Non-steroidal anti-inflammatory drugs in the oncological surgical population: beneficial or harmful? A systematic review of the literature.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesic drugs. Recent studies have indicated a potential beneficial effect on long-term survival outcomes after cancer surgery but a negative impact on anastomotic leaks. The objective of this study was to objectively assess the implications of the perioperative NSAIDs use on anastomotic leaks and cancer recurrence. METHODS: We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to mid-January 2017. Randomized controlled trials (RCTs) and observational studies in adults undergoing cancer surgery were included for quality assessment. We excluded animal studies, in vitro experiments and case reports. The selected sudies were graded using the Jadad score or Newcastle-Ottawa scale for RCTs and observational retrospective studies, respectively. RESULTS: The systematic review identified 25 trials that explored the impact of NSAIDs on anastomotic leaks and 16 trials that assessed the association between perioperative NSAIDs and cancer recurrence. Meta-analyses were not performed because of high heterogeneity and low quality of the included studies. CONCLUSIONS: The literature is not conclusive on whether the use of NSAIDs is associated with anastomotic leaks after gastrointestinal cancer surgery. Also, the current evidence is equivocal regarding the effects of short-term NSAIDs on cancer recurrence after major cancer surgery. Three RCTs are being conducted to assess the impact of NSAIDs on cancer recurrence. There are no registered RCTs that are testing the hypothesis of whether the perioperative use of NSAIDs increases the rate of anastomotic leaks.

The Saccharomyces cerevisiae hyperrecombination mutant hpr1Delta is synthetically lethal with two conditional alleles of the acetyl coenzyme A carboxylase gene and causes a defect in nuclear export of polyadenylated RNA.

In a screen for mutants that display synthetic lethal interaction with hpr1Delta, a hyperrecombination mutant of Saccharomyces cerevisiae, we have isolated a novel cold-sensitive allele of the acetyl coenzyme A (CoA) carboxylase gene, acc1(cs), encoding the rate-limiting enzyme of fatty acid synthesis. The synthetic lethal phenotype of the acc1(cs) hpr1Delta double mutant was only partially complemented by exogenous fatty acids. hpr1Delta was also synthetically lethal with a previously isolated, temperature-sensitive allele of ACC1, mtr7 (mRNA transport), indicating that the lethality of the acc1(cs) hpr1Delta double mutant was not allele specific. The basis for the interaction between conditional acc1 alleles and hpr1Delta was investigated in more detail. In the hpr1Delta mutant background, acetyl-CoA carboxylase enzyme activity was reduced about 15-fold and steady-state levels of biotinylated Acc1p and ACC1 mRNA were reduced 2-fold. The reduced Acc1p activity in hpr1Delta cells, however, did not result in an altered lipid or fatty acid composition of the mutant membranes but rendered cells hypersensitive to soraphen A, an inhibitor of Acc1p. Similar to mtr7, hpr1Delta and acc1(cs) mutant cells displayed a defect in nuclear export of polyadenylated RNA. Oversized transcripts were detected in hpr1Delta, and rRNA processing was disturbed, but pre-mRNA splicing appeared wild type. Surprisingly, the transport defect of hpr1Delta and acc1(cs) mutant cells was accompanied by an altered ring-shaped structure of the nucleolus. These observations suggest that the basis for the synthetic lethal interaction between hpr1Delta and acc1 may lie in a functional overlap of the two mutations in nuclear poly(A)+ RNA production and export that results in an altered structure of the nucleolus.

A novel cold-sensitive allele of the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase, affects the morphology of the yeast vacuole through acylation of Vac8p.

The yeast vacuole functions both as a degradative organelle and as a storage depot for small molecules and ions. Vacuoles are dynamic reticular structures that appear to alternately fuse and fragment as a function of growth stage and environment. Vac8p, an armadillo repeat-containing protein, has previously been shown to function both in vacuolar inheritance and in protein targeting from the cytoplasm to the vacuole. Both myristoylation and palmitoylation of Vac8p are required for its efficient localization to the vacuolar membrane (Y.-X. Wang, N. L. Catlett, and L. S. Weisman, J. Cell Biol. 140:1063-1074, 1998). We report that mutants with conditional defects in the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase (ACC1), display unusually multilobed vacuoles, similar to those observed in vac8 mutant cells. This vacuolar phenotype of acc1 mutant cells was shown biochemically to be accompanied by a reduced acylation of Vac8p which was alleviated by fatty acid supplementation. Consistent with the proposed defect of acc1 mutant cells in acylation of Vac8p, vacuolar membrane localization of Vac8p was impaired upon shifting acc1 mutant cells to nonpermissive condition. The function of Vac8p in protein targeting, on the other hand, was not affected under these conditions. These observations link fatty acid synthesis and availability to direct morphological alterations of an organellar membrane.

The role of centromere alignment in meiosis I segregation of homologous chromosomes in Saccharomyces cerevisiae.

During meiosis, homologous chromosomes pair and then segregate from each other at the first meiotic division. Homologous centromeres appear to be aligned when chromosomes are paired. The role of centromere alignment in meiotic chromosome segregation was investigated in Saccharomyces cerevisiae diploids that contained one intact copy of chromosome I and one copy bisected into two functional centromere-containing fragments. The centromere on one fragment was aligned with the centromere on the intact chromosome while the centromere on the other fragment was either aligned or misaligned. Fragments containing aligned centromeres segregated efficiently from the intact chromosome, while fragments containing misaligned centromeres segregated much less efficiently from the intact chromosome. Less efficient segregation was correlated with crossing over in the region between the misaligned centromeres. Models that suggest that these crossovers impede proper segregation by preventing either a segregation-promoting chromosome alignment on the meiotic spindle or some physical interaction between homologous centromeres are proposed.

Mapping of the ACC1/FAS3 gene to the right arm of chromosome XIV of Saccharomyces cerevisiae.

The ACC1/FAS3 gene has been mapped to the right arm of chromosome XIV by both genetic and physical methods. The gene is closely linked to RNA2 and is allelic to the ABP2 gene of chromosome XIV.

Mycobacterium bovis osteomyelitis involving a hip arthroplasty after intravesicular bacille Calmette-Guérin for bladder cancer.

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is one of the most effective agents in the treatment of superficial bladder cancer. BCG osteomyelitis is an infrequent complication of intravesicular BCG therapy; only five cases of BCG vertebral osteomyelitis have been reported in the literature. Similarly, the infection of an indwelling extravascular device by BCG is rare; there is only one previous report documenting infection associated with an automated implantable cardiac defibrillator. We report a case of BCG osteomyelitis involving a hip arthroplasty that occurred after intravesicular administration of BCG for bladder cancer, and we review the risk factors predisposing to such infections and their treatment.

The secretion of aspartyl proteinase, a virulence enzyme, by isolates of Candida albicans from the oral cavity of HIV-infected subjects.

Prevalence, serotype and in vitro secretion of aspartyl proteinase, a virulence enzyme, were studied in Candida isolates from the oral cavity of 337 HIV-infected subjects. Controls were 95 age-sex-matched HIV- (seronegative) subjects, belonging to either HIV-risk categories (47) or to the normal, general population (48). Fungi were isolated from 155 HIV+ subjects. C. albicans was the most prevalent species (85.8% of all isolates). 94.6% of C. albicans isolates were serotype A and all were agglutinated by a monoclonal antibody (AF1) directed against a major mannoprotein immunogen of the candidal cell wall, confirming previous results with C. albicans isolates from non-immunodeficient subjects. With regard to the stage of HIV infection, there were no statistically significant differences in the incidence of oral Candida carriage between asymptomatic (stage II) HIV+ and HIV- subjects, and between stage II and lymphadenopathic (stage III) individuals. Also, the low (3.8%) incidence of oral candidiasis in the subjects of the latter stage was insignificant with respect to stage II subjects. However, the incidence of C. albicans in stage IV (AIDS) subjects (46.8%) was significantly higher than in all other subjects, and in almost all cases, fungal isolation was accompanied by oral thrush and lower CD4+ lymphocyte counts (less than 400 x 10(6)/L). All isolates of C. albicans were proteolytic in vitro, as assessed by scoring the proteinase activity on BSA agar and monitoring the secreted proteinase antigen by a highly sensitive (1 ng) and specific immunoenzymatic assay.(ABSTRACT TRUNCATED AT 250 WORDS)