Chemotherapy in patients with resectable liver metastases from colorectal cancer

New chemotherapy drugs and, more recently, targeted therapies have significantly improved the outcome of patients with resected stage III colon cancer (adjuvant chemotherapy) and patients with unresectable metastases (palliative therapy). These advances raise several questions about the place of chemotherapy after and before surgery in patients with resectable liver metastases. To date, only a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen has clearly demonstrated a relapse-free survival benefit. Yet, this approach is restricted to specialized centers, mainly because of technical difficulties and locoregional toxicities. The role of systemic use of oxaliplatin- and irinotecan-based regimens is currently under investigation. Planned trials will assess the role of anti-angiogenic and anti-epidermal growth factor receptor agents. We review the main trials performed in patients with resectable metastases, and discuss their potent impact on clinical practice.     

Electrophysiologic target localization in posteroventral pallidotomy

Summary The current interest in stereotactic posteroventral pallidotomy (PVP) for treating Parkinson's disease and the variability of published results have raised questions regarding techniques for target localization. In our technique the probe is guided to the optimum target at the most ventral pallidum and ansa lenticularis by macroelectrode stimulation of the internal capsule and optic tract from within the globus pallidus, with the thresholds providing a relative measure of the electrode proximity to these structures. We have characterized these localizing macroelectrode stimulation parameters in 57 posteroventral pallidotomies with consistent anatomic lesion placement, excellent outcome, and no complications.Using a 1.8 × 2.0 mm radiofrequency electrode for macroelectrode stimulation (RFG-3C, Radionics Inc.), minimum voltages (thresholds) to activate motor (at a frequency of 2 Hz) or visual (at a frequency of 100 Hz) responses as well as impedance measurements were obtained at the final target (Tf) and at distances proximal to Tf along the electrode trajectory. The visual and motor threshold voltages at Tf via our standard approach angles (50 ° above base plane, 20 ° from the sagittal plane), had a range of 1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that as the probe approaches Tf there is a significant decrease in voltage thresholds for motor (P<.0001) and visual (P<.0001) responses in an individual patient indicating that the probe is converging on these structures. Increases in impedance between Tf, 2–3 mm, and 4–5 mm proximal to Tf were also statistically significant (P<.0001). Microelectrode recording of electrophysiological neuronal activity at various points along the trajectory towards the target showed distinct firing patters providing identification of the globus pallidus externus and internus, ansa lenticularis, and optic tract.Macroelectrode electrophysiological stimulation within the target volume, inducing threshold responses in the internal capsule and optic tract, provides for accurate localization of the most effective PVP target in the ansa lenticularis. In unresponsive patients, the utilization of microelectrode recording for the identification of the pallidal borders and the optic tract improves safety.     

Effects of endurance exercise on the morphology of mouse neuromuscular junctions during ageing

Summary It has been suggested that age changes in the morphology of the neuromuscular junction (NMJ) may reflect altered physical activity levels rather than the unique effects of ageing. Additionally, previous studies have indicated that the structure of the NMJ may be modulated with exercise. To investigate these questions, quantitative morphometry was determined on soleus and extensor digitorum longus (EDL) nerve terminals stained with zinc iodide-osmium from C57BL/6NNia mice under control and endurance exercised conditions at 12, 18 and 24 months of age.As previously observed, the area, perimeter, extent length and branch number of nerve terminals increased with age in both soleus and EDL. The changes were similar between the muscle types, although the changes were more pronounced in the phasic EDL. In 12-month-old animals, 2 months of endurance exercise resulted in significantly larger nerve terminals in both soleus and EDL, suggesting a functional adaptation. Exercised 18- and 24-month-old nerve terminals were smaller than corresponding controls, which indicated that exercise minimized or prevented further age-related nerve terminal elaboration. At all ages the exercised nerve terminals comprised a more homogeneous population than corresponding controls, which indicates that uniform physical activity can modulate NMJ morphometry. The magnitude of the changes suggests that subtle alterations in normal cage activity with advancing age do not have a significant effect on the morphology of nerve terminals. However, the morphology of the NMJ does change significantly in response to physical exercise training.     

Establishment and characterization of a new human Burkitt's lymphoma cell line (WSU-BL)

A new human cell line, WSU-BL, was established from a malignant ascitic fluid occurring in a patient with Burkitt's lymphoma. The established line grows in a single-cell suspension with a doubling time of 19 hours and expresses L3 morphologic features by the French-American-British classification. Immunologic study revealed that WSU-BL cells express IgM-lambda both in the cytoplasm and on the surface and react with monoclonal antibodies to B-cell antigens (B1, B4, BL3, BL4, HLA-DR, and common acute lymphoblastic leukemia antigen [CALLA]). These cells are negative for T-cell and myeloid/monocyte antigens as well as Epstein-Barr virus nuclear antigen (EBNA). These results suggest that WSU-BL corresponds to an intermediate stage of B-cell differentiation. Both fresh tumor and WSU-BL cells had a hyperdiploid karyotype carrying the 8;14 chromosome translocation. Molecular studies showed that WSU-BL has a rearrangement of c-myc proto-oncogene and expresses c-myc RNA. Phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and interferon-gamma (IFN-gamma) were able to induce several phenotypic changes on WSU-BL cells. Two-dimensional gel electrophoresis of total cellular protein showed that either TPA or IFN-gamma induced both the synthesis or loss of several proteins. Analysis of the protein patterns indicated that some proteins were uniquely responsive to either TPA or IFN-gamma and others were common to both. This cell line should be valuable for future studies of cell proliferation, differentiation, and oncogenesis concerning this neoplasm.     

Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome.

BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response.     

Combined endovascular and surgical treatment of infected carotid-carotid bypass graft.

PURPOSE: To present a complex case involving an infected carotid-carotid bypass graft that was successfully treated with a stent-graft and subsequent surgical removal of the infected graft. CASE REPORT: A 75-year-old woman presented with persistent purulent drainage of an infected and exposed carotid-carotid prosthetic bypass graft. Wound cultures revealed methicillin-resistant Staphylococcus aureus. She was treated with appropriate intravenous antibiotic therapy without improvement in wound drainage. Because of her comorbid conditions, a decision was made to pursue endovascular revascularization of her left and right common carotid arteries (CCA), with subsequent surgical removal of the infected prosthetic graft. The patient underwent balloon angioplasty; a 7x18-mm Omnilink stent was deployed in the innominate artery and a 7x18-mm Herculink stent in the ostial left CCA. During the same procedure, the carotid-carotid bypass graft was excluded with deployment of an 8x50-mm Viabahn stent-graft in the right CCA. Several days later, the infected and now thrombosed carotid-carotid bypass graft was surgically removed, and an area of adjacent muscle was used to patch the previously excluded connection of the bypass from the right CCA. A saphenous vein patch was used to repair the defect in the left CCA. Her postoperative course was uneventful. At 1 year, the clinical and duplex examinations revealed satisfactory wound healing and patent left and right CCAs. CONCLUSION: This case indicates that a combined endovascular and surgical approach may be a safe and effective option in the treatment of carotid-carotid bypass graft infection.     

Screening of the antiradical action of vegetable oils

Information on radical scavenging activity (RSA) and antioxidant potential of vegetable oils are not reported, or reporting has been rather limited. Such data is of importance for the evaluation of nutritional and health impact of these oils. The main objective of this short study was to compare the antiradical performance of some common and unusual vegetable oils. The described arrangement for our simple experiment uses the addition of stable radicals 1,1-diphenyl-2-picrylhydrazyl (DPPH) to vegetable oils, which are decomposed by components having antioxidant properties. The order of effectiveness of oils in inhibiting free radicals was as follows: coriander>blackcumin>cottonseed>peanut>sunflower>walnut>hemp seed>linseed>olive>niger seed. This initial survey might serve as a springboard for future research into this area.     

Laparoscopic flip-flap technique versus conventional inguinal hernia repair in children.

BACKGROUND AND OBJECTIVES: Inguinal hernia repair is one of the most frequently performed pediatric surgical operations. Several pediatric laparoscopic inguinal hernia repair techniques have been introduced. But debate is unresolved regarding the feasibility of laparoscopy for treating pediatric inguinal hernias. METHODS: A retrospective cohort study enrolled 33 patients who underwent congenital inguinal hernia repair by either the new laparoscopic flip-flap technique or conventional open repair. Patients were divided into 2 groups according to the type of surgery: Group A included those who underwent the new laparoscopic technique, and Group B included those who underwent conventional open repair. RESULTS: Group A comprised 15 patients (mean age, 39 months), and group B comprised 18 (mean age, 44 months). Mean operative time was 47.5 minutes for Group A versus 27.5 minutes for Group B. Intraoperative complications for Group A included 1 case (7%) of vas deferens injury, and 3 cases (20%) in which the flaps were torn during suturing. In Group B, no intraoperative complications were encountered. In both groups, the mean postoperative hospital stay was 5.5 hours. Postoperative follow-up of 3 months revealed recurrence in 4 patients in Group A (27%), while there were no recurrences in Group B. CONCLUSION: Our preliminary experience shows unsatisfactory outcomes with laparoscopic flip-flap hernia repair in children. In spite of advancement in the application of laparoscopy in pediatric surgery, conventional open hernia repair is still the gold standard for children, in our experience. Future studies with more numbers and longterm follow-up should be conducted.