Ustekinumab therapy for Crohn's disease during pregnancy: a case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVES: The safety of continued ustekinumab (UST) therapy during pregnancy remains unclear in patients with Crohn's disease (CD). There are no meta-analysis reports of exposure to UST during pregnancy. The objective was to describe a case of a pregnant patient with CD who was successfully treated with UST maintenance therapy throughout the pregnancy and delivered a baby boy without any congenital malformations, neurological abnormalities or birth defects. CASE SUMMARY: A 37-year-old patient with CD treated with UST became pregnant. She had been receiving UST for 8 months at the time. After discussion with the patient and the obstetric team, the UST therapy was continued. The result of treatment was an uneventful pregnancy with delivery, at term, of a healthy boy and the maintenance of clinical, biological and endoscopic remission of CD during and after pregnancy. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first reported use of continued UST therapy for CD throughout a pregnancy. The result of treatment was an uncomplicated pregnancy with the mother giving birth to a healthy boy at term and the maintenance of clinical biological and endoscopic remission of CD during and after pregnancy.

[Uncommon etiology of gastrointestinal bleeding: duodenal metastases from renal cell carcinoma]. / Causa poco habitual de hemorragia digestiva alta: metástasis duodenal de adenocarcinoma renal.

Because of its unpredictable behavior, renal cell carcinoma is one of the most controversial neoplasms. On the one hand, patients frequently show metastases at diagnosis because of its slight manifestations, while on the other, the neoplasm can remain stable after nephrectomy and can then metastasize many years later. When this happens, the metastases usually involve more than 2 organs. The most frequent sites of metastases are the lung and lymph nodes, followed by the bones and liver, while duodenal involvement is rare. Indeed, intestinal metastases are found in only 2% of autopsies and of these, renal cell carcinoma metastases account for 7.1%. We present a case of a solitary late recurrence presenting as upper gastrointestinal bleeding 19 years after nephrectomy for clear cell renal carcinoma.

Causa poco habitual de hemorragia digestiva alta: metástasis duodenal de adenocarcinoma renal / Uncommon etiology of gastrointestinal bleeding: duodenal metastases from renal cell carcinoma

El adenocarcinoma renal es una de las neoplasias más controvertidas debido a su comportamiento impredecible. En muchas ocasiones los pacientes presentan enfermedad metastásica en el momento del diagnóstico dada su escasa expresividad clínica, y en otras, tras una nefrectomía, el tumor puede permanecer estable y metastatizar años después. Cuando la enfermedad metastásica ocurre, suele ser múltiple y los lugares afectados con mayor frecuencia son el pulmón, los ganglios, el hueso y el hígado, mientras que la afectación intestinal es inusual. De hecho, la afectación intestinal como zona de implantación de metástasis es infrecuente y representa sólo el 2% de las autopsias. De este pequeño porcentaje, el 7,1% corresponde a metástasis de adenocarcinoma renal. Presentamos un caso de metástasis única duodenal que se manifestó como hemorragia digestiva alta al cabo de 19 años de una nefrectomía por carcinoma renal de células claras

Because of its unpredictable behavior, renal cell carcinomais one of the most controversial neoplasms. On the one hand, patients frequently show metastases at diagnosis because of its slight manifestations, while on the other, the neoplasm can remain stable after nephrectomy and can then metastasize many years later. When this happens, the metastases usually involve more than 2 organs. The most frequent sites of metastases are the lung and lymph nodes, followed by the bones and liver, while duodenal involvement is rare. Indeed, Intestinal metastases are found in only 2% of autopsies and of these, renal cell carcinoma metastases account for 7.1%. We present a case of a solitary late recurrence presenting as upper gastrointestinal bleeding 19 years after nephrectomy for clear cell renal carcinoma

[Systemic candidiasis and infliximab therapy]. / Candidiasis sistémica y tratamiento con infliximab.

The use of infliximab in patients with luminal or fistulizing Crohn's disease refractory to medical treatment (steroids and immunomodulatory drugs) is increasingly widespread. Although the incidence of serious infections in patients undergoing infliximab treatment is not higher than that of controls, systemic fungal infections in patients treated with this antibody have been anecdotally described. We report a case of systemic candidiasis in a patient with refractory Crohn's disease who was treated with infliximab associated with corticosteroids and azathioprine and discuss the role that infliximab could have played in the development of this complication.

[Incidence and prevalence of autoimmune hepatitis in the area of the Hospital de Sagunto (Spain)]. / Incidencia y prevalencia de hepatitis autoinmune en el área sanitaria del Hospital de Sagunto.

Thirteen cases of autoimmune hepatitis (AIH) were diagnosed from 1990 to 2003 in the area of the Hospital de Sagunto (Valencia, Spain), which attends a population of 112,003 inhabitants aged more than 14 years (54,622 males and 57,381 females). The diagnostic criteria of the International Autoimmune Hepatitis Group were used and patients who, despite having a probable diagnosis of AIH, presented hepatitis C virus infection were excluded. The diagnosis was probable in one patient and definitive in 12. All patients, 11 females and two males aged 45.9 12.2 years (range: 28-66), were classified as AIH type 1. Among the population aged more than 14 years, the mean annual incidence of AIH was 0.83 cases/100,000 inhabitants (95% CI, 0.44-1.42) (range: 0-2.68), showing a significant trend to increase (b = 0.132; p = 0.019). The incidence was higher in women than in men (RR = 5.24; 95% CI, 1.16-23.62). The mean annual incidence was 1.37 (95% CI, 0.68-2.46) (range: 0-3,49) in women and was 0.26 (95% CI, 0.02-0.96) (range: 0-1.83) in men. By age, the maximum mean annual incidence was observed in the group aged 55-64 years (1.6 cases/100,000 inhabitants). The prevalence of AIH in September 2003 was 11.61 cases/100,000 inhabitants aged more than 14 years (95% CI, 6.78-19.86). The prevalence was 3.66 (95% CI, 1-13.35) in men and was 19.17 (95% CI, 10.70-34.33) in women.

HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease.

HYPOTHESIS AND OBJECTIVES: the hypothesis of this study is that genes involved in the regulation of the immune system, expressed by HLA antigens and anti-neutrophil cytoplasmic antibodies (ANCA), could be determinants of disease susceptibility and behavior in inflammatory bowel disease (IBD). MATERIAL AND METHOD: seventy patients with a diagnosis of inflammatory bowel disease, 46 with ulcerative colitis and 24 with Crohn"s disease were included. HLA class I (A and B) and II (DR) antigens were studied by serological techniques. Detection of ANCA was carried out in all patients by an indirect immunofluorescence method. The relative frequencies of HLA antigens were compared with a control group made up of 156 blood donors. The control group for the ANCA study was made up of 100 individuals. RESULTS: we found a significant increased frequency of HLA-DR2 in patients with ulcerative colitis. No significant differences were found between patients with Crohn"s disease and controls regarding HLA typing. We detected a significant increase of HLA-DR3 in extensive forms of ulcerative colitis. Detection of ANCA was positive in 46% of the patients with ulcerative colitis and in 12% of the patients with Crohn"s disease (p <0.05). We observed an increased frequency of ANCA in patients with UC and HLA-DR2 (p = 0.15). CONCLUSIONS: the association found between HLA-DR3 and extensive forms of ulcerative colitis provides evidence of genetic heterogeneity. The relationship between ANCA and HLA phenotype (although not significant) supports this concept.

[Plastic linitis as a manifestation of metastases from breast cancer]. / Linitis plástica como manifestación metastásica del cáncer de mama.

We present the case of a woman of 48 years old, with a gastric metastases from breast lobular carcinoma that was operated eight years ago, being free of illness until today. The symptoms who presented her were totally inespecific and the diagnostic techniques of image realized were compatible with the diagnostic of plastic linitis. The histological findings of biopsy and hormonals receptors study confirmed the diagnostic of gastric metastases of primary breast carcinoma after a comparative study with the initial surgical piece. After starting hormonal and cistostatic treatment, the patient presented a partial improvement of her symptomatology with a survival that exceeds ten months. The gastric metastases of lobular carcinoma are not so infrequent as it was believed, and its diagnostic require a high index of suspicion, given the inespecifity of symptomatology that it used to present.

Evolutive pattern in Crohn's disease: a simplified index using clinical parameters predicts obstructive behaviour.

BACKGROUND: Two clearly differentiated evolutive patterns of Crohn's disease, obstructive and fistulizing, exist, but the early clinical parameters which can predict the evolution are unknown. AIM: To evaluate whether clinical variables, present at the time of diagnosis, may help in predicting a subsequent evolutive behaviour. PATIENTS AND METHODS: Ninety out of 140 evaluable patients were included. After a median of 50.2 months since diagnosis, 64 patients (71%) followed an obstructive pattern while 26 patients (28.9%) had a fistulizing form. Clinical variables were analysed as predictors of outcome. Logistic regression was carried out in order to obtain a mathematical model that would predict the evolution. The individual ability of the mathematical model to predict evolution was assessed using relative receiver operating characteristic (ROC) curves. RESULTS: The variables which were retained in the model were duration of disease before diagnosis (DD), onset of symptoms (OS), presence of anal disease (AD) and the presence of abdominal mass (AM). The equation z = -9.49 + 2.2643 (AD) - 0.0066 (DD) + 2.5282 (AM) + 1.3433 (OS) was obtained. The probability of evolution towards an obstructive form was P = 1/(1 + e(-Z)). This model can predict 96.88% of obstructive forms but only 53.85% of fistulizing forms. The mathematical point section (ROC curve) corresponds to a probability of 45.2%. Considering an obstructive pattern when the probabilities are above this point, the sensitivity is 98% and the specificity is 50%. CONCLUSIONS: The prediction of an obstructive pattern is feasible using simple clinical variables. The mathematical model obtained is useful for predicting this but not the fistulizing pattern.

[Azathioprine and 5-ASA in the prevention of postoperative recurrence of Crohn's disease]. / Azatioprina y 5-ASA en la prevención de la recurrencia posquirúrgica de la enfermedad de Crohn.

Recurrence of Crohn's disease (CD) lesions in the neo-ileum after apparently curative resection frequently occurs after surgery. The most appropriate prophylactic treatment has not been clearly defined. This study evaluated the efficacy of 5-ASA and azathioprine in decreasing postoperative recurrence and analysed the presence of variables associated with recurrence. Thirty-nine patients (mean age 32.8 years, range 18-61) with a history of ileal or ileocecal surgical resection were studied. They received 5-ASA (3 mg/day) or azathioprine (50 mg/day) immediately after the operation and for 2 years thereafter. Patients were followed clinically (Crohn's disease activity index) and serologically every 3 months and by imaging methods every 6 months. The latter included colonoscopy with ileoscopy and if not available, small bowel barium or ultrasonographic study. Laboratory tests included ESR, C-reactive protein, white blood cell and platelet count, fibrinogen and albumin. The end-point evaluated included clinical recurrence (CR), serological recurrence (SR: alteration of at least three of the above-mentioned variables) and morphologic recurrence (MR: endoscopic recurrence > 1 according to Rutgeerts score or radiological or ultrasonographic recurrence). Eighteen patients received azathioprine and 21 received 5-ASA. Thirty-four patients were evaluated. The cumulative proportion of patients with recurrence was 29% (CR), 35% (SR) and 50% (MR). Statistical analysis did not show significant differences between the two groups. Twenty-seven patients completed the 2-year study (11 in the azathioprine group and 16 in the 5-ASA group). Crude relapse rates were 37% (CR), 44% (SR) and 69% (MR) in the 5-ASA group and 36% (CR), 45% (SR) and 64% (MR) in the azathioprine group. No statistically significant differences were observed between groups. No variables associated with recurrence were detected. In conclusion, treatment does not prevent a high percentage of postsurgical recurrence. 5-ASA (3 g/day) and azathioprine (50 mg/day) showed similar efficacy in the prevention of recurrence.

[Morphological, histochemical and immunochemical characteristics of the terminal ileum of patients with ulcerative colitis. Relationship with the development of pouchitis]. / Características morfológicas, histoquímicas e inmunohistoquímicas del íleon terminal de los pacientes con colitis ulcerosa. Relación con el desarrollo de reservoritis.

UNLABELLED: Pouchitis is the most frequent long-term complication of the ileoanal reservoirs. Its etiology is unknown and it is currently believed to be a recurrence of ulcerative colitis in the mucosa of the ileal reservoir. AIM: To evaluate whether the mucosa of the terminal ileum of patients with ulcerative colitis is different from that of patients free of this disease and whether there are morphological and immunological alterations which might predispose to inflammation of the reservoir. PATIENTS AND METHODS: Colectomy samples from the terminal ileum of 20 patients (12 women, 8 men) with ulcerative colitis who had undergone restorative proctocolectomy with ileoanal reservoir and of 10 controls who had undergone right hemicolectomy for other causes were studied. During follow-up (46.9 months) seven patients were diagnosed with pouchitis (Sandborn > 7). In all patients, morphometric histopathologic, histochemical and immunohistochemical studies of the ileal mucosa were performed. RESULTS: Chronic inflammatory infiltrate and the degree of villous atrophy and of global chronic inflammation were significantly higher in the terminal ileum of patients with ulcerative colitis than in the control group. There were no differences in the mucin content between the two groups and IgA, IgG and B lymphocyte expression was significantly higher in the terminal ileum of patients with ulcerative colitis. Chronic inflammatory infiltrate, degree of atrophy, villous atrophy and of global chronic infiltration, macrophage and CD8 lymphocyte expression were higher in the terminal ileum of patients with pouchitis, but differences was not significant. CONCLUSIONS: The terminal ileum of patients with ulcerative colitis has histopathologic, morphometric and immunohistochemical characteristics that are different from those of patients without this disease. These results may eventually lead to an association between alterations in the ileum and the subsequent development of pouchitis.

[Significance of the determination of antineutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis and Crohn's disease]. / Significado de la determinación de anticuerpos frente al citoplasma de los neutrófilos (ANCA) en la colitis ulcerosa y en la enfermedad de Crohn.

We have studied prospectively 126 consecutive patients recruited with a known diagnosis of ulcerative colitis (UC; n = 78) and Crohn's disease (CD; n = 48) for anti-neutrophil cytoplasmatic antibodies (ANCA) by indirect immunofluorescence (IFI). Forty-six percent of UC and 18% of CD patients were found positive. The sensitivity and specificity for UC diagnosis were 0.46 and 0.81, respectively. We evaluated the pattern of IFI exhibited (perinuclear: pANCA and cytoplasmatic: cANCA). cANCA was found in 77% of CD and in only 30% of UC patients (p = 0.01). Sera from all CD patients were positive at a 1:20 dilution (and not at higher dilution) and it occurred in only in 14 UC patients (30%). Positive sera were also tested to characterize the antigen specificity by enzyme-linked immunosorbent assay (ELISA) but the antigenic nature of ANCA could not be identified in most cases. No differences were found between ANCA positive and ANCA negative patients regarding colonic extension (UC) or colonic involvement (CD), activity and colectomy. We conclude that ANCA may be a helpful diagnostic test in UC patients but it not seems to be important as a marker of activity. ANCA positivity can reflect disease heterogeneity in UC patients, perhaps discriminating those with immunologic disturbances.

[Acute hepatocellular lesion induced by amoxicillin-clavulanic acid]. / Lesión hepatocelular aguda inducida por amoxicilina-ácido clavulánico.

Since first description in 1988, numerous cases of amoxycillin-clavulanic acid hepatotoxicity have been reported. Most of them are cholestatic hepatitis. A case of acute hepatocellular injury by amoxycillin-clavulanic acid is reported in a 23-years-old male, with a favourable outcome after 18 weeks.

Relationship between smoking and colonic involvement in inflammatory bowel disease.

UNLABELLED: The effects of smoking on the onset and clinical course of inflammatory bowel disease (IBD) have been widely debated. Although smoking appears to have a clearly unfavorable effect on the course in Crohn's Disease (CD), the relationship between smoking and localization of the disease is less clear. AIM: To evaluate, in our group of patients, the relationship between smoking and the development of ulcerative colitis (UC) or CD, and between smoking and the localization of CD in the large bowel or in other sites. PATIENTS AND METHODS: The smoking habits of 171 patients at the time of diagnosis were assessed with a questionnaire. Subjects were classified into three subgroups as smokers, nonsmokers and ex-smokers. Current smokers were grouped according to their level of consumption as those who smoked fewer than or more than 10 cigarettes per day. A total of 161 patients were studied (UC n = 69, CD n = 92). Patients with CD were divided into those with colonic disease and those with no colonic involvement. We evaluated the relationship between smoking and the form of IBD, localization (colonic or noncolonic) and the presence of perianal disease (PAD) in CD. The results were analyzed with the chi-squared test. RESULTS: Smoking was more frequent in patients with CD than in those with UC (72.8% vs 31.9%). Among patients with CD, more patients without colonic involvement were smokers (84.6% vs 64.2%). However, among patients with CD involving the colon, smoking was significantly more common (64.2%) than among patients who had UC (31.9%). CONCLUSIONS: Our findings confirm a relationship between smoking and CD. Smoking seems to be associated with some degree of protection of the colonic mucosa, especially in heavy smokers.

[Dysfunction of a TIPS (transjugular intrahepatic porto-systemic shunt) and chylous ascites]. / Disfunción de TIPS (transjugular intrahepatic porto systemic shunt) y ascitis quilosa.

We reported a 66 year old woman diagnosed of cirrhosis secondary to VHC. A TIPS (transjugular intrahepatic portosystemic shunt) placement was used for the treatment of recurrent variceal hemorrhage and, a chyloperitoneum with hepatorenal syndrome developed after shunt occlusion. We discuss the pathological processes that might be responsible and the poor prognosis of this no reported complication.

[Surgery of benign obstruction of the bile tract. Current opinion status]. / Cirugía de la obstrucción benigna de la vía biliar. Estado actual de opinión.

Treatment of the benign obstruction of the main bile duct remains controversial. A questionnaire, containing the different aspects of the treatment, was mailed in order to learn the general opinion about its management in our country; 140 specialists were surveyed with the following results: 35% gave valid answers. Most of those surveyed (85%) use antibiotic prophylaxis, preferably (79%) pre and postoperatively. Ultrasonography is used in 100% of the cases, and the second most common examination is endoscopic retrograde colangiopan-creatography. Among the intraopreoperative examinations, colangiography is the most used (100%), followed by choledochoscopy. A majority (90.4%) of those surveyed employ the T-tube and 67.5% prefer choledochoduodenostomy if an internal bile drainage must be performed. In obstructive jaundice, only 27.5% recommend preoperative percutaneous drainage. Endoscopic sphinterotomy is the elective technique for suppurative cholangitis and for patients with choledocholitiasis and previous cholecystectomy.

[Familial prevalence in chronic intestinal inflammatory disease. Differences among groups of patients with and without a familial history]. / Afectación familiar en la enfermedad inflamatoria crónica intestinal. Diferencias entre grupos de pacientes con y sin historia familiar.

OBJECTIVE: To assess the prevalence of familial occurrence in patients with inflammatory bowel disease and to evaluate the differences among groups of patients with and without familial history. PATIENTS AND METHODS: Complete information about sex, age of onset of inflammatory bowel disease, initial location, extracolonic manifestations and perianal disease (in Crohn's disease) was obtained from 187 patients, 99 with Crohn's disease, and 88 with ulcerative colitis. RESULTS: In 9 patients (9%) with Crohn's disease and 11 (12.5%) with ulcerative colitis, at least one first-degree relative also had inflammatory bowel disease. Three relatives of patients with Crohn's disease had ulcerative colitis and no relative of patients with ulcerative colitis had Crohn's disease. As compared with the group of patients with ulcerative colitis and no familial history, patients with familial history had more frequently distal location and extra-colonic manifestations. No differences were observed among patients with Crohn's disease and familial or non familial history. CONCLUSIONS: Prevalence of inflammatory bowel disease in relatives of patients with Crohn's disease or ulcerative colitis is increased. In ulcerative colitis, it is possible to segregate two different groups according to familial history.