A systematic review of risk-reducing cancer surgery outcomes for hereditary cancer syndromes.

Cancer predisposition genes are rare mutations that confer a high risk of cancer. For many hereditary cancer syndromes, risk reducing surgery is the single most effective strategy for preventing cancer, but it is irreversible. It has recently attracted significant media attention, following celebrity endorsement, which has led to a perceived lack of ill-effect and guaranteed successful outcome by the general public. Given these high expectations for risk-reducing surgery, a systematic review was performed to evaluate the reported complications for patients undergoing risk-reducing surgery. A systematic review of MEDLINE, EMBASE, CINAHL, AMED and PubMed work was conducted using PRISMA for risk-reducing surgery in adults for cancer predisposition genes in breast, ovary, stomach, thyroid and colorectal. The main outcomes were 30-day morbidity and mortality associated with these procedures. Twenty-five studies (2366 patients) reporting on outcomes following risk-reducing surgery were analysed, 5 related to breast and/or ovary, 3 for stomach, 2 for thyroid and the remaining 15 were colorectal. Risk-reducing surgery was uniformly associated with 30-day morbidity, particularly for breast (variable rates), colorectal (311/1400 patients (22%)) and stomach (35/75 patients (47%)) surgery. The 30-day morbidity for ovarian risk-reducing surgery was relatively low (11/244 patients (5%)). There was also a small mortality risk associated with colorectal (1/1400 patients) and stomach (1/75 patients). This study provides an important and necessary summary of the current data, enabling clinicians to better inform patients of the associated short and long-term outcomes in risk-reducing surgery for cancer predisposition genes.

A systematic review of population-based studies examining outcomes in primary retroperitoneal sarcoma surgery.

Retroperitoneal sarcomas (RPS) are rare mesenchymal tumours. Their rarity challenges our ability to understand expected outcomes. The aim of this systematic review was to examine 30-day morbidity and mortality, overall survival rates and prognostic predictors from population-based studies for patients undergoing curative resection for primary RPS. A systematic literature review of EMBASE, MEDLINE, PUBMED and the Cochrane library was performed using PRISMA for population-based studies reporting from nationally registered databases on primary RPS surgical resections in adults. The main outcomes evaluated were 30-day morbidity and mortality and overall survival rates. The use of additional treatment modalities and predictors of overall survival were also examined. Fourteen studies (n = 12 834 patients) reporting from 3 national databases, (Surveillance, Epidemiology and End Results (SEER), the United States National Cancer Database (US NCDB) and the American College of Surgeons' National Surgical Quality Improvement Program (ACS NSQIP)) were analysed. The reported overall 30-day morbidity and mortality were 23% (n = 191/846) and 3% (n = 278/10 181) respectively. Reported use of perioperative radiotherapy was 28%. No study reported loco-regional recurrence rates. Overall reported 5-year survival ranged from 52% to 62%. Independent predictors of overall survival were age of the patient, resection margin, tumour grade and size, histological subtype and receipt of radiotherapy. This review of population-based data demonstrated relatively low 30-day morbidity rates in patients undergoing curative surgical resections for primary RPS. Thirty-day mortality rates were similar to other abdominal tumour groups. There remains a paucity of data reporting recurrence rates, however 5-year survival rates ranged from 52 to 62%.

Intratumoral T cell infiltration, MHC class I and STAT1 as biomarkers of good prognosis in colorectal cancer.

OBJECTIVE: To evaluate immunosurveillance/editing in colorectal cancer. DESIGN: Transformation stimulates the production of interferon gamma (IFNgamma) which signals via the IFNgamma receptor (IFNGR1) on tumours. This results in stimulation of nuclear STAT1 (nSTAT1), inhibition of tumour growth and upregulation of major histocompatibility complex (MHC) while promoting T cell extravasation. In contrast, downregulation of MHC class I by allele loss results in loss of T cell recognition. A tissue microarray of 462 colorectal tumours with mean follow-up of 42 months (range 1-116) was stained by immunohistochemistry for markers which predict immunosurveillance/editing. RESULTS: The presence of a high level of intratumoral T cells (ITTC) correlated with improved survival compared with a low level of ITTC, with a mean difference in survival of 16.3 months (p=0.006). There was a direct correlation between nSTAT1 expression and ITTC (p<0.001). Patients whose tumours had a high level of ITTC and nSTAT1 survived 20 months longer than those whose tumours had a low level of ITTC and no nSTAT1. A strong correlation was seen between ITTC and MHC class I expression (p=0.0002). A mean survival advantage of 26.1 months was seen in patients whose tumours had strong MHC I expression and high levels of ITTC over those who had weak MHC I and low levels of ITTC (log-rank test=12.023, p=0.034). Both MHC I and ITTC are independent predictors of good survival. CONCLUSIONS: ITTC, nSTAT1 and strong MHC class I expression on tumours identify patients with improved survival and an intact tumour immune system that may benefit from immunotherapy. Conversely, loss of these markers identifies patients whose tumours have escaped immunosurveillance and are unlikely to benefit from immunotherapy.