positive for regional metastases were less likely to proceed to surgery. Locoregional surgery does confer a survival advantage in Stage IV breast cancer. Assessment of preoperative axillary cytology may preclude some patients from proceeding to potentially beneficial locoregional surgery.

MicroRNA-146a is upregulated by and negatively regulates TLR2 signaling.

TLR signaling is a crucial component of the innate immune response to infection. MicroRNAs (miRNAs) have been shown to be upregulated during TLR signaling. Specifically, microRNA-146a (miR-146a) plays a key role in endotoxin tolerance by downregulating interleukin-1 receptor-associated kinase 1 (IRAK-1). The aim of this study was to assess the role of miR-146a in the TLR2 signaling and development of bacterial lipoprotein (BLP) self-tolerance and cross-tolerance to bacteria. Expression of miR-146a increased in a dose- and time-dependent manner in BLP-stimulated human THP-1 promonocytic cells. In BLP-tolerised cells miR-146a was even further upregulated in response to BLP re-stimulation (p<0.001). Re-stimulation of BLP-tolerised cells with heat-killed gram-negative Salmonella typhimurium (S. typhimurium), but not gram-positive Staphylococcus aureus (S. aureus), led to significant overexpression of miR-146a (p<0.05). Transfection of naive cells with a miR-146a mimic substantially suppressed TNF-α production (p<0.05). Furthermore, overexpression of miR-146a resulted in strong reduction in IRAK-1 and phosphorylated IκBα expression in naive and S. typhimurium-stimulated THP-1 cells. Collectively, miR-146a is upregulated in response to BLP and bacterial stimulation in both naive and BLP-tolerised cells. Overexpression of miR-146a induces a state analogous to tolerance in BLP-stimulated cells and therefore may represent a future target for exogenous modulation of tolerance during microbial infection and sepsis.

Who's talking about breast cancer? Analysis of daily breast cancer posts on the internet.

OBJECTIVE: Breast cancer is the cancer most commonly searched for on the internet. Our aim was to assess daily new breast cancer related posting on the internet. METHODS: We analyzed numbers of new daily posts for common cancers for one month and subsequently analyzed content of 1426 breast cancer related posts. We also assessed use of online discussion forums for breast cancer related dialogue. RESULTS: Breast related topics had significantly more posts per day compared to others (mean 66.7, p < 0.01). Most posts were on media sites (65.8%). Accuracy levels were high (87.5%) but significantly lower where posted on blogs and discussion forums (p < 0.001). Anonymous posts were common (55%) and less likely to be accurate (p < 0.001). Use of discussion forums has exponentially increased over the last five years (p < 0.001). CONCLUSIONS: The internet has become a primary forum within which health information, particularly relating to breast cancer, is both sought and shared. Increasingly information is provided by patients themselves.

The emerging role of microRNA in regulation of endotoxin tolerance.

Endotoxin tolerance is a phenomenon where cells show reduced responsiveness toward repeated endotoxin stimulation. Regulation of tolerance occurs at multiple levels of the cell signaling cascade, and many of these levels are potentially regulated by miRNA, which are a class of small RNA that bind to mRNA to down-regulate gene expression at the post-transcriptional level. Roles have been identified for miR-146a, miR-221, miR-579, miR-125b, miR-155, let-7e, and miR-98 in regulating the TLR4 signaling pathway during the development of endotoxin tolerance at receptor, signaling pathway, and gene transcription and translational levels. miRNA represent exciting, new potential targets in attempts to exogenously modulate development of endotoxin tolerance.