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Background: High rates of reoperation following breast‐conserving surgery (BCS) for positive margins are associated with costs to healthcare providers. The aim was to assess the quality of evidence on reported re‐excision costs and compare the direct patient‐level costs between patients undergoing successful BCS versus reoperations after BCS. Methods: The study used data from women who had BCS with or without reoperation at a single institution between April 2015 and March 2016. A systematic review of health economic analysis in BCS was conducted and scored using the Quality of Health Economic Studies (QHES) instrument. Financial data were retrieved using the Patient‐Level Information and Costing Systems (PLICS) for patients. Exchange rates used were: US $1 = £0·75, £1 = €1·14 and US $1 = €0·85. Results: The median QHES score was 47 (i.q.r. 32·5–79). Only two of nine studies scored in the upper QHES quartile (score at least 75). Costs of initial lumpectomy and reoperation were in the range US $1234–11786 and $655–9136 respectively. Over a 12‐month interval, 153 patients had definitive BCS and 59 patients underwent reoperation. The median cost of reoperations after BCS (59 patients) was £4511 (range 1752–18 019), representing an additional £2136 per patient compared with BCS without reoperation (P < 0·001). Conclusion: The systematic review demonstrated variation in methodological approach to cost estimates and a paucity of high‐quality cost estimate studies for reoperations. Extrapolating local PLICS data to a national level suggests that getting BCS right first time could result in substantial savings. Reoperations expensive [ABSTRACT FROM AUTHOR]

Background: Surgical subspecialization has resulted in mastitis and breast abscesses being managed with unnecessary admission to hospital, prolonged inpatient stay, variable antibiotic prescribing, incision and drainage rather than percutaneous aspiration, and loss to specialist follow‐up. The objective was to evaluate a best‐practice algorithm with the aim of improving management of mastitis and breast abscesses across a multisite NHS Trust. The focus was on uniformity of antibiotic prescribing, ultrasound assessment, admission rates, length of hospital stay, intervention by aspiration or incision and drainage, and specialist follow‐up. Methods: Management was initially evaluated in a retrospective cohort (phase I) and subsequently compared with that in two prospective cohorts after introduction of a breast abscess and mastitis pathway. One prospective cohort was analysed immediately after introduction of the pathway (phase II), and the second was used to assess the sustainability of the quality improvements (phase III). The overall impact of the pathway was assessed by comparing data from phase I with combined data from phases II and III; results from phases II and III were compared to judge sustainability. Results: Fifty‐three patients were included in phase I, 61 in phase II and 80 in phase III. The management pathway and referral pro forma improved compliance with antibiotic guidelines from 34 per cent to 58·2 per cent overall (phases II and III) after implementation (P = 0·003). The improvement was maintained between phases II and III (54 and 61 per cent respectively; P = 0·684). Ultrasound assessment increased from 38 to 77·3 per cent overall (P < 0·001), in a sustained manner (75 and 79 per cent in phases II and III respectively; P = 0·894). Reductions in rates of incision and drainage (from 8 to 0·7 per cent overall; P = 0·007) were maintained (0 per cent in phase II versus 1 per cent in phase III; P = 0·381). Specialist follow‐up improved consistently from 43 to 95·7 per cent overall (P < 0·001), 92 per cent in phase II and 99 per cent in phase III (P = 0·120). Rates of hospital admission and median length of stay were not significantly reduced after implementation of the pathway. Conclusion: A standardized approach to mastitis and breast abscess reduced undesirable practice variation, with sustained improvements in process and patient outcomes. Outcomes improve [ABSTRACT FROM AUTHOR]

The advent of sentinel lymph node biopsy has revolutionised surgical management of axillary nodal disease in patients with breast cancer. Patients undergoing neo-adjuvant chemotherapy for large breast primary tumours may experience complete pathological response on a previously positive sentinel node whilst not eliminating the tumour from the other lymph nodes. Results from 2 large prospective cohort studies investigating sentinel lymph node biopsy after neo-adjuvant chemotherapy demonstrate a combined false negative rate of 12.6-14.2% and identification rate of 80-89% with the minimal acceptable false negative rate and identification rate being set at 10% and 90%, respectively. A false negative rate of 14% would have been classified as unacceptable when compared to the figures obtained by the pioneers of sentinel lymph node biopsy which was 5% or less., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: Four-node axillary sampling for breast cancer is an established method of staging the axilla in the United Kingdom. We report the sensitivity of sentinel node (SN) biopsy and compare it with that of four-node sampling., Methods: SN identification was attempted in 234 consecutive patients with unifocal breast cancers up to 25 mm in diameter on pre-operative ultrasound. A combination of isotope-labelled nanocolloid and patent blue dye techniques were used and SN were identified in 221 (94.5%). All patients underwent back-up four-node sampling and those with positive sentinel nodes on frozen section (FS) underwent immediate full axillary clearance., Results: Among those patients who had SN successfully identified, an average of 1.38 SN were identified per patient. Histological examination of the SN alone would have identified all node-positive patients that the four-node sample identified., Conclusion: In patients who have SN identified, four-node axillary sampling does not provide any additional information.

The aim of this study was to assess the efficacy of free-hand percutaneous core biopsy (FHCB) and to determine the role of fine needle aspiration cytology (FNAC) as diagnostic tools for palpable radiologically-suspicious breast lumps. This retrospective study was based on reviewing the clinical records of all patients diagnosed as having breast cancer between January 1999 and December 2000 and patients who had benign lesions, but suspicious breast imaging at triple assessment. Absolute sensitivity of FHCB for diagnosing cancer in palpable lesions was 98.7% compared with 51.3% for FNAC. The difference in the sensitivity of FHCB and FNAC was statistically significant (P<0.005, Wilcoxon matched pair test). Since 94.8% of radiologically-suspicious lumps were shown to be cancers, we advocate FHCB for all patients presenting with radiologically suspicious palpable lumps to our breast clinic. We also conclude that the sensitivity of FHCB for the diagnosis of malignancy in palpable radiologically-suspicious breast lesions is so high that image-guidance is unnecessary.

The proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) are produced within the lung during sepsis, and may induce neutrophil sequestration resulting in neutrophil-mediated lung injury. We hypothesized that, if there is a cause and effect between TNF alpha or IL-1 production and lung neutrophil sequestration during chronic sepsis, TNF alpha mRNA and IL-1 mRNA levels in the lung after cecal ligation and puncture should correlate with the number of sequestered neutrophils as measured by the myeloperoxidase (MPO) content of the lung. To test this hypothesis, Swiss Webster mice were subjected to varying degrees of infectious challenge by single and double-puncture cecal ligation and puncture, or simultaneous antibiotic treatment, and their lungs and blood were harvested at 24 h. Lung TNF alpha and IL-1 beta mRNAs were measured by the reverse-transcription differential polymerase chain reaction, and MPO was measured by colorimetric assay. TNF alpha serum levels showed no correlation with the MPO content of the lung, whereas IL-1 levels were undetectable. Lung TNF alpha mRNA correlated weakly, and IL-1 beta mRNA exhibited a strong correlation with lung MPO (r = .9, p < .01), but administration of anti-TNF alpha- or anti-IL-1-neutralizing antibodies did not prevent a rise in lung MPO. IL-1 beta mRNA in bronchoalveolar macrophages correlated well with whole lung tissue IL-1 beta mRNA levels (r = .91, p < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Macrophage tumour necrosis factor-alpha (TNF-alpha) production is thought to represent an important pathogenic mechanism by which Gram-negative sepsis is mediated. We compared the effects of caecal ligation and puncture (CLP) on endotoxin-sensitive (C3H/HeSnJ) and endotoxin-resistant (C3H/HeJ) mice. Mortality after CLP for C3H/HeSnJ mice compared with C3H/HeJ mice was not significantly different (32% and 55%, respectively). When survivors were injected with lipopolysaccharide intraperitoneally on the 7th day after CLP, the mortality rate was 82% for C3H/HeSnJ mice versus 0% for C3H/HeJ mice (P < 0.0001). Serum endotoxin levels at 24 h after CLP were only slightly elevated. Serum TNF levels and peritoneal macrophage TNF production were undetectable in C3H/HeJ mice and were only slightly elevated in C3H/HeSnJ mice by 24 h after CLP. Peritoneal macrophage mRNA levels for TNF-alpha, IL-1 beta, and I-A alpha displayed a similar pattern in the two strains of mice, with a 2- to 3-fold increase in TNF-alpha and IL-1 beta mRNA levels by 24 h and a sharp decrease in I-A alpha mRNA by 24 h. The cause of mortality in mice that undergo CLP cannot be attributed to overwhelming endotoxemia and/or TNF production.

Background: Our preliminary results showed that pentoxifylline improves survival after cecal ligation and puncture (CLP), even though in this model inhibition of tumor necrosis factor (TNF) activity decreases survival. In this study we tested the hypothesis that pentoxifylline improves survival after CLP, not by inhibiting TNF synthesis but by exerting its effect on leukocyte adhesiveness, neutrophil sequestration, recruitment of cells into the focus of sepsis, and interleukin-1 (IL-1) expression., Methods: Pentoxifylline, 10 or 100 mg/kg/day, was administered to mice after CLP by infusion for 3 days. The following was measured at 24 hours for the group with improved survival: (1) serum TNF by enzyme-linked immunosorbent assay, (2) TNF and IL-1 beta mRNAs in lung and peritoneal macrophages by the differential polymerase chain reaction, (3) lung myeloperoxidase by a colorimetric assay, (4) leukocyte CD11b/CD18 by flow cytometry, and (5) peritoneal exudate cells by manual counting., Results: Only the low-dose pentoxifylline increased survival. Pentoxifylline reduced IL-1 beta mRNA expression in lung and peritoneal macrophages but not TNF mRNA or immunoreactive TNF in the serum. The myeloperoxidase content of lung was reduced by pentoxifylline, but leukocyte CD11b/CD18 expression did not change. Pentoxifylline increased the number of cells in the peritoneum after CLP., Conclusions: Pentoxifylline improves survival after CLP without inhibiting TNF synthesis or expression of CD11b/CD18 on leukocytes. Pentoxifylline treatment reduced lung neutrophil sequestration and IL-1 beta mRNA levels and increased cell recruitment in the peritoneum.

Tumor necrosis factor (TNF) has been implicated as a key mediator of the septic response. Although very high serum levels of TNF are detected in animal models of endotoxemia or gram-negative bacteremia, human patients with sepsis rarely have greatly elevated TNF serum levels. It has therefore been postulated that TNF may act in a paracrine fashion to cause local injury. In order to examine the role of locally produced TNF in sepsis, we compared serum TNF levels and TNF messenger RNA (mRNA) expression in various tissues following cecal ligation and puncture (CLP) or intraperitoneal injection of a sublethal dose of endotoxin. TNF mRNA expression was determined by the reverse transcription differential polymerase chain reaction using beta-actin as an internal standard. Serum levels of TNF were threefold higher after endotoxin administration compared to CLP. TNF mRNA in peritoneal macrophages rose fourfold after both endotoxin injection and CLP, with rapid return to normal in endotoxin-treated animals. There was a significant increase in TNF mRNA in the liver and lung, but not the spleen, during the first 24 hr after CLP. An increase in TNF mRNA was seen in all three tissues after injection of endotoxin. These results support the concept of locally produced TNF as a contributing factor in tissue damage and multiple organ failure during sepsis.

A method for coating liposomes with transferrin is described. Such liposomes have been used for carrying exogenous DNA to rabbit bone marrow (BM) precursor cells, in vivo. A large amount of the DNA contained in the liposomes was delivered specifically into the erythroblasts of the test animals.