The importance of extended postoperative venous thromboembolism prophylaxis in IBD: a National Surgical Quality Improvement Program analysis.

BACKGROUND: The National Comprehensive Cancer Network recommends that patients who have colorectal cancer receive up to 4 weeks of postoperative out-of-hospital venous thromboembolism prophylaxis. Patients with IBD are at high risk for venous thromboembolism, but there are no recommendations for routine postdischarge prophylaxis. OBJECTIVE: The purpose of this study was to compare the postoperative venous thromboembolism rate in IBD patients versus patients who have colorectal cancer to determine if IBD patients warrant postdischarge thromboembolism prophylaxis. DESIGN: This study is a retrospective review of IBD patients and patients who had colorectal cancer who underwent major abdominal and pelvic surgery. PATIENTS: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program (2005-2010). MAIN OUTCOME MEASURES: The primary outcome was 30-day postoperative venous thromboembolism in IBD patients and patients who had colorectal cancer. Risk factors for venous thromboembolism were analyzed with the use of univariate testing and stepwise logistic regression. RESULTS: A total of 45,964 patients were identified with IBD (8888) and colorectal cancer (37,076). The 30-day postoperative rate of venous thromboembolism in IBD patients was significantly higher than in patients who had colorectal cancer (2.7% vs 2.1%, p < 0.001). In a model with 15 significant covariates, the OR for venous thromboembolism was 1.26 (95% CI, 1.021-1.56; p = 0.03) for the IBD patients in comparison with the patients who have colorectal cancer. LIMITATIONS: This study was limited by the retrospective design and the limitations of the data included in the database. CONCLUSIONS: Patients with IBD had a significantly increased risk for postoperative venous thromboembolism in comparison with patients who had colorectal cancer. Therefore, postdischarge venous thromboembolism prophylaxis recommendations for IBD patients should mirror that for patients who have colorectal cancer. This would suggest a change in clinical practice to extend out-of-hospital prophylaxis for 4 weeks in postoperative IBD patients.

A high-throughput chemotaxis assay for pharmacological characterization of chemokine receptors: Utilization of U937 monocytic cells.

INTRODUCTION: Higher-throughput chemotaxis assays have had limited use in chemokine receptor pharmacology studies mainly because of the unavailability of optimal assay formats in addition to an incompatibility of chemotactic cell backgrounds with other pharmacological assays. Here, we developed a high-throughput 96-well chemotaxis assay for leukocytic cell lines and identified the human U937 monocytic line as an excellent cell background for both chemotaxis and the high-throughput calcium mobilization Fluorescent Imaging Plate Reader (FLIPR) assay. METHODS: Optimal chemotactic conditions were developed using the Neuroprobe MBA96 nondisposable and the Millipore MultiScreen-MIC disposable apparatuses with responses to CXC chemokine receptor (CXCR)-4 endogenously expressed on the human H9 T lymphoma line, and confirmed with Jurkat T cell and U937 monocytic cell lines. RESULTS: The U937 cell line was chosen for site-directed mutagenesis studies with CC chemokine receptor (CCR)-7 because this cell line did not endogenously express this receptor, it demonstrated a good chemotaxis index, and it showed an exceptional ability to mobilize calcium measured via FLIPR. Using the Millipore MultiScreen-MIC and FLIPR assays, alanine substitutions at K130 and Q227 caused threefold shifts in potency for the CCR7 ligand, CCL19, whereas that at K137 had no effect. DISCUSSION: Because these CCR7 mutations have previously been shown not to affect ligand binding, our results here show that these residues are specifically involved in receptor activation signals critical to chemotaxis and underscore the importance of using the U937 cell background to confirm results of chemotaxis with those of the FLIPR assay.

Routine endoscopic surveillance for local recurrence of rectal cancer is futile.

BACKGROUND: National Comprehensive Cancer Network guidelines for rectal adenocarcinoma regarding routine surveillance with proctoscopy for local recurrence have been evolving. The purpose of this study was to examine the utility of rectal surveillance. METHODS: This is a single-center, retrospective review of patients (2004 to 2011) who underwent total mesorectal excision for rectal cancer. The primary end point was cancer recurrence, with detection method(s) noted. The number of surveillance procedures was collected. RESULTS: The study included 112 patients. There were no local recurrences identified by rectal surveillance. There were 1 local recurrence and 17 distant recurrences (16%). The local recurrence was identified by carcinoembryonic antigen and symptoms. There were 20 anoscopies, 44 proctoscopies, and 495 flexible sigmoidoscopies performed, with estimated charges of $266,000. CONCLUSIONS: Rectal surveillance at this center was not beneficial. This study supports the recent (2015) change in the National Comprehensive Cancer Network guidelines, which no longer recommend routine rectal surveillance and challenge other society guidelines.

A survey of American College of Surgery fellows evaluating their use of antibiotic prophylaxis in the placement of subcutaneously implanted central venous access ports.

BACKGROUND: Currently, there is no standard of care for prophylactic antibiotics (PABX) at the time of placement of fully implanted central venous access ports (CVAPs). A survey of fellows of the American College of Surgeons was undertaken to determine the current practice pattern of PABX in CVAP placement. METHODS: A survey was mailed to 5,000 fellows of the American College of Surgeons. RESULTS: The response rate was 21.7%, with 73.1% of respondents nonacademic surgeons. PABX were given by 88.2% of the respondents. Of those who did not use PABX, the primary reasons were "not justified" or "not standard of care." General comments regarding reasons for use of PABX included "medicolegal," "required by hospital," and "liability." CONCLUSIONS: In this survey, the overwhelming majority of responding American College of Surgeons fellows indicated that they use preoperative antibiotic prophylaxis for CVAP placement, despite there being no accepted standard of care or definitive evidence regarding PABX use for fully implanted CVAPs.

A comparison of postoperative outcomes utilizing a continuous preperitoneal infusion versus epidural for midline laparotomy.

BACKGROUND: Postoperative pain management with a continuous preperitoneal infusion (CPI) for locoregional anesthesia has been shown to have improved postoperative outcomes. This is the first direct comparison of CPI versus epidural infusion (EPI), both in conjunction with systemic analgesia. METHODS: A retrospective review was performed of midline laparotomy cases, comparing the use of CPI with systemic patient-controlled analgesia to EPI with systemic patient-controlled analgesia for postoperative outcomes. RESULTS: A total of 240 cases from 2007 to 2009 were reviewed. There were 41.3% using CPI and 58.7% with EPI. There were no differences with respect to age, body mass index, or American Society of Anesthesiologists score between CPI and EPI cases. In a multivariate model, total hospital stay was 2 days shorter for the CPI group (P < .001), and the total admission cost was less for CPI (by $6,164; P < .001). CONCLUSIONS: The use of CPI results in decreased length of hospital stay, decreased number of days with a Foley catheter, and lower hospital costs, compared with EPI use. These findings show that the routine use of CPI for pain management after laparotomy is a safe alternative to EPI.

Antibiotic prophylaxis in the placement of totally implanted central venous access ports.

BACKGROUND: Antibiotic prophylaxis during placement of implanted central venous access ports (CVAP) has not been studied. This retrospective review compared the rate of catheter-related infections (CRIs) with and without perioperative antibiotics. METHODS: This was a single-center study that compared patients treated with and without a single dose of antibiotics during CVAP placement. CRIs were defined as a patient treated with antibiotics for port site induration, positive blood cultures, or suspicion of infection that led to port removal within 30 days of placement. RESULTS: CVAP were placed in 459 patients, 103 of whom (22.4%) received antibiotic prophylaxis. Surgical technique and patient demographics were similar to those patients not receiving antibiotics (356). All 9 (2%) CRIs occurred in the non-prophylactic antibiotic group (P = .218), with 5 infections resulting in port removal. CONCLUSIONS: Single-dose perioperative antibiotics may decrease CVAP infection rates and should be studied further in a prospective randomized trial.

Pharmacological characterization of CXC chemokine receptor 3 ligands and a small molecule antagonist.

The CXC chemokine receptor 3 (CXCR3) is predominantly expressed on T helper type 1 (Th1) cells that are involved in inflammatory diseases. The three CXCR3 ligands CXCL9, CXCL10, and CXCL11 are produced at sites of inflammation and elicit migration of pathological Th1 cells. Here, we are the first to characterize the pharmacological potencies and specificity of a CXCR3 antagonist, N-1R-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl-N-pyridin-3-ylmethyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-acetamide (NBI-74330), from the T487 small molecule series. NBI-74330 demonstrated potent inhibition of [(125)I]CXCL10 and [(125)I]CXCL11 specific binding (K(i) of 1.5 and 3.2 nM, respectively) and of functional responses mediated by CXCR3, such as ligand-induced guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding, calcium mobilization, and cellular chemotaxis (IC(50) of 7 to 18 nM). NBI-74330 was selective for CXCR3 because it showed no significant inhibition of chemotactic responses to other chemokines and did not inhibit radioligand binding to a panel of nonchemokine G-protein coupled receptors. There was a striking difference in potencies among the three CXCR3 ligands, with CXCL11 >> CXCL10 > CXCL9. A comparison of the rank order of K(i) values with the rank order of monocyte production levels of these three ligands revealed a precise inverse correlation, suggesting that the weaker receptor affinities of CXCL9 and CXCL10 were physiologically compensated for by an elevated expression, perhaps to maintain effectiveness of each ligand under physiological conditions.