A prospective evaluation of endoscopic markers for identifying celiac disease in patients with high and low probability of having the disease.

BACKGROUND/OBJECTIVES: the usefulness of duodenoscopic markers for predicting celiac disease (CD) has been questioned. We assessed the diagnostic efficacy of endoscopic markers of mucosal atrophy in individuals with different pretest probability of CD. METHODS: we prospectively performed endoscopic intestinal biopsies and CD-related serology tests in 661 individuals, including 143 consecutive patients attending a malabsorption clinic (high pretest probability) and 518 subjects randomly selected fom those undergoing routine endoscopy because of upper GI symptoms (low pretest probability). Duodenoscopic markers reported were: mosaic pattern, scalloped folds, and reduction in number or loss of Kerkring's folds. RESULTS: sixty-three (44.1%) and 18 (3.5%) patients were diagnosed with CD in the high and low risk groups, respectively Among high pretest subjects, the presence of any marker had very high sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the identification of CD (92.1%, 93.8%, 92.1%, 93.8% and 93.0%, respectively). The performance of these parameters for the presence of any marker in the low pretest population were 61.1%, 96.8%, 40.7%, 98.6% and 95.6%, respectively. Sensitivity (p < 0.004) and positive predictive value (p < 0.0001) of markers were significantly higher for the high risk patients. The identification of a reduction in number or loss of Kerkring'sfolds was not a reliable finding unless other signs were also present. CONCLUSIONS: we confirm that endoscopic markers are useful in predicting CD in different clinical scenarios. The high negative predictive value in the low probability group suggests that intestinal biopsy is not required if endoscopic markers are absent.

The enteric nervous system in chagasic and idiopathic megacolon.

Chagas disease frequently causes megacolon. We investigated the enteric nervous systems in patients with chagasic megacolon compared to idiopathic megacolon and controls. Surgical specimens were obtained from 12 patients with chagasic megacolon (1 woman, 11 men, age range 41 to 72 y) and 9 patients with idiopathic megacolon (3 women, 6 men, age range 39 to 68 y), undergoing surgery for intractable constipation. A control group of 10 patients (9 women, 1 man, age range 43 to 75 y) undergoing left hemicolectomy for nonobstructing colorectal cancer was also studied. Colonic sections were investigated by conventional and immunohistochemical methods, also taking into consideration the presence of lymphocytes. Compared to controls, the 2 megacolon groups showed a decrease of enteric neurons (not due to increased apoptosis) and of enteric glial cells (all more important in chagasic patients). The interstitial cells of Cajal subtypes were decreased but not absent in megacolons, although an increase of the intramuscular subtype was found, suggesting a possible compensative mechanism. An increased amount of fibrosis was found in the smooth muscle and the myenteric plexus of chagasic patients compared to the idiopathic megacolon and the control group. A mild lymphocytic infiltration of the enteric plexuses (more evident in Chagas disease) was also found in megacolons but not in controls. Patients with chagasic megacolon display important abnormalities of several components of the enteric nervous system. Similar alterations, although of lesser severity, may be found in patients with idiopathic megacolon.

Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa.

BACKGROUND/AIMS: Our aims were to establish the clinical utility of assessing the intraepithelial lymphocyte (IEL) density in intestinal biopsies from a large series of individuals and to determine the best threshold discriminating celiac disease (CD) patients and controls in two populations with different pre-test prevalence. METHODS: We prospectively performed intestinal biopsy and CD-related serology in 349 subjects undergoing upper GI endoscopy. While 116 had symptoms suggestive of a small bowel disorder (high prevalence), 233 individuals were randomly selected from patients referred to endoscopy because upper GIsymptoms (low prevalence). Diagnosis of CD was based on the concordance of classical histological features and a positive CD serology. RESULTS: While 58 patients had a newly diagnosed CD (52 in the high and 6 in the low prevalence groups), 291 subjects did not meet diagnostic criteria of the disorder. Patients had a highly significant greater IEL density than controls (p < 0.00001). Based on the ROC curve, a count of 22.8 IEL/100 epithelial cells had the highest performance for diagnosing CD in the overall population and for subjects in the high pre-test probability subgroup and 22.5% was ,he best cut-off for those diagnosed in the low risk population (area under the curves: 0.979, 0.979 and 0.993, respectively). An abnormal CD serology confirmed the diagnosis of CD in all the four patients with counts below 22.8%. CONCLUSIONS: Our study confirms that an IEL density of 22.8% is an adequate threshold to discriminate CD patients and controls in individuals irrespective of the prevalence of the disorder.

Celiac disease serology in dermatitis herpetiformis. Which is the best option for detecting gluten sensitivity?

BACKGROUND: Dermatitis herpetiformis (DH), a well-established gluten-sensitive skin disorder presenting variable degrees of enteropathy, constitutes a very useful model in order to assess the utility of the celiac disease (CD)-related serology in patients with mild intestinal damage. OBJECTIVE: Our aim was to explore comparatively the performance of a panel of CD-related serologic tests in patients with DH. METHODS: We assessed a series of 18 consecutive patients with skin biopsy proven DH presenting the overall spectrum of intestinal damage ranging from normal mucosa (n = 6) to total villous atrophy (TVA) (n = 6) through partial villous atrophy (PVA) (n = 6). Sera were obtained from all patients while consuming a gluten containing diet. Serologic tests were antiendomysial, anti-tissue transglutaminase and antigliadin antibodies, and newly developed tests detecting both antibody isotypes (IgA and IgG) against deamidated synthetic gliadin-derived peptides (a-GDP). RESULTS: Serologic tests had a variable behaviour depending on the degree of enteropathy. While the majority of tests detected patients with TVA, only 50% of those with normal histology had positive assays. Patients with PVA had discordant results. Classical CD-specific tests were positive in only some patients with mild damage while all of them were identifed by a single assay detecting both isotypes of a-GDR CONCLUSION: The detection of a-GDP antibodies was the most reliable tool in order to identify gluten sensitivity in DH patients presenting a wide range of intestinal damage. Further studies should explore if these findings can be extrapolated to patients with CD having mild enteropathy.

Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution.

BACKGROUND: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. AIM: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. MATERIALS: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. RESULTS: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers (78% and 66%). Survivors had a favorable outcome. While 11 patients persists asymptomatic, two other cases still have mild diarrhea and one low body weight. CONCLUSIONS: We confirm that RS is a severe celiac disease-related disorder with very high mortality. Diagnosis of overt lymphoma (12%) in our long-term follow-up was not as frequent as was reported by other groups. A proportion of patients persist in good health for a long time irrespective of the nature of the IEL infiltration or the presence of UJ.

Multidrug resistance gene (MDR-1) expression in the colonic mucosa of patients with refractory ulcerative colitis.

BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.

Significance of smooth muscle/anti-actin autoantibodies in celiac disease.

BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with a more severe clinical outcome.

Antibodies against synthetic deamidated gliadin peptides as predictors of celiac disease: prospective assessment in an adult population with a high pretest probability of disease.

BACKGROUND: Noninvasive serologic tests have shown high diagnostic accuracy for celiac disease (CD) in selected populations. Our aim was to determine prospectively the performance of CD-related serology in individuals undergoing intestinal biopsy because of clinical suspicion of small-bowel disorders. METHODS: We enrolled 141 unselected consecutive adult patients attending a small-bowel disease clinic. Patients underwent endoscopy and biopsy; serum samples were obtained at that time for measurements of anti-tissue transglutaminase (a-tTG), IgA and IgG anti-deamidated gliadin-related peptide (a-DGP), and IgA antiactin antibodies (AAAs). Characterization of patients was based on histological criteria (Marsh type II lesion or greater). RESULTS: The prevalence of CD was 42.5%. Sensitivity, specificity, and positive and negative predictive values were >90% for most assays. Diagnostic accuracy based on ROC curve analysis was similar for all assays [area under the curve (95% CI): 0.996 (0.967-0.998) for a-tTG, 0.995 (0.964-0.998) for IgA a-DGP, 0.989 (0.954-0.999) for IgG a-DGP, 0.996 (0.966-0.998) for blended conjugated of IgA + IgG a-DGP in a single assay, and 0.967 (0.922-0.990) for AAA]. The combinations of 2 tests, IgG a-DGP plus IgA a-tTG or the single blended conjugate detecting IgA + IgG a-DGP plus IgA a-tTG had 100% positive and negative predictive values if concentrations of both tests in either combination were above or below the cutoff. CONCLUSIONS: In a population with high pretest probability, the newly developed a-DGP tests have diagnostic accuracy that is at least equivalent to that of established assays.

Accuracy of testing for antibodies to synthetic gliadin-related peptides in celiac disease.

BACKGROUND & AIMS: Our aim was to explore the diagnostic value of a newly developed synthetic peptide antibody assay addressing specific synthetic gliadin-derived deamidated peptides (AGA II) for the diagnosis of celiac disease (CD). METHODS: We assayed serum samples obtained prospectively at diagnosis from a population of 92 consecutive adult patients with CD and 113 non-CD controls. Patients were reevaluated after 6 months (n = 56) and 1 year (n = 20) of treatment. All patients and controls underwent intestinal biopsy and a set of CD-related serology tests. A newly developed enzyme-linked immunosorbent assay (ELISA) for detecting IgA and IgG antibodies against synthetic deamidated gliadin epitopes was used. RESULTS: At diagnosis, sensitivity and specificity were 94.6% and 99.1% for AGA II IgA and 92.4% and 100% for AGA II IgG. Absolute values and the proportion of positive samples for both antibodies were significantly reduced at 6 months (P < .0000) and 1 year (P < .001) after initiation of a gluten-free diet. Compared with conventional AGA, the peptide antibodies had greater sensitivity, specificity, positive and negative predictive values, accuracy, and likelihood ratios. Compared with antitissue transglutaminase antibodies, AGA II had similar sensitivity but greater specificity and predictive values, better likelihood ratios, and an excellent agreement (kappa statistic = .92). CONCLUSIONS: This study assessed the value of an ELISA assay in detecting antibodies to gliadin-related peptides. This assay appears to be a reliable tool for diagnosing CD and suggests promising accuracy that may be very useful in clinical practice.

Azathioprine in refractory sprue: results from a prospective, open-label study.

OBJECTIVE: Refractory sprue is a rare and severe malabsorptive disorder that mimics celiac disease but is refractory to a gluten-free diet and is without initial evidence of overt lymphoma. Treatment is largely empiric and often ineffective, with steroids and immunosuppression being the mainstream therapeutic options. The aim of this study was to evaluate prospectively the effect of azathioprine on a group of patients diagnosed with refractory sprue. METHODS: We studied seven consecutive patients (five women and two men) with a well-defined diagnosis of refractory sprue and a lack of response to oral or parenteral steroids. At diagnosis, five patients had endoscopic evidence of ulcerative jejunitis, and five underwent exploratory laparotomy for exclusion of malignancies. The characteristic monoclonal TCRgamma gene rearrangement was shown in five of six patients studied. Patients were treated for a mean of 11 months (range 8-12 months), and clinical, biochemical, molecular, and histological parameters were reassessed at the end of the trial. The study was a prospective, open-label, non-placebo-controlled study using azathioprine (2 mg/kg/ day) plus oral prednisone (1 mg/kg/day). A gluten-free diet (n = 7) as well as enteral (n = 6) and parenteral nutrition (n = 5) were administered during the trial. RESULTS: After treatment, five patients had a complete clinical remission, and biochemical and nutritional parameters were significantly improved. Steroids were tapered after the onset of azathioprine, and no patient was on steroids at the end of the trial. Intestinal histology improved significantly in all cases (normal histology in three cases and minor infiltration in the lamina propria in two). Two patients did not respond to treatment at any time and died in months 10 and 9, of an irreversible ventricular fibrillation and sepsis, respectively. No overt lymphoma was demonstrated during the follow-up. CONCLUSIONS: The present study confirms earlier anecdotal reports on the efficacy of azathioprine in refractory sprue, with clear clinical and histological improvement shown in most patients. However, monoclonality persisted after treatment. We consider that a larger number of patients should be evaluated before a definitive recommendation is adopted for use of this drug in refractory sprue.

Multidrug resistance gene (MDR-1) expression in the colonic mucosa of patients with refractory ulcerative colitis / Expresión del gen de multirresistencia a drogas (MDR-1) en la mucosa colónica de pacientes con colitis ulcerosa refractaria

BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.

Antecedentes. La glicoproteína P (P-gp), un producto del gen MDR-1, es una bomba de eflujo transmembranainvolucrada en el transporte de drogas, descripta por primera vez en el cáncer refractario. En el intestino normal, P-gp se detecta sobre las célulasepiteliales superficiales, pero no se la ha descripto en el epitelio de las criptas. El papel de P-gp y su expresiónintestinal en la colitis ulcerosa (CU) refractaria a esteroides es controvertido. Objetivo. Comparar elpatrón de inmunotinción de P-gp en células epiteliales colónicas de pacientes con CU refractaria vs.respondedora a esteroides. Métodos. Se estudió P-gp por inmunohistoquímica en biopsias rectales obtenidasde 19 pacientes con CU activa, incluyendo muestras prequirúrgicas de 11 pacientes refractarios que fueronsometidos a una colectomía y muestras de 8 respondedores. Ideamos un score de 5 puntos (0-4), según elporcentaje de superficie epitelial con inmunotinción positiva en el epitelio superficial y críptico (áreas apical,lateral y citoplásmica). Resultados. Comparados con los respondedores, los pacientes refractarios a esteroides tenían scores de inmunotinción significativamente mayores en el epitelio superficial, tanto en lasáreas celulares apical (2.8+0.5 vs. 1.1+0.5, p=0.023) como citoplásmica (2.7+0.5 vs. 1.2+0.5, p=0.032). Se detectó frecuentemente inmunotinción positiva en el epitelio superficial en los pacientes refractarios (apical: 9/11 casos, citoplásmica: 10/11 casos), pero la misma se observó sólo en 4/8 respondedores. P-gp también sedetectó en áreas similares del epitelio de las criptas en 6/11 pacientes refractarios, en tanto que fue infrecuenteen el grupo de los 8 respondedores (1 caso en el área apical y 2 en la citoplásmica). Fuerón estudiadasbiopsias de la mucosa de la anastomosis pouch ileal - anal, obtenidas varios años después del procedimeinto quirúrgico, observándose un patrón de...

Celiac disease serology in dermatitis herpetiformis: which is the best option for detecting gluten sensitivity? / Serología de enfermedad celíaca en dermatitis herpetiforme. ¿Cuál es la mejor opción para detectar sensibilidad al gluten?

Background: Dermatitis herpetiformis (DH), a wellestablished gluten-sensitive skin disorder presenting variable degrees of enteropathy, constitutes a very useful model in order to assess the utility of the celiac disease (CD)-related serology in patients with mild intestinal damage. Objective: Our aim was to explore comparatively the performance of a panel of CD-related serologic tests in patients with DH. Methods: We assessed a series of 18 consecutive patients with skin biopsy proven DH presenting the overall spectrum of intestinal damage ranging from normal mucosa (n=6) to total villous atrophy (TVA) (n=6) through partial villous atrophy (PVA) (n=6). Sera were obtained from all patients while consuming a gluten containing diet. Serologic tests were antiendomysial, anti-tissue transglutaminase and antigliadin antibodies, and newly developed tests detecting both antibody isotypes (IgA and IgG) against deamidated synthetic gliadin-derivedpeptides (a-GDP). Results: Serologic tests had a variable behaviour depending on the degree of enteropathy. While the majority of tests detected patients with TVA, only 50% of those with normal histology had positive assays. Patients with PVA had discordant results. Classical CD-specific tests were positive in only some patients with mild damage while all of them were identified by a single assay detecting both isotypes of a-GDP. Conclusion: The detection of a-GDP antibodies was the most reliable tool in order to identify gluten sensitivity in DH patients presenting a wide range of intestinal damage. Further studies should explore if these findings can be extrapolated to patients with CDhaving mild enteropathy.

Introducción: la dermatitis herpetiformis (DH), una lesión dermatológica consecuencia de sensibilidad al gluten y asociada a grados variables de enteropatía, constituye un modelo muy útil con el objeto de evaluar la eficacia de la serología de la enfermedad celíaca(EC) en pacientes con daño intestinal leve. Objetivo: explorar comparativamente la utilidad de una serie de anticuerpos empleados en EC en pacientes con DH. Métodos: analizamos una serie de 18 pacientes consecutivos con diagnóstico de DH por biopsia de piel que presentaban el más amplio espectro de daño intestinal variando desde una mucosa normal (n=6) a la atrofia vellosa total (AVT) (n=6) y pasando por atrofia vellosaparcial (AVP) (n=6). Se obtuvo plasma de todos los pacientes mientras consumían gluten. Las pruebas serológicas empleadas fueron anticuerpos antiendomisio, anti-transglutaminasa y atigliadina, y unas pruebas recientemente desarrolladas que detectan anticuerpos IgA e IgG dirigidos contra péptidos sintéticos deamidados derivados de la gliadina (a-GDP). Resultados: las diferentes pruebas tuvieron un comportamiento variable dependiendo del grado de lesión intestinal. Mientras que la mayoría de las pruebas detectaron a todos los pacientes con AVT, sólo el 50% de aquellos con histologíanormal tuvieron resultados positivos. Los pacientes con AVP tuvieron resultados discordantes. Así las pruebas clásicas fueron positivas en sólo algunos pacientescon daño leve, mientras que todos ellos fueron positivos a una prueba para detectar ambos isotipos del a-GDP. Conclusión: la determinación de anticuerpos a-GDP fue la herramienta más confiable con el objeto de identificar serológicamente la sensibilidad al gluten en pacientes con DH que presentan variables grados de daño intestinal. Otros estudios deberían explorar si estos hallazgos podrían ser extrapolados a pacientes conEC con enteropatía de grado leve.

Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution / Características clínicas y evolución a largo plazo de una serie de pacientes con sprue refractario diagnosticados en una sola institución

BACKGROUND: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. AIM: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. MATERIALS: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. RESULTS: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers...

Introducción: El sprue refractario (SR) es una rara y severa entidad consistente en una enteropatía tipo celíaca que no responde a una estricta dieta libre degluten. Aún cuando el pronóstico es generalmente pobre, poco es conocido acerca de la evolución de lospacientes a largo plazo. Objetivo: reportar las característicasclínicas y la evolución a largo plazo de una serie de pacientes diagnosticados y tratados en una solainstitución. Materiales: Reportamos una cohorteretrospectiva de 25 pacientes consecutivos (15 mujeres; edad media 46 años; rango 28-71) diagnosticadoscomo SR sobre la base de una enteropatía tipo celíaca que no respondió a la dieta libre de gluten. Todos los pacientes recibieron un tratamiento intensivo consistenteen dieta libre de gluten, alimentación enteral o parenteral, corticosteroides e inmunosupresión. Resultados: Los elementos clínicos y biológicos sugierenque 24 pacientes exhibían claras evidencias de enfermedadcelíaca. Los genes HLA DQ2/DQ8 estuvieron presentes en los 24 pacientes estudiados y se excluyó laenteropatía autoinmune en todos los casos. De acuerdo al genotipo, 12 pacientes presentaron una poblaciónlinfocitaria intraepitelial policlonal (SR tipo I) y 13 exhibieron un rearreglo genético monoclonal del TCR-γ (SR tipo II). Dieciséis pacientes presentaron evidencias de yeyunitis ulcerativa (YU) (7 en SR tipo I y 9 enel tipo II). El tiempo promedio de seguimiento luego del diagnóstico de SR fue 29 meses/paciente (rango 7 -204) (45 y 24 meses para tipo I y tipo II, respectivamente). La mortalidad global fue del 48% (12 pacientes),6 en cada tipo de SR. Ocho pacientes con YU (50%) murieron durante el seguimiento, 3 con linfoma(dos de células T y uno de células B) y cuatro(44%) individuos sin úlceras también fallecieron. Lascausas de muerte fueron vasculares (n=3), sepsis en elmarco de deterioro progresivo sin desarrollo de malignidad(n=5) y desnutrición progresiva (n=1)...

Linfomas del intestino delgado y cirugía / Primary small bowel lymphomas and surgery

Se presentan 45 casos de linfomas primarios de intestino delgado estudiados entre 1983 y febrero de 1995, de los cuales 2 correspondieron a la variedad Hodgkin (4,4 por ciento) y 43 a linfomas No Hodgkin (95,6 por ciento), incluyendo en éstos tres casos de enfermedad linfoproliferativa de intestino delgado. Se destaca que la localización más frecuente fue el yeyuno (51,2 por ciento), seguida del ileón y el duodeno encontrándose localizaciones múltiples en 23,2 por ciento. Las complicaciones obstructivas, perforativas y hemorrágicas fueron en el 93 por ciento de los pacientes lo que motivó la indicación quirúrgica. Se pone énfasis sobre la necesidad de la laparotomía exploradora con el fin de lograr el estudio histopatológico correcto, estadificar la lesión y evaluar la posibilidad de resección con criterio curativo o paliativo. Se analiza la supervivencia global de los linfomas No Hodgkin, que demuestra una diferencia significativa entre los operadores con criterio paliativo y curativo, 26 por ciento para los primeros y 47 por ciento en los segundos a los 70 meses, marcando también una significativa diferencia cuando existe o no compromiso ganglionar, 27 por ciento contra 52 por ciento a los 5 años

Lesiones sincrónicas en el cáncer colorrectal avanzado / Synchronous lesions in the advanced colorectal cancer

Desde ene'82 a jun'91 fueron realizados 3701 fibrocolonoscopía, diagnosticándose cáncer colorrectal (CCR) en 554 pacientes (pac.). De ellos, se llegó a ciego en 283 pac (51,1// ) (Masc: 175 pac; Fem: 108 pac) ya sea en el momento del diagnóstico o dentro de los 6 primeros meses posteriores a la cirugía. La distribución de pólipos sincrónicos (p) en 87 pac (30,7//) = 61 pac. tuvieron 1p; 16 pac, 2p; y 10 pac, 3p. En total: 105 p. Adenomas: 59/105p. 11/105p representaron carcinoma temprano, hsitológicamente confirmado (representando 11/59 adenomas). La distribución de los mismos fue: 5/11 en el mismo segmento colorrectal; 6/11 en diferentes segmento. 1pac. tuvo 3 carcinomas tempranos. Cáncer colorrectal avanzado sincrónico fue presentado por 9 pac (Masc./Fem = 2/1). Todos ellos localizados en distinto segmento colorrectal que el tumor primario. En conclusión, la alta frecuencia de presentación de lesiones premalignas (adenomas) y malignas (cáncer temprano y/o avanzado), y el alto riesgo de presentación de las mismas en diferentes segmentos que el tumor primario, muestra a la colonoscopía como el método más eficiente en la detección ( y eventual extracción) de lesiones sincrónicas del cáncer colorrectal

Acción de la SAMe en hepatopatía alcohólica / Effect of SAMe in alcoholic liver disease

Se presenta una experiencia en el tratamiento de la hepatopatia alcohólica con sulfo-adenosil-L-metionina (SAMe). La misma, se efectuó en un grupo de 20 pacientes durante 60 días y en una dosis de 200 mg/día de SAMe (i.m.) durante 30 días y 100 mg/día los 30 restantes. La respuesta clínica, valorada en forma subjetiva, evidenció una mejoría en el apetito, la astenia y la respuesta intelectual. Desde el punto de vista analítico se observaron mejorías significativas (p < .05 en adelante) en la gamaGT, TGP, TGO, bilirrubinemia, tiempo de Quick y colesterolemia. Los autores concluyen que la SAMe constituye un elemento terapéutico en la hepatopatía alcohólica, permitiendo una mejoría de la función hepática expresada mediante la clínica y las pruebas de síntesis proteica, de necrosis y de colestasis

Tumores quísticos del páncreas / Cystic tumors of pancreas

Antecedentes: Los tumores quísticos de páncreas son infrecuentes y presentan gran variedad anatomopatológica. Plantean problemas clínicos, diagnósticos y terapéuticos con aspectos controvertidos. Objetivo: Analizar una serie consecutiva de casos, aspectos diagnósticos, terapéuticos y correlación anatomopatológica. Lugar de aplicación: Servicios de Cirugía de referencia de patología pancreática. Diseño: Estudio retrospectivo de 26 casos de tumores quísticos de páncreas. Conclusiones en cuanto a diagnóstico y terapéutica. Población: Se estudia una muestra consecutiva de 26 pacientes intervenidos quirúrgicamente entre 1976 y 1996; 21 (80,8 por ciento) de sexo femenino. Métodos: Se realizó evaluación clínica y diagnóstica por imágenes. En los casos resecables no se efectuó biopsia preoperatoria. Siempre que fue posible se realizó resección completa del tumor quístico y estudio anatomopatológico. Se emplearon técnicas de H/E, tricrómico, PAS, inmunohistoquímica con cromogranina, enolasa, gastrina, insulina, glucagón y vip. Se evaluó mortalidad operatoria y supervivencia actuarial. Resultados: Los hallazgos anatomopatológicos fueron: tumores quísticos benignos 16 casos: cistoadenoma seroso 12 (único 8, macrofolicular 1 y microfolicular 3), mucinoso 3 y enterógeno 1. Tumores quísticos malignos 10: cistoadenocarcinoma mucinoso 5, ductal 3 y neuroendocrino 2. Se resecan 21 casos: pancreaticoduodenectomía cefálica en 2 pacientes (cistoadenoma seroso y macrofolicular de cabeza; pancreatectomía total en 1 (carcinoma ductal quístico); esplenopancreatectomía izquierda, la operación más frecuente en 13 casos (cistoadenoma seroso 5, mucinoso 3, neuroendocrino 2, cistoadenocarcinoma mucinoso 1, carcinoma ductal 1 y enterógeno 1); resección caudal del páncreas en 1 (cistoadenoma micro-folicular) y enucleación en 2 (cistoadenoma seroso). En 2 casos la resección por razones anatómicas fue parcial y 5 tumores fueron considerados irresacables ( cistoadenocarcinoma mucinoso y ductal quístico). No hubo mortalidad operatoria. El promedio de seguimiento de los quistes serosos fue 58,8 meses falleciendo 2 por otras causas. En los tumores malignos la supervivencia estuvo limitada, siendo más satisfactoria en los resecados. Un carcinoma ductal a forma quística resecado con esplenopancreatectomía vive 12 meses después y otro con pancreatectomía total lleva 5 meses de supervivencia. Conclusiones...

Linfoma gástrico primario y cirugía / Primary gastric lymphoma and surgery

Antecedentes: Los linfomas primarios no Hodgkin gástricos (LPNHG) presentan aspectos clínicos controvertidos en cuanto al diagnóstico, clasificación y tratamiento. Objetivos: Evaluar el rol de la cirugía en los LPNHG en el diagnóstico, estadificación, tratamiento y supervivencia. Diseño: Estudio retrospectivo analizando los hallazgos anatomopatológicos, estadificación y tratamiento en relación con la supervivencia. Pablación: 39 pacientes estudiados entre 1983 y aabril 1999. Métodos: Se estudian los pacientes por imágenes y endoscopía. La estadificación fue efectuadasiguiendo la clasificación de Ann Arbor y TNM. En base a la clasificación de Ann Arbor se siguió un algoritmo diagnóstico-tratamiento. Se consideran linfomas primarios los IE y IIE. La secuencia en el tratamiento es 1ro. Cirugía y después tratamiento quimioterápico. Quirúrgicamente se obtiene material para estudio histopatológico de la lesión, de ambos lóbulos hepáticos y de médula ósea de cresta iliaca. Se efectuaron técnicas habituales y de inmunohistoquímica especiales. Se siguió la clasificación REAL de los linfomas no Hodgkin. Los pacientes con lesiones avanzadas no resecados y en los resecados cuando tenían serosa y/o ganglios positivos fueron sometidos a quimioterapia (CHOP). La supervivencia fue valorada con el método actuarial de Kaplan-Meir y la diferencia de curvas con el test de log-reank. Resultados: De 39 LPNHG pertenecian al sexo masculino el 56.4 por ciento (22/39), el promedio de edad 55.8 años (33-78). El diagnóstico preoperatorio se estableció en el 51.2 por ciento. Fueron operados 35 y en el 46.2 por ciento la resección fue con criterio curativo. Los tipos histológicos fueron: linfoma T2 casos y linfoma B37 casos (94.9 por ciento); siendo éstos malt 36 y 1 del monton...

Evaluacion de sensibilidad, especificidad y valor predictivo de seis metodos serologicos cualitativos para la deteccion de anticuerpos contra el Helicobacter pylori / Evaluation of sensitivity, specificity and predictive value of six qualitative serological methods for the detection of Helicobacter pylori antibodies

El diagnóstico de infección por H.P. incluye: test rápido de la ureasa y cultivo de biopsia gástrica, urea breath test y detección de Atc Ig G. Existe una fuerte correlación entre la positividad de estos tests y la demonstración histológica de dicho microorganismo. El objetivo de nuestro trabajo fue: determinar y comparar la sensibilidad, especificidad y valor predictivo positivo y negativo de seis equipos comerciales para la detección serológica cualitativa de atc IgG, para el diagnóstico de H.P. Se estudiaron 52 pacientes (58 por ciento masculino, 42 por ciento femenino) con edad promedio 42,4 años con diagnóstico úlcera péptica gastro-duodenal o gastritis erosiva, H. Pylori positivo por test de la ureasa e histología convencional (Giemsa) en 2 biopsias de antro y 2 de cuerpo. El grupo control incluía 10 individuos con histología y test de la ureasa negativos. Los seis tests serológicos evaluados tenían sensibilidad y especificidad comparable, (89-95 por ciento) y (77-83 por ciento) respectivamente. La presencia de anticuerpos específicos contra H.P. en pacientes infectados reveló una fuerte correlación con la demonstración histológica del microorganismo. Recomendamos estos tests serológicos cualitativos debido a su alta sensibilidad y especificidad, bajo costo, sencillez y rapidez para su realización.

Linfoma primario de intestino delgado y malabsorción / Primary lymphoma of the small bowel and malabsorption

En la evaluación retrospectiva de la historia clínica de 69 pacientes portadores de linfomas que involucraban el tracto gastrointestinal, entre los años 1974 y 1984, 10 comprometieron al intestino delgado y se asociaron con malabsorción. De ellos, 7 pacientes cumplían los criterios que Dawson y colaboradores establecieron para considerar como primario a un linfoma intestinal. En base a datos clínicos, en los tres restantes pudo suponerse que el linfoma era primario intestinal, esto no pudo corroborarse. La biopsia peroral de intestino delgado demostró en 7 pacientes histológia compatible con la enfermedad celíaca, presentando en algunas muestras rasgos particulares como alteraciones parcelares, seudoestratificación inconstante del epitelio y ulceraciones superficiales. Sólo en dos casos se encontraron elementos celulares atípicos sugerentes de linfoma. La radiología sólo evidenció hallazgos inespecíficos malabsortivos en más del 50% de los pacientes. En los restantes se observó además yeyunitis ulcerativa (doble contraste), úlceras gigantes solitarias y estenosis. El laboratorio general y especializado fue el típico de malabsorción. La respuesta a la dieta sin gluten y/o corticoides resultó temporaria e inconstante. La laparotimía fue el método diagnóstico más efectivo, realizándose en un caso por un cuadro perforativo y en otros seis electivamente. El linfoma con malabsorción es una entidad de difícil diagnóstico, constituyendo el problema principal establecer el diagnóstico diferencial con la enfermedad celíca o la asociación de ambas patologías