Enteral Stents for Malignancy: A Report of 46 Consecutive Cases over 10 years,with Critical Review of Complications

Background  Current management of malignant gastric outlet obstruction (GOO) includes surgical diversion or enteral stent placement for unresectable cancer. We analyzed the long-term results, predictive factors of outcomes, and complications associated with enteral stents with focus on their management. Methods  Between 1997 and 2007, 46 patients with malignant GOO underwent placement of self-expandable metal stents (SEMS) for palliation. Patients were captured prospectively after 2001 and followed until complication or death. Patency, management of complications, and long-term survival were analyzed. Results  Forty-six patients had a mean survival of 152 ± 235 days and a mean SEMS patency rate of 111 ± 220 days. SEMS patency rates of 98%, 74%, and 57% at 1, 3, and 6 months were seen. Thirteen patients presented with obstruction and included two SEMS migration, two early occlusion, one fracture, four malignant ingrowth, and four with delayed clinical failure. Interventions included seven endoscopic revisions with three SEMS replacements. Six had percutaneous endoscopic gastrostomy with jejunal arm placed. Two patients eventually underwent surgical bypass. Two patients required surgery for complications including delayed duodenal perforation and aortoenteric fistula. Conclusions  SEMS effectively palliate gastric outlet obstructions that result from upper gastrointestinal malignancies. Their benefits offset potential complications or malfunctions, when a pluridisciplinary approach is adopted. Presented at Digestive Disease Week/SSAT, May 2008, San Diego, California.     

Presence of simian virus 40 in diffuse large B-cell lymphomas in Tunisia correlates with germinal center B-cell immunophenotype, t(14;18) translocation, and P53 accumulation.

Previously we have reported the presence of simian virus 40 DNA in 56% of diffuse large B-cell lymphomas in Tunisia. Here, we investigated the relationship between the status of simian virus 40 and t(14;18) translocation, germinal center status, and P53 and BCL2 expression to assess the clinical and biological relevance of simian virus 40 presence in diffuse large B-cell lymphomas. Therefore, we evaluated by immunohistochemistry the expression patterns of CD10, BCL6, MUM1, BCL2, and P53 in 86 diffuse large B-cell lymphomas (48 simian virus 40-positive and 38 simian virus 40-negative cases). The t(14;18) translocation was investigated by polymerase chain reaction. Immunostaining patterns for CD10, BCL6, and MUM1 were used to subclassify diffuse large B-cell lymphoma cases as germinal center or non-germinal center phenotypes. Germinal center phenotype, t(14;18), P53, and BCL2 expression were found in 71, 30, 55, and 65% of cases, respectively. Interestingly, germinal center phenotype, t(14;18), and P53 accumulation were found to be more frequent in simian virus 40-positive cases than in simian virus 40-negative ones (81, 44, 69 vs 58, 13, 37%; P=0.018, 0.002, and 0.003, respectively). However, there were no correlations between the presence of simian virus 40 and the expression of CD10, BCL6, MUM1 and BCL2, patient's age and gender, clinical stage, or the International Prognosis Index. Multivariate logistic regression analyses revealed that the germinal center phenotype, P53 accumulation, and t(14;18) were independent factors for simian virus 40 association (P=0.029, 0.006, and 0.014, respectively). There were no significant differences in overall survival regarding P53, BCL2, or t(14;18) status. However, patients with germinal center phenotype or low International Prognosis Index scores displayed a significantly better survival than those with non-germinal center phenotype or high International Prognosis Index scores (P=0.003 and 0.0001, respectively). These two prognosis factors remain independent in multivariate analyses (P=0.001 and <0.0001, respectively). Interestingly, among patients with germinal center phenotype, simian virus 40-positive subgroup displayed a significantly shorter survival than simian virus 40-negative subgroup (P=0.034). In summary, these findings support a role of simian virus 40 in the pathogenesis of diffuse large B-cell lymphomas. On other hand, they suggest that a significant proportion of diffuse large B-cell lymphoma cases with germinal center phenotype may result from early transformation by simian virus 40, mainly those harboring the t(14;18).Modern Pathology (2008) 21, 282-296; doi:10.1038/modpathol.3800993; published online 28 December 2007.     

The subjective quality of life in deficit and nondeficit schizophrenic patients.

We assessed the subjective quality of life (QOL) of 30 deficit schizophrenic patients compared to 112 nondeficit schizophrenic patients. The deficit patients did not differ in term of QOL, total score of positive symptoms, general psychopathology from the nondeficit patients. This result suggested an absence of impact of primary negative symptoms on the subjective QOL in schizophrenic patients.     

CD14 receptor occupancy in severe sepsis: results of a phase I clinical trial with a recombinant chimeric CD14 monoclonal antibody (IC14)

OBJECTIVE: Binding of bacterial cell wall components to CD14 and co-receptors on myeloid cells results in cellular activation and production of proinflammatory mediators. A recombinant anti-CD14 monoclonal antibody (IC14) has been shown to decrease lipopolysaccharide-induced responses in animal and human models of endotoxemia. This study was performed to evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical pharmacology of IC14 in patients with severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled, dose-ranging, multiple-center trial. SETTING: Six medical and surgical intensive care units located in Germany and The Netherlands. PATIENTS: Forty patients with severe sepsis. INTERVENTIONS: IC14 was administered intravenously to eight patients/cohort as single (1 mg/kg or 4 mg/kg) or multiple doses (4 mg/kg daily for 4 days, or 4 mg/kg on day 1 followed by 2 mg/kg daily for 3 days). A placebo group (two patients/cohort) was also included. MEASUREMENTS AND MAIN RESULTS: The overall incidence and types of adverse events were similar among treatment groups. One patient in the group receiving multiple-dose IC14 4 mg/kg daily for 4 days experienced an anaphylactic reaction after receiving the first dose of study drug. IC14 did not induce antibody formation or increase the incidence of secondary bacterial infection. A mean IC14 serum concentration of approximately 1 microg/mL was required to achieve 50% of maximum membrane-bound CD14 receptor occupancy on peripheral blood monocytes. The pattern of proinflammatory and anti-inflammatory cytokines, chemokine, soluble receptor, soluble E-selectin, and acute phase proteins in response to treatment was highly variable by patient and IC14 treatment group. CONCLUSIONS: Single and multiple doses of IC14 were generally well tolerated and did not induce antibody formation or increase the incidence of secondary bacterial infection. The results suggest that CD14 blockade with IC14 warrants further clinical investigation to determine its ability to attenuate the proinflammatory response due to infection.     

An overview of targeted treatments in cancer

BACKGROUND: The concept behind cancer treatment has evolved over the past decade from systemic, nonspecific, high-dose chemotherapy to targeted therapy and the introduction of cancer vaccines. Advanced technology and a better understanding of the cellular mechanisms that control cancer biology have helped in the development of such targeted treatment. OBJECTIVE: The aim of this article was to review some of the new and commonly used targeted treatments in cancer, emphasizing their mechanisms of action, safety profiles, and clinical applications. METHODS: The terms cancer, chemotherapy, monoclonal antibodies, targeted treatment, tyrosine kinase, epidermal growth factors, epidermal growth factor receptor, and cancer vaccines were used to search MEDLINE for English-language studies in humans, published between 1966 and March 2003. Identified publications addressing the objectives of this article were selected for review. RESULTS: All-trans-retinoic acid, imatinib, gemtuzumab ozogamicin, rituximab, alemtuzumab, trastuzumab, cetuximab, and gefitinib are recently developed cancer therapies that target specific types of cells and receptors. They have been used in a variety of hematologic and solid tumors, and their tolerability makes them attractive for use even in elderly and extensively pretreated patients. Vaccines using dendritic cells, tumor cells, and fusions of tumor cells and antigen-presenting cells have also shown some promise in research, but further study is needed to obtain better, sustained results. CONCLUSIONS: Targeted treatment and cancer vaccines are novel approaches in the treatment of cancer. Both fields are expanding rapidly, with new technology and ongoing medical research. The clinical implications of such agents, administered either solely or in combination with established chemotherapeutic agents, may ultimately lead to better regimens and improved clinical responses.     

Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study

OBJECTIVE: To study the efficacy of cognitive rehabilitation combined with acetylcholinesterase inhibitor (AChE-I) treatment in patients with mild Alzheimer's disease and their relatives. METHOD: Thirteen patients with mild Alzheimer's disease treated with rivastigmine 6-12 mg/day for more than two months started cognitive rehabilitation training. Before and after the cognitive rehabilitation training patients were assessed through cognitive tests, activities of daily living scale, neuropsychological battery and scales to evaluate caregivers' depressive and anxiety symptoms. Six patients were randomized to a combined treatment group (AChE-I plus cognitive rehabilitation and caregiver support) and seven patients to a control group (AChE-I only) and followed up for five months. RESULTS: Mini-Mental State Examination (MMSE) scores (p = 0.047) and backward digit span scores (p = 0.018) were significantly different between the groups on follow-up. The combined treatment group showed a better positive treatment effect on cognitive and neuropsychological tests applied to patients and reduction of psychiatric symptoms was observed in their caregivers (nonsignificant). CONCLUSION: Cognitive rehabilitation associated with AChE-I treatment can potentially be useful to stabilize or improve cognitive and functional performance of patients with mild Alzheimer's disease and can reduce caregivers' psychiatric symptoms.     

Association between SARS-CoV-2 infection during pregnancy and postpartum depressive and anxiety symptoms: finding from the International Registry of Coronavirus Exposure in Pregnancy (IRCEP) study

Archives of Women's Mental Health - While there has been concern over the perinatal mental health implications of the COVID-19 outbreak, evidence on the risk of postpartum depression and...     

The effects of tamoxifen and its metabolites on platelet function and release of reactive oxygen intermediates

Tamoxifen is effective in the prevention and treatment of breast cancer, but its use is associated with an increased risk of thrombosis. The mechanism for this effect is unknown. Reactive oxygen intermediates enhance platelet-dependent thrombosis, and in oncological studies, tamoxifen has been shown to increase production of reactive oxygen species. Therefore, the effects of tamoxifen and its bioactive metabolites on platelet activity and platelet reactive oxygen species were determined. Platelets were incubated with tamoxifen or the metabolites 4-hydroxy-tamoxifen (4-OH), N-desmethyl tamoxifen, or 4-hydroxy-N-desmethyl tamoxifen (endoxifen). Tamoxifen metabolites have been previously shown to possess enhanced bioactivity, and consistent with this observation, tamoxifen metabolites but not tamoxifen modestly increased platelet aggregation. These effects were similar with platelets isolated from male or female subjects. Platelet nitric oxide release or cGMP levels were not altered by incubation with tamoxifen or any of its metabolites. Incubation with tamoxifen metabolites increased stimulation-dependent platelet superoxide release [8.1 +/- 1.6 arbitrary units (a.u.) for control versus 15.2 +/- 3.5 a.u. for 4-OH; P < 0.01]. Coincubation with a superoxide dismutase mimetic eliminated the tamoxifen metabolite-induced enhancement of platelet aggregation. Corresponding to increased superoxide release, incubation with tamoxifen metabolites enhanced the functional activation of NADPH oxidase as determined by phosphorylation of its subunits p47(phox) and p67(phox). In summary, incubation of platelets with the active metabolites of tamoxifen increases stimulation-dependent superoxide release through a NADPH oxidase-dependent mechanism. This results in modest changes in platelet function and seems to be consistent with previous oncological studies demonstrating tamoxifen-dependent increase in reactive oxygen species generation.