Long-term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials.

PURPOSE: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. PATIENTS AND METHODS: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression-free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). RESULTS: About 1227 patients were included. The 7-year OS was 84.3% (95% CI 80.8-87.2) for ABVD vs 87.7% (95% CI 84.5-90.2) for BEACOPP. Two follow-up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP  = 1.59; 95% CI 1.09-2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7-year PFS was 71.1% (95% CI 67.1-74.6) for ABVD vs 81.1% (95% CI 77.5-84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP. CONCLUSIONS: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT.

Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma.

The main purpose of this study was to assess whether it is possible to improve the prognostic impact of international prognostic index (IPI) score by combining it with peripheral blood counts. Thus, we evaluated the prognostic power of lymphocyte, neutrophil, and monocyte counts in 520 patients with diffuse large B cell lymphoma treated with R-CHOP, confirming that these parameters have a strong impact on overall survival (OS). Using revised IPI (R-IPI), 44% of patients were categorized as poor-risk and showed an OS at 5 years of 46%. As OS at 5 years of the 520 patients is 67%, it is clearly evident that R-IPI tends to overestimate the proportion of patients with poor prognosis. Accordingly, in an attempt to improve the discriminating power of R-IPI, we evaluated and compared three different scores by combining the neutrophil lymphocyte ratio (NLR) and absolute monocyte count (AMC) with the following values: (a) IPI score 3-5, (b) age > 60 years and performance status, (c) age ≥ 65 years and LDH > ULN. The three indexes studied, had a similar 5 years OS for the high-risk group (46%-52%), but the proportion of patients classified as poor-risk were 37%, 20%, and 32%, respectively, which are lower than 44% identified with R-IPI. Thus, while R-IPI overestimates the number of high-risk patients, after applying our models, it is possible to recognize patients who are truly at high-risk. Of the three scores, the most accurate appears to be that based on NLR, AMC, LDH > ULN and age ≥ 65 years, which identifies 32% of high-risk patients, correlating well with what is seen in clinical practice.

Intestinal T-cell lymphoma with enteropathy-associated T-cell lymphoma-like features arising in the setting of adult autoimmune enteropathy.

Enteropathy-associated T-cell lymphoma is regarded as a dismal, late complication of coeliac disease, though a single case of T-cell lymphoma with such features arising in the setting of autoimmune enteropathy of the adult has been reported to date. We aim to describe the case of a 41-year-old woman complaining of severe malabsorption syndrome, who was diagnosed with autoimmune enteropathy based on the presence of flat intestinal mucosa unresponsive to any dietary restriction and positivity for enterocyte autoantibodies. Steroid therapy led to a complete recovery of both mucosal and clinical findings over 12 years, when disease relapse was accompanied by the appearance of monoclonal rearrangement of T-cell receptor-γ and peculiar T-cell phenotypic abnormalities, leading to a rapid transition to an overt T-cell lymphoma with features of the enteropathy-associated subtype. Despite intensive treatment, the patient developed cerebral metastasis and died 9 months later. Our case enhances the concept of enteropathy-associated T-cell lymphoma as a disease that may arise in the setting of enteropathies other than coeliac disease, thus representing a heterogeneous entity. Moreover, our observations support the need of a close follow-up of these patients, coupled with comprehensive characterization of mucosal biopsies.

Neutrophil-lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: results of a large multicenter study involving 990 patients.

Several studies have demonstrated the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with solid tumors and non-Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)-cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression-free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression-free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS-cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS-cHL patients.

Long-Term Results of the HD2000 Trial Comparing ABVD Versus BEACOPP Versus COPP-EBV-CAD in Untreated Patients With Advanced Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi.

PURPOSE: The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years. PATIENTS AND METHODS: Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months). RESULTS: The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively). CONCLUSION: With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.

The Prognosis of Patients with Liver Metastases from Colorectal Cancer still Depends on Anatomical Presentation more than on Treatments.

BACKGROUND: The best management of liver metastases from colorectal cancer is still debated and little is known about the true impact of treatments on survival. MATERIALS AND METHODS: The study involved 122 patients (77 males), aged 64.0 ± 11.0 years (range: 27.8-86.1) at diagnosis of liver metastatization (synchronous in 59). All underwent chemotherapy and at least one procedure of radiofrequency ablation; 53 also had partial hepatic resections. Demographics, tumor characteristics and survival outcomes from liver metastatization were analyzed with univariate and multivariate techniques. This analysis was performed also taking into account relative survival as the best estimate of specific survival. RESULTS: The analysis with observed survival selected the categorized number of involved lymph nodes in the colorectal specimens as the only statistically significant predictor, while the analysis with relative survival also showed site of the primary tumor (above the sigmoid colon or otherwise) and number of liver metastases as significant factors. The standardized mortality ratio was 9.673 (95% CI: 7.668-11.663) and a total of 201.85 years of life were lost in comparison with the survival of the reference population. CONCLUSIONS: The computation of relative survival ­ better than observed survival ­ selected a more adequate number of predictors, making investigation of even limited series of patients with confounding factors reliable. The finding that prognosis was mainly dependent on the anatomical presentation of the primary tumor and of liver metastases ­ instead of treatments ­ could explain the still contrasting opinions on the role of the available therapies in this field.

Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn's disease mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and cell-cell contact.

INTRODUCTION: Crohn's disease (CD) is a disabling chronic enteropathy sustained by a harmful T-cell response toward antigens of the gut microbiota in genetically susceptible subjects. Growing evidence highlights the safety and possible efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this condition. Therefore, we aimed to investigate the effects of bone marrow-derived MSCs on pathogenic T cells with a view to clinical application. METHODS: T-cell lines from both inflamed and non-inflamed colonic mucosal specimens of CD patients and from healthy mucosa of control subjects were grown with the antigen muramyl-dipeptide in the absence or presence of donors' MSCs. The MSC effects were evaluated in terms of T-cell viability, apoptotic rate, proliferative response, immunophenotype, and cytokine profile. The role of the indoleamine 2,3-dioxygenase (IDO) was established by adding a specific inhibitor, the 1-methyl-DL-tryptophan, and by using MSCs transfected with the small interfering RNA (siRNA) targeting IDO. The relevance of cell-cell contact was evaluated by applying transwell membranes. RESULTS: A significant reduction in both cell viability and proliferative response to muramyl-dipeptide, with simultaneous increase in the apoptotic rate, was found in T cells from both inflamed and non-inflamed CD mucosa when co-cultured with MSCs and was reverted by inhibiting IDO activity and expression. A reduction of the activated CD4(+)CD25(+) subset and increase of the CD3(+)CD69(+) population were also observed when T-cell lines from CD mucosa were co-cultured with MSCs. In parallel, an inhibitory effect was evident on the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interferon-γ, interleukin-17A and -21, whereas that of the transforming growth factor-ß and interleukin-6 were increased, and production of the tolerogenic molecule soluble HLA-G was high. These latter effects were almost completely eliminated by blocking the IDO, whose activity was upregulated in MSCs co-cultured with CD T cells. The use of a semipermeable membrane partially inhibited the MSC immunosuppressive effects. Finally, hardly any effects of MSCs were observed when T cells obtained from control subjects were used. CONCLUSION: MSCs exert potent immunomodulant effects on antigen-specific T cells in CD through a complex paracrine and cell-cell contact-mediated action, which may be exploited for widespread therapeutic use.

Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation.

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 ± 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index ≤0.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc ≥2 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention.

Long-Term Follow-Up of Crohn Disease Fistulas After Local Injections of Bone Marrow-Derived Mesenchymal Stem Cells.

OBJECTIVE: To assess the long-term outcome of patients treated with serial intrafistular injections of autologous bone marrow-derived mesenchymal stem cells (MSCs) for refractory Crohn fistulas in terms of safety and efficacy. PATIENTS AND METHODS: Starting from January 10, 2007, through June 30, 2014, clinical evaluation, calculation of the Crohn disease activity index (CDAI), therapeutic management, and documentation of adverse events in 8 of the 10 patients (5 men; median age, 37 years) who had been injected locally with MSCs were prospectively recorded for 72 months. Cumulative probabilities of fistula recurrence and medical or surgical treatment were estimated using a Kaplan-Meier method, whereas differences among the pre- and post-MSC CDAI values were calculated with the Mann-Whitney U test. RESULTS: Following disease remission observed after 12 months from MSC treatment (P<.001), the mean CDAI score increased significantly during the subsequent 2 years (P=.007), and was then followed by a gradual decrease, with the patients achieving remission again (P=.02) at the end of the 5-year follow-up. The probability of fistula relapse-free survival was 88% at 1 year, 50% at 2 years, and 37% during the following 4 years, and the cumulative probabilities of surgery- and medical-free survival were 100% and 88% at 1 year, 75% and 25% at 2, 3, and 4 years, and 63% and 25% at 5 and 6 years, respectively. No adverse events were recorded. CONCLUSION: Locally injected MSCs constitute a safe therapy that rescues refractory patients and regains responsiveness to drugs previously proved ineffective.

Absolute Monocyte Count and Lymphocyte-Monocyte Ratio Predict Outcome in Nodular Sclerosis Hodgkin Lymphoma: Evaluation Based on Data From 1450 Patients.

OBJECTIVE: To verify whether absolute monocyte count (AMC) and lymphocyte- monocyte ratio (LMR) at diagnosis are valid prognostic parameters in classical Hodgkin lymphoma (cHL). PATIENTS AND METHODS: Data were collected from 1450 patients with cHL treated in Israel and Italy from January 1, 1988, through December 31, 2007. RESULTS: The median age of the patients was 33 years (range, 17-72 years), and 70% (1017) of the patients had nodular sclerosis (NS); the median follow-up duration was 87 months. The best cutoff value for AMC was 750 cells/mm(3), and the best ratio for LMR was 2.1. The adverse prognostic impact of an AMC of more than 750 cells/mm(3) was confirmed for the entire cohort, and its clinical significance was particularly evident in patients with NS histology. The progression-free survival (PFS) at 10 years for an AMC of more than 750 cells/mm(3) was 65% (56%-72%), and the PFS at 10 years for an AMC of 750 cells/mm(3) or less was 81% (76%-84%; P<.001). The overall survival (OS) at 10 years for an AMC of more than 750 cells/mm(3) was 78% (70%-85%), and the OS at 10 years for an AMC of 750 cells/mm(3) or less was 88% (84%-90%; P=.01). In multivariate analysis, both AMC and LMR maintained prognostic significance for PFS (hazard ratio [HR], 1.54, P=.006, and HR, 1.50, P=.006) after adjusting for the international prognostic score, whereas the impact on OS was confirmed (HR, 1.56; P=.04) only in patients with NS and an AMC of more than 750 cells/mm(3). CONCLUSION: This study confirms that AMC has prognostic value in cHL that is particularly significant in patients with NS subtype histology. This finding links the known impact of macrophages and monocytes in Hodgkin lymphoma with routine clinical practice.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

BACKGROUND: Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. METHODS: Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. RESULTS: 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. CONCLUSIONS: Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

Medication prescription and adherence disparities in non valvular atrial fibrillation patients: an Italian portrait from the ARAPACIS study.

Non-valvular atrial fibrillation (NVAF) represents a major health-care problem, needing an extensive and strict thrombosis prevention for stroke and cardiovascular (CV) disease risks. NVAF management guidelines recommend adequate antithrombotic and anti-atherosclerotic therapies. Medication adherence has been recognized as a pivotal element in health quality promotion and in the achievement of better clinical outcomes. We conducted a post-hoc analysis of the "Atrial fibrillation Registry for Ankle-brachial index Prevalence Assessment-Collaborative Italian Study (ARAPACIS)" with the aim of discerning differences in pharmacological management and medication adherence among NVAF Italian patients. Furthermore, data were analysed according to Italian geographical macro-regions (North, Center, South) to evaluate whether socioeconomic conditions might also influence medication adherence. Thus, we selected 1,366 NVAF patients that fulfilled the Morisky Medication Adherence Scale-4 items. Regional disparities in drug prescriptions were observed. In particular, in high-risk patients (CHA2DS2-VASc ≥2) oral anticoagulants were more prescribed in Northern and Center patients (61 and 60 %, respectively) compared to 53 % of high-risk Southern patients. Also, medication adherence showed a progressive decrease from North to South (78 vs. 60 %, p < 0.001). This disparity was independent of the number of drugs consumed for any reason, since prevalence of poly-therapy among the three macro-regions was similar. Our results show regional differences in NVAF patients' antithrombotic management and medication adherence, potentially reflecting well-known disparities in socioeconomic status among Italian regions. Future interventions promoting campaigns to global health-care education may be desirable to improve clinical outcomes in NVAF patients.

A second duodenal biopsy is necessary in the follow-up of adult coeliac patients.

INTRODUCTION: Coeliac disease is a chronic enteropathy requiring a close follow-up. However, the best way to follow up coeliac patients has not yet been established. In the last 14 years, we have been offering patients a thorough series of periodical examinations including a histological re-evaluation at 12-18 months. PATIENTS AND METHODS: The notes of all coeliac patients attending our clinic between September 1999 and March 2013 were examined. RESULTS: Data from 317 adult patients were collected. Duodenal biopsy showed a lack of satisfactory histological response in 25/317 patients; endomysial antibodies were still positive in 76, and diet adherence and clinical response were unsatisfactory in 58 and 97, respectively. Correlations of serological data, clinical response, and diet adherence with histological findings were evaluated. Although the P values showed statistically significant differences, sensitivity and specificity were disappointing: 64% and 80% for serological response, 48% and 71% for clinical response, 56% and 85% for diet adherence. CONCLUSIONS: After 12-18 months on a gluten-free diet, 8% of the patients do not present a satisfactory histological response; only some of them could have been identified with a serological and/or clinical re-evaluation. Therefore, a duodenal biopsy seems to be the only tool that could identify patients with unsatisfactory histological response.

Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients.

PURPOSE: The presence of a bulky tumour at staging on CT is an independent prognostic factor in malignant lymphomas. However, its prognostic value is limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on (18)F-FDG PET/CT could give a better evaluation of the total tumour burden and may help patient stratification. Different methods of TMTV measurement established in phantoms simulating lymphoma tumours were investigated and validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. METHODS: Data were processed by two nuclear medicine physicians in Reggio Emilia and Créteil. Nineteen phantoms filled with (18)F-saline were scanned; these comprised spherical or irregular volumes from 0.5 to 650 cm(3) with tumour-to-background ratios from 1.65 to 40. Volumes were measured with different SUVmax thresholds. In patients, TMTV was measured on PET at staging by two methods: volumes of individual lesions were measured using a fixed 41% SUVmax threshold (TMTV41) and a variable visually adjusted SUVmax threshold (TMTVvar). RESULTS: In phantoms, the 41% threshold gave the best concordance between measured and actual volumes. Interobserver agreement was almost perfect. In patients, the agreement between the reviewers for TMTV41 measurement was substantial (ρ c = 0.986, CI 0.97 - 0.99) and the difference between the means was not significant (212 ± 218 cm(3) for Créteil vs. 206 ± 219 cm(3) for Reggio Emilia, P = 0.65). By contrast the agreement was poor for TMTVvar. There was a significant direct correlation between TMTV41 and normalized LDH (r = 0.652, CI 0.42 - 0.8, P <0.001). Higher disease stages and bulky tumour were associated with higher TMTV41, but high TMTV41 could be found in patients with stage 1/2 or nonbulky tumour. CONCLUSION: Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation. It should be evaluated in prospective studies.

Tumor burden in Hodgkin's lymphoma: much more than the best prognostic factor.

The intense immunological crosstalk between the rare neoplastic cells and the prevalent reactive ones is responsible for the development of signs and symptoms of Hodgkin's lymphoma. It is likely the reason for the superior predictivity constantly demonstrated by the tumor burden, as the final expression of the whole cytological disorder. Moreover, the tumor burden is related to the probability of response and its 1-year stability, showing different relationships according to the treatment administered. The relative risk of early treatment failure can be predicted on the basis of the tumor burden at diagnosis and the therapy chosen. Tumor burden is measured from the diagnostic whole body computed tomography (CT) scan, but can also be indirectly calculated from some staging parameters when the CT-aided assessment cannot be performed. Preliminary promising results have been obtained with a semi-automatic positron emission tomography/CT scan measuring metabolically active volumes, instead of whole visible masses.

Low incidence but poor prognosis of complicated coeliac disease: a retrospective multicentre study.

BACKGROUND: Coeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease. METHODS: Retrospective multicenter case-control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded. RESULTS: Between 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2-0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1-0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan-Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease. CONCLUSIONS: Complications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality.

Prevalence and natural history of potential celiac disease in adult patients.

OBJECTIVE: Potential celiac disease (PCD) is a form of CD characterized by positive endomysial/tissue transglutaminase antibodies and a preserved duodenal mucosa despite a gluten-containing diet (GCD); it can evolve into flat, active CD. This evolution is, however, not certain. Our aim was to retrospectively study the prevalence and the natural history of adult patients with PCD. METHODS: The clinical notes of all 47 patients with PCD attending our clinic between September 1999 and October 2011 were retrospectively reevaluated. To study their clinical features, patients with active CD, randomly selected and matched for sex and date of birth, served as controls. Symptoms, associated diseases, familiarity, and laboratory data at diagnosis were compared. RESULTS: Prevalence of PCD among all celiac patients directly diagnosed in our center was 42/187, (1/4.4, 18.3%, 95% confidence interval (CI) 13.3-23.4%). Age at diagnosis, laboratory data, prevalence of symptoms, associated diseases, and familiarity for CD did not differ between patients with PCD and those with active CD. Some patients with PCD maintained a normal duodenal mucosa for many years and their symptoms spontaneously improved despite maintaining a GCD. CONCLUSIONS: PCD is not a rare form of CD. Having found no difference at all in age at diagnosis and clinical features between PCD and active CD could suggest that PCD is not a prodrome of CD but is a separate entity that can only subsequently evolve into active CD.