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.

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.

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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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Melanoma is an aggressive skin cancer that carries an extremely poor prognosis when local invasion, nodal spread or systemic metastasis has occurred. Recent advances in melanoma biology have revealed that RAS-RAF-MEK-ERK signalling plays a pivotal role in governing disease progression and treatment resistance. Proof-of-concept clinical studies have shown that direct BRAF inhibition yields impressive responses in advanced disease but these are short-lived as treatment resistance rapidly emerges. Therefore, there is a pressing need to develop new targeted strategies for BRAF mutant melanoma.As such, oncolytic viruses represent a promising cancer-specific approach with significant activity in melanoma.This study investigated interactions between genetically-modified vaccinia virus (GLV1h68) and radiotherapy in melanoma cell lines with BRAF mutant, Ras mutant or wildtype genotype. Pre-clinical studies revealed that GLV-1h68 combined with radiotherapy significantly increased cytotoxicity and apoptosis relative to either single agent in V600D BRAF/ V600E BRAF mutant melanoma in vitro and in vivo. The mechanism of enhanced cytotoxicity with GLV-1h68/radiation was independent of viral replication and due to attenuation of JNK, p38 and ERK MAPK phosphorylation specifically in BRAF mutant cells. Further studies showed that JNK pathway inhibition sensitized BRAF mutant cells to GLV-1h68-mediated cell death, mimicking the effect of radiation. GLV1h68 infection activated MAPK signalling in V600D BRAF/ V600E BRAF mutant cell lines and this was associated with TNF-α secretion which, in turn, provided a prosurvival signal.Combination GLV-1h68/radiation (or GLV-1h68/JNK inhibition) caused abrogation of TNF-α secretion. These data provide a strong rationale for combining GLV-1h68 with irradiation in V600D/E BRAF mutant tumors.3

Preoperative core needle biopsy for retroperitoneal sarcomas is safe and does not affect oncological outcome.

Pruritus is a distressing symptom in burns rehabilitation and its treatment represents a challenge for the multidisciplinary burns team. We conducted a comparative study of two different therapeutic approaches in hospitalized burns patients using a combination of pharmacological agents. The observed symptomatic response to gabapentin as monotherapy as well as in combination therapy with two antihistamines was higher than chlorpheniramine alone and in combination with another two antihistamines (t = 3.70, df = 89, P < .001 for monotherapy and chi(2) = 12.2, df = 1, P = .001 for polytherapy). Patients with higher initial itch scores needed a combination of pharmacologic agents for effective symptomatic relief. A linear regression model showed that the likelihood of failure of monotherapy was marginally associated with decreasing patient age (P = .013) and increasing TBSA (P = .021, sum of square = 1.986, df = 2, P = .04). A combined approach using centrally and peripherally acting agents is most effective in the treatment of acute burns pruritus.