RESUMEN
BACKGROUND: Prevalence of upper gastrointestinal (GI) tract involvement in adult Crohn's disease (CD) has been reported to be very low (0.3-5%). In routine practice, upper endoscopy is recommended only in CD patients with upper GI symptoms. Available data concerning the prevalence of asymptomatic upper GI lesions in CD patients are controversial. The aim of this study was to prospectively evaluate the prevalence of upper GI CD involvement in CD patients, irrespective of upper GI symptoms. METHODS: A series of 119 consecutive CD patients underwent clinical assessment, including occurrence and score of upper GI symptoms, and upper endoscopy with biopsy samples for histological assessment and Helicobacter pylori (Hp) infection detection. In an attempt to further recognize the upper GI tract lesions as CD or other form of inflammation, in a subgroup of CD patients, the histological and endoscopic evaluation was repeated following 12 weeks of anti-TNF-α or other treatments in association with proton-pump inhibitors. RESULTS: Upper CD involvement was found in 19/119 (16%) patients. Hp infection was detected in 10/119 (8.4%) CD patients. Hp-negative focally active chronic gastritis was found in 34/119 (28.6%) CD patients. At presentation, 12/19 patients (63%) showing upper CD involvement were asymptomatic and 7 (37%) symptomatic. CONCLUSION: A high prevalence of upper GI tract involvement has been observed in CD patients, irrespective of upper symptoms. This finding suggests the usefulness of routine upper endoscopy in the diagnostic work-up of CD patients in order to correctly classify the distribution and extent of the disease.
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Enfermedad de Crohn/patología , Endoscopía del Sistema Digestivo/métodos , Tracto Gastrointestinal Superior/patología , Adulto , Distribución por Edad , Anciano , Biopsia con Aguja , Estudios de Cohortes , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Duodenitis/diagnóstico , Duodenitis/tratamiento farmacológico , Duodenitis/epidemiología , Esofagitis/diagnóstico , Esofagitis/tratamiento farmacológico , Esofagitis/epidemiología , Femenino , Estudios de Seguimiento , Gastritis/diagnóstico , Gastritis/tratamiento farmacológico , Gastritis/epidemiología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Inhibidores de la Bomba de Protones/uso terapéutico , Medición de Riesgo , Distribución por Sexo , Resultado del Tratamiento , Tracto Gastrointestinal Superior/efectos de los fármacos , Tracto Gastrointestinal Superior/fisiopatología , Adulto JovenRESUMEN
Crohn's disease (CD) is a chronic, relapsing disease, the continuous cycle of which deeply affects the long-term course which, eventually, leads to fibrosis and development of transmural complications. It is well known that CD is an immune-mediated clinical condition and that tumor necrosis factor-alpha (TNF-alpha) plays a fundamental role in the pathogenesis of the disease. Current clinical guidelines recommend that patients with mild to moderate active CD should be treated initially with corticosteroids. Although this approach is effective in inducing remission, some patients may become dependent on, or refractory to, these drugs in the long term, thus increasing the risk of developing steroid-related adverse effects. A recent Cochrane systematic review established that infliximab (IFX) is effective in inducing remission in patients with CD. Although only a few published studies have assessed IFX for the maintenance of remission in the long term, there is evidence that IFX is superior to placebo in sustaining clinical remission and fistula healing; moreover, corticosteroid-sparing effects have been demonstrated. IFX is associated with the formation of antibodies to IFX which can lead to infusion reactions and shorter duration of response, but when comparing episodic vs scheduled maintenance treatment, the latter appears to sensibly reduce immunogenicity, thus offering improved efficacy and tolerance. The final point to consider is the best time to introduce IFX in the therapeutic algorithm of CD. Early use of IFX has been suggested to be more effective than late, and may potentially change the natural history of the disease. Effective induction and maintenance therapy with IFX is the only means with which to maintain long-lasting clinical and mucosal remission which, in turn, may modify the long-term course of the disease. Furthermore, when treating inflammatory bowel disease patients with IFX, an appropriate risk-benefit balance has to be taken into consideration, because the precise risk of serious adverse events associated with anti-TNF treatment in CD remains to be fully elucidated.
RESUMEN
Crohn's disease and ulcerative colitis represent the most common forms of inflammatory bowel disease (IBD), clinical conditions affecting the small and/or large bowel. It is well known that IBD is an immune-mediated condition and that TNF-alpha plays a pivotal role in the pathogenesis of the disease. TNF-alpha has been scrupulously studied as a target for therapeutic intervention in this setting. A number of biologic compounds have been developed, including the European Medicine Agency (EMEA)-approved agents, infliximab and adalimumab. Although their efficacy in induction and maintenance of remission has been established by several clinical trials, many issues regarding safety remain to be elucidated. In fact, anti-TNF treatment may be associated with a number of rare, but serious, adverse events, including infusion reactions, infections, lymphomas and other malignancies. A black-box warning has to be taken into consideration when looking at potential serious infections such as tuberculosis. Active infections, demyelinating disorders and severe heart failure are contraindications for anti-TNF treatment. This review focuses on drug toxicity and adverse events related to infliximab treatment in IBD.
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Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Adalimumab , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Ensayos Clínicos como Asunto , Etiquetado de Medicamentos , Humanos , Infliximab , Inducción de Remisión/métodos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
AIM: To prospectively investigate a new high resolution MRI technique for dynamic evaluation of the enhancement kinetics of bowel parietal layers and to correlate it with CDAI, CRP, endoscopic activity and histologic features. METHODS: About 16 consecutive patients with proven diagnosis of CD underwent ileocolonoscopy with biopsy and serial bowel dynamic contrasted-MRI (D-CE-MRI) evaluated in blind fashion. Quantitative analysis of bowel wall enhancement kinetics was performed basing on signal to noise ratio (SNR) of inner parietal layers (Mucosa-Submucosa, M-SM) and outer parietal layers (Muscular-Serosa, Ms-S). Disease activity was defined by CDAI > 150, serum CRP > 5 mg/dL and histologic results. RESULTS: About 9 patients showed a layered enhancement of bowel wall (8 active, 1 inactive), whereas inactive (7 cases) group presented a homogeneous pattern. In active patients we found a significant difference in parietal layered enhancement curves (M-SM vs. Ms-S, P < 0.03) not observed in inactive disease and controls (intra-group analysis). M-SM and Ms-S enhanced curves in clinically active patients were significantly different respect to those of patients with inactive CD (P < 0.001) (inter-group analysis). Parietal D-CE-MRI pattern well correlated with histologic features (r = 0.8; P < 0.001, Spearman test). CONCLUSIONS: D-CE-MRI can be a useful tool for clinical follow-up and in the treatment strategies in CD patients.
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Enfermedad de Crohn/diagnóstico , Íleon , Imagen por Resonancia Magnética/métodos , Adulto , Medios de Contraste , Diagnóstico Diferencial , Endoscopía Gastrointestinal , Femenino , Gadolinio DTPA , Humanos , Masculino , Estudios Prospectivos , Estadísticas no ParamétricasRESUMEN
AIM: To evaluate the safety and efficacy of a long-term therapy with infliximab in Crohn's disease (CD) and ulcerative colitis (UC) patients retrospectively. METHODS: The medical charts of 50 patients (40 CD and 10 UC), who received after a loading dose of 3 infliximab infusions scheduled re-treatments every 8 wk as a maintenance protocol, were reviewed. RESULTS: Median (range) duration of treatment was 27 (4-64) mo in CD patients and 24.5 (6-46) mo in UC patients. Overall, 32 (80%) CD and 9 (90%) UC patients showed a sustained clinical response or remission throughout the maintenance period. Three CD patients shortened the interval between infusions. Eight (20%) CD patients and 1 UC patient underwent surgery for flare up of disease. Nine out of 29 CD and 4 out of 9 UC patients, who discontinued infliximab scheduled treatment, are still relapse-free after a median of 16 (5-30) and 6.5 (4-16) mo following the last infusion, respectively. Ten CD patients (25%) and 1 UC patient required concomitant steroid therapy during maintenance period, compared to 30 (75%) and 9 (90%) patients at enrollment. Of the 50 patients, 16 (32%) experienced at least 1 adverse event and 3 patients (6%) were diagnosed with cancer during maintenance treatment. CONCLUSION: Scheduled infliximab strategy is effective in maintaining long-term clinical remission both in CD and UC and determines a marked steroid sparing effect. Long-lasting remission was observed following infliximab withdrawal.
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Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Adulto , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Infliximab , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios RetrospectivosRESUMEN
Control of the G1/S-phase transition as well as angiogenic switch are two of the most studied mechanisms in cancer. The current study examined the correlation between the immunohistochemical expression of pRb2/p130, VEGF, EZH2, p53, p16, p21waf-1, p27, and PCNA in Barrett's esophagus (BE). Overall, p53 showed a much higher expression in BE patients (up to 50%) than in controls (1-10%) (P < 0.005). Also p21 showed a downregulation in BE when compared to normal esophagus (70% of cells vs. 65%), but the difference did not show any statistical significance (P = 0.45). pRb2/p130 was detected in 80% of cells in normal controls, but showed positive in only 20% of cells in BE biopsies. Additionally, Rb2/p130 expression was inversely correlated to that of VEGF, EZH2, and PCNA (P < 0.0001, P = 0.0032, P < 0.001, respectively). p27 stained more intensely and in a widespread manner (70%) cells in normal esophageal tissues but about only 30% in BE samples (P < 0.001). Lastly, in accordance with other reports, we also found p16 expressed by immunohistochemistry at high levels in normal controls and at low levels in BE (P < 0.001). In conclusion, p16, p21, p27, and p53 staining confirmed previously published data. Interestingly, pRb2/p130 expression was found significantly decreased in metaplastic epithelium compared to normal controls and showed significant inverse correlation with the expression of other markers, such as VEGF, EZH2, and PCNA. These data, taken together, indicate that these molecular events occurring in Barrett's metaplasia (BM) may represent one of the many steps taking place during esophageal malignant progression such as impairment of cell-cycle control, altered differentiation, and unbalanced angiogenesis.
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Esófago de Barrett/metabolismo , Biomarcadores/análisis , Esófago/química , Anciano , Esófago de Barrett/patología , Biopsia , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/análisis , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/análisis , Proteínas de Unión al ADN/análisis , Proteína Potenciadora del Homólogo Zeste 2 , Esófago/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Complejo Represivo Polycomb 2 , Antígeno Nuclear de Célula en Proliferación/análisis , Proteína p130 Similar a la del Retinoblastoma/análisis , Factores de Transcripción/análisis , Proteína p53 Supresora de Tumor/análisis , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
OBJECTIVES: It has been demonstrated that dilation of intercellular spaces of esophageal epithelium is a marker of tissue injury in GERD patients with a pathological esophageal acid exposure time. To evaluate the relationship among ultrastructural changes, acid esophageal exposure, and GERD symptoms, intercellular space diameters have been assessed in nonerosive reflux disease (NERD) patients with/without abnormal acid exposure time. METHODS: Following a pharmacological wash-out, 20 NERD patients underwent upper endoscopy, esophageal manometry, and 24-h pH monitoring. Biopsies were taken at 5 cm above the lower esophageal sphincter and intercellular space diameters were measured on transmission electron microscopy photomicrographs. Seven asymptomatic controls underwent the same protocol. RESULTS: Acid exposure time was in the normal range in all controls and in 11 patients (NERD pH-negative); it was abnormal in 9 patients (NERD pH-positive). Mean intercellular space diameter in NERD pH-negative and in NERD pH-positive patients was three times greater than in controls (1.45 and 1.49 microm vs 0.45, p < 0.001). Mean values of maximum intercellular spaces in all NERD patients were greater, two-fold or more, than those in controls (p < 0.001). No difference in mean and maximal space diameters was observed between NERD pH-positive and pH-negative patients. CONCLUSIONS: Dilation of intercellular spaces is a feature of NERD patients, irrespective of esophageal acid exposure, and can be considered an objective, structural marker of GERD symptoms. Impaired esophageal mucosal resistance, even to small amounts of acid refluxate, plays a key role in the pathophysiology of NERD.
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Reflujo Gastroesofágico/patología , Adulto , Anciano , Biopsia , Dilatación Patológica , Células Epiteliales/ultraestructura , Espacio Extracelular , Femenino , Reflujo Gastroesofágico/fisiopatología , Humanos , Concentración de Iones de Hidrógeno , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Factores de TiempoRESUMEN
Crohn's disease (CD) is a chronic inflammatory bowel disease that may involve the whole gut. Marked intestinal T cell and macrophage activation is a key feature of the disease. Polymorphonuclear cell infiltration is also observed in the diseased gut, mainly during active inflammation. Scintigraphic detection of granulocytes and activated lymphocytes infiltrating the gut wall may be useful in identifying a subgroup of patients with clinically inactive CD who are undergoing early clinical relapse. The aims of the present study were (a) to compare the effectiveness of scintigraphy with (99m)Tc-labelled interleukin-2 ((99m)Tc-IL2) and with (99m)Tc-HMPAO labelled granulocytes ((99m)Tc-WBC) in detecting the presence and extent of bowel inflammation in patients with long-term inactive CD (>12 months) and (b) to assess the accuracy of these techniques in predicting future disease relapse. We studied 29 patients with ileal and/or colonic CD in stable clinical remission (Crohn's Disease Activity Index <150 for at least 12 months) using both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy in order to evaluate the extent of acute and chronic inflammation in the bowel. Planar and single-photon emission tomography images were acquired in each patient at 1 h p.i. For quantitative analysis of (99m)Tc-IL2 uptake, the abdomen was divided into 32 regions of interest. Despite the absence of symptoms, 18 patients (62%) showed a positive (99m)Tc-IL2 and 18 (62%) a positive (99m)Tc-WBC scan. Only 12 patients (41.4% of the total group) were positive on both scans, and the sites of IL2 and granulocyte bowel uptake were usually located in different segments, indicating that in CD, acute and chronic inflammation can be present in different sites. As far as the prognostic role of the two scans in predicting future disease relapse is concerned, both (99m)Tc-IL2 and (99m)Tc-WBC scintigraphy showed a high negative predictive value (1.00 and 0.91, respectively) but a weak positive predictive value (0.44 and 0.39, respectively). Nevertheless, Kaplan-Meier curves generated between scintigraphic findings and time free from disease relapse were statistically different only for (99m)Tc-IL2 scintigraphy (log-rank test, P=0.013). These results indicate that (99m)Tc-IL2 scintigraphy can be useful in selecting CD patients in clinical remission who could benefit from preventive therapy to avoid disease relapse.