Primary Tumor Resection in Patients with Incurable Localized or Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: To assess the impact of primary tumor resection (PTR) on survival and morbidity in incurable colorectal cancer. METHODS: Systematic literature review and meta-analysis to compare PTR versus primary tumor intact (PTI). RESULTS: Seventy-seven studies were included, reporting on 159,991 participants (94,745 PTR; 65,246 PTI). PTR improved overall survival (hazard ratio [HR] 0.59, P < 0.0001; mean difference [MD] 7.27 months, P < 0.0001), cancer-specific survival (HR 0.47, MD 10.80), and progression-free survival (HR 0.76, MD 1.67). Overall survival remained significantly improved during subgroup analysis of asymptomatic patients (HR 0.69, MD 3.86), elderly patients (HR 0.46, MD 7.71), patients diagnosed after 2000 (HR 0.62, MD 7.29), patients with colon (HR 0.58, MD 6.31) or rectal (HR 0.54, MD 6.88) primary tumor, patients undergoing resection of primary tumor versus non-resectional surgery (NRS) to treat primary tumor complications (HR 0.56, MD 8.72), and of studies with propensity score analysis (HR 0.65, MD 5.68). Overall survival per treatment strategy was: [PTI/chemotherapy] 14.30 months, [PTI/bevacizumab] 17.27 months, [PTR/chemotherapy] 21.52 months, [PTR/bevacizumab] 27.52 months. PTR resulted in 4.5% perioperative mortality and 22.4% morbidity (major adverse events 10.2%, minor 18.5%, reoperation 2.5%, intraabdominal collection/sepsis 2.2%). PTI had 21.7% morbidity (obstruction 14.4%, anemia 11.0%, hemorrhage 1.5%, perforation 0.6%, adverse events requiring surgery 15.8%). NRS resulted in 10.6% perioperative mortality and 21.7% morbidity (major 7.9%, minor 21.7%, reoperation 0.1%). CONCLUSIONS: PTR in patients with incurable colorectal cancer results in a limited improvement of survival without a significant increase in morbidity. PTR should be considered by the multidisciplinary team on an individual patient basis.

Characteristics of Surgical Site Infection Following Colorectal Surgery in a Tertiary Center: Extended-spectrum ß-Lactamase-producing Bacteria Culprits in Disease.

INTRODUCTION: Surgical site infection (SSI) is a well-known complication of colorectal surgery associated with increased morbidity and hospital stay. Antimicrobial prophylaxis can reduce the risk of SSI by as much as 75%. Extended-spectrum ß-lactamase (ESBL)-producing pathogens make the successful use of such prophylaxis a challenge and are a real threat to patient care following colorectal surgery. OBJECTIVE: The aim of this study is to report the common characteristics of SSIs after colorectal surgery and to highlight the prevalence, risk factors, and clinical relevance of ESBL infections among these patients in a tertiary center. MATERIALS AND METHODS: All patients who underwent bowel resection operation (ie, laparoscopy, laparotomy, or laparoscopic-assisted colectomy) for benign or malignant colorectal disease were identified retrospectively from the prospective database of the colorectal department in the authors' tertiary center from March 2015 to March 2016. RESULTS: There were 123 patients included in this study, of which 21% (n = 26) had a SSI. The microorganisms isolated in the surgical sites included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, Proteus mirabilis, Morganella morganii, and Enterobacter cloacae. Thirty-eight percent of the wound infections grew ESBL-producing pathogens in their wound cultures and 62% grew non-ESBL microbes. CONCLUSIONS: More than one-third of the wound infections were due to ESBL-producing pathogens, which were resistant to the antibiotic prophylaxis given. Inappropriate antibiotic usage can delay postoperative recovery. High-risk patients for ESBL colonization may benefit from preoperative screening based on an established protocol. The cost effectiveness of an ESBL screening program needs to be further studied.

FBXW7-mutated colorectal cancer cells exhibit aberrant expression of phosphorylated-p53 at Serine-15.

FBXW7 mutations occur in a variety of human cancers including colorectal cancer (CRC). Elucidating its mechanism of action has become crucial for cancer therapy; however, it is also complicated by the fact that FBXW7 can influence many pathways due to its role as an E3-ubiquitin ligase in proteasome degradation. FBXW7 and TP53 are tumour suppressors intensively implicated in colorectal carcinogenesis. Deletion mutations in these two genes in animal models mark the progression from adenoma to carcinoma. Although still largely unknown, the last defense mechanism against CRC at the molecular level could be through a synergistic effect of the two genes. The underlying mechanism requires further investigation. In our laboratory, we have used a phospho-kinase profiler array to illustrate a potential molecular link between FBXW7 and p53 in CRC cells. In vitro and in vivo assessments demonstrated aberrant induction of phosphorylated p53 at Serine 15 [phospho-p53(Ser15)] in human FBXW7-deficient CRC cells as compared to their FBXW7-wild-type counterparts. FBXW7 loss in HCT116 cells promoted resistance to oxaliplatin. Immunoblotting data further confirmed that reduction of phospho-p53(Ser15) may contribute to the decreased efficacy of therapy in FBXW7-mutated CRC cells. The findings may suggest the applicability of phospho-p53(Ser15) as an indicative marker of FBXW7-mutations. Phospho-p53(Ser15) regulation by FBXW7 E3-ligase activity could provide important clues for understanding FBXW7 behavior in tumour progression and grounds for its clinical applicability thereafter.