Routine preoperative abdominal computed tomography in colon cancer: a utility study

Background There is no proven utility for preoperative scanning of intraperitoneal colonic cancer with computed tomography (CT). A prospective study was conducted where CT was preoperatively incorporated into the management algorithm to ascertain its role in patient treatment. Methods Thoraco-abdominal CT was performed in both the elective and emergency settings in an unselected group of 73 patients referred to a coloproctology unit established over the last 30 months at the Queen Elizabeth Hospital, Barbados. CT and operative findings were compared to determine the influence that the preoperative CT had on surgical decision making. Results Unexpected additional pathology was found in 6.8% of patients. Sensitivity for the detection of visceral metastatic disease was 84.6%. Preoperative CT was deemed to be of clinical value in 24.7% of cases and to definitively alter surgical management in 13.7% of patients. These alterations in management included several types of multivisceral resections, the need for ureteric stenting or reimplantation, the utilization of stomas alone and the avoidance of resection in known metastatic disease. Conclusions Preoperative CT of intraperitoneal colonic cancer adds important technical information to the conduct of the surgery and alters therapy in a selected patient group.     

Free-paced high-performance brain-computer interfaces

Neural prostheses aim to improve the quality of life of severely disabled patients by translating neural activity into control signals for guiding prosthetic devices or computer cursors. We recently demonstrated that plan activity from premotor cortex, which specifies the endpoint of the upcoming arm movement, can be used to swiftly and accurately guide computer cursors to the desired target locations. However, these systems currently require additional, non-neural information to specify when plan activity is present. We report here the design and performance of state estimator algorithms for automatically detecting the presence of plan activity using neural activity alone. Prosthesis performance was nearly as good when state estimation was used as when perfect plan timing information was provided separately ( approximately 5 percentage points lower, when using 200 ms of plan activity). These results strongly suggest that a completely neurally-driven high-performance brain-computer interface is possible.     

Reconstruction of goat femur segmental defects using triphasic ceramic-coated hydroxyapatite in combination with autologous cells and platelet-rich plasma

Segmental bone defects resulting from trauma or pathology represent a common and significant clinical problem. In this study, a triphasic ceramic (calcium silicate, hydroxyapatite and tricalcium phosphate)-coated hydroxyapatite (HASi) having the benefits of both HA (osteointegration, osteoconduction) and silica (degradation) was used as a bone substitute for the repair of segmental defect (2 cm) created in a goat femur model. Three experimental goat femur implant groups – (a) bare HASi, (b) osteogenic-induced goat bone marrow-derived mesenchymal stem cells cultured HASi (HASi + C) and (c) osteogenic-induced goat bone marrow-derived mesenchymal stem cells cultured HASi + platelet-rich plasma (HASi + CP) – were designed and efficacy performance in the healing of the defect was evaluated. In all the groups, the material united with host bone without any inflammation and an osseous callus formed around the implant. This reflects the osteoconductivity of HASi where the cells have migrated from the cut ends of host bone. The most observable difference between the groups appeared in the mid region of the defect. In bare HASi groups, numerous osteoblast-like cells could be seen together with a portion of material. However, in HASi + C and HASi + CP, about 60–70% of that area was occupied by woven bone, in line with material degradation. The interconnected porous nature (50–500 μm), together with the chemical composition of the HASi, facilitated the degradation of HASi, thereby opening up void spaces for cellular ingrowth and bone regeneration. The combination of HASi with cells and PRP was an added advantage that could promote the expression of many osteoinductive proteins, leading to faster bone regeneration and material degradation. Based on these results, we conclude that bare HASi can aid in bone regeneration but, with the combination of cells and PRP, the sequence of healing events are much faster in large segmental bone defects in weight-bearing areas in goats.     

Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 3. Therapeutic efficacy and safety studies in ovarian cancer xenograft model

Purpose The objective of this study was to evaluate the anti-tumor efficacy and lack of systemic toxicity of paclitaxel when administered in pH-sensitive poly(ethylene oxide) (PEO)-modified poly(beta-amino ester) (PbAE) nanoparticles in mice bearing human ovarian adenocarcinoma (SKOV-3) xenograft. Methods Paclitaxel-encapsulated PEO-modified PbAE (PEO–PbAE) nanoparticles were prepared by the solvent displacement method. PEO-modified poly(epsilon-caprolactone) (PCL) (PEO–PCL) nanoparticles were used as a non pH-responsive control formulation. Efficacy studies were conducted in SKOV-3 tumor-bearing athymic (Nu/Nu) mice at an equivalent paclitaxel dose of 20 mg/kg with the control and nanoparticle formulations. Safety of the drug when administered in the control and nanoparticle formulation was determined from blood cell counts and changes in body weight of the animals. Results The formulated paclitaxel-containing PEO–PbAE and PEO–PCL nanoparticles had a particle size in the range of 100–200 nm and a surface charge of + 39.0 and − 30.8 mV, respectively. After intravenous administration of paclitaxel in these formulations, the tumor growth was inhibited significantly. Both of the formulated nanoparticles tested have shown improved therapeutic efficacy as compared to the paclitaxel aqueous solution. Additionally, significantly lower toxicity profile of paclitaxel was observed with PEO-modified nanoparticles as compared to the aqueous solution formulation Conclusion PEO-modified PbAE nanoparticles are a unique pH-sensitive drug delivery system that elicits enhanced efficacy and safety profile in solid tumor therapy.     

Elevated soluble CD30 characterizes patients with hepatitis C virus-induced liver allograft cirrhosis

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) significantly accelerates progression to allograft cirrhosis. Current biochemical parameters to monitor progression of chronic HCV after OLT have yielded low specificity and sensitivity. Here we investigated the HCV-specific immunity and serum levels of soluble CD30 (sCD30), a novel marker of Th2 immunity, in patients with and without allograft cirrhosis. Patients with hepatic inflammation but no cirrhosis (HIN, n=20) revealed elevated serum interferon (IFN)-gamma and high frequency of IFN-gamma producing CD4 T(h1) cells compared to those with hepatic cirrhosis (HFC, n=20) that had high interleukin (IL)-5 and IL-5 producing CD4 T(h2) cells. Patients with HFC, but not HIN, were found to have significantly higher levels of sCD30. Therefore, we conclude that lack of optimal Th1-type CD4 T cells is associated with HCV-induced allograft cirrhosis. Further, sCD30 may represent a novel marker for surveillance of hepatic cirrhosis in transplant recipients with chronic HCV infection.     

Efficacy of percutaneous electrical nerve stimulation and therapeutic exercise for older adults with chronic low back pain: a randomized controlled trial

Chronic low back pain (CLBP) in older adults may be disabling and therapeutically challenging, largely because of the inefficacy and/or morbidity associated with traditional pain treatment. We conducted a randomized controlled trial in 200 men and women > or = age 65 with CLBP to evaluate the efficacy of percutaneous electrical nerve stimulation (PENS) with and without general conditioning and aerobic exercise (GCAE), for reducing pain and improving physical function. Participants were randomized to receive (1) PENS, (2) control-PENS (brief electrical stimulation to control for treatment expectancy), (3) PENS+GCAE, or (4) control-PENS+GCAE, twice a week for 6 weeks. All four groups experienced significantly reduced pain (range -2.3 to -4.1 on the McGill Pain Questionnaire short form), improved self-reported disability (range -2.1 to -3.0 on Roland scale) and improved gait velocity (0.04-0.07 m/s), sustained at 6 months. The GCAE groups experienced significantly fewer fear avoidance beliefs immediately post-intervention and at 6 months than non-GCAE groups. There were no significant side effects. Since brief electrical stimulation (i.e., control-PENS) facilitated comparably reduced pain and improved function at 6 months as compared with PENS, the exact dose of electrical stimulation required for analgesia cannot be determined. GCAE was more effective than PENS alone in reducing fear avoidance beliefs, but not in reducing pain or in improving physical function.     

Postoperative wound complications and systemic recurrence in breast cancer

Many factors involved in wound healing can stimulate tumour growth in the experimental setting. This study examined the relationship between wound complications and the development of systemic recurrence after treatment of primary breast cancer. One thousand and sixty-five patients diagnosed with operable primary invasive breast cancer between 1994 and 2001 were assessed for development of systemic recurrence according to whether or not a wound complication occurred after surgery, with a median follow-up of 54 months (range 15-119). There were 93 wound complications (9%). There was a statistically significant greater risk of developing systemic recurrence in patients with wound problems than those without (hazard ratio (HR) 2.87; 95% CI: 1.97, 4.18; P<0.0001). This remained in a multivariate analysis after adjustment for case mix variables, including Nottingham Prognostic Index (NPI) and oestrogen-progesterone receptor status (HR: 2.52; 95% CI: 1.69, 3.77; P<0.0001). In the good prognostic NPI group, 4 out of 27 patients (15%) with wound problems vs 11 out of 334 (3%) without wound problems developed systemic recurrence. The corresponding figures were 10 out of 35 (29%) vs 48 out of 412 (12 %) in the moderate prognostic group and 18 out of 29 (62%) vs 75 out of 199 (38%) in the poor prognostic group. In 29 patients NPI could not be calculated. Smokers at the time of diagnosis were more likely to develop metastatic disease than the non-smokers (HR: 1.50; 95% CI: 1.04, 2.15; P=0.03) after adjustment for other factors. The results suggest that patients with wound complications at primary surgery have increased rates of systemic recurrence of breast cancer.