Long-term outcomes following resection of retroperitoneal recurrence of colorectal cancer.

BACKGROUND: The role of curative-intent surgery for retroperitoneal recurrence (RPR) of colorectal cancer (CRC) remains controversial. We previously showed 0% mortality and acceptable morbidity in patients who underwent resection of RPR.(1) Here we examine long-term overall and disease-free survival (OS, DFS). METHODS: We identified patients who underwent resection for RPR of CRC between 01/1999 and 02/2010 from two prospective CRC databases. RESULTS: The study cohort was composed of 48 patients (26 women) whose median age was 60 (36-80) years. Eleven patients had previously undergone resection of a different focus of disease recurrence, and 8 patients had additional site(s) of distant metastatic disease at the time of RPR resection. Following surgery for RPR, 5 patients were left with gross residual disease, and 6 had microscopically positive margins. Median follow-up was 32 (3-127) months. At last follow-up, 13 patients had died of cancer and 1 of other causes. For the entire cohort of 48 patients, 5-year OS was 70% (median 80 mo). In univariate analysis, OS was reduced in younger patients (p = 0.003) and in those with gross residual disease (p = 0.033). In patients who had grossly complete resection, 5-year DFS was 49% (median 38 mo). Predictors of reduced DFS on multivariable analysis were young age and R1 resection. CONCLUSION: OS and DFS after resection of RPR in well-selected patients were favorable. Patients with RPR of CRC should be considered for curative-intent surgery with careful discussion at multidisciplinary cancer conference.

Anti-leukemia activity of in vitro-expanded human gamma delta T cells in a xenogeneic Ph+ leukemia model.

Gamma delta T cells (GDTc) lyse a variety of hematological and solid tumour cells in vitro and in vivo, and are thus promising candidates for cellular immunotherapy. We have developed a protocol to expand human GDTc in vitro, yielding highly cytotoxic Vgamma9/Vdelta2 CD27/CD45RA double negative effector memory cells. These cells express CD16, CD45RO, CD56, CD95 and NKG2D. Flow cytometric, clonogenic, and chromium release assays confirmed their specific cytotoxicity against Ph(+) cell lines in vitro. We have generated a fluorescent and bioluminescent Ph(+) cell line, EM-2eGFPluc, and established a novel xenogeneic leukemia model. Intravenous injection of EM-2eGFPluc into NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice resulted in significant dose-dependent bone marrow engraftment; lower levels engrafted in blood, lung, liver and spleen. In vitro-expanded human GDTc injected intraperitoneally were found at higher levels in blood and organs compared to those injected intravenously; GDTc survived at least 33 days post-injection. In therapy experiments, we documented decreased bone marrow leukemia burden in mice treated with GDTc. Live GDTc were found in spleen and bone marrow at endpoint, suggesting the potential usefulness of this therapy.

Human Vδ1 γδ T cells expanded from peripheral blood exhibit specific cytotoxicity against B-cell chronic lymphocytic leukemia-derived cells.

BACKGROUND AIMS: There is increasing interest in using γδ T cells (GDTC) for cancer immunotherapy. Most studies have been concerned with the Vδ2 subset in blood, for which several expansion protocols exist. We have developed a protocol to expand Vδ1 and Vδ2 preferentially from human blood. We have characterized these subsets and their specificities for leukemic targets. METHODS: GDTC were isolated from the peripheral blood mononuclear cells (PBMC) of healthy donors via positive magnetic cell sorting; their proliferation in vitro was induced by exposure to the mitogen concanavalin A (Con A). CD107 and cytotoxicity (Cr(51)-release and flow cytometric) assays were performed. GDTC clones and target cells were immunophenotyped via flow cytometry. RESULTS: Longer initial exposure to Con A typically resulted in higher Vδ1 prevalence. Vδ1 were activated by and cytotoxic to B-cell chronic lymphocytic leukemia (B-CLL)-derived MEC1 cells, whereas Vδ2 also responded to MEC1 but more so to the Philadelphia chromosome-positive [Ph+] leukemia cell line EM-enhanced green fluorescent protein (2eGFPluc). Vδ2 clone cytotoxicity against EM-2eGFPluc correlated with Vδ2 T-cell antigen receptor (TCR) and receptor found on Natural Killer cells and many T-cells (NKG2D), whereas Vδ1 clone cytotoxicity versus MEC1 correlated with Vδ1 TCR, CD56 and CD95 expression. Vδ1 also killed Epstein-Barr Virus (EBV)-negative B-CLL-derived TMD2 cells. Immunophenotyping revealed reduced HLA-ABC expression on EM-2eGFPluc, whereas MEC1 and TMD2 exhibited higher Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAILR1). CONCLUSIONS: Our ability to expand peripheral Vδ1 cells and show their cytotoxicity to B-CLL-derived cell lines suggests that this novel approach to the cellular treatment of B-CLL may be feasible.

Wavelength extrapolation to zero extinction: a gamma-ray case. The quantitative effect of the extrapolation function on the kinematical limit value.

To ensure that a true zero-extinction kinematical limit value has been attained by extrapolation of a series of measurements on one reflection, the proper dependence of a function of F versus the function of the physical variable involved in the measurements has to be identified. To demonstrate this point, the multiwavelength gamma-ray data on seven reflections of NiF(2) reported by Palmer & Jauch [Acta Cryst. (1995), A51, 662--667] have been utilized. A new physical component has been introduced into the relationship between diffracted intensity and wavelength--that due to the decrease in angular divergence of diffraction from crystallites with decrease in wavelength. For gamma-rays, this leads to a function of F(2) in respect of wavelength, viz F(2) = F(0)(2) - alphalambda + betalambda(2), which is different from that derived from Zachariasen-type models, viz F(2) = F(0)(2) - klambda(2). Comparison of the limit values according to Palmer & Jauch and according to Mathieson & Stevenson demonstrates the advantage of the functional dependence proposed in this study.

Magnetic resonance imaging-guided neurosurgery in the magnetic fringe fields: the next step in neuronavigation.

OBJECTIVE: We describe the development of an alternative approach to intraoperative magnetic resonance imaging (iMR)-guided neurosurgery and report our initial experience with 22 craniotomies and 16 brain biopsies. The advantages and disadvantages of each approach are examined. METHODS: An iMR suite houses a 0.2-T open configuration system (Siemens Medical Systems, Erlangen, Germany) and is equipped with anesthetic gases and a magnetic resonance imaging (MRI)-compatible anesthesia machine and monitor. Standard operating instruments and equipment were tested for safety and compatibility in the magnetic fringe fields surrounding the open MRI system. We then performed brain biopsies and craniotomies in the iMR suite. RESULTS: Standard operating equipment functioned properly in the 0.5- to 10-mT zone and was not affected by the magnet's attractive force. Twenty-two craniotomies and 16 brain biopsies were performed in the interventional suite, using serial intraoperative MRI guidance, without injury to patients or operating room staff. CONCLUSION: Full neurosurgical procedures may be performed in the weak fringe fields surrounding an MRI system, using standard operating room equipment. This approach to iMR-guided neurosurgery offers a significant cost advantage over retrofitting an entire operative suite with "MRI-compatible" surgical equipment. The surgeon's familiarity with standard equipment and the reliability of the equipment are additional advantages. Neurosurgery in the fringe fields allows the neurosurgeon to utilize serial MRI with a minimum of inconvenience, disruption, and change to the standard neurosurgical procedure. Serial intraoperative imaging to visualize the changes in the brain that are associated with neurosurgical intervention seems to enhance the ability to safely and effectively accomplish neurosurgical goals.

Factors affecting the use of research in practice.

The nursing literature has often discussed the difficulty of encouraging more nurses to adopt evidence-based practices. One study identified seven factors indicating that nurses used research in their practice, including a high level of autonomous professional practice and holding a high level qualifications.