Multiple sclerosis incidence in Tuscany from administrative data.

BACKGROUND: Italy is a high-risk area for multiple sclerosis with 110,000 prevalent cases estimated at January 2016 and 3400 annual incident cases. To study multiple sclerosis epidemiology, it is preferable to use population-based studies, e.g., with a registry. A valid alternative to obtain data on entire population is from administrative sources. OBJECTIVE: To estimate the incidence of multiple sclerosis in Tuscany using a case-finding algorithm based on administrative data. METHODS: In a previous study, we calculated the prevalence in Tuscany using a validated case-finding algorithm based on administrative data. Incident cases were identified as a subset of prevalent cases among those patients not traced in the years before the analysis period, and the date of the first multiple sclerosis-related claim was considered the incidence date of multiple sclerosis diagnosis. We examined the period 2011-2015. RESULTS: We identified 1147 incident cases with annual rates ranged from 5.60 per 100,000 in 2011 to 6.58 in 2015. CONCLUSIONS: We found a high incidence rate, similarly to other Italian areas, especially in women, that may explain the increasing prevalence in Tuscany. To confirm this data and to calculate the possible bias caused by our inclusion method, we will validate our algorithm for incident cases.

Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience.

BACKGROUND: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase. OBJECTIVES: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008. METHODS: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8-126) months. RESULTS: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing-remitting course (31%) had a 6-12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression. CONCLUSIONS: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing-remitting phase of the disease.

The use of thiopurines for the treatment of inflammatory bowel diseases in clinical practice.

BACKGROUND: Thiopurines are the most commonly used immunomodulatory drugs in inflammatory bowel diseases. AIM: To evaluate the use, the therapeutic and safety profiles of thiopurines in a large sample of IBD patients. METHODS: We reviewed 3641 case histories of IBD patients. Thiopurines were prescribed in 582 patients (16.0%); the analysis was performed on the 553 (267 ulcerative colitis, 286 Crohn's disease) with exhaustive clinical data. RESULTS: The main indications for treatment were steroid-dependence (328/553, 59.3%) and steroid-resistance (113/553, 20.7%). Thiopurines were started when CD were younger than UC patients (p<0.001) but earlier from diagnosis in UC than in CD patients (p=0.003). Efficacy was defined as optimal (258/553, 46.6%), partial (108/553, 19.5%), absent (85/553, 15.4%) and not assessable (102/553, 18.4%). Efficacy was independent of disease type, location/extension or duration and age at starting. Side effects were observed in 151/553 (27.3%) patients, leading to drug discontinuation in 101 (18.3%). 15 out of the 130 (11.5%) patients who took thiopurines for more than 4 years relapsed, more frequently in CD than in UC (OR=3.67 95% C.I. 0.98-13.69; p=0.053). CONCLUSIONS: Thiopurines confirm their clinical usefulness and acceptable safety profile in managing complicated IBD patients. The majority of patients treated for longer than 4 years maintain response. No clinical and demographic predictive factors for efficacy and side effects were identified.

Colonoscopy practice in Italy: a prospective survey on behalf of the Italian Association of Hospital Gastroenterologists.

BACKGROUND: Examining the current practice is important for the benchmarking of quality of colonoscopy and the comparison with the standards and recommendations expected by professional societies. AIM: To describe colonoscopy practice in Italy, on the basis of prospective analysis of a large number of examinations performed by operators with different levels of expertise in a wide range of unselected centres. DESIGN AND SETTING: Cross-sectional, prospective and multicentre study. METHODS: The main features of each endoscopy centre (structure indicators) were collected through the use of a standardised questionnaire. A second questionnaire was used to prospectively record details of all the consecutive colonoscopies performed in a 2-week study period. RESULTS: Data from 278 centres and 12,835 consecutive colonoscopies were evaluated. Centres were uniformly distributed throughout Italy - north, centre and south - as was their organizational complexity and workload. Overall, adequate facilities (i.e. cleaning area for disinfection/reprocessing, equipped recovery room), and safety equipment (i.e. pulse oximetry, equipment for emergency cardiopulmonary resuscitation) were lacking in a considerable amount of centres, especially in those with a lower degree of organizational complexity. Written informed consent was routinely required in 87% of the centres, but a specific consent for colonoscopy, including detailed information on adverse events, was adopted by 66%. Regular programs for recording some quality indicators (i.e. cecal intubation, quality of bowel cleansing, patients' satisfaction and complications) were implemented in a minority of centres. About 93% of the colonoscopies were performed for diagnostic purpose; screening and surveillance accounted for 13.7% and 25.3% of the indications, respectively. Sedation and/or analgesia was administered in about half of the patients. Overall, colonoscopies were completed to the cecum in 80.7% of cases, and only 22.1% of the centres reported a cecal intubation rate >or=90%; this figure was reported in 33.1% of centres with high-organizational complexity and in 14.4% of outpatient units. The overall incidence of immediate complications was low (2 perforations, 26 bleedings and 32 serious cardiorespiratory complications). CONCLUSIONS: This study documented a wide variation in colonoscopy practice between centres and highlighted problem areas where interventions are needed to improve performance and safety of the examinations.

Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up.

BACKGROUND: Severe ulcerative colitis is a life-threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy. AIM: To evaluate short- and long-term effectiveness and safety of infliximab in severe refractory ulcerative colitis. METHODS: Eighty-three patients with severe ulcerative colitis (i.v. glucocorticoids treatment-refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short-term outcome was colectomy/death 2 months after the first infusion. Long-term outcome was survival free from colectomy. Safety data were recorded. RESULTS: Twelve patients (15%) underwent colectomy within 2 months. One died of Legionella pneumophila infection 12 days after infliximab. Early colectomy rates were higher in patients receiving one infusion (9/26), compared with those receiving two/more infusions (3/57, P = 0.001, OR = 9.53). Seventy patients who survived colectomy and did not experience any fatal complications were followed-up for a median time of 23 months; 58 patients avoided colectomy during the follow-up. Forty-two patients were maintained on immunosuppressive drugs. No clinical features were associated with outcomes. CONCLUSIONS: Infliximab is an effective and relatively safe therapy to avoid colectomy and maintain long-term remission for patients with severe refractory ulcerative colitis. In the short term, two or more infusions seem to be more effective than one single infusion.

Effectiveness of a continuous quality improvement program on colonoscopy practice.

BACKGROUND AND STUDY AIM: Continuous quality improvement (CQI) is recommended by professional societies as part of every colonoscopy program, but little is known with regard to its effectiveness for colonoscopy outcomes. We prospectively assessed whether the implementation of a CQI program in routine clinical practice influences the quality performance of colonoscopy. METHODS: In an open-access endoscopy unit at a secondary care center in Northern Italy, 6-monthly audit cycles were carried out over a 4-year period, to identify reasons for poor colonoscopy outcomes and institute appropriate changes to improve performance. The colonoscopy completion rate and the polyp detection rate as detected by endoscopists were considered to be key measures for improvement. RESULTS: The initial crude colonoscopy completion rate was 84.6%, with a range for individual endoscopists 80.4%-94%. Four endoscopists had a completion rate lower than 90%. The overall polyp detection rate was 34%, with a wide variation among endoscopists (range 14%-42%). Poor patient tolerance and differences in colonoscopist expertise were the main determinants of lack of completion and variation in polyp detection rate. Changes to sedation practice, greater access to endoscopy sessions for the endoscopists with the lowest performance rates, and other organizational arrangements, were implemented to improve quality performance. The crude completion rates improved consistently, up to 93.1%, over the study period. This trend was confirmed even when adjusted completion rates were calculated. All endoscopists reached a crude completion rate of 90% or more and a polyp detection rate of over 20%. The introduction of CQI did not significantly change the overall incidence of procedure-related complications. CONCLUSIONS: The effectiveness of colonoscopy can be improved by implementing a CQI program in routine colonoscopy practice.

Segmental colitis associated with diverticula: a 7-year follow-up study.

BACKGROUND AND STUDY AIMS: We performed a long-term follow-up study of patients with segmental colitis associated with diverticula, in order to clarify the natural history of this disease. PATIENTS AND METHODS: We identified 15 patients who were diagnosed as having segmental colitis associated with diverticula during 1997. We assessed these patients by means of periodic follow-up visits from 1997 to 2004. RESULTS: Eight of the 15 patients had no clinical recurrence during follow-up. Five patients had sporadic recurrences that were clinically mild (on average, one in 5 years), which responded to topical therapy and often to self-medication. Only two patients were diagnosed during the follow-up period as having Crohn's disease; notably, these were the only patients who did not have hematochezia as the main symptom at onset. CONCLUSION: The course of this disease appears to be substantially benign.

Infliximab and newly diagnosed neoplasia in Crohn's disease: a multicentre matched pair study.

BACKGROUND AND AIMS: The widespread use of anti-tumour necrosis factor alpha antibody (Infliximab) in Crohn's disease (CD) raises concerns about a possible cancer risk in the long term. In a matched pair study, we assessed whether Infliximab is associated with an increased risk of neoplasia. METHODS: In a multicentre matched pair study, 404 CD patients treated with Infliximab (CD-IFX) were matched with 404 CD patients who had never received Infliximab (CD-C). Cases and controls were matched for sex, age (+/-5 years), site of CD, age at diagnosis (+/-5 years), immunosuppressant use, and follow up. New diagnoses of neoplasia from April 1999 to October 2004 were recorded. RESULTS: Among the 404 CD-IFX, neoplasia was diagnosed in nine patients (2.22%) while among the 404 CD-C, seven patients developed neoplasia (1.73%) (odds ratio 1.33 (95% confidence interval 0.46-3.84); p=0.40). The survival curve adjusted for patient year of follow up showed no differences between CD-IFX and CD-C (p=0.90; log rank test). In the CD-IFX group, there was one cholangiocarcinoma, three breast cancers, one skin cancer, one leukaemia, one laryngeal cancer, and two anal carcinomas. Among the 7/404 (1.73%) CD-C, there were three intestinal adenocarcinomas (two caecum, one rectum), one basalioma, one spinalioma, one non-Hodgkin's lymphoma, and one breast cancer. Age at diagnosis of neoplasia did not differ between groups (CD-IFX v CD-C: median 50 (range 40-70 years) v 45 (27-72); p=0.50). CONCLUSION: In our multicentre matched pair study, the frequency of a new diagnosis of neoplasia in CD patients treated with Infliximab was comparable with CD patients who had never received Infliximab.

Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database.

Over the last decade, hematopoietic stem cells transplantation (HSCT) has been increasingly used in the treatment of severe progressive autoimmune diseases. We report a retrospective survey of 183 multiple sclerosis (MS) patients, recorded in the database of the European Blood and Marrow Transplantation Group (EBMT). Transplant data were available from 178 patients who received an autologous graft. Overall, transplant related mortality (TRM) was 5.3% and was restricted to the period 1995-2000, with no further TRM reported since then. Busulphan-based regimens were significantly associated with TRM. Clinical status at the time of transplant and transplant techniques showed some correlations with toxicity. No toxic deaths were reported among the 53 patients treated with the BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan)/antithymocyte globulin (ATG) regimen without graft manipulation, irrespective of their clinical condition at the time of the transplant. Improvement or stabilization of neurological conditions occurred in 63% of patients at a median follow-up of 41.7 months, and was not associated with the intensity of the conditioning regimen. In this large series, HSCT was shown as a promising procedure to slow down progression in a subset of patients affected by severe, progressive MS; the safety and feasibility of the procedure can be significantly improved by appropriate patient selection and choice of transplant regimen.

Is the supine position as safe and effective as the prone position for endoscopic retrograde cholangiopancreatography? A prospective randomized study.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is usually performed with the patient lying in the prone position, on the assumption that this position is optimal for cannulation of the papilla and for obtaining good-quality radiographic images. The supine position, however, may be more comfortable for the patient and may facilitate airway management, and this study aimed to compare the two positions in terms of procedure outcome, safety, and patient tolerance. PATIENTS AND METHODS: Consecutive patients who were undergoing ERCP were randomized to start the procedure in either the prone position or the supine position. Patients under the age of 18 years, intubated patients, and those who had already undergone endoscopic sphincterotomy were excluded. The difficulty of cannulation was assessed using the Freeman score (1=one to five attempts; 2=six to 15 attempts; 3=more than 15 attempts; 4=failure of cannulation). Total procedure time, patient tolerance, willingness to undergo ERCP in the future, and procedure-related adverse cardiorespiratory events (oxygen desaturation, tachycardia, bradycardia) were also recorded. RESULTS: A total of 34 patients were evaluated (21 men, 13 women; mean age 68, range 20-96), 17 patients in each group. Demographic and clinical features, and the indications for the procedure were similar for the two patient groups. The median Freeman score was significantly lower in the prone group compared with the supine group (1 vs. 3, P=0.0047, rank sum test). Biliary cannulation was achieved in all patients in the prone group, but was not achieved in five patients (29%) in the supine group (P=0.052). In four of these five patients, biliary cannulation was successfully achieved after turning the patient into the prone position. The percentage of patients unwilling to repeat the ERCP procedure in the future was higher in the supine group (29% vs. 6%, P=0.087); the mean tolerance score and mean total procedure time were similar in the two groups. Seven patients in the supine group experienced at least one adverse cardiorespiratory event, compared with only one patient in the prone group (41% vs. 6%, P=0.039). CONCLUSIONS: ERCP performed with the patient in the supine position is technically more demanding for operators used to working with patients in the prone position and carries a greater risk of adverse cardiorespiratory events in nonintubated patients.

Thyroid papillary cancers: microcarcinoma and carcinoma, incidental cancers and non-incidental cancers - are they different diseases?

OBJECTIVE: Tumour size represents a much-debated prognostic factor in papillary cancer, and the necessity to perform a fine-needle aspiration (FNA) on small nodules is a frequent matter of discussion. We compared some prognostic histological features for various sizes of papillary cancers (PCs) and, with regard to these prognostic features, we compared non-incidental with incidental PCs. We also considered the possibility that ultrasonography could detect nodules harbouring the most aggressive cancers. DESIGN AND PATIENTS: We have studied patients with a histological diagnosis of PC from 1999 to 2003. FNA was performed on all nodules > 1.0 cm and on hypoechoic nodules with irregular margins or microcalcification when the size was < 1.0 cm (3321 FNAs in total). We were able to consider several different types of patients: those with PC diagnosed by FNA before surgery; those with large goitre and PC of small size diagnosed after histological examination and in whom a careful examination of the presurgical ultrasonography could show a distinct highly suspicious nodule that was not subjected to FNA, and patients with real incidental PC (that is, those with nodular goitre who correctly underwent FNA on suspicious nodules but in whom thyroid cancer was discovered only at histological examination). We considered two groups of patients with PC. Group 1 PCs were diagnosed before surgery with FNA (128 cases); in this group we also considered the two cases that were not correctly diagnosed before surgery. Group 2 real incidental PCs (12 cases) were found in goitres at histological examination after thyroidectomy for goitre (282 thyroidectomies). Group 1 was divided into three subgroups according to the maximum size of the PC at histological examination: (a) 44 PCs with maximum size < 10 mm, (b) 47 PCs with maximum size between 10 mm and 20 mm, and (c) 39 PCs with maximum size 20 mm. In all subgroups 1 as well as in group 2, the following four histological features were considered separately: multifocality, extracapsular extension, lymph-node involvement and its extent, and special aggressive features (dedifferentiation and/or insular aspects, tall and columnar variants). RESULTS: In subgroups 1a, 1b and 1c the results were, respectively: multifocality 56.8, 57.4 and 51.2%; extracapsular extension 27.2, 23.4 and 46.3% (P = 0.01, subgroups 1a and 1b vs. subgroup 1c); lymph-node metastasis 13.5, 23.3 and 46.1% (P = 0.003 subgroup 1a vs. 1c; P = 0.04, subgroup 1b vs. 1c); special aggressive features 11.3, 25.5 and 28.2% (P = ns). Group 2 showed one case of multifocality (8.3%) in a patient with prior exposure to radiotherapy in childhood, while no case was found of extracapsular invasion or lymph-node involvement, and only one patient had a PC with features of dedifferentiation. CONCLUSIONS: Non-incidental cancer, apart from multifocality, showed a classical progression for all prognostic factors from microcarcinoma to larger cancers. However, real incidental PC seemed to be different from non-incidental PC microcarcinoma regarding the main prognostic features. We conclude that ultrasonography is useful not only in terms of revealing the presence of cancer but also in identifying the most aggressive cancers.

Increased prevalence of migraine in patients with uninvestigated dyspepsia referred for open-access upper gastrointestinal endoscopy.

BACKGROUND AND STUDY AIMS: The association between gastrointestinal symptoms and headache is frequently unrecognized. The aim of the present study was to determine the prevalence of migraine in dyspeptic outpatients referred for upper gastrointestinal endoscopy. PATIENTS AND METHODS: Patients aged 18 - 55 years undergoing upper gastrointestinal endoscopy for dyspeptic symptoms in three endoscopic units were recruited consecutively. All of the patients were given a validated questionnaire on headache symptoms in order to determine the prevalence of migraine. Patients were divided into four groups (ulcer-like dyspepsia, reflux-like dyspepsia, dysmotility-like dyspepsia, only nausea and/or vomiting). Age-matched blood donors were given the same questionnaires and served as controls. RESULTS: A total of 378 patients (mean age 40 +/- 11, 52 % men) and 310 controls (mean age 39 +/- 11, 56 % men) were enrolled. No differences were observed between the two groups in the prevalence of migraine (15 % vs. 11 %; P = 0.12). A higher prevalence of migraine was found among women in both groups (P < 0.006). In patients with reflux-like and ulcer-like dyspepsia, the prevalence of migraine did not differ from that in the control individuals (8 % and 7 %, respectively), whereas a higher prevalence of migraine was noted in patients with dysmotility-like dyspepsia (23 %; P < 0.02 vs. controls, those with ulcer-like dyspepsia and those with reflux-like dyspepsia) and in patients with nausea and/or vomiting alone (53 %; P < 0.002 vs. all other groups). The multivariate analysis confirmed that the symptom pattern and sex were the only variables independently associated with migraine. CONCLUSIONS: A diagnosis of migraine should be considered in young patients referred for upper gastrointestinal endoscopy due to nausea and/or vomiting or for dysmotility-like dyspepsia.

Appropriateness of immunosuppressive drugs in inflammatory bowel diseases assessed by RAND method: Italian Group for IBD (IG-IBD) position statement.

INTRODUCTION: Despite the explosion of biological therapies, the old immunosuppressants continue to play a pivotal role in the management of inflammatory bowel diseases. AIM: To assess the appropriateness of immunosuppressants-azathioprine, 6-mercaptopurine, methotrexate, cyclosporine A, tacrolimus (FK506), mycophenolate mofetil and thalidomide-in the treatment of inflammatory bowel disease by using RAND/University of California Appropriateness Method. METHODS: The RAND method consists of a combination of evidence from the literature and experts' opinions. Appropriateness has been defined to mean that the expected health benefit exceeds the expected negative consequences by a sufficiently wide margin. A panel of 10 experts from the Italian Group for Inflammatory Bowel Disease has rated, in two rounds, on a scale from 1 to 9, the appropriateness of each indication selected by the Promoter Centre, on the basis of their own clinical experience. An indication was considered appropriate if the median of the panelists' ratings fell within the area 7-9, inappropriate in the area 1-3 and uncertain in the area 4-6. A total of 2781 indications were grouped into 13 categories (mild to moderate Crohn's disease; severe Crohn's disease; fistulizing Crohn's disease; steroid-dependant and -resistant Crohn's disease; maintenance of remission induced by medical treatment in Crohn's disease; maintenance of remission induced by surgery in Crohn's disease; mild to moderate ulcerative colitis; severe ulcerative colitis; steroid-dependant and -resistant ulcerative colitis; maintenance of remission induced by medical treatment in ulcerative colitis; extra-intestinal manifestations in inflammatory bowel disease; pregnancy and inflammatory bowel disease; azathioprine-resistant or -intolerant inflammatory bowel disease patients). RESULTS: Of the 2781 scenarios, 212 (7.6%) were rated appropriate, 645 (23.2%) uncertain and 1924 (69.2%) inappropriate. The most relevant results were: in steroid-dependant or -resistant Crohn's disease, azathioprine, 6-mercaptopurine and methotrexate were defined as appropriate in 25 (86.2%) and 14 (48.3%) of the 29 scenarios respectively; in Crohn's disease, azathioprine and 6-mercaptopurine were defined as appropriate combined with Infliximab (bridge therapy); in steroid-dependant or -resistant ulcerative colitis, azathioprine and 6-mercaptopurine were defined as appropriate in 45 (77.6%) out of 58 scenarios, while methotrexate was defined appropriate only after previous azathioprine failure; in severe ulcerative colitis, cyclosporine A was defined as appropriate only after previous failure with steroids; in azathioprine-intolerant or -resistant inflammatory bowel disease patients, methotrexate was appropriate in 20 (66.7%) out of 30 scenarios; it is inappropriate to stop azathioprine treatment before conception in the presence of active disease. The use of FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate or uncertain. CONCLUSIONS: Results of this study show that only azathioprine, 6-mercaptopurine and methotrexate are appropriate in the treatment of inflammatory bowel diseases. Cyclosporine A was found to be appropriate only in severe ulcerative colitis after the failure of steroids. FK506, mycophenolate mofetil and Thalidomide resulted as inappropriate but experience with these agents is somewhat limited.

Infliximab in the treatment of Crohn's disease: predictors of response in an Italian multicentric open study.

BACKGROUND: Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. AIMS.: To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. PATIENTS AND METHODS: Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI)>220-400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endpoints of the study were clinical response and clinical remission for luminal refractory and fistulising disease. We evaluated at univariable and multivariable analysis the following variables: number of infusions, sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, and type of fistulas. RESULTS: Patients with luminal refractory disease: 322 patients (84.1%) had a clinical response and 228 (59.5%) reached clinical remission. Patients with fistulising disease: 187 patients (72%) had a reduction of 50% of the number of fistulas and in 107 (41%) a total closure of fistulas was observed. For luminal disease, single infusion (OR 0.49, 95% CI 0.28-0.86) and previous surgery (OR 0.53, 95% CI 0.30-0.93) predicted a worse response for fistulising disease. Other fistulas responded worse than perianal fistulas (OR 0.57, 95% CI 0.303-1.097). CONCLUSION: In Crohn's disease infliximab is effective in luminal refractory and in fistulising disease. A single infusion and previous surgery predicted a worse response in luminal disease whereas perianal fistulas predicted a better response than other type of fistulas.

Ischemic colitis associated with rofecoxib.

Rofecoxib is a selective cyclooxygenase-2 inhibitor that has been approved for the treatment of osteoarthritis and management of acute pain. Recent debate has emerged regarding the prothrombotic potential and the cardiovascular safety of this new drug, especially at doses greater than 25mg. We describe two extensively investigated cases of self-limited ischemic colitis in patients who were briefly treated with 50mg rofecoxib daily for acute pain. In both cases, the onset of symptoms correlated temporally with rofecoxib use and symptoms abated with drug discontinuation. There was no evidence of other possible causes of colon ischemia. A causal relationship between the start of rofecoxib treatment and the colon ischemia cannot be definitely established on the basis of the evidence, but the temporal relationship is striking and the pathophysiological rationale could be founded.

Intense immunosuppression followed by autologous stem cell transplantation in severe multiple sclerosis.

Aggressive forms of multiple sclerosis (MS) represent a limited group of demyelinating diseases that rapidly progress to severe disability. Currently available therapies are poorly effective against these clinical entities. Recently, it has been demonstrated that intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI. We report the result of the Italian phase 2 GITMO study, a multicentre study in which 21 MS patients, who were rapidly deteriorating and not responding to the usual therapeutic strategies, were treated with this procedure. The clinical effect of the treatment is long lasting, with a striking abrogation of inflammation detected by MRI findings. These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies.

Prevalence of the E1317Q variant of the APC gene in Italian patients with colorectal adenomas.

Loss of APC is an initial, rate-limiting event in inherited and sporadic colorectal tumorigenesis. Rare germline APC mutations have been identified in patients with multiple colorectal adenomas. Recently, the E1317Q APC variant has been associated with a predisposition to the development of multiple colorectal adenomas. In this study, the prevalence of the E1317Q variant was examined in 182 patients with single or multiple colorectal adenomas, and in 235 controls. In all, E1317Q was identified in two of 182 patients with adenomatous polyps (1.1%) and in two of 235 controls (0.8%) (p = 0.59). The risk of harboring adenoma(s) among subjects bearing the E1317Q variant was 1.29 (95% CI 0.09-18.0). No difference in the prevalence of E1317Q between cases with single (2.0%) or multiple colorectal adenomas (0.7%) and controls (0.8%) was found. None of the subjects with a family history of colorectal cancer carried the E1317Q variant. In conclusion, our results confirm that only a very small fraction of colorectal adenomas may be associated with the presence of E1317Q.

Virtual colonoscopy.

Computed axial colonography, usually called virtual colonoscopy, is a new diagnostic method potentially useful for investigating polyps and tumors of the colon and rectum. It uses spiral axial tomography data to build up images similar to those given by conventional colonoscopy, offering advantages in that it causes no adverse reactions, and is accepted well by patients, who do not need to be sedated. Reports to date show its sensitivity and specificity vary in identifying polyps in the colon, and there are still many problems with the new method, such as its cost, its learning curve, the identification of flat lesions, and detection of extracolonic abnormalities. There is a pressing need to establish the accuracy and cost-effectiveness of virtual colonoscopy as a screening method for colorectal tumors, and for post-polypectomy surveillance.

Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS.

BACKGROUND: Autologous hematopoietic stem cell transplantation (ASCT) has been recently utilized with encouraging results in patients with poorly controlled MS. OBJECTIVE: To determine in severe cases of MS the effect of ASCT on gadolinium (Gd)-enhanced MRI and to obtain information on clinical course and safety. METHODS: In a cooperative study, 10 patients with rapidly evolving secondary progressive MS were transplanted, after BEAM conditioning regimen (carmustine, etoposide, cytosine-arabinoside, and melphalan), with unmanipulated autologous peripheral blood SC mobilized with high-dose cyclophosphamide (CY; 4 g/m2) and granulocyte-colony-stimulating factor. Triple-dose Gd-enhanced scans were performed monthly for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI for the following 6 months and then once every 3 months. RESULTS: The median follow-up is now 15 months (range 4 to 30 months). The number of Gd-enhancing lesions decreased immediately after mobilization with CY and finally dropped to zero in all cases after the conditioning regimen. The number of new T2-weighted positive lesions paralleled data obtained for Gd-enhanced MRI. Clinically, patients improved slightly or remained stable. CONCLUSION: These results demonstrate that the therapeutic sequence CY-BEAM-ASCT has the capacity to completely suppress MR-enhancing activity, an effect that is sustained with time. The final impact of this procedure on disease course remains to be established.

Routine versus "on demand" sedation and analgesia for colonoscopy: a prospective randomized controlled trial.

BACKGROUND: The safety and tolerance of routine sedation and analgesia versus "on demand" sedation were compared in patients undergoing colonoscopy. METHODS: Two hundred forty-nine outpatients were randomly assigned to one of two groups. Group A (n = 125) received midazolam, 0.07 mg/kg intravenously plus meperidine, 0.77 mg/kg intravenously immediately preceding the colonoscope insertion. Group B (n = 124) received the same medication upon request during the procedure. Tolerance was assessed 24 hours later by phone interview performed by a nurse blinded to the medication regimen administered. RESULTS: Eighty-three patients (66%) in Group B required sedation during colonoscopy. Among men in Group B more than 60 years of age, only 23% required sedation. The proportion of patients reporting moderate or severe pain (34% vs. 12.1%, p < 0.001) and of those stating they would not be willing to undergo colonoscopy again in the future (22% vs. 9.7%, p < 0.005) was significantly higher in the "on demand" sedation group. By multivariate analysis the randomization group was the single variable independently associated with both such outcomes. The frequency of side effects was similar in the two groups. CONCLUSIONS: Administration of sedative and analgesic drugs routinely before colonoscopy is superior to "on demand" sedation in terms of tolerance and is not associated with an increase in side effects.