Radiotherapy plays a central part in curing cancer. For decades, most research on improving treatment outcomes has focussed on modulating radiation-induced biological effects on cancer cells. Recently, we have better understood that components within the tumour microenvironment have pivotal roles in determining treatment outcomes. In this Review, we describe vascular, stromal and immunological changes induced in the tumour microenvironment by irradiation and discuss how they may promote radioresistance and tumour recurrence. Subsequently, we highlight how this knowledge is guiding the development of new treatment paradigms in which biologically targeted agents will be combined with radiotherapy.

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Purpose Anastomotic leaks in colorectal surgery are associated with significant morbidity and mortality and may result in poor functional and oncological outcomes. Diagnostic difficulties may delay identification and appropriate management of leaks. The aim of this study was to look at the diagnosis, clinical management and outcomes of anastamotic leaks in our department.Method A retrospective audit and case note review of all patients who underwent the formation of a colorectal anastomosis between January 1996 and December 2002 (n = 1421) was performed. An anastomotic leak was defined as sepsis identified to have arisen from an anastomosis that subsequently required surgery, radiological drainage or intravenous antibiotics. Forty-one patients (25 male, 16 female) with a median age of 60 years (range 7-89 years) were identified as having suffered an anastomotic leak. ResultsThe median time to diagnosis of an anastomotic leak following surgery was 7 days (range 3-29). At re-operation, 21 patients (51%) underwent formation of a stoma, and any who required the anastomosis to be formally taken down have been left with a 'permanent' stoma. Currently only four of 12 patients (33%) who required a stoma for an anastomotic leak following anterior resection have undergone stoma reversal. Eleven of 16 patients (69%) who had received a stoma following another colorectal procedure had undergone stoma reversal. The mortality associated with an anastamotic leak in this series was 5% (n = 2).Conclusion Although anastomotic leaks following colorectal surgery are associated with significant morbidity and stoma formation, early and aggressive management should result in a low overall mortality. If an anastomosis is taken down following an anastomotic leak after anterior resection, this will usually result in a 'permanent' stoma.

BIA-ALCL is a rare neoplasm with a good prognosis. Our data support the recommendation that stage I disease be managed with surgery alone. Adjuvant chemotherapy may be required for more invasive disease and our experience has shown the efficacy of Brentuximab as a second line treatment.

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