RESUMEN

BACKGROUND: Right-sided colonic tumours appear to have poorer survival after resection of colorectal liver metastases, although this may be confounded by various factors including advanced stage and emergency presentation. METHODS: Medical records of consecutive patients undergoing resection of colorectal liver metastases at a single centre from 2008 to 2015 were retrospectively reviewed. Cases were categorised by primary tumour location (right colon, left colon, rectum). Each primary location was weighted using propensity scores to balance covariates, including staging and mode of presentation. Cox regression was then applied to derive multivariable hazard ratios (HR) of survival after liver resection. Primary outcomes were 10-year overall survival (OS) and 5-year disease-free survival (DFS) after liver resection based on PTL. RESULTS: 414 patients were included in the analysis. Left colonic tumours were significantly associated with higher rates of bilobar liver metastasis (36.2% vs. 20.1% and 30.1%) and larger maximum size of liver metastases compared with rectal and right-sided tumours, respectively. There was no difference in rates of extra-hepatic metastases, recurrence in the liver after resection or RAS, BRAF or p53 mutational status. After propensity weighting and Cox-regression, right-sided tumours were independently associated with significantly reduced 10 year OS (HR 1.56, 95% CI 1.03-2.36, p = 0.04) but not 5 year DFS (HR 1.36, 95% CI 0.89-2.08, p = 0.15). CONCLUSIONS: Compared with left colonic and rectal tumours, right-sided colonic tumours are independently associated with inferior OS after resection of CRLM. This is despite higher rates of bilobar liver metastases and larger metastases with left-sided tumours.

Asunto(s)

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide. Despite significant advances in screening, surgical management and adjuvant therapies, average 5-year survival seldom exceeds 60% in most developed nations. Metastatic disease represents the primary cause of mortality in patients with CRC, and the liver is the most common location for distant tumour spread. Up to 25% of patients are found to have synchronous liver metastases at the time of diagnosis and a further 30%-40% will develop metachronous disease in the course of follow-up. It has been suggested that primary tumour location [right side versus left side, primary tumour location (PTL)] can influence oncological outcomes in this patient group and that this should be considered in prognostic models and therapeutic decision-making algorithms. This suggestion is not universally accepted and there have been conflicting reports in the literature to date. AIM: To provide a comprehensive summary of the available evidence regarding the impact of PTL on oncological outcomes in patients with colorectal cancer liver metastases (CRCLM). METHODS: MEDLINE, EMBASE and COCHRANE were searched for relevant publications using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Data on oncological outcomes was then extracted from full text articles that met the predefined inclusion criteria. RESULTS: A total of 41 studies were identified that met predefined inclusion criteria for this review. In 21 out of 38 studies that provided data on overall survival, a statistically significant improvement in overall survival was reported in patients with left sided primary tumours. These studies included a total of 13897 patients compared with 4306 patients in the studies that did not show a significant difference. Eight studies noted a similar trend towards improved disease-free or progression-free survival. Several authors observed distinct patterns of relapse after treatment of hepatic metastases according to PTL; for example hepatic recurrence after treatment of CRCLM appears to occur more aggressively with right-sided CRC. CONCLUSION: Taken together, the findings of the present review indicate that PTL may have a role as an independent prognostic factor when determining treatment and disease surveillance strategies in CRC. The mechanisms responsible for this variation remain poorly understood, but are likely to relate to molecular, histological and embryological differences, as well as inherent differences in therapeutic sensitivity.

RESUMEN

BACKGROUND: The increasing age of the population and prolonged life expectancy result in a widening of age limit criteria for a variety of surgical procedures. Oesophagectomy and total gastrectomy are complex operations associated with significant risks of post-operative complications. METHODS: This is a single-centre cohort study of patients operated with curative intent due to oesophageal or gastric cancer. RESULTS: From 2007 to 2017, 548 patients underwent surgery with curative intent, with 122 patients (22.3%) classified as elderly (≥75 years). There was no difference in total complication rates between the groups. The adjusted odds ratio for 90-day mortality after oesophageal resection in the elderly group was 3.65 (95% confidence interval (CI): 1.33-10.03) and after gastrectomy was 1.62 (95% CI: 0.55-4.79). The adjusted hazard ratio for 1-year mortality after oesophagectomy was 2.29 (95% CI: 1.25-4.19), and after gastrectomy the adjusted hazard ratio was 1.48 (95% CI: 0.75-2.92). In the event of a complication with Clavien-Dindo score IIIb or higher, there was a statistically significant increase of 90-day mortality to over 50% among elderly patients both after oesophagectomy and gastrectomy (50.0% versus 19.8%; P = 0.005 and 57.1% versus 17.4%; P = 0.012, respectively). CONCLUSION: There is a statistically significant increase in 90-day mortality after oesophageal and gastric cancer surgery in elderly compared with younger patients. Post-operative complications with high Clavien-Dindo score in patients undergoing oesophagectomy or gastrectomy, with age ≥75 years, are a dramatic risk factor for post-operative death.

Asunto(s)

RESUMEN

BACKGROUND AND STUDY AIMS: Preoperative biliary drainage in patients with periampullary tumors and jaundice has been popularized to improve the quality of life and minimize the risks associated with subsequent radical surgery. The aim of this study was to investigate the possible superiority of self-expandable metal stents (SEMS) over plastic stents, by comparing the amount of bacteria in intraoperatively collected bile and using this variable as a proxy for the efficacy of the respective biliary drainage modalities. PATIENTS AND METHODS: In this randomized clinical trial, 92 patients with obstructive jaundice were enrolled; 45 were allocated to the plastic stent group and 47 to the SEMS group. The primary outcome was the extent and magnitude of biliary bacterial growth at the time of surgical exploration. Secondary outcomes were: macroscopic grading of inflammation of the stented bile ducts, occurrence of adverse events after stenting, stent dysfunction, recognized surgical complexities, and incidence of postoperative complications. RESULTS: The patients were well matched regarding clinical and disease-specific characteristics. At surgery, there were no group differences in the bacterial amount and composition of the bile cultures or the perceived difficulty of surgical dissection. During the preoperative biliary drainage period, more instances of stent dysfunction requiring stent replacement were recorded in the plastic stent group (19 % vs. 0 %; P  = 0.03). Postoperative complications in patients who underwent curative surgery were more common in patients with plastic stents (72 % vs. 52 %), among which clinically significant leakage from the pancreatic anastomoses seemed to predominate (12 % vs. 3.7 %); however, none of these differences in postoperative adverse events reached statistical significance. CONCLUSION: This randomized clinical study was unable to demonstrate any superiority of SEMS in the efficacy of preoperative bile drainage, as assessed by the amount of bacteria in the intraoperatively collected bile. However, some data in favor of SEMS were observed among the clinical secondary outcomes variables (preoperative stent exchange rates) without increases in local inflammatory reactions.

RESUMEN

BACKGROUND: Galectin-3 is an animal lectin that has been implicated in wound healing and is decreased in inflammatory bowel disease (IBD). Matrix metalloproteinase-7 (MMP7), also known as matrilysin-1, a protease shown to cleave extracellular matrix proteins, is highly expressed in IBD tissues, especially at the leading edge of gastrointestinal ulcers. The ability of MMP7 to cleave galectin-3 and influence wound healing has not been reported previously. The aim was to determine whether MMP7 cleaves galectin-3 and modulates wound healing in intestinal epithelial cells. METHODS: The cleaved fragments of galectin-3 were identified by N-terminal sequencing and mass spectrometry. Western blotting was used to detect the cleaved galectin-3 products in a colonic epithelial cell line (T84 cells). Cell migration was studied by the in vitro scratch method. RESULTS: We demonstrate for the first time that MMP7 cleaves galectin-3 in vitro, resulting in three cleaved fragments (20.2 kDa, 18.9 kDa, and 15.5 kDa). Exogenous treatment of T84 cells with recombinant MMP7 resulted in the appearance of secreted galectin-3 cleavage fragments in the supernatant. MMP7 inhibited cell migration and resulted in wound retraction and the addition of MMP7 to galectin-3 abrogated the wound healing and cell migration induced by galectin-3. CONCLUSIONS: We have demonstrated that galectin-3 is a substrate for MMP7. Cleavage of galectin-3 may be one mechanism by which MMP7 inhibits wound healing. This study has significance in understanding delayed wound healing in chronic intestinal diseases like intestinal ulcers and IBD, where MMP7 protein expression is elevated with a decreased galectin-3 protein expression.

Asunto(s)

RESUMEN

Analytical reactions in which short DNA strands are used in combination with DNA ligases have proven useful for measuring, decoding, and locating most classes of macromolecules. Given the need to accumulate large amounts of precise molecular information from biological systems in research and in diagnostics, ligation reactions will continue to offer valuable strategies for advanced analytical reactions. Here, we provide a basis for further development of methods by reviewing the history of analytical ligation reactions, discussing the properties of ligation reactions that render them suitable for engineering novel assays, describing a wide range of successful ligase-based assays, and briefly considering future directions.

Asunto(s)