Comparison of Quality of Life and Anorectal Function After Artificial Sphincter Implantation

PURPOSE: Quality of life, a major outcome parameter in the treatment of anal incontinence, has not been assessed after artificial sphincter implantation. The purpose of this single-center, prospective, nonrandomized study was to assess quality-of-life differences in patients before and after artificial sphincter implantation and compare them with clinical incontinence scores and anal manometry. METHODS: Quality of life was assessed in 16 patients (14 females; mean age, 43 years) consecutively implanted with an Acticon NeosphincterTM. The Fecal Incontinence Quality of Life Scale, a quality-of-life instrument specifically designed for analysis of anal incontinence, included 27 items grouped in four domains: lifestyle, coping/behavior, depression/self-perception, and embarrassment. Fecal Incontinence Quality of Life Scale score (0 to 1, with 1 indicating better quality of life) was calculated preoperatively and postoperatively and compared with the Fecal Incontinence Score (on a scale of 0 to 120, with 120 being complete incontinence), an evacuation score, and maximal resting pressure. RESULTS: At a mean (standard deviation) of 25 (15) months,12 patients had an activated device, and 11 had satisfactory anorectal function. Significant improvement was observed postoperatively in the four separate quality-of-life domains. Mean (standard deviation) Fecal Incontinence Quality of Life Scale scores increased from 0.44 (0.14) preoperatively to 0.86 (0.18), 0.94 (0.06), and 0.83 (0.16) at 6, 12, and 24 months after implantation, respectively. For the same time periods, the mean (standard deviation) Fecal Incontinence Scores were 105 (14), 24 (26), 32 (35), and 32 (28), respectively (P< 0.05). A linear correlation was found between the improvement over time in quality of life measured by the Fecal Incontinence Quality of Life Scale and clinical evaluation of incontinence measured by the Fecal Incontinence Score (r2 = 0.97; P = 0.03). Mean (standard deviation) maximal resting pressure increased similarly from 42 (24) cm H2O preoperatively to 97 (23) cm H2O at the end of follow-up (P < 0.0001). CONCLUSION: After artificial sphincter implantation, quality of life as assessed by a new Fecal Incontinence Quality of Life Scale instrument was significantly improved. These results correlated with clinical assessment of anal incontinence and were associated with a significant increase in maximal anal resting pressure on manometry.     

Netrin-4 delays colorectal cancer carcinomatosis by inhibiting tumor angiogenesis

A close relationship between tumor angiogenesis, growth, and carcinomatosis has been observed. Netrin-4 (NT-4) has been shown to regulate angiogenic responses. We aimed to examine the effects of NT-4 on colon tumor angiogenesis, growth, and carcinomatosis. We showed that NT-4 was expressed in human colon cancer cells (LS174). A 20-fold increase in NT-4 expression was stably induced by NT-4 pcDNA in LS174 cells. In vivo, a Matrigel angiogenesis assay showed that NT-4 overexpression altered vascular endothelial growth factor (VEGF)/basic fibroblast growth factor-induced angiogenesis. In nude mice with LS174 xenografts, NT-4 overexpression inhibited tumor angiogenesis and growth. In addition, these NT-4-involved inhibitory effects were associated with decreased tumor cell proliferation and increased tumor cell apoptosis. Using an orthotopic peritoneal carcinomatosis model, we demonstrated that NT-4 overexpression decreased colorectal cancer carcinomatosis. Moreover, carcinomatosis-related ascites formation was significantly decreased in mice transplanted with NT-4 LS174 cells versus control LS174 cells. The antiangiogenic activity of NT-4 was probably mediated by binding to its receptor neogenin. Netrin-4 had a direct effect on neither in vitro apoptosis and proliferation of cultured LS174 cells nor the VEGF-induced acute increase in vascular permeability in vivo. We propose that NT-4 overexpression decreases tumor growth and carcinomatosis, probably via an antiangiogenic effect, underlying the potential therapeutic interest in NT-4 in the treatment of colorectal cancer growth and carcinomatosis.     

Variables to be controlled in the assessment of blood innate immune responses to Toll-like receptor stimulation

Variability in TLR function influences susceptibility to infectious as well as immune-mediated diseases. Given the outbred nature of humans, identifying functional Toll-like receptor variability and its role in clinical disease requires such analysis to be conducted in large, often multi-centered cohorts. Yet the technically complex measurements involved in innate immune analysis benefit from centralized processing of samples. Centralization requires shipping of samples or prolonged storage, possibly even cryopreservation. Deviation from standard operating procedures (SOP) for sample procurement, storage and processing may alter the final innate immune read out. We here set out to define the impact of variables most likely to be encountered during large, multi-site studies: (i) the source of the sample, (ii) time between sample procurement to processing, and (iii) processing of fresh vs. cryopreserved samples. We found that all of these variables exert a profound impact on the final innate response to TLR stimulation. Specific innate responses appeared to be affected in response to specific TLR stimuli by a particular variable under study, proving it impossible to provide global generalizations. Based on our studies and other published work on this topic, we propose a minimal list of variables that have to be met for samples to be comparable within and across studies: a) timing between procurement and processing cannot vary by more than 10%; b) all samples have to be stored the same; and c) the source of samples needs to be the same. In summary, for innate immune analysis scrupulous adherence to standard operating procedures is paramount.     

Satisfaction of patients treated for chronic hepatitis C with the peginterferon alfa-2b pen device: the VISA observational study

OBJECTIVES: This observational study aimed at evaluating the satisfaction of patients with chronic hepatitis C using the peginterferon (peg-IFN) alfa-2b pen device. METHODS: Consecutive patients were included when prescribed the pen device. Self-administered questionnaires relating to the progress brought by the pen, convenience/comfort, and the mode and security of injection were completed after the first injection and at 12 weeks. RESULTS: Six hundred and forty eight patients aged 45.7 +/- 12.1 years completed the 1st questionnaire; 70% were naive for any hepatitis C treatment. Five hundred and twenty five (81%) patients completed the 2nd questionnaire. Adherence to the pen device was >or=80% in more than 80% of the patients. Most (85%) patients declared that the pen brought important progress compared to traditional syringes. Satisfaction was high after the 1st injection and further increased 12 weeks later, with ease of use scoring 7.7 then 8.0 (P=0.007, 10-point scale), and rapidity of use scoring 8.0 then 8.2 (P=0.008); less painful injection scoring 7.9 at both time points. The proportion of self-injectors (no intervention of a health professional) increased from 32% to 58% (P<0.0001). Reasons for self-injecting were: easier injection (58%), no product/syringe handling (50%/41%), and assurance of exact dosing (45%). CONCLUSION: Patients were satisfied with the peg-IFN alfa-2b pen device. The proportion of self-injectors doubled over 12 weeks. Good treatment adherence, which is mandatory for therapeutic success, is expected from use if this device.     

Management of HCV-HIV patients

Reciprocal interactions between Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) are characterized by the absence of clear impact of HCV on HIV; by contrast, HIV markedly modified the natural history of HCV (high viral load, more severe liver disease) at least before the introduction of highly active antiretroviral therapies (HAART). HAART has completely modified the pattern of hepatic events in HIV infection and the liver disease is one of the leading causes of morbidity and mortality nowadays, reflecting several non-exclusive pathogenic processes that include drug-related hepatotoxicities, chronic hepatitis C infection, other liver diseases such as steatosis or non-alcoholic steato-hepatitis (NASH) and other liver diseases that are common in the setting of alcohol or drug abuse. The harmful impact of HIV underlines the need for improving: