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.

Cannabis and schizophrenia.

BACKGROUND: Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. OBJECTIVES: To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia. To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia. To assess the effects of cannabinoids (cannabis-related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (August 2013) and all references of articles selected for further relevant trials. We contacted the first author of included studies for unpublished trials or data. SELECTION CRITERIA: We included all randomized controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed: (1) treatments to reduce cannabis use in people with schizophrenia and (2) the effects of cannabinoids on people with schizophrenia. CONCLUSIONS: Results are limited and inconclusive due to the small number and size of randomized controlled trials available and quality of data reporting within these trials. Currently, there is no evidence to demonstrate that one type of adjunct psychological therapy or one type of drug therapy is more effective than another. There is also insufficient evidence to show that cannabidiol has an antipsychotic effect.

Cannabis and schizophrenia.

BACKGROUND: Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. OBJECTIVES: To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data. SELECTION CRITERIA: We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia. DATA COLLECTION AND ANALYSIS: We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence. MAIN RESULTS: We identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction in cannabis use. Overall, data were poorly reported for many outcomes of interest. Our main outcomes of interest were medium-term data for cannabis use, global state, mental state, global functioning, adverse events, leaving the study early and satisfaction with treatment. 1. Reduction in cannabis use: adjunct psychological therapies (specifically about cannabis and psychosis) versus treatment as usualResults from one small study showed people receiving adjunct psychological therapies specifically about cannabis and psychosis were no more likely to reduce their intake than those receiving treatment as usual (n = 54, 1 RCT, MD -0.10, 95% CI -2.44 to 2.24, moderate quality evidence). Results for other main outcomes at medium term were also equivocal. No difference in mental state measured on the PANSS positive were observed between groups (n = 62, 1 RCT, MD -0.30 95% CI -2.55 to 1.95, moderate quality evidence). Nor for the outcome of general functioning measured using the World Health Organization Quality of Life BREF (n = 49, 1 RCT, MD 0.90 95% CI -1.15 to 2.95, moderate quality evidence). No data were reported for the other main outcomes of interest 2. Reduction in cannabis use: adjunct psychological therapy (specifically about cannabis and psychosis) versus adjunct non-specific psychoeducation One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At three-month follow-up, the use of cannabis in the previous four weeks was similar between treatment groups (n = 47, 1 RCT, RR 1.04 95% CI 0.62 to 1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Pscychiatric Rating Scale-Expanded were similar between groups (n = 47, 1 RCT, MD 3.60 95% CI - 5.61 to 12.81, moderate quality evidence). No data were reported for the other main outcomes of interest: global state, general functioning, adverse events, leaving the study early and satisfaction with treatment. 3. Reduction in cannabis use: antipsychotic versus antipsychotic In a small trial comparing effectiveness of olanzapine versus risperidone for cannabis reduction, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR 1.80 95% CI 0.52 to 6.22, moderate quality evidence). The number of participants leaving the study early at medium term was also similar (n = 28, 1 RCT, RR 0.50 95% CI 0.19 to 1.29, moderate quality evidence). Mental state data were reported, however they were reported within the short term and no difference was observed. No data were reported for global state, general functioning, and satisfaction with treatment.With regards to adverse effects data, no study reported medium-term data. Short-term data were presented but overall, no real differences between treatment groups were observed for adverse effects. 4. Cannabinoid as treatment: cannabidiol versus amisulprideAgain, no data were reported for any of the main outcomes of interest at medium term. There were short-term data reported for mental state using the BPRS and PANSS, no overall differences in mental state were observed between treatment groups. AUTHORS' CONCLUSIONS: Results are limited and inconclusive due to the small number and size of randomised controlled trials available and quality of data reporting within these trials. More research is needed to a) explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment,for those that use cannabis and have schizophrenia b) decide the most effective drug treatment in treating those that use cannabis and have schizophrenia, and c) assess the effectiveness of cannabidiol in treating schizophrenia. Currently evidence is insufficient to show cannabidiol has an antipsychotic effect.