Impact of a dedicated cancer center surveillance program on guideline adherence for patients with stage II and III colorectal cancer.

UNLABELLED: Surveillance after curative treatment for stage II/III colorectal cancer identifies surgically resectable disease and improves survival. We evaluated adherence to guidelines and outcomes for 408 patients enrolled in an innovative follow-up program at our cancer center. We found that a dedicated intensive surveillance program can impact adherence to guidelines for patients with colorectal cancer. BACKGROUND: Our aims were to evaluate adherence to guidelines on colorectal cancer surveillance and outcomes for patients enrolled in an innovative follow-up program at our cancer center. PATIENTS AND METHODS: A retrospective chart review was conducted at the Cross Cancer Institute in Edmonton, Canada. Patients with stage II/III colorectal cancer who completed treatment and who entered into the program from December 1, 2007, to December 31, 2009, were identified. The minimum standard of care follow-up was defined as (1) carcinoembryonic antigen (CEA) testing every 120 days for 3 years; (2) computed tomography of chest, abdomen, and pelvis at 10 to 14 months and 22 to 26 months after surgery; and (3) colonoscopy within 14 months of surgery. RESULTS: A total of 408 patients met inclusion criteria. Two hundred (49.0%) patients were adherent to all 3 components of surveillance. Among all patients, 57 (14.0%) were nonadherent to computed tomography imaging, 135 (33.1%) were nonadherent to colonoscopy, and 96 (23.5%) were nonadherent to CEA testing. Determinants of nonadherence are described. In total, 192 (47.2%) patients had an abnormal surveillance investigation that led to 307 follow-up events. After a median of 1.6 years, 69 (16.9%) patients had documented tumor recurrence. Sixty-one (88.4%) of these 69 patients had recurrence diagnosed via surveillance, and 31 (44.9%) patients were considered potentially resectable. CONCLUSIONS: Our study demonstrated an improvement in CEA testing since the program began; however, adherence rates for all components are not yet optimal. Alterations to surveillance program management are outlined. Further investigation will determine whether intense follow-up improves patient survival locally.

The actin cytoskeleton controls the efficiency of killer Ig-like receptor accumulation at inhibitory NK cell immune synapses.

Killer cell Ig-like receptors (KIRs) are MHC class I-specific receptors expressed in NK and T lymphocytes. KIR antagonism of activation signals occurs at the immune synapse between the effector and target cells. The processes that regulate clustering of KIR are not well defined. We have expressed KIR-GFP receptor chimeras in two human NK-like lines, YTS and NK92. In this study, we show that the frequency of KIR enrichment at the synapse was decreased for a KIR that lacks a portion of the cytoplasmic tail. Strikingly, blocking actin polymerization with a high dose of cytochalasin D also substantially decreased clustering of KIR as well as KIR-induced clustering of HLA-C-GFP in target cells. However, the effect of inhibiting actin polymerization was only clearly evident at the earlier time points after cell mixing, and eventually clustering of KIR and HLA-C occurred independently of actin remodeling. Although treatment with anti-LFA-1 also decreased conjugate formation, the frequency of KIR clustering remained normal within the population of conjugates that did form, suggesting that the effect of cytochalasin D is not solely through LFA-1. Collectively, these data suggest that the actin cytoskeleton and the cytoplasmic tail of KIR regulate the efficiency by which KIR accumulates at inhibitory NK cell synapses.

KIR enrichment at the effector-target cell interface is more sensitive than signaling to the strength of ligand binding.

Target cell lysis by natural killer cells is inhibited by killer cell immunoglobulin-like receptors (KIR) that bind major histocompatibility complex class I molecules. Many lymphocyte receptors, including KIR, become enriched at the interface with ligand-bearing cells. The contribution of the enrichment to inhibitory signaling has not been determined. We now describe a KIR variant with enhanced green fluorescent protein (EGFP) at the N terminus that can mediate inhibitory signaling, but its enrichment is markedly reduced. This receptor is only slightly weaker at inhibiting lysis than the same KIR tagged with EGFP in the cytoplasmic tail, even though the latter enriched as extensively as wild-type KIR. A slight defect was also detected in the ability of the receptor to reduce adhesion to target cells and for binding of a soluble counterpart to cell surface HLA-C. Our findings suggest that the strength of the interaction required to readily detect receptor enrichment exceeds that required for signaling.

Functional and mutational analysis of conjugative transfer region 1 (Tra1) from the IncHI1 plasmid R27.

The conjugative transfer region 1 (Tra1) of the IncHI1 plasmid R27 was subjected to DNA sequence analysis, mutagenesis, genetic complementation, and an H-pilus-specific phage assay. Analysis of the nucleotide sequence indicated that the Tra1 region contains genes coding for mating pair formation (Mpf) and DNA transfer replication (Dtr) and a coupling protein. Insertional disruptions of 9 of the 14 open reading frames (ORFs) in the Tra1 region resulted in a transfer-deficient phenotype. Conjugative transfer was restored for each transfer mutant by genetic complementation. An intergenic region between traH and trhR was cloned and mobilized by R27, indicating the presence of an origin of transfer (oriT). The five ORFs immediately downstream of the oriT region are involved in H-pilus production, as determined by an H-pilus-specific phage assay. Three of these ORFs encode proteins homologous to Mpf proteins from IncF plasmids. Upstream of the oriT region are four ORFs required for plasmid transfer but not H-pilus production. TraI contains sequence motifs that are characteristic of relaxases from the IncP lineage but share no overall homology to known relaxases. TraJ contains both an Arc repressor motif and a leucine zipper motif. A putative coupling protein, TraG, shares a low level of homology to the TraG family of coupling proteins and contains motifs that are important for DNA transfer. This analysis indicates that the Mpf components of R27 share a common lineage with those of the IncF transfer system, whereas the relaxase of R27 is ancestrally related to that of the IncP transfer system.