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.

Antibiotic prophylaxis in breast cancer surgery (PAUS trial): randomised clinical double-blind parallel-group multicentre superiority trial.

BACKGROUND: Participants were patients with invasive breast cancer undergoing primary surgery. The aim was to test whether a single dose of amoxicillin-clavulanic acid would reduce wound infection at 30 days postoperatively, and to identify risk factors for infection. METHODS: Participants were randomised to either a single bolus of 1.2 g intravenous amoxicillin-clavulanic acid after the induction of anaesthesia (intervention) or no antibiotic (control). The primary outcome was the incidence of wound infection at 30 days postoperatively. RESULTS: There were 871 evaluable patients. Of these, 438 received prophylactic antibiotic and 433 served as controls. Seventy-one (16.2 per cent) patients in the intervention group developed a wound infection by 30 days, while there were 83 (19.2 per cent) infections in the control group. This was not statistically significant (odds ratio (OR) 0.82, 95 per cent c.i. 0.58 to 1.15; P = 0.250). The risk of infection increased for every 5 kg/m2 of BMI (OR 1.29, 95 per cent c.i. 1.10 to 1.52; P = 0.003). Patients who were preoperative carriers of Staphylococcus aureus had an increased risk of postoperative wound infection; however, there was no benefit of preoperative antibiotics for patients with either a high BMI or who were carriers of S. aureus. CONCLUSION: There was no statistically significant or clinically meaningful reduction in wound infection at 30 days following breast cancer surgery in patients who received a single dose of amoxicillin-clavulanic acid preoperatively. REGISTRATION NUMBER: N0399145605 (National Research Register).

There is little research about antibiotics in breast cancer surgery. Surgeons are not certain whether or not to use antibiotics for their patients. The aim of the Prophylactic Antibiotic Use in Surgery (PAUS) trial was to ask a question, 'Do preoperative antibiotics have any benefit for patients having surgery for breast cancer?' In the PAUS trial patients were given information to decide whether they wished to take part in the trial or not. Participants were randomly placed in one of two groups. Half were given one dose of the amoxicillin­clavulanic acid antibiotic at the time of their operation. The other half had no antibiotic. Neither the patient nor the surgeon knew which group the patient was in. Patients were carefully checked until 30 days after their operation for signs of wound infection. Altogether, 871 patients agreed to take part in the PAUS trial. Of these, 438 patients had the antibiotic and 433 had no antibiotic. The PAUS trial showed that there was no difference in the number of wound infections when comparing the two groups. Seventy-one patients (16.2 per cent) who had been given the antibiotic developed a wound infection by 30 days versus 83 (19.2 per cent) in the group who had not been given the antibiotic. This trial shows that antibiotics may not be needed for breast cancer surgery. PAUS may help to cut down on unnecessary antibiotic use.

Prognostic role of preoperative circulating systemic inflammatory response markers in primary breast cancer: meta-analysis.

BACKGROUND: Circulating markers of the systemic inflammatory response are prognostic in several cancers, but their role in operable breast cancer is unclear. A systematic review and meta-analysis of the literature was carried out. METHODS: A search of electronic databases up to August 2020 identified studies that examined the prognostic value of preoperative circulating markers of the systemic inflammatory response in primary operable breast cancer. A meta-analysis was carried out for each marker with more than three studies, reporting a HR and 95 per cent confidence interval for disease-free survival (DFS), breast cancer-specific survival (BCSS) or overall survival (OS). RESULTS: In total, 57 studies were reviewed and 42 were suitable for meta-analysis. Higher neutrophil-to-lymphocyte ratio (NLR) was associated with worse overall survival (OS) (pooled HR 1.75, 95 per cent c.i. 1.52 to 2.00; P < 0.001), disease-free survival (DFS) (HR 1.67, 1.50 to 1.87; P < 0.001), and breast cancer-specific survival (BCSS) (HR 1.89, 1.35 to 2.63; P < 0.001). This effect was also seen with an arithmetically-derived NLR (dNLR). Higher platelet-to-lymphocyte ratio (PLR) was associated with worse OS (HR 1.29, 1.10 to 1.50; P = 0.001) and DFS (HR 1.58, 1.33 to 1.88; P < 0.001). Higher lymphocyte-to-monocyte ratio (LMR) was associated with improved DFS (HR 0.65, 0.51 to 0.82; P < 0.001), and higher C-reactive protein (CRP) level was associated with worse BCSS (HR 1.22, 1.07 to 1.39; P = 0.002) and OS (HR 1.24, 1.14 to 1.35; P = 0.002). CONCLUSION: Current evidence suggests a role for preoperative NLR, dNLR, LMR, PLR, and CRP as prognostic markers in primary operable breast cancer. Further work should define their role in clinical practice, particularly reproducible thresholds and molecular subtypes for which these may be of most value.

[Latest international guidelines for screening, prevention and treatment of familial breast cancer - implications for the relevant practice in Hungary]. / Az örökletes emlorák szurésének, megelozésének és kezelésének új nemzetközi irányvonalai - hazai vonatkozásokkal.

INTRODUCTION: Screening, prevention and treatment of familial breast cancer require a multidisciplinary approach. New guidelines were published in the United Kingdom for the management of familial breast cancer. AIM: The authors summarise these new guidelines and analyse the relevant practice in Hungary. METHOD: Relevant guidelines of the National Institute for Health and Care Excellence and Familial Breast Cancer Report (NHS Scotland) are described. RESULTS: New guidelines will increase the number of genetic tests as well as genetic counselling. An increase in the number of breast magnetic resonance imaging is expected, too. Chemoprevention can be offered for individuals with medium risk and above. Promising trials are underway with platinum based chemotherapy and polyADP-ribose polimerase inhibitors for the systemic treatment of familial breast cancer. The increase in the number of genetic tests, counselling, and breast magnetic resonance imaging may have a significant impact on health care budget. CONCLUSIONS: These guidelines will change some aspects of the current management of familial breast cancer. Orv. Hetil., 2016, 157(28), 1117-1125.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

[Oncologic safety of skin-sparing mastectomy followed by immediate breast reconstruction: rate and localization of recurrences, and impact of reconstruction techniques]. / Borkímélo (skin-sparing) mastectomia és azonnali emlorekonstrukció onkológiai biztonságossága a recidívaarány, recidívalokalizáció és a rekonstrukciós technika függvényében.

INTRODUCTION: Oncological safety of skin-sparing mastectomy followed by immediate breast reconstruction is widely debated. Current evidence is relatively poor since it is based mostly on short-term follow-up data of highly selected patient populations. AIM: Recurrence rates of a large cohort of non-selected patients, i. e. "all-comers" were analyzed during a 10-year follow up. METHODS: Patient records and follow-up data of 253 consecutive cases treated with of skin-sparing mastectomy and immediate breast reconstruction between 1995 and 2000 were studied. During this time period "all-comers" policy was applied, which meant that all patients treated with mastectomy were offered immediate breast reconstruction regardless of tumour stage. RESULTS: "All-comers" approach resulted in a large proportion of patients with more advanced disease. During the 112 months mean follow-up 8.2% locoregional, 2.9% local, 10.6% distal and 18.8% overall recurrence rates were detected. Breast cancer specific survival rate was 90.9%. Autologous breast reconstruction was applied more frequently in patients with higher tumour stage; therefore recurrence rate was higher compared to patients undergoing implant-based reconstruction. CONCLUSION: Based on these long-term follow-up data skin-sparing mastectomy combined with immediate breast reconstruction is an oncologically safe treatment option. Therefore, application of "all-comers" policy for breast cancer patients treated with skin-sparing mastectomy followed by immediate breast reconstruction is feasible.

[Intraoperative, postoperative and long-term oncosurgical safety of therapeutic mammaplasty]. / Terápiás emloplasztika intraoperatív, közvetlen posztoperatív és hosszú távú onkosebészeti biztonsága.

INTRODUCTION: (Pre)malignant lesion in the breast requiring mastectomy conventionally may be treated with breast conservation by using oncoplastic breast surgical techniques, which is called therapeutic mammaplasty. However, no reliable data has been published so far as regards the oncological safety of this method. AIM: The aim of the authors was to analyse the oncological safety of therapeutic mammaplasty in a series of patients. METHOD: 99 patients were treated with therapeutic mammaplasty and data were collected in a breast surgical database prospectively. Results were analysed with respect to intraoperative, postoperative and long-term oncological safety. RESULTS: Incomplete resection rate was 14.1%, which correlated with tumour size (p = 0.023), and multifocality (p = 0.012). Time between surgery (therapeutic mammaplasty) and chemotherapy was similar to time between conventional breast surgeries (wide excision, mastectomy, mastectomy with immediate reconstruction) and chemotherapy (mean 29-31 days; p<0.05). Overall recurrence rate was 6.1%, locoregional recurrence rate was 2% during 27 month (1-88) mean follow-up. CONCLUSIONS: Since literature data are based on relatively short follow-up and low patient number, it is highly important that all data on therapeutic mammaplasty is collected in a prospectively maintained breast surgical database in order to determine true recurrence after long-follow-up.

Extreme Oncoplasty: Breast Conservation in Patients with Large, Multifocal, and Multicentric Breast Cancer.

INTRODUCTION: Extreme Oncoplastic Breast Conservation Surgery (EOBCS) is offered in selected patients with multifocal or multicentric breast cancer (MFMC). Recent evidence has suggested that EOBCS may be a valuable resource for patients with MFMC who may avoid the risk associated with mastectomy in favour of the benefits of breast conservation without risking their oncological outcomes. Our study examined the practice of EOBCS in two regional breast units in Glasgow, United Kingdom. MATERIALS AND METHODS: A prospectively collected database of 50 patients treated with EOBC in two breast units in Glasgow between 2007 and 2018 were evaluated, and clinical outcomes were observed. RESULTS: Fifty patients (median age 55) underwent EOBCS, of which 43 (86%) had invasive disease. Median tumour size was 55mm (50-90) and multifocal disease was identified in 22 (44%) patients. Nine patients (18%) were found to have positive margins and underwent a second procedure, with 6 (12%) proceeding to mastectomy. Five-year disease free survival rate was 91.5%, while cancer-specific survival was 95.7%. CONCLUSION: EOBCS is oncologically safe in short-term follow-up. Large scale studies are required to confirm these preliminary results, in order to offer EOBCS as a valid option to patients with advanced or multifocal breast cancer.

A prospective cohort study of the safety of breast cancer surgery during COVID-19 pandemic in the West of Scotland.

INTRODUCTION: In order to minimise the risk of breast cancer patients for COVID-19 infection related morbidity and mortality prioritisation of care has utmost importance since the onset of the pandemic. However, COVID-19 related risk in patients undergoing breast cancer surgery has not been studied yet. We evaluated the safety of breast cancer surgery during COVID-19 pandemic in the West of Scotland region. METHODS: A prospective cohort study of patients having breast cancer surgery was carried out in a geographical region during the first eight weeks of the hospital lockdown and outcomes were compared to the regional cancer registry data of pre-COVID-19 patients of the same units (n = 1415). RESULTS: 188 operations were carried out in 179 patients. Tumour size was significantly larger in patients undergoing surgery during hospital lockdown than before (cT3-4: 16.8% vs. 7.4%; p < 0.001; pT2 - pT4: 45.5% vs. 35.6%; p = 0.002). ER negative and HER-2 positive rate was significantly higher during lockdown (ER negative: 41.3% vs. 17%, p < 0.001; HER-2 positive: 23.4% vs. 14.8%; p = 0.004). While breast conservation rate was lower during lockdown (58.6% vs. 65%; p < 0.001), level II oncoplastic conservation was significantly higher in order to reduce mastectomy rate (22.8% vs. 5.6%; p < 0.001). No immediate reconstruction was offered during lockdown. 51.2% had co-morbidity, and 7.8% developed postoperative complications in lockdown. There was no peri-operative COVID-19 infection related morbidity or mortality. CONCLUSION: breast cancer can be safely provided during COVID-19 pandemic in selected patients.

Intraoperative determination of PTH concentrations in fine needle tissue aspirates to identify parathyroid tissue during parathyroidectomy.

BACKGROUND: Exact tissue identification during parathyroidectomy is essential to successfully cure hyperparathyroidism. PTH level determination from tissue aspirates has been advocated as a "biochemical frozen section" for parathyroid tissue identification. We investigated the sensitivity and specificity of this method in a large cohort of consecutive patients who underwent parathyroidectomy in a tertiary referral center. METHODS: PTH levels of 359 tissue aspirates were measured intraoperatively in 223 consecutive patients from March 2006 to December 2008. Suspected parathyroid and control tissues were aspirated with a standardized technique immediately after their excision. Samples were processed for quick-PTH assay with peripheral blood samples before and after excision. PTH levels from tissue aspirates were correlated with pathological diagnosis. The Mann-Whitney test was used to determine statistical significance (P < 0.05). RESULTS: A total of 255 parathyroid (196 adenoma, 30 hyperplasia, 4 carcinoma, 25 normal parathyroid) and 104 nonparathyroid tissue (88 thyroid, 16 lymph node, thymus, or fat) aspirates were compared. A highly significant difference was found between PTH levels of parathyroid (8,120 +/- 2,711 pg/ml; interquartile range (IQR): 4,949-9,075) and nonparathyroid (0.8 +/- 9.29 pg/ml; IQR: 0.4-1.4) tissue aspirates (P < 0.005). This test is 100% sensitive and 100% specific to identify parathyroid tissue for values >84 pg/ml. Furthermore, PTH levels of pathological parathyroid aspirates (8,169 +/- 2,597; IQR: 5,634-9,109) were higher than that of normal parathyroid aspirates (4,130 +/- 2,952; IQR: 2,569-8,284; P = 0.0011). CONCLUSIONS: PTH level determination from tissue aspirates is a highly reliable, quick, and simple method to differentiate parathyroid and nonparathyroid tissues during parathyroidectomy. This method can obviate frozen sections in patients undergoing surgery for hyperparathyroidism.

Evidence-based use of enteral nutrition in acute pancreatitis.

PURPOSE: A systematic review was carried out to analyze current evidence-based data on the use of enteral nutrition in the management of acute pancreatitis. METHODS: Literature search was performed on "Pubmed" and "Medline" databases to identify articles investigating the role and potential effect of enteral nutrition on the outcome of patients with acute pancreatitis. Relevant data were analyzed from the viewpoints of possible benefits and complications, route and timing of administration, and composition of nutrients. RESULTS: Thirty-two prospective randomized controlled trials and 15 meta-analyses of those were identified and included in this overview. Strong evidence suggests that enteral nutrition significantly reduces mortality rate of severe acute pancreatitis. While both nasogastric and nasojejunal feeding appear to be safe in severe pancreatitis, early low-fat oral diet is possibly beneficial in patients with mild pancreatitis. Since maintenance of the gut barrier function is one of the crucial effects of enteral nutrition, enteral feeding should be commenced within the first 24 h after hospital admission, in order to prevent early bacterial translocation. However, it seems that neither immunonoenhanced nutrients nor probiotic supplementation are able to reduce mortality further, and--therefore--cannot be recommended for patients with acute pancreatitis. CONCLUSION: Although enteral nutrition is undoubtedly a key component of the management of acute pancreatitis, the exact role of that is needed to be defined yet. In particular, conflicting data from studies on nutrient compositions will require further clarification in the future.

Solid pseudopapillary neoplasm of the pancreas--proposed algorithms for diagnosis and surgical treatment.

PURPOSE: The incidence of solid pseudopapillary neoplasm (SPN) of the pancreas is rising. Although the evidence for proper management is accumulating, we still lack diagnostic and therapeutic guidelines. In this paper, therefore, we propose an algorithm for diagnosis and treatment of this rare type of tumor. METHODS: A literature search was carried out on "Medline" and "Pubmed" databases to identify studies investigating the clinicopathologic features, pathogenesis, diagnostic, and differential diagnostic pathways, and surgical and adjuvant treatment options. Evidence from relevant published literature was completed with data of six patients treated with SPN in our institution. RESULTS: This study included case series and retrospective reviews only, since no higher level of evidence exists in the relevant literature. The articles emphasized that preoperative diagnosis is desirable to set up a precise plan for surgical treatment. Further, an R0 organ-sparing resection for primary SPN and an en bloc resection of locally advanced SPN are advised, while resection of synchronous as well as metachronous distant metastases is strongly advocated for this rare type of pancreatic cancer. The role of adjuvant chemo- or radiotherapy still needs to be defined. Finally, a diagnostic and therapeutic algorithm is devised in this paper to aid proper management of SPN. CONCLUSION: Current recommendations for treatment of SPN of the pancreas rely mainly on case series as single institutional experiences and retrospective reviews. Although the level of evidence is relatively low, the way of management discussed above is likely to provide an excellent prognosis in typically young patients with SPN.

Protein kinase inhibitor-induced endothelial cell cytotoxicity and its prediction based on calculated molecular descriptors.

Protein kinase inhibitors (PKIs) as potent signal transduction therapeutic compounds represent a very rapidly expanding group of anticancer drugs. These agents may be toxic for endothelial cells, however, very few experimental data exist on the cytotoxicity of PKIs. The aim of this study was to set up an appropriate test system for endothelial cells and to assess the structure-related cytotoxic effects of a selected library of PKIs. The inhibitor library contains several lead molecules with different basic structures and a set of modified derivatives of the lead compounds. The toxicity of PKIs did not correlate directly with the structural features of the molecules. However, we successfully built up a model based on 15 calculated molecular descriptors, which is capable of predicting cytotoxicity with acceptable probability. Our results show that the cytotoxic effects of PKIs should be taken into account for optimal drug development to overcome endothelial cell-related side effects.

A detailed investigation of maternally inherited diabetes and deafness (MIDD) including clinical characteristics, C-peptide secretion, HLA-DR and -DQ status and autoantibody pattern.

BACKGROUND: This article presents a clinically characterization of the mitochondrial DNA mutation (A3243G) associated with maternally inherited diabetes and deafness (MIDD) syndrome in two families. METHODS: Six patients with MIDD and one mutation-positive relative with normal glucose tolerance (NGT) were examined. Fasting serum C-peptide was measured in all subjects and compared with controls having NGT (n = 14). C-peptide response to an intravenous glucose tolerance test (IVGTT) was investigated in the diabetic patients not treated with insulin (n = 3) and in the mutation-positive healthy individual and compared with the controls. RESULTS: The A3243G heteroplasmy value varied between 5 and 30%. All A3243G carriers had HLA-DR1-DQ5 haplotype, and either the -DQ5 or the -DQ6 allele. The fasting and the serum C-peptide levels at 120 min during the IVGTT did not differ between the A3243G carriers and the controls. A missing first phase and a decreased total C-peptide response was detected in the mutation-positive diabetics compared with controls (p < 0.0001). The same abnormality was found in the A3243G carrier with NGT. Circulating islet cell antibody (ICA) was present in three patients with MIDD. Glutamic acid decarboxylase (GAD), tyrosine phosphatase-like protein IA-2 (IA-2) and mitochondrial antibodies were missing. The diagnosis of MIDD was delayed in each case. CONCLUSIONS: A missing first phase and a decreased total C-peptide response during an IVGTT was characteristic for the A3243G mutation. The fasting C-peptide level of the carriers did not differ from the controls. Circulating ICA was present in some patients, but GAD, IA-2 and mitochondrial antibodies were absent. All subjects had HLA-DR1-DQ5 haplotype, and either -DQ5 or -DQ6 alleles.

Variation in the management of elderly patients in two neighboring breast units is due to preferences and attitudes of health professionals.

Introduction: Elderly breast cancer patients have been shown to be managed less aggressively than younger patients. There is evidence that their management varies between institutions. We audited the management of elderly patients in two neighboring units in Glasgow and aimed to identify reasons for any differences in practice found. Methods: Patients aged ≥70 years, who were managed for a new diagnosis of breast cancer in the two units between 2009 and 2013, were identified from a prospectively maintained database. Tumor pathology, treatment details, postcode and consultant in charge of care were obtained from the same database. Comorbidities were obtained from each patient's electronic clinical record. Questionnaires were distributed to members of each multidisciplinary teams. Results: 487 elderly patients in Unit 1 and 467 in Unit 2 were identified. 76.2% patients in Unit 1 were managed surgically compared to 63.7% in Unit 2 (p<0.0001). There was no difference between the two units in patient age, tumor pathology, deprivation or comorbidity. 16.2% patients managed surgically in Unit 1 had a comorbidity score of 6 and above compared to 11% of surgically managed patients in Unit 2 (p=0.036). Responses to questionnaires suggested that staff at Unit 1 were more confident of the safety of general anesthetic in elderly patients and were more willing to consider local anesthetic procedures. Conclusion: A higher proportion of patients aged >70 years with breast cancer were managed surgically in Unit 1 compared to Unit 2. Reasons for variation in practice seem to be related to attitudes of medical professionals toward surgery in the elderly, rather than patient or pathological factors.

Oncoplastic breast conservation occupies a niche between standard breast conservation and mastectomy - A population-based prospective audit in Scotland.

INTRODUCTION: The role of oncoplastic breast conservation (OBC) surgery is not fully defined in terms of whether it is equivalent to standard breast conservation (SBC), or more an alternative to mastectomy, or whether it occupies its own niche somewhere between the two. Therefore, we have carried out a population-based prospective audit of the current OBC practice in Scotland. METHODS: All patients diagnosed with breast cancer in the whole of Scotland between 01/01/2014 and 31/12/2015 were prospectively recorded within the National Managed Clinical Networks databases. Patients treated with OBC were compared to patients who had SBC, mastectomy and mastectomy with immediate reconstruction (MIR). RESULTS: 8075 patients were included (OBC:217(2.7%); SBC:5241(64.9%); mastectomy:1907(23.6%); MIR:710(8.8%)). OBC patients were younger than SBC or mastectomy, but older than MIR (p < 0.0001). OBC patients were between SBC and mastectomy patients in terms of clinical and pathological tumour size (all p < 0.001), rates of lobular cancers (v.SBC:p = 0.015 and v.mastectomy:p < 0.001), high-grade tumours (v.SBC:p = 0.030 and v.mastectomy:p = 0.008), ER negative (v.SBC: p = 0.042) and HER-2 positive (v.SBC: p = 0.003) tumours, and nodal metastasis (v.mastectomy: p < 0.001). More OBC patients received (neo)adjuvant chemo- and hormonal therapy (p ≤ 0.001), adjuvant radiotherapy (p = 0.005), trastuzumab (p < 0.001) than SBC. More OBC patients presented through screening (v.mastectomy/MIR: p < 0.0001). Time to surgery from diagnosis was longer for OBC than SBC/mastectomy (p < 0.0001), but shorter than MIR (p = 0.007). CONCLUSION: This national audit demonstrates that OBC occupies its own niche between SBC, mastectomy and MIR in the surgical treatment of breast cancer in Scotland. We recommend that OBC should be recorded separately in other national breast cancer registries.

Tolerization with BLP down-regulates HMGB1 a critical mediator of sepsis-related lethality.

Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.

Early enteral nutrition in acute pancreatitis--benefits and limitations.

INTRODUCTION: The application of enteral feeding as part of the treatment of acute pancreatitis goes back more than a decade now. In this review, the authors outline the indications and limitations of enteral feeding in the treatment of acute pancreatitis using up-to-date evidence-based data. RESULTS AND DISCUSSION: Latest meta-analyses suggest that early enteral feeding reduces effectively the incidence of infective complications and shortens hospital stay. In addition, recently published randomized controlled trials indicate that it may reduce mortality as well. CONCLUSION: However, the role of immune-enhancing ingredients, such as glutamine or omega-3 fatty acids, combined with enteral nutrition is uncertain, and the published studies are too few to make any treatment recommendation. Supplementation of enteral feeding with probiotics is a potentially promising alternative, but further well-designed multi-centric trials are necessary to prove their role in the treatment of acute pancreatitis.

[Oncoplastic approach in breast cancer surgery--a new challenge for the future breast surgeon?]. / Onkoplasztikai szemlélet az emlorák sebészetében--új kihívás a jövo emlosebészeinek?

The future challenge of breast surgery, the so-called oncoplastic approach is reviewed in this article. The authors discuss the most frequently applied surgical techniques as well as their indications. Medline and pubmed search was carried out using the following keywords and cross-references: "oncoplastic breast surgery", "breast reconstruction", "breast conserving surgery" and "reduction mammoplasty". Original and review papers published in English language and their references were included. In the literature surprisingly, a large variety of breast oncoplastic surgical procedures has been described. Although reconstructions with local flaps are relatively easy procedures, proper indications for these are critical in order to improve cosmesis after breast conservation. Applications of pedicled flaps are technically more demanding, and only properly trained oncoplastic breast or plastic surgeons are able to provide the possibly best aesthetic outcome after mastectomy or breast conserving surgery. Finally, carrying out free flap reconstructions after mastectomy should be assigned exclusively to plastic surgeons qualified in microsurgical techniques, and not to surgical oncologists. As conclusions oncoplastic approach will be an integral element of the surgical treatment of breast cancer in the future. Breast oncoplastic training is an interdisciplinary task, which combines surgical oncological management of breast cancers with aesthetic/reconstructive breast surgery.

A population-based audit of surgical practice and outcomes of oncoplastic breast conservations in Scotland - An analysis of 589 patients.

INTRODUCTION: Current evidence for oncoplastic breast conservation (OBC) is based on single institutional series. Therefore, we carried out a population-based audit of OBC practice and outcomes in Scotland. METHODS: A predefined database of patients treated with OBC was completed retrospectively in all breast units practicing OBC in Scotland. RESULTS: 589 patients were included from 11 units. Patients were diagnosed between September 2005 and March 2017. High volume units performed a mean of 19.3 OBCs per year vs. low volume units who did 11.1 (p = 0.012). 23 different surgical techniques were used. High volume units offered a wider range of techniques (8-14) than low volume units (3-6) (p = 0.004). OBC was carried out as a joint operation involving a breast and a plastic surgeon in 389 patients. Immediate contralateral symmetrisation rate was significantly higher when OBC was performed as a joint operation (70.7% vs. not joint operations: 29.8%; p < 0.001). The incomplete excision rate was 10.4% and was significantly higher after surgery for invasive lobular carcinoma (18.9%; p = 0.0292), but was significantly lower after neoadjuvant chemotherapy (3%; p = 0.031). 9.2% of patients developed major complications requiring hospital admission. Overall the complication rate was significantly lower after neoadjuvant chemotherapy (p = 0.035). The 5 year local recurrence rate was 2.7%, which was higher after OBC for DCIS (8.3%) than invasive ductal cancer (1.6%; p = 0.026). 5-year disease-free survival was 91.7%, overall survival was 93.8%, and cancer-specific survival was 96.1%. CONCLUSION: This study demonstrated that measured outcomes of OBC in a population-based multi-centre setting can be comparable to the outcomes of large volume single centre series.