Franca Forni

Faecal calprotectin assay after induction with anti-Tumour Necrosis Factor α agents in inflammatory bowel disease: Prediction of clinical response and mucosal healing at one year.

BACKGROUND Faecal calprotectin levels correlate with inflammation in inflammatory bowel disease. We evaluated the role of faecal calprotectin after anti-Tumour Necrosis Factor α induction in inflammatory bowel disease patients to predict therapeutic effect at one year. METHODS Faecal calprotectin levels were measured in stools of 63 patients before and after induction of anti-Tumour Necrosis Factor α therapy. Clinical activity, measured by clinical indices, was assessed before and after biologic treatment. Clinical responders after induction were included in the study and colonoscopy was performed before and after one year of treatment to assess mucosal healing. RESULTS 63 patients (44 Crohns disease, 19 ulcerative colitis) were prospectively included (41.2% males, mean age at diagnosis 33 years). A sustained clinical response during the first year was observed in 57% of patients; median faecal calprotectin was 106 μg/g after induction versus 308 μg/g pre-induction (p<0.0001). Post-induction faecal calprotectin was significantly lower in responders versus non-responders (p=0.0002). Post-induction faecal calprotectin had 83% sensitivity and 74% specificity (cut-off ≤ 168 μg/g) for predicting a sustained clinical response at one year (p=0.0001); also, sensitivity was 79% and specificity 57% (cut-off ≤ 121 μg/g) for predicting mucosal healing (p=0.0001). CONCLUSIONS In inflammatory bowel disease faecal calprotectin assay after anti-Tumour Necrosis Factor α induction can be used as a marker to predict sustained clinical response and mucosal healing at one year.

Squamous Cell Carcinoma Antigen in Patients with Locally Advanced Cervical Carcinoma Undergoing Preoperative Radiochemotherapy: Association with Pathological Response to Treatment and Clinical Outcome

Objective: We investigated the role of squamous cell carcinoma (SCC) at presentation (pre-SCC) and after treatment (post-SCC) as predictor of pathological response and outcome in locally advanced cervical cancer (LACC) patients undergoing preoperative chemoradiation. Methods: One hundred and twenty-three consecutive LACC patients underwent preoperative chemoradiation including cisplatin and 5-fluorouracil plus external radiotherapy to the whole pelvic region. Clinical responders underwent radical surgery. SCC levels were expressed in nanograms/milliliter. Results: Ninety-five of 123 (77.2%) and 15/113 (13.3%) cases were classified as having high pre-SCC and high post-SCC levels. Complete pathological response was documented in 51 cases (41.5%), while persistence of microscopic foci was shown in 40 cases (32.5%). In the univariate analysis, FIGO (International Federation of Gynecology and Obstetrics) stage, clinical response to treatment and post-SCC levels were associated with pathological response to chemoradiation. In the multivariate analysis, only clinical response to treatment and post-SCC levels retained an independent role as predictors of pathological response to treatment. Cases with high post-SCC status had a shorter disease-free survival than cases with low post-SCC levels (p = 0.028). In the multivariate analysis, lack of a pathological complete response/persistence of microscopic foci to treatment retained an independent negative prognostic role for disease-free survival. Conclusions: Post-SCC identifies LACC patients with a poor chance of pathological response to chemoradiation and an unfavorable outcome.

Multiple tumor marker elevation in androgen ablation-refractory prostate cancer with long-term response to metronomic chemotherapy: a case report.

Outcomes in hormone-refractory prostate cancer are very poor. The time from progression to death is only 12–19 months. We present the case of a 69-year-old man with hormone-refractory prostate cancer and bone metastases treated with metronomic chemotherapy (cyclophosphamide based). He had had a colon adenocarcinoma ten years before. The atypical features of this case were an unusually long-lasting response to metronomic chemotherapy and an increase in serum levels of some non-prostate-specific tumor markers (CEA and CA 19–9) that was not related to a relapse of colon cancer. We hypothesize a potential role of hypoxia inducing CA 19–9 and CEA expression in tumor cells, which may predict the development of progressive resistance to antiangiogenic therapies.

Regression of endothelial dysfunction in patients with endometriosis after surgical treatment: a 2-year follow-up study

STUDY QUESTION How does endothelial function change in women with endometriosis after surgical treatment? SUMMARY ANSWER Surgical treatment of endometriosis leads to endothelial function improvement, resulting in reduction of cardiovascular risk. WHAT IS KNOWN ALREADY Some recent studies have demonstrated that in young women with endometriosis, even if structural alterations are absent, endothelial dysfunction, expressed as flow-mediated dilation (FMD) impairment, can nevertheless occur. However, there are no data about changes of endothelial function in women with endometriosis after surgical treatment of endometriosis. STUDY DESIGN, SIZE, DURATION This is a follow-up study carried out in 68 women enrolled in a previous study. Endothelial function was evaluated 2 years after surgical procedure and compared with baseline values. PARTICIPANTS/MATERIALS, SETTING, METHODS Twenty-two patients who had undergone surgical treatment of endometriosis (named as patients with STE) and 10 control subjects without endometriosis, from the original study sample participated in this follow-up study. Assessment of endothelial function by FMD evaluation and measurements of serum markers of endothelial activation and inflammation were done in all these subjects. MAIN RESULTS AND THE ROLE OF CHANCE After a 2-year follow-up period, FMD increased significantly with respect to baseline values among patients with STE [average pre- to post-difference: 5.07%, 95% confidence intervals (CI) 3.50, 6.63%; P < 0.001] but not among controls (average pre- to post-difference: 1.56%, 95% CI -0.55, 3.67%; P = 0.13). Follow-up FMD values were not significantly different between patients with STE and controls (average difference 1.50%, 95% CI -1.24, 4.23%; P = 0.27). Follow-up markers of inflammation and endothelial cells activation were similar among patients with STE and controls. LIMITATIONS, REASONS FOR CAUTION Although this study represents the first in the literature assessing endothelial function after surgical treatment of endometriosis, further longitudinal studies are desirable to define better the real risk that women with a history of endometriosis will develop cardiovascular events. WIDER IMPLICATIONS OF THE FINDINGS Endothelial dysfunction may be a better predictor of future cardiovascular events than traditional risk factors and the improvement in endothelial function we observed in patients after STE may have significant implications for their future cardiovascular risk. STUDY FUNDING/COMPETING INTEREST(S) No external funding has been either sought or obtained for this study. There are no conflicts of interest to declare.

491 Prediction of Clinical Response and Mucosal Healing At One Year by Faecal Calprotectin Assay After Induction With Anti-TNF Alpha Agents in IBD Patients

BACKGROUND: Measurement of antibodies to infliximab (ATI) and the correlation observed between serum drug concentration and disease status have provided both insight into infliximab (IFX) immunogenicity and clinical utility to these markers for managing IBD patients on IFX. For adalimumab, such data are not readily available nor is clinical utility known. The prevalence of antibodies to adalimumab (ATA) in IBD patients is sparsely reported outside of one company sponsored clinical trial (2.6%). Correlation between ATA/ drug concentration and objective markers of inflammation (CRP) as well as clinical symptoms is poorly described. METHODS: An independent investigator-initiated cross-sectional study prospectively recruited 54 IBD patients on ADA (2 with ulcerative colitis) from a tertiary center to determine 1) prevalence of detectable ATA and drug concentration; 2) correlation between ATA /drug concentration and an objective measure of inflammation, C-reactive protein (CRP); and 3) whether stratified category of ATA/ drug concentration correlated with patients self-described symptoms (remission, response, active flare). Patients were approached based on use of ADA for Crohns or ulcerative colitis and not clinical status (remission, response, active). Questionnaire of symptoms, IBD history, ADA dosing, weight and CRP measurement were conducted within two weeks of ATA/drug concentration measurement. ATA/drug concentration blood draw was performed at trough, just prior to next ADA dose, and processed by Prometheus Laboratories. Detectable ATA was defined as .= 1U/ml and detectable drug as .=1 mcg/ml. RESULTS: The prevalence of detectable ATA was 22.2% (n=12/54) and detectable ADA concentration was 90.7% (n=49/54). Serum concentration of ,5 mcg/ml of ADA was associated with an elevated CRP (p=0.001). Detectable ATA was positively associated with an elevated CRP, and notably this correlation was independent of drug concentration (p=0.002) (Figure). Stratification of patients based on ATA/drug concentration demonstrated more active disease in patients with low drug concentration (,5 mcg/ml) and/or detectable ATA (p=0.01). CONCLUSION: Antibodies to adalimumab in ADA-treated IBD patients are more prevalent than reported in clinical trials and almost all patients on ADA have a detectable drug concentration. Both detectable ATA and ADA drug concentration ,5 mcg/ml have an important association with increased inflammation. The observation that detectable ATA correlates with elevated CRP independent of drug concentration is a novel finding and suggests preventing ATA may be the more critical of the two variables to address for maximizing clinical efficacy. That detectable ATA/ low drug concentration correlates with active disease suggests there may be clinical utility in obtaining these measurements, however longer-term data are needed.

Enzymatic determinations in acute rejection after liver transplantation: preliminary report on necrosis index

The catalytic activities of some mitochondrial and cytoplasmic enzymes were measured in plasma from 19 patients after orthotopic liver transplantation, in order to detect and monitor the evolution of hepatocellular damage and to predict liver rejection. The enzymatic activities determined were: mitochondrial isoenzyme of aspartate aminotransferase, glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltranspeptidase and alkaline phosphatase. The results of all enzymatic activities were normalized by expressing them as multiples of the upper limit of the relevant reference range and then the necrosis index (NI) has been calculated. The proposed NI consists of percent ratio of the normalized mitochondrial enzymatic activities over the sum of cytoplasmic and mitochondrial normalized activities. We observed that NI values higher than 30% correctly identified all but two acute rejection events which were documented by liver biopsies showing a diagnostic sensitivity of 90%, specificity of 78% and a predictive value of 90%.

P214 Faecal calprotectin assay after induction with anti-TNF alpha agents in IBD patients: prediction of clinical response and mucosal healing at one year

P214 Faecal calprotectin assay after induction with anti-TNF alpha agents in IBD patients: prediction of clinical response and mucosal healing at one year L. Guidi1 *, M. Marzo1, G. Andrisani1, C. Felice1, D. Pugliese1, I. De Vitis1, A. Papa1, G.L. Rapaccini1, F. Forni2, A. Armuzzi1. 1Internal Medicine and Gastroenterology Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy, 2Clinical Laboratory Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy