The iTOP trial: Comparing immediate techniques of oncoplastic surgery with conventional breast surgery in women with breast cancer - A prospective, controlled, single-center study.

INTRODUCTION: Oncoplastic techniques allow resection of larger tumors, permitting breast conservation in cases otherwise requiring mastectomy. We sought to prospectively compare quality of life (QoL) in patients undergoing oncoplastic surgery as compared to conventional breast conservation (CBC) or mastectomy is lacking. METHODS: Patients diagnosed with BIRADS IV-VI lesion were eligible if resection of ≥10% of the breast volume was planned. Patients were allowed to decide whether they wanted to undergo CBC or oncoplastic breast conservation (OBC). Patients who underwent mastectomy and immediate breast reconstruction (IBR) were also included for comparison. The primary endpoint was breast self-esteem using the Breast Image Scale (BIS) at 12 months, secondary endpoints were perioperative morbidity and QoL using the BREAST-Q questionnaire. RESULTS: From 2011 to 2016, 205 patients were included in the study. 116 patients (56.6%) received CBC, 46 (22.4%) OBC and 43 (21%) MIBR. Women in the OBC group were more likely to have tumors ≥ 2 cm than those in the CBC group (34.7% vs. 17.5%, respectively). Women who underwent MIBR were more likely to have tumors > 5 cm than those in the CBC and OBC groups (23% vs 1% and 10%, respectively). The BIS and BREAST-Q improved in each group after 12 months but did not differ significantly between groups at any time point. Surgical complications (seroma, bleeding, infection, necrosis) were numerically more likely in the OBC and MIBR groups. CONCLUSION: OBC and the MIBR allow for resection of larger tumors with a similar quality of life as CBC.

Retrospective, Multicenter Analysis Comparing Conventional with Oncoplastic Breast Conserving Surgery: Oncological and Surgical Outcomes in Women with High-Risk Breast Cancer from the OPBC-01/iTOP2 Study.

INTRODUCTION: Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). METHODS: Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. RESULTS: A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 ("ink on tumor") in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. CONCLUSIONS: Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI.

Insight into the expression of toll-like receptors 2 and 4 in patients with abdominal aortic aneurysm.

An abdominal aortic aneurysm (AAA) is a relatively common, life-threatening disease prevalent in persons over the age of 65. In recent years, an increasing number of studies have suggested that pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), may serve as important regulators in the development of AAAs. In this study, we evaluated the TLR2 and TLR4 expression in the aortic wall and blood of patients with AAA. The TLR2 and TLR4 mRNA expression were significantly higher in the blood of patients with AAA than in the blood of healthy volunteers (p = 0.009 and p = 0.010, respectively). The expression of TLR2 and TLR4 transcripts was also higher in the blood compared with the aortic wall tissue of AAA patients (p = 0.001 for both). Higher TLR2 protein expression was observed in the aortic wall of AAA patients compared with the blood (p = 0.026). A significantly higher concentration of TNF-α and IL-4 in patients with AAA than in healthy volunteers (p < 0.001 for both) was noticed. This study suggests that TLR2 may play a role in the inflammatory response in the aorta, both locally and systemically, in patients with AAA.

Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin.

This study was undertaken to verify whether simvastatin modulates Cav-1/eNOS expression, and if this modulation is associated with changes in pro- and anti-inflammatory cytokine and Toll-like receptor 4 (TLR4) level in abdominal aortic aneurysm (AAA). It is a 1:2 case-control study of non-statin (n=12) and simvastatin-treated patients (n=24) who underwent open AAA repair. Simvastatin treatment decreased Cav-1 (p<0.05) and increased eNOS expression (p<0.01) in the AAA wall. These changes might be dose dependent. The changes in Cav-1 and eNOS were associated with a trend towards decreased IL-6 and IL-17 concentration (p>0.05) and increased IL-10 concentration (p=0.055); however, TLR4 expression was unaffected, suggesting that simvastatin influences Cav-1 and eNOS in the AAA wall by other mechanisms. Simvastatin may modulate Cav-1 and eNOS expression in the aneurysmal wall, indicating a potentially beneficial role for statins in AAA patients.

Analysis of host Toll-like receptor 3 and RIG-I-like receptor gene expression in patients with abdominal aortic aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a vascular disease relatively common in the elderly population. Although some events that contribute to the development and progression of AAA are known, there are limited data examining the association of Toll-like receptor 3 (TLR3) and RIG-I-like receptor expression with the pathogenesis of AAAs. In this study, we investigated the gene and protein expression of TLR3 and RIG-I-like receptors (RIG-I and MDA5) in aortic wall and blood of AAA patients and examined the relationship between their expression and immune response. METHODS: Total RNA was extracted from aortic wall tissues and blood samples collected from 20 patients with AAA and blood samples of 17 healthy volunteers without aortic aneurysm. To evaluate the DDX58 (RIG-I), IFIH1 (MDA5), and TLR3 gene expression level, quantitative real-time polymerase chain reaction was used. Extracellular cytokine and pattern recognition receptor levels were quantified by enzyme-linked immunosorbent assays. RESULTS: TLR3, RIG-I, and MDA5 were constitutively expressed in both aortic tissues and blood samples from AAA patients and healthy volunteers. In patients with AAA, higher TLR3 expression in aortic tissues than in blood was found (P = .004). The DDX58 messenger RNA expression was higher in blood of patients with AAA compared with healthy subjects (P = .021). A significantly higher level of plasma interleukin 4 was noticed in patients with AAA than in healthy individuals (P = .008). CONCLUSIONS: This study suggests that RIG-I and TLR3 seem to be important factors in the pathogenesis of AAA.

Adjuvant Bisphosphonate Therapy in Postmenopausal Breast Cancer.

OPINION STATEMENT: Bone health and breast cancer are two connected subjects, because breast cancer patients have a higher prevalence of osteopenia/osteoporosis and reduced bone health parameters than healthy woman of the same age. Therefore, the positive effect of adjuvant bisphosphonate therapy plays an important role in breast cancer treatment. Several randomized trials have studied bisphosphonates in the adjuvant setting in postmenopausal woman and demonstrated their potential to prevent treatment-induced bone loss. The prevention of fractures and the subsequent preservation of patients' quality of life are important arguments for the use of adjuvant bisphosphonates in postmenopausal breast cancer patients. In addition, trials of adjuvant bone-targeted agents showed a reduction of recurrences in and outside bone and an improved outcome in patients treated with bisphosphonates.

Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study.

OBJECTIVES: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens. METHODS: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray. RESULTS: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001). CONCLUSIONS: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.

Optimal duration of adjuvant endocrine therapy: how to apply the newest data.

BACKGROUND: The benefit of 5 years of adjuvant endocrine therapy for women with hormone receptor-positive (HR+) breast cancer (BC) is beyond discussion. Nevertheless, the risk of recurrence of luminal BC persists for 15 years or more after diagnosis. Consequently, approaches of extended adjuvant therapy have been investigated in large clinical trials, with the ultimate aim of further reducing the risk of recurrence in patients with HR+ BC. METHODS: A review of recently published trial data is presented to provide a solid basis for discussion. A discussion of the side effects of long-term endocrine treatment, multigenetic tests aiming to identify patients at particular risk, and an outlook for further promising targets are additional aims of this review. CONCLUSION: Extended adjuvant therapy seems beneficial in reducing distant relapse and contralateral BC for a selected group of patients with HR+ BC, particularly if aromatase inhibitors (AIs) are used after initial tamoxifen therapy. However, patients with lower risk of recurrence and initial AI therapy may suffer more from side effects than benefit from extended therapy.

Reconstruction and 3D visualisation based on objective real 3D based documentation.

Reconstructions based directly upon forensic evidence alone are called primary information. Historically this consists of documentation of findings by verbal protocols, photographs and other visual means. Currently modern imaging techniques such as 3D surface scanning and radiological methods (computer tomography, magnetic resonance imaging) are also applied. Secondary interpretation is based on facts and the examiner's experience. Usually such reconstructive expertises are given in written form, and are often enhanced by sketches. However, narrative interpretations can, especially in complex courses of action, be difficult to present and can be misunderstood. In this report we demonstrate the use of graphic reconstruction of secondary interpretation with supporting pictorial evidence, applying digital visualisation (using 'Poser') or scientific animation (using '3D Studio Max', 'Maya') and present methods of clearly distinguishing between factual documentation and examiners' interpretation based on three cases. The first case involved a pedestrian who was initially struck by a car on a motorway and was then run over by a second car. The second case involved a suicidal gunshot to the head with a rifle, in which the trigger was pushed with a rod. The third case dealt with a collision between two motorcycles. Pictorial reconstruction of the secondary interpretation of these cases has several advantages. The images enable an immediate overview, give rise to enhanced clarity, and compel the examiner to look at all details if he or she is to create a complete image.

A picture is worth a thousand words--the utility of 3D visualization illustrated by a case of survived pancreatic transection.

It is one of the most important tasks of the forensic pathologist to explain the forensically relevant medical findings to medical non-professionals. However, it is often difficult to comment on the nature and potential consequences of organ injuries in a comprehensive way to individuals with limited knowledge of anatomy and physiology. This rare case of survived pancreatic transaction after kicks to the abdomen illustrates how the application of dedicated software programs for three-dimensional reconstruction can overcome these difficulties, allowing for clear and concise visualization of complex findings.

Suicidal knife wound to the heart: challenges in reconstructing wound channels with post mortem CT and CT-angiography.

We present a case of an individual who stabbed himself through the heart with a large knife. Post mortem computed tomography (CT) and CT-angiography were used to assess the stab channel and to reconstruct the sequence of events. After penetrating injuries to the chest, both the intra-thoracic organs and the injury causing instrument may shift (e.g. from pnemothorax) and render forensic reconstructions more challenging. This case report illustrates the potentials and the pitfalls of CT for the reconstruction of penetrating injures to the chest.

Gunshot energy transfer profile in ballistic gelatine, determined with computed tomography using the total crack length method.

By measuring the total crack lengths (TCL) along a gunshot wound channel simulated in ordnance gelatine, one can calculate the energy transferred by a projectile to the surrounding tissue along its course. Visual quantitative TCL analysis of cut slices in ordnance gelatine blocks is unreliable due to the poor visibility of cracks and the likely introduction of secondary cracks resulting from slicing. Furthermore, gelatine TCL patterns are difficult to preserve because of the deterioration of the internal structures of gelatine with age and the tendency of gelatine to decompose. By contrast, using computed tomography (CT) software for TCL analysis in gelatine, cracks on 1-cm thick slices can be easily detected, measured and preserved. In this, experiment CT TCL analyses were applied to gunshots fired into gelatine blocks by three different ammunition types (9-mm Luger full metal jacket, .44 Remington Magnum semi-jacketed hollow point and 7.62 × 51 RWS Cone-Point). The resulting TCL curves reflected the three projectiles' capacity to transfer energy to the surrounding tissue very accurately and showed clearly the typical energy transfer differences. We believe that CT is a useful tool in evaluating gunshot wound profiles using the TCL method and is indeed superior to conventional methods applying physical slicing of the gelatine.