Meta-analysis of transanal total mesorectal excision versus laparoscopic total mesorectal excision in management of rectal cancer.

OBJECTIVES: To evaluate comparative outcomes of transanal total mesorectal excision (TaTME) and laparoscopic TME (LaTME) in patients with rectal cancer. METHODS: We systematically searched multiple databases and bibliographic reference lists. A combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators, and limits were applied. Overall intraoperative complications, overall postoperative complications, anastomotic leak, surgical site infections (SSIs), completeness of mesorectal excision, R0 resection, distal (DRM) and circumferential resection margin (CRM), number of harvested lymph nodes, and procedure time were the evaluated outcome parameters. RESULTS: We identified 18 comparative studies reporting a total of 2048 patients evaluating outcomes of TaTME (n = 1000) and LaTME (n = 1048) in patients with rectal cancer. TaTME was associated with significantly higher number of R0 resection (OR 1.67, P = 0.01) and harvested lymph nodes (MD 1.08, P = 0.01), and lower rate of positive CRM (OR 0.67, P = 0.04) and conversion to an open procedure (OR 0.17, P < 0.00001) compared with LaTME. However, there was no significant difference in intraoperative complications (OR 1.18, P = 0.54), postoperative complications (OR 0.89, P = 0.24), anastomotic leak (OR 0.88, P = 0.42), SSIs (OR 0.64, P = 0.26), completeness of mesorectal excision (OR 1.43, P = 0.19), DRM (MD 1.87, P = 0.16), CRM (MD 0.36, P = 0.58), and procedure time (MD - 10.87, P = 0.18) between TaTME and LaTME. Moreover, for low rectal tumours, TaTME was associated with significantly lower rate of anastomotic leak and higher number of lymph nodes (MD 2.06, P = 0.002). CONCLUSIONS: Although the meta-analysis of best available evidence (level 2) demonstrated that TaTME may be associated with better short-term oncological outcomes and similar clinical outcomes compared with LaTME, the differences between the two groups were small questioning their clinical relevance. No solid conclusions can be made due to lack of high quality randomised studies.

Proteomic profiling of urine for the detection of colon cancer.

BACKGROUND: Colorectal cancer is the second most common cause of cancer related death in the developed world. To date, no blood or stool biomarkers with both high sensitivity and specificity for potentially curable early stage disease have been validated for clinical use. SELDI and MALDI profiling are being used increasingly to search for biomarkers in both blood and urine. Both techniques provide information predominantly on the low molecular weight proteome (<15 kDa). There have been several reports that colorectal cancer is associated with changes in the serum proteome that are detectable by SELDI and we hypothesised that proteomic changes would also be detectable in urine. RESULTS: We collected urine from 67 patients with colorectal cancer and 72 non-cancer control subjects, diluted to a constant protein concentration and generated MALDI and SELDI spectra. The intensities of 19 peaks differed significantly between cancer and non-cancer patients by both t-tests and after adjusting for confounders using multiple linear regressions. Logistic regression classifiers based on peak intensities identified colorectal cancer with up to 78% sensitivity at 87% specificity. We identified and independently quantified 3 of the discriminatory peaks using synthetic stable isotope peptides (an 1885 Da fragment of fibrinogen and hepcidin-20) or ELISA (beta2-microglobulin). CONCLUSION: Changes in the urine proteome may aid in the early detection of colorectal cancer.

Increased hepcidin expression in colorectal carcinogenesis.

AIM: To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anaemia and whether it might have a role in colorectal carcinogenesis. METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation was determined using immunohistochemistry. RESULTS: We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was positively associated with increasing T-stage of colorectal cancer (P<0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repression. This was supported by hepcidin immunoreactivity in colorectal cancer tissue. CONCLUSION: We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.