Natural history of stage II/III breast cancer, bone metastasis and the impact of adjuvant zoledronate on distribution of recurrences.

AIM: The prognosis for women with breast cancer has improved markedly over recent decades. However, mortality from breast cancer remains high and, for those developing metastatic disease, curative therapy is not possible. Here, we report the frequency and distribution of disease recurrence(s) in a large population of women with AJCC stage II/III breast cancer and evaluate the impact of adjuvant treatment with the bisphosphonate zoledronate on clinical outcomes. PATIENTS AND METHODS: In the context of the AZURE study (ISRCTN7981382), 3359 patients with histologically confirmed stage II/III breast cancer were randomised to receive standard adjuvant treatment ± zoledronate for five years. Patients were followed up for 10 years and all patients with recurrent disease in that time identified. The site of first recurrence, the first distant recurrence site(s) and bone metastasis at any time were recorded and outcomes in the control and zoledronate treatment groups compared. Survival after recurrence was also evaluated. RESULTS: In the study population as a whole, disease recurrence at a median follow-up of 117 months occurred in 1010/3359 (30%) women with a relatively constant rate of disease relapse of around 3% per year. 727 (72%) first recurrences were at distant sites, 178 locoregional (18%) and 105 (10%) both locoregional and distant relapses occurred synchronously. Bone was the most frequent first recurrence site occurring in 463 (14%) of all patients and was the only distant metastatic site in 265 (7.9%). 69% of the control group who developed recurrent disease had bone metastases identified. Bone metastases were more frequent in those with oestrogen receptor (ER) positive disease and recurrences overall, especially at visceral sites, were more likely with ER negative disease. Zoledronate reduced bone metastases in both ER subgroups but increased the proportion with extra-skeletal metastases, particularly in women who were not definitely postmenopausal at study entry. Adjuvant zoledronate also reduced bone metastases after recurrence at an extra-skeletal site. CONCLUSIONS: This analysis provides contemporary information on the frequency and pattern of recurrences after treatment for stage II/III breast cancer that may be of value in planning future adjuvant trials. It confirms the ongoing importance of bone metastases and describes in detail for the first time the effects of adjuvant zoledronate on the pattern of metastasis.

Anticipatory governance of solar geoengineering: conflicting visions of the future and their links to governance proposals.

This article identifies diverse rationales to call for anticipatory governance of solar geoengineering, in light of a climate crisis. In focusing on governance rationales, we step back from proliferating debates in the literature on 'how, when, whom, and where' to govern, to address the important prior question of why govern solar geoengineering in the first place: to restrict or enable its further consideration? We link these opposing rationales to contrasting underlying visions of a future impacted by climate change. These visions see the future as either more or less threatening, depending upon whether it includes the possible future use of solar geoengineering. Our analysis links these contrasting visions and governance rationales to existing governance proposals in the literature. In doing so, we illustrate why some proposals differ so significantly, while also showing that similar-sounding proposals may emanate from quite distinct rationales and thus advance different ends, depending upon how they are designed in practice.

Leadership and management in UK medical school curricula.

Purpose Although medical leadership and management (MLM) is increasingly being recognised as important to improving healthcare outcomes, little is understood about current training of medical students in MLM skills and behaviours in the UK. The paper aims to discuss these issues. Design/methodology/approach This qualitative study used validated structured interviews with expert faculty members from medical schools across the UK to ascertain MLM framework integration, teaching methods employed, evaluation methods and barriers to improvement. Findings Data were collected from 25 of the 33 UK medical schools (76 per cent response rate), with 23/25 reporting that MLM content is included in their curriculum. More medical schools assessed MLM competencies on admission than at any other time of the curriculum. Only 12 schools had evaluated MLM teaching at the time of data collection. The majority of medical schools reported barriers, including overfilled curricula and reluctance of staff to teach. Whilst 88 per cent of schools planned to increase MLM content over the next two years, there was a lack of consensus on proposed teaching content and methods. Research limitations/implications There is widespread inclusion of MLM in UK medical schools' curricula, despite the existence of barriers. This study identified substantial heterogeneity in MLM teaching and assessment methods which does not meet students' desired modes of delivery. Examples of national undergraduate MLM teaching exist worldwide, and lessons can be taken from these. Originality/value This is the first national evaluation of MLM in undergraduate medical school curricula in the UK, highlighting continuing challenges with executing MLM content despite numerous frameworks and international examples of successful execution.

Aspergillus Osteomyelitis of the Skull.

Osteomyelitis of the craniofacial skeleton is rare, with fungal pathogens least commonly implicated. The authors present 2 patients of osteomyelitis of the skull caused by Aspergillus spp. and discuss the diagnosis, clinicopathological course, and management strategies.Late recurrence seen in this type of infection warrants long-term follow-up and a high index of suspicion for the clinical signs associated with recurrence.Such patients would benefit from their surgical debridement being planned and managed via a specialist craniofacial unit, so as to utilize the most aesthetically sensitive approach and the experience of specialists from several surgical disciplines.

DIEP breast reconstruction following multiple abdominal liposuction procedures.

OBJECTIVE: Previous abdominal wall surgery is viewed as a contraindication to abdominal free tissue transfer. We present two patients who underwent multiple abdominal liposuction procedures, followed by successful free deep inferior epigastric artery perforator flap. We review the literature pertaining to reliability of abdominal free flaps in those with previous abdominal surgery. METHODS: Review of case notes and radiological investigations of two patients, and a PubMed search using the terms "DIEP", "deep inferior epigastric", "TRAM", "transverse rectus abdominis", "perforator" and "laparotomy", "abdominal wall", "liposuction", "liposculpture", "fat graft", "pfannenstiel", with subsequent appraisal of relevant papers by the first and second authors. RESULTS: Patient 1 had 3 episodes of liposuction from the abdomen for fat grafting to a reconstructed breast. Subsequent revision reconstruction of the same breast with DIEP flap was preceded by CT angiography, which demonstrated normal perforator anatomy. The reconstruction healed well with no ischaemic complications. Patient 2 had 5 liposuction procedures from the abdomen to graft fat to a wide local excision defect. Recurrence of cancer led to mastectomy and immediate reconstruction with free DIEP flap. Preoperative MR angiography demonstrated a large perforator right of the umbilicus, with which the intraoperative findings were consistent. The patient had an uneventful recovery and good healing with no fat necrosis or wound dehiscence. CONCLUSIONS: We demonstrate that DIEP flaps can safely be raised without perfusion-related complications following multiple liposuction procedures to the abdomen. The safe interval between procedures is difficult to quantify, but we demonstrate successful free flap after 16 months.

Centromedullary manipulation and stabilization of completely displaced proximal humerus fractures in adolescents.

Completely displaced metaphyseal fractures of the proximal humerus in older children may need reduction and stabilization. The authors describe a technique for closed reduction and intramedullary stabilization of these fractures using a centromedullary pin inserted from the distal humerus through a small distal incision. This technique was used successfully in 2 adolescents. Retrograde elastic nails avoid scars in front of the shoulder, impingement problems from prominent extramedullary metal work, and further surgery of a similar magnitude to remove the metalwork. Based on the authors' experience, they recommend this method for reduction and stabilization of displaced irreducible metaphyseal fractures of the proximal humerus in older children and adolescents.