Down-Regulation of Serum/Glucocorticoid Regulated Kinase 1 in Colorectal Tumours Is Largely Independent of Promoter Hypermethylation

Background: We have previously shown that serum/glucocorticoid regulated kinase 1 (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal tissue. As hyper-methylation of promoter regions is a well-known mechanism of gene silencing in cancer, we tested whether the SGK1 promoter region was methylated in colonic tumour samples. Methodology/Principal Findings: We investigated the methylation profile of the two CpG islands present in the promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We further confirmed our findings in a panel of 10 normal and 10 tumour colonic tissue samples of human origin. We observed CpG methylation only in the smaller and more distal CpG island in the promoter region of SGK1 in both normal and tumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylation of the corresponding CpG. Conclusions/Significance: Our results show that even though partial methylation of the promoter region of SGK1 is present

The impact of synchronous liver resection on the risk of anastomotic leakage following elective colorectal resection. A propensity score match analysis on behalf of the iCral study group

Introduction: how best to manage patients with colorectal cancer and synchronous liver metastasis is still controversial, with specific concerns of increased risk of postoperative complications following combined resection. We aimed at analyzing the influence of combined liver resection on the risk of anastomotic leak (AL) following colorectal resection. Methods: we reviewed the iCral prospectively maintained database to compare the relative risk of AL of patients undergoing colorectal resection for cancer to that of patients receiving simultaneous liver and colorectal resection for cancer with isolated hepatic metastases. The incidence of AL was the primary outcome of the analysis. Perioperative details and postoperative complications were also appraised. Results: out of a total of 996 patients who underwent colorectal resection for cancer, 206 receiving isolated colorectal resection were compared with a matched group of 53 patients undergoing simultaneous liver and colorectal resection. Combined surgery had greater operative time and resulted in longer postoperative hospitalization compared to colorectal resection alone. The proportion of overall morbidity following combined resection was significantly higher than after isolated colorectal resection (56.6% vs. 37.9%, p = 0.021). Overall, the two groups of patients did not differ neither on the rate of major postoperative complications, nor in terms of AL (9.4% vs. 6.3%, p = 0.381). At specific multivariate analysis, the duration of surgery was the only risk factor independently associated with the likelihood of AL. Conclusions: combining hepatic with colorectal resection for the treatment of synchronous liver metastasis from colorectal cancer does not increase significantly the incidence of AL

Coronary artery disease, cerebral non-fatal ischemic stroke in retinal vein occlusion: An 8-yr follow-up

Forty-five consecutive subjects (26M, 19F; mean age 54 ± 14 yrs) with a diagnosed retinal vein occlusion (RVO), were followed-up for 8 yrs. As many as 145 sex-age- and blood pressure-matched individuals (78M, 67F; mean age 54.4 ± 13.5 yrs), that did not experience any vascular event, served as controls. At the time of the RVO, controls and subjects did not differ as to hypercholesterolemia, hypertrigliceridemia, diabetes mellitus, smoking habits, inherited/acquired thrombophilia. At the follow-up completion, they differed as to statin consumption (p = 0.016). During the 8-yrs follow-up, in the control population, 11 out of 145 (7.6%) subjects had experienced a major vascular event (8 coronary artery disease; 3 cerebral non-fatal ischemic stroke). In contrast, of the 45 subjects with a history of RVO, as many as 10 (22.2%) had experienced a major vascular event: 4 coronary artery disease; 4 cerebral non-fatal ischemic stroke; 2 cardiovascular + cerebrovascular event (p = 0.012). A prolonged antiplatelet treatment, prior to the major vascular event, was found in 5/45 cases (11.1%) vs 23/145 (15.9%) controls (p = 0.63). In contrast, a long-lasting administration of anti-hypertensive drugs, to achieve a control of blood pressure, was found in 83.4% of controls and only in 46.7% of cases (p < 0.0001). In conclusion, in a 8-yr follow-up, coronary artery disease and/or non-fatal ischemic stroke were more common in subjects with a history of RVO than in a large setting of subjects comparable for cardiovascular risk factors. These data also argue for RVO as a vascular disease in which aggressive anti-hypertensive therapy to prevent stroke and/or myocardial infarction is needed

Anastomotic leakage after elective colorectal surgery: a prospective multicentre observational study on use of the Dutch leakage score, serum procalcitonin and serum C-reactive protein for diagnosis

The purpose of this study was to test use of the Dutch leakage score (DLS), serum C-reactive protein (CRP) and serum procalcitonin (PCT) in the diagnosis of anastomotic leakage (AL) after elective colorectal resection in a prospective observational study

Colorectal surgery in Italy: a snapshot from the iCral study group

During a recent prospective trial on early diagnosis of anastomotic leakage (AL) after colorectal surgery, we gathered a large database on more than 1500 procedures performed in 19 surgical centers in Italy over a 12-month period. Main purpose of the present paper is to show the epidemiological data about colorectal procedures and anastomotic leakage. Prospective enrollment for all elective colorectal resections with anastomosis (September 2017-September 2018). Primary endpoint was AL; secondary endpoints were morbidity and mortality rates, readmission and reoperation rates, and length of post-operative hospital stay (ClinicalTrials.gov; Identifier: NCT03560180). There were 1546 enrolled cases (56.9% of 2717 total resected cases). The rate of minimally invasive resections was 83.5%. Overall AL rate was 4.92% (76 cases; range per center 0-12.12%). Mean ± SD time to AL diagnosis was 5.95 ± 4.78 days (median 5, range 1-31). Overall morbidity rate was 30.20%, mortality 1.29% (20 cases; range per center 0-3.27), readmission 0.90%, and reoperation 6.92%. Mean ± SD post-operative LOS was 7.89 ± 5.97 days (median 6; range 1-120). AL significantly influenced all other secondary endpoints. This study offers a good snapshot of colorectal resections in Italy. There was a high rate of laparoscopic resections, reflecting the special interest in this kind of surgery by the participating centers. AL, morbidity, mortality, readmission and reoperation rates are compared to those reported in previous population-based studies. Compared to series dealing with open colorectal resections, the time to diagnosis of AL was shortened by several days