AL has a negative prognostic impact on local recurrence after restorative resection of rectal cancer. A significant association between colorectal AL and reduced long-term cancer specific survival was also noted. No association between AL and distant recurrence was found.

Collagen structure has been shown to influence tumor cell invasion, metastasis and clinical outcome in breast cancer. However, it remains unclear how it affects other solid cancers. Here we utilized multi-photon laser scanning microscopy and Second Harmonic Generation to identify alterations to collagen fiber structure within the tumor stroma of head & neck, esophageal and colorectal cancers. Image segmentation algorithms were then applied to quantitatively characterize these morphological changes, showing that elongated collagen fibers significantly correlated with poor clinical outcome (Log Rank p < 0.05). We used TGF-β treatment to model fibroblast conversion to smooth muscle actin SMA-positive cancer associated fibroblasts (CAFs) and found that these cells induce the formation of elongated collagen fibers in vivo. However, proteomic/transcriptomic analysis of SMA-positive CAFs cultured ex-vivo showed significant heterogeneity in the expression of genes with collagen fibril organizing gene ontology. Notably, stratifying patients according to stromal SMA-positivity and collagen fiber elongation was found to provide a highly significant correlation with poor survival in all 3 cancer types (Log Rank p ≤ 0.003). In summary, we show that increased collagen fiber length correlates with poor patient survival in multiple tumor types and that only a sub-set of SMA-positive CAFs can mediate the formation of this collagen structure.

LLR has short-term advantages and seemingly equivalent long-term outcomes and can be considered a feasible alternative to open surgery in experienced hands.

Background The precise contribution of IORT to the management of locally advanced and recurrent colorectal cancer (CRC) remains uncertain. We performed a systematic review and meta-analysis to assess the value of IORT in this setting. Methods Studies published between 1965 and 2011 that reported outcomes after IORT for advanced or recurrent CRC were identified by an electronic literature search. Studies were assessed for methodological quality and design, and evaluated for technique of IORT delivery, oncological outcomes, and complications following IORT. Outcomes were analysed with fixed-effect and random-effect model meta-analyses and heterogeneity and publication bias examined. Results 29 studies comprising 14 prospective and 15 retrospective studies met the inclusion criteria and were assessed, yielding a total of 3003 patients. The indication for IORT was locally advanced disease in 1792 patients and locally recurrent disease in 1211 patients. Despite heterogeneity in methodology and reporting practice, IORT is principally applied for the treatment of close or positive margins. When comparative studies were evaluated, a significant effect favouring improved local control (OR 0.22; 95% CI=0.05-0.86; p=0.03), disease free survival (HR 0.51; 95% CI=0.31-0.85; p=0.009), and overall survival (HR 0.33; 95% CI=0.2-0.54; p=0.001) was noted with no increase in total (OR 1.13; 95% CI=0.77-1.65; p=0.57), urologic (OR 1.35; 95% CI=0.84-2.82; p=0.47), or anastomotic complications (OR 0.94; 95% CI=0.42-2.1; p=0.98). Increased wound complications were noted after IORT (OR 1.86; 95% CI=1.03-3.38; p=0.049). Conclusions Despite methodological weaknesses in the studies evaluated, our results suggest that IORT may improve oncological outcomes in advanced and recurrent CRC.

Background:Colorectal cancer peritoneal metastasis (CPM) confers an exceptionally poor prognosis, and traditional treatment involving systemic chemotherapy (SC) is largely ineffective. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly advocated for selected patients with CPM; however, opinions are divided because of the perceived lack of evidence, high morbidity, mortality, and associated costs for this approach. As there is no clear consensus, the aim of this study was to compare outcomes following CRS+HIPEC vs SC alone for CPM using meta-analytical methodology, focusing on survival outcomes. Secondary outcomes assessed included morbidity, mortality, quality of life (QOL), and health economics (HE).Methods:An electronic literature search was conducted to identify studies comparing survival following CRS+HIPEC vs SC for CPM. The odds ratio (OR) was calculated using the Mantel–Haenszel method with corresponding 95% confidence intervals (CI) and P-values. Heterogeneity was examined using the Q-statistic and quantified with I2. The fixed-effect model (FEM) was used in the absence of significant heterogeneity. For included studies, 2- and 5-year survival was compared for CRS+HIPEC vs SC alone.Results:Four studies (three case–control, one RCT) provided comparative survival data for patients undergoing CRS+HIPEC (n=187) vs SC (n=155) for CPM. Pooled analysis demonstrated superior 2-year (OR 2.78; 95% CI 1.72–4.51; P=0.001) and 5-year (OR 4.07; 95% CI 2.17–7.64; P=0.001) survival with CRS+HIPEC compared with SC. Mortality ranged from 0 to 8%. No data were available for the assessment of QOL or HE.Conclusions:Although limited by between-study heterogeneity, the data support the assertion that in carefully selected patients, multimodal treatment of CPM with CRS+HIPEC has a highly positive prognostic impact on medium- and long-term survival compared with SC alone. There is a paucity of comparative data available on morbidity, QOL, and HE.