Does the Antitumor Necrosis Factor-α Therapy Decrease the Vertebral Fractures Occurrence in Inflammatory Bowel Disease?

BACKGROUND/OBJECTIVE: Osteoporosis and osteoporotic fracture risk are extraintestinal manifestations of the inflammatory bowel disease, whose etiopathogenic mechanisms have not been determined yet. Anti-tumor necrosis factor (TNF)-α are used in treatment of inflammatory bowel disease (IBD), but it is unknown if they play a role in osteoporotic fracture prevention. The objective of this study was to know if anti-TNF decreases fracture risk or modifies bone mineral density. To determine the possible risk factors associated with fractures, and assess the incidence of vertebral fractures in IBD patients. METHODS: Longitudinal prospective cohort study (7 yr of follow-up); which included 71 IBD patients, 23 received anti-TNF-α; the remaining 48 received conventional treatment, constituted the control group. Patients participated in a questionnaire which gathered risk factors associated with the development of osteoporosis and fractures. Radiographs of the dorsolumbar-spine were performed and also a bone density measurement. Their biochemical and bone remodeling parameters were determined. RESULTS: Although patients who did not receive anti-TNF-α, suffered more fractures but biologic therapy did not reduce the risk of new vertebral fractures. The increase of bone mass was significantly higher the group treated with anti-TNF-α. The increase in the lumbar spine was of 8% and in the femoral neck was of 6.7%. The only determinant factor for the incidence of vertebral fractures was a history of previous fractures (odds ratio of 12.8; confidence interval 95% 2.37-69.9; p = 0.003). The incidence of vertebral fractures in IBD patients was considerably high: 26.7/700 patient-yr. CONCLUSIONS: Anti-TNF-α, although increased bone mass in these patients, did not reduce the risk of new vertebral fractures. In this study, patients with IBD have a considerably high incidence of fractures. Only the existence of previous vertebral fractures was a predictive factor for consistent fractures.

Effectiveness and Safety of CT-P13 (Biosimilar Infliximab) in Patients with Inflammatory Bowel Disease in Real Life at 6 Months.

BACKGROUND: CT-P13 is a biosimilar of Remicade®, an agent approved in some countries for use in inflammatory bowel disease (IBD). Controlled clinical trials have demonstrated the efficacy and safety of CT-P13 in rheumatic diseases, but not in IBD. AIMS: To assess the effectiveness and safety of CT-P13 in IBD patients in real clinical practice. METHODS: This is a prospective observational study in patients with moderate to severe Crohn's disease or ulcerative colitis treated with CT-P13. The study was performed in one single center. Patients included were naive or switched to anti-TNF treatment from the reference infliximab (Remicade®) to CT-P13. Efficacy and safety were assessed in naive and switched patients who were in remission at the time of the switch at months 3 and 6 of therapy. RESULTS: 87.5 and 83.9% of switched CD patients who were in remission at the time of the switch continued in remission, and 66.7 and 50% of naive CD patients reached remission, at months 3 and 6. In UC switched cases, 92 and 91.3% of patients in remission at the time of the switch continued in remission, at 3 and 6 months. In naive UC patients, the remission rates were 44.4 and 66.7%, at months 3 and 6. Adverse events occurred in 7.5% of patients during 6 months of study. CONCLUSIONS: CT-P13 was efficacious and well tolerated in patients with CD or UC.

Characteristics and treatment of pyoderma gangrenosum in inflammatory bowel disease.

BACKGROUND: Pyoderma gangrenosum is a serious cutaneous complication seen in approximately 1 % of patients with inflammatory bowel disease (IBD). Oral corticosteroids are the mainstay treatment, although the evidence supporting their use is weak. AIMS: The purpose of this study was to investigate the characteristics of pyoderma gangrenosum associated with Crohn's disease or ulcerative colitis and which treatments are prescribed in Spanish clinical practice. METHODS: In this retrospective, observational study, the medical records from all patients with IBD and a diagnosis of pyoderma gangrenosum attended by the gastroenterology departments of 12 Spanish hospitals were reviewed. Data on patient demographics and characteristics, underlying IBD and treatment, and pyoderma gangrenosum characteristics, treatment, and outcome were collected and analyzed. RESULTS: The data from 67 patients were analyzed (41 [61.2 %] women, 41 [61.2 %] with Crohn's disease, 25 [37.3 %] with ulcerative colitis, and 1 [1.5 %] with indeterminate disease). The underlying disease was in remission in approximately one-third of patients at the time of presentation of pyoderma gangrenosum. Healing was achieved in all patients (in 3 without any systemic therapy). Oral corticosteroids were taken by 51 patients (76.1 %), almost always as first-line treatment, although definitive healing was attained in 19 (28.4 %). Biologic agents such as infliximab and adalimumab were taken by 31 patients (46.3 %) at some point (first-line in 6 patients [9.0 %]), with definitive healing in 29 patients (93.5 %). CONCLUSIONS: Oral corticosteroid therapy remains the most common treatment for pyoderma gangrenosum associated with inflammatory bowel disease. Biologic therapies such as infliximab and adalimumab should also be considered.

Efficacy of adalimumab in patients with Crohn's disease and failure to infliximab therapy: a clinical series.

BACKGROUND: adalimumab, a human anti-TNF, is an effective induction and maintenance therapy for patients with moderate to severe Crohn's disease. It seems to be effective in patients with resistance to infliximab, too, though the experience is more limited. AIM: to evaluate the efficacy of adalimumab, in patients with Crohn's disease (CD) and failure to previous treatment with infliximab. METHODS: twenty-five patients with CD and failure to previous treatment with infliximab were enrolled; they were treated with 160/80 (24 patients) and 80/40 (1 patient) induction doses. We analyze clinical response to treatment with adalimumab by the Crohn's disease Activity Index (CDAI) and plasma concentration of C-reactive protein (CRP), steroid sparing and complete fistula closure at week 48. RESULTS: eighteen out of twenty-five patients (72%) achieved clinical remission (CDAI score < 150) at week 24 and 15/25 (60%) patients at week 48. There was a statistically significant difference(p < 0.01) in CRP serum levels from 21 to 8 mg/dl at week 48.Nine out of fifteen patients (60%) treated with corticosteroids were able to discontinue steroids. Three out of eleven patients (27%) with fistulizing Crohn's disease had complete fistula closure after the treatment. Seventy two percent of the patients (18/25) needed to increase adalimumab to weekly dose, in order to maintain clinical response. Five out of twenty-five patients (20%) had adverse events; two of them (8%) with serious adverse events (tuberculous meningitis and abdominal abscess) that forced the withdrawal of treatment. CONCLUSIONS: according to these data, adalimumab provides a clinical and analytical improvement in patients with CD and failure to previous therapy with infliximab.

PillCamColon Capsule for the study of colonic pathology in clinical practice. Study of agreement with colonoscopy.

INTRODUCTION: several studies have pointed out the effectiveness of the PillCam colon capsule endoscopy (CCE) compared with the colonoscopy in the study of the colonic pathology. AIMS AND METHODS: the objective of our study was to assess the agreement in the diagnosis of CCE with conventional colonoscopy as well as its sensitivity and specificity, and to describe the findings of the CCE in our clinical practice. Consecutive patients with abdominal symptoms were included in the study. The CCE was performed as previously reported (with PEG and sodium phosphate as laxative agents). The nature and location of the findings, colonic transit time, complications, cleanliness degree and consistency with diagnostic colonoscopy, when performed, were analyzed. RESULTS: a total of 144 subjects (67 women and 77 men); (52.17 ± 16.71 years) with the following indications were included: screening of Colorectal cancer (88 patients), control after polipectomy (24), incomplete colonoscopy (7), rectal bleeding (10), anemia (8), diarrhea (7). The CCE exploration was complete in 134/144 cases (93%), with no case of retention. The preparation was good-very good in 88/134 (65,6%), fair in 26/134 (19,4%) and poor in 20/134 (15%) of the cases. The average colonic transit was of 140.76 min (9-603). Any adverse effect was notified.In 44 cases a colonoscopy was carried out after CCE (results were hidden from another endoscopist). Compared to colonoscopy, the rate of agreement was 75,6%, the sensitivity was 84% and the specificity 62,5%, PPV was 77,7% and NPV was 71,4%.The colonic findings in 134 CCE were: in 34 cases CCE it did not show lesions, diverticulosis in 63 explorations, polyps in 43, angiodysplasias in 15, Crohn's Disease in 9 and ulcerative colitis in other 8 cases. CONCLUSIONS: the CCE is an effective and reliable technique for the detection of lesions in colon, and because of its high agreement with the colonoscopy, it could be useful in clinical practice. Further studies with large seria and cost-effectiveness analysis are needed to confirm these data.

Macroscopic small bowel mucosal injury caused by chronic nonsteroidal anti-inflammatory drugs (NSAID) use as assessed by capsule endoscopy.

OBJECTIVE: To evaluate the type, frequency, and severity of macroscopic small bowel mucosal injury after chronic NSAID intake as assessed by capsule endoscopy (CE), as well as to correlate the severity of gastroduodenal and intestinal damage in these patients. MATERIAL AND METHODS: A prospective, endoscopist-blind, controlled trial. Sixteen patients (14F/2M; age: 57.06 +/- 10.16 yrs) with osteoarthritis (OA) on chronic therapy with NSAIDs underwent CE and upper gastrointestinal endoscopy (UGE). Seventeen patients with OA (9F/2M; age: 57.47 +/- 9.82 yrs) who did not take NSAIDs were included as a control group. A scale ranging from 0 to 2 (0 = no lesions, 1-minor = red spots or petechiae, denuded areas and/or 1-5 mucosal breaks; 2-major = > 5 mucosal breaks and/or strictures, or hemorrhage) was designed to assess the severity of small bowel mucosal injuries. RESULTS: CE found intestinal lesions in 75% (12/16) of patients in the study group and in 11.76% (2/17) of controls (p < 0.01). Seven out of 16 NSAID consumers (43.75%) and none in the control group (0%) had a major small bowel mucosal injury (p < 0.01). The percentages of patients with grade 1 and 2 gastroduodenopathy in the study group, as assessed by UGE, were 37.14 and 23.81%, respectively. There was no significant difference in the rate of major enteropathy between patients with none or minor gastroduodenal injury, and those with major gastroduodenopathy (43.75 vs. 40%; p = N.S.). CONCLUSIONS: Chronic NSAID intake is associated with a high rate of small bowel mucosal injuries. Our data have failed to demonstrate a relationship between the severity of gastroduodenal and intestinal injury.

[Is capsule endoscopy useful in children with chronic abdominal pain?]. / Es útil la cápsula endoscópica en niños con dolor abdominal crónico?

Chronic abdominal pain is highly prevalent in school-aged children and is one of the most frequent disorders in our environment. The aim of the present study was to evaluate the usefulness of capsule endoscopy (CE) in patients with chronic abdominal pain. Sixteen patients (nine boys and seven girls), aged between 5 and 16 years old, with chronic abdominal pain for at least 12 months were studied. In all patients the results of hemograms, biochemical investigations, urine sediment test, Helicobacter pylori breath test and celiac serology were normal. In all children, gastroscopy, small bowel follow-through, abdominal ultrasound and colonoscopy were normal. All patients received CE by mouth. In 43.75 % of the patients studied (7/16), the capsule showed evidence of nodular lymphoid hyperplasia, mainly located in the ileum. In one girl, oxyuriasis was observed in the cecum and in another girl aphthous lesions were observed in the ileum. These lesions suggested small bowel Crohn's disease. CE mainly showed images compatible with nodular lymphoid hyperplasia, with unknown clinical significance. Consequently, we conclude that CE does not provide useful information in patients with abdominal pain without other symptoms.

Diagnostic yield of 335 push video-enteroscopies.

BACKGROUND AND OBJECTIVES: The diagnostic yield of push enteroscopy (PE) varies widely from 13 to 78% of cases, according to the various series. The aim of this retrospective cohort study was to determine the endoscopic and histological yield of PE in our health area. PATIENTS AND METHODS: A total of 355 consecutive patients (190 males/165 females; mean age 45 years, range 15-89) underwent PE over a 6-year period, from 1997 to 2003. PE was performed under sedation and without overtube. Small-bowel mucosa biopsies were taken in 199 explorations (56%). Clinical indications for PE included: chronic diarrhea (35%), occult digestive bleeding (ODB) or iron-deficiency anemia (28%), suspected small-bowel malignancy (16%), chronic abdominal pain (28/355; 8%), follow-up of polyposis or malabsorption syndromes (7%), and abnormal radiographic findings (6%). RESULTS: PE detected lesions in 122 cases (34%); in 6 cases (6%) lesions were within the reach of esophagogastroduodenoscopy. A normal macroscopic appearance of the small intestinal mucosa with an abnormal histological study was seen in 16 patients (6%). Major findings included: malabsorptive diseases (14%), nonspecific enteropathy (5%), angiodysplasia (3,5%), lymphangiectasia (3%); jejunal polyps (2%), Crohn s disease (2%), intestinal tumors (2%), extrinsic jejunal strictures (0.5%), and other (10/355; 3%). Abnormal radiographic findings (62%), chronic diarrhea (37%) and ODB (31%) were the indications with a higher diagnostic yield. No major complications were seen. CONCLUSIONS: According to our experience, PE is a safe and useful tool for the evaluation of small-bowel disease, especially in some indications (abnormal radiographic findings, chronic diarrhea, and ODB). Small-bowel biopsy increases PE's diagnostic yield in patients with chronic diarrhea.

Previously unknown stricture due to radiation therapy diagnosed by capsule endoscopy.

Radiation enteritis is a complex clinical entity secondary to the affectation of intestinal epithelial cells as a result of radiation in the management of pelvic malignancies that may occasionally cause intestinal strictures. We present the case of a 60 year-old woman who had been diagnosed ten years before with endometrial adenocarcinoma, and who underwent hysterectomy with double adnexectomy and subsequent radiation therapy. The patient consulted for abdominal pain and ferropenic anemia of several years standing, and had negative results following radiographic and endoscopic conventional techniques, reason why she was subjected to a capsule endoscopy study that revealed the presence of an ulcerated ileal stricture, which caused the asymptomatic retention of the capsule within the ileum. A laparotomy was subsequently performed--the strictured segment was resected and the capsule retrieved. The histologic examination of the resected segment confirmed the capsule endoscopy-raised suspicion of radiation enteritis. This case shows the role capsule endoscopy may play in the diagnosis of this condition.

[Severe liver failure in erythropoietic protoporphyria. A report of a case treated by liver transplantation]. / Fallo hepático grave en la protoporfiria eritropoyética. Comunicación de un caso tratado con trasplante hepático.

Severe liver failure is a rare complication of erythropoietic protoporphyria (PEP), which is associated with a high rate mortality. Until now, 31 patients with this hepatic complication had underwent a liver transplantation, with a high rate of survival, but their long-term outcome is not well established. We report the first case in Spain of PEP in 59-year-old, whose acute liver failure was treated with liver transplantation, without postoperative complications. The patient is in good clinical condition 30 months later. Nevertheless during the first eleven months of follow-up the plasma levels of protoporphyrin remained elevated, which was accompanied of biochemical and histological evidence of relapse of the metabolic disease in the graft. Cases such as this stress the usefulness of liver transplantation, but also the need of more efficient measures to decrease the protoporphyrin levels before and after the transplant, in order to prevent hepatic and extrahepatic complications in these patients.

Utility of the endo-rectal ultrasonography with sectorial transducer in the study of rectoanal pathology.

OBJECTIVE: Assessing the usefulness of endorectal ultrasonography with a sectorial transducer to diagnose and determine the degree of rectoanal disease. MATERIAL AND METHODS: We used a 5 MHz sectorial echographic transducer to study 61 successive patients, 22 of them with a suspicion or diagnosis of anorectal neoplasia (group I); 25 with perianal suppurating disease (group II); 9 with faecal incontinence (group III) and 5 with chronic idiopathic anal disease (group IV). RESULTS: In group I, 3 patients (13.63%) were sent to us with a suspicion of anorectal cancer which was not confirmed for any of them. For other 3 patients (13.63%) we had to rule out a neoplastic relapse which was only confirmed in one case; in 16 patients (72.72%) we had to establish tumour stage, which we achieved in 81.25% of cases. In group II, 2 patients had Crohn's perianal disease (8%), 10 patients showed a perianal abscess (40%) and 13 (52%) individuals had fistula tracts whose internal orifices could be found in 53.84% of cases. In all patients sent with faecal incontinence (group III) we could delimit sphincter interruption. A sphincter abscess was found in one of the 5 patients sent to us with chronic idiopathic anal pain, although it had not been diagnosed before. CONCLUSIONS: Sectorial endorectal ultrasonography is a very useful technique in the study of tumour and rectoanal suppurating diseases, as well as of faecal incontinence. It is also of great importance for patients with chronic idiopathic anal pain.

Wireless endoscopy.

Wireless endoscopy consists of a small-sized device which allows gastrointestinal tract images to be taken as it physiologically advances along its lumen after being orally ingested. Its primary contribution is the study of small bowel conditions, a gastrointestinal tract segment in which diagnosis difficulties still arise when using current tests, including enteroscopy. Preliminary studies in animals and healthy subjects have revealed data on image quality, sensitivity, specificity, and safety that demonstrate the benefits of this new technique. This review discusses technical aspects, indications and contraindications, as well as studies reported so far on this endoscopic diagnostic procedure.

Use of recombinant factor VII in hepatology.

Understanding the key role of factor VII (FVII) in the cascade of blood coagulation has led to consider its administration as an effective treatment for selected situations with altered haemostasis. Advances in genetic engineering have made it possible to obtain this factor by recombinant techniques (rFVII), rendering it both safe and widely available as a haemostatic treatment. So far, it has been commonly used for haemophilic patients with inhibiting antibodies against factors FVIII-FIX, but its use is currently extending to other areas. The presence of decreased FVII levels in patients with advanced, chronic liver disease has recently raised an interest in the study of this molecule as a new therapeutic option in the field of Hepatology. This paper will discuss the characteristics, indications, and studies existing to this day on the use of rFVII, particularly in cirrhotic patients.

Role of capsule endoscopy in the management of patients with obscure gastrointestinal bleeding.

The recent emergence of capsule endoscopy has entailed a relevant diagnostic imaging advance for gastrointestinal conditions, especially those involving the small bowel. Gastrointestinal haemorrhage of obscure origin is probably the most widely accepted indication for this new technique, and promising results have been reported from series extant to date. In view of data available on this new modality, and looking forward to having wide, well designed studies fr corroboration, this paper suggests a tentative algorithm for the management of this patient group.

Deflazacort for long-term maintenance of remission in type I autoimmune hepatitis.

OBJECTIVE: most patients with autoimmune hepatitis require long-term treatment, but up to 80% of them will develop collateral effects. The aim of this study was to evaluate the efficacy of deflazacort, an oxazolinic derivative of prednisolone with fewer effects on bone and glucose metabolism, in the maintenance of remission of type I autoimmune hepatitis in patients treated previously with conventional immunosuppressive therapy. METHODS: fifteen patients with type I autoimmune hepatitis were included. All patients had been treated previously with prednisone with or without azathioprine until biochemical remission was obtained and the dose could be reduced. Prednisone was then discontinued and deflazacort was started at a dose adjusted to a ratio of 5 mg prednisone per 7.5 mg deflazacort. The biochemical activity (serum ALT and IgG levels) of liver disease was monitored during a follow-up period of 25.8 +/- 7. 7 months. RESULTS: prednisone therapy was followed by a statistically significant decrease in serum ALT (0P: 386 +/- 345 U/L vs 2M 80 +/- 22 U/L, p < 0.02) and IgG (0P 3029 +/- 1934 mg/dL vs 2M 2064 +/- 933 mg/dL, p < 0.05), from the second month of treatment. After changing to deflazacort no alterations in ALT and IgG serum levels were detected except for a mild, transient increase in serum IgG during the first 3 months. During follow-up, 94% of the patients had normal or slightly increased (less than 50% above normal) ALT levels. The titers of ANA and ASMA remained the same in 82% of the patients, decreased in 12%, and increased in the remaining 6%. During follow-up no patient developed arterial hypertension, diabetes mellitus, or changes in visual acuity. Eight patients, all women, complained of dorsolumbar pain which was not related to osteoporosis. CONCLUSIONS: deflazacort seems to be useful in maintaining remission of autoimmune hepatitis during a prolonged period of follow-up. Future studies should include a histological evaluation of the patients and a prospective comparative analysis of side-effects.

[The assessment of colonic polyps found via colonoscopy]. / Valoración de los pólipos colónicos hallados mediante colonoscopia.

AIM: To evaluate the histopathological characteristics of colonic polyps, found during colonoscopy examination and endoscopic polypectomy, and their relation to age, tumor location, sex, histological type and degree of epithelial dysplasia. MATERIAL AND METHODS: Between 1996 and 1997, 2,465 total colonoscopies were performed at the Gastroenterology Department of the Virgin Macarena University Hospital in Seville. Different size polyps were found in 318 patients who had been referred because of several symptoms/by several centers. The mean age was 59.2 years in men and 61.5 years in women. RESULTS: 446 polyps were removed by endoscopic polypectomy, 32 (7.2%) were hyperplastic polyps, 402 were adenomas (90.2%) and 12 (2.6%) were adenomas with adenocarcinoma. Seventy-five percent of adenomas were located in the left colon and rectum and 25% in right colon. Hyperplastic polyps were found in left colon. Of the polyps removed, 55.1% were smaller than 1 cm, 26.5% were between 1 and 2 cm and 18.4% were between 2 and 7 cm. Histopathologic study of adenomas revealed that 17% were villous adenoma, 80% were tubular adenomas and 3% were tubulovillous adenomas. Adenocarcinomas were found in 12 (2.8%) adenomas. Of the adenomatous polyps, 87.4% had low-grade dysplasia and 12.6% high-grade dysplasia. Statistical analysis showed a strong correlation between size of adenoma and degree of dysplasia (p < 0.05). Similar significant relation was found between histological type and size (p < 0.05) but there were no statistically significant differences between location, sex or age, and degree of dysplasia (p < 0.05). CONCLUSIONS: Size of colonic polyps is related to epithelial dysplasia and histological type (p < 0.05). No correlation was found between location, sex or age and degree of dysplasia.

[Utility of capsule endoscopy in pediatric gastroenterology]. / Utilidad de la cápsula endoscópica en gastroenterología pediátrica.

Wireless endoscopy is a new noninvasive diagnostic method that is able to visualize small bowel lesions. The instrument is small and carries a battery and microcamera that takes two photographs per second. It is indicated in cases of bleeding of unknown origin and for the diagnosis of inflammatory bowel disease, among other disorders. To date, it has mainly been used in adults. We believe that this instrument could play an important role in the pediatric age group since it is noninvasive and can be used to diagnose small bowel lesions, thus avoiding unnecessary diagnostic tests. We report the case of a girl with suspicion of Crohn's disease that was unconfirmed by conventional endoscopic techniques. The capsule showed small bowel lesions compatible with Crohn's disease. Corticosteroid treatment was initiated and the patient is now in clinical remission.