A clinical and molecular portrait of non-metastatic anal squamous cell carcinoma.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk Human papillomavirus (HPV) infection. Despite improved outcomes in non-metastatic ASCC, definitive chemoradiotherapy constitutes the standard treatment for localized disease. Evidences for predictive and prognostic biomarkers are limited. Here, we performed a viral, immune, and mutational characterization of 79 non-metastatic ASCC patients with complete definitive chemoradiotherapy. HPV-16 was detected in 91% of positive cases in single infections (78%) or in coinfections with multiple genotypes (22%). Fifty-four percent of non-metastatic ASCC cases displayed mutations affecting cancer driver genes such as PIK3CA (21% of cases), TP53 (15%), FBXW7 (9%), and APC (6%). PD-L1 expression was detected in 57% of non-metastatic ASCC. Increased PD-L1 positive cases (67%) were detected in patients with complete response compared with non-complete response to treatment (37%) (p = 0.021). Furthermore, patients with PD-L1 positive tumors were significantly associated with better disease-free survival (DFS) and overall survival (OS) compared with patients with PD-L1 negative tumors (p = 0.006 and p = 0.002, respectively). PD-L1 expression strongly impacts CR rate and survival of non-metastatic ASCC patients after standard definitive chemoradiotherapy. PD-L1 expression could be used to stratify good versus poor responders avoiding the associated morbidity with abdominal perineal resection.

Prognostic Impact of An Integrative Landscape of Clinical, Immune, and Molecular Features in Non-Metastatic Rectal Cancer.

Rectal Cancer (RC) is a complex disease that involves highly variable treatment responses. Currently, there is a lack of reliable markers beyond TNM to deliver a personalized treatment in a cancer setting where the goal is a curative treatment. Here, we performed an integrated characterization of the predictive and prognostic role of clinical features, mismatch-repair deficiency markers, HER2, CDX2, PD-L1 expression, and CD3-CD8+ tumor-infiltrating lymphocytes (TILs) coupled with targeted DNA sequencing of 76 non-metastatic RC patients assigned to total mesorectal excision upfront (TME; n = 15) or neoadjuvant chemo-radiotherapy treatment (nCRT; n = 61) followed by TME. Eighty-two percent of RC cases displayed mutations affecting cancer driver genes such as TP53, APC, KRAS, ATM, and PIK3CA. Good response to nCRT treatment was observed in approximately 40% of the RC cases, and poor pathological tumor regression was significantly associated with worse disease-free survival (DFS, HR = 3.45; 95%CI = 1.14-10.4; p = 0.028). High neutrophils-platelets score (NPS) (OR = 10.52; 95%CI=1.34-82.6; p = 0.025) and KRAS mutated cases (OR = 5.49; 95%CI = 1.06-28.4; p = 0.042) were identified as independent predictive factors of poor response to nCRT treatment in a multivariate analysis. Furthermore, a Cox proportional-hazard model showed that the KRAS mutational status was an independent prognostic factor associated with higher risk of local recurrence (HR = 9.68; 95%CI = 1.01-93.2; p <0.05) and shorter DFS (HR = 2.55; 95%CI = 1.05-6.21; p <0.05), while high CEA serum levels were associated with poor DFS (HR = 2.63; 95%CI = 1.01-6.85; p <0.05). Integrated clinical and molecular-based unsupervised analysis allowed us to identify two RC prognostic groups (cluster 1 and cluster 2) associated with disease-specific OS (HR = 20.64; 95%CI = 2.63-162.2; p <0.0001), metastasis-free survival (HR = 3.67; 95%CI = 1.22-11; p = 0.012), local recurrence-free survival (HR = 3.34; 95%CI = 0.96-11.6; p = 0.043) and worse DFS (HR = 2.68; 95%CI = 1.18-6.06; p = 0.012). The worst prognosis cluster 2 was enriched by stage III high-risk clinical tumors, poor responders to nCRT, with low TILs density and high frequency of KRAS and TP53 mutated cases compared with the best prognosis cluster 1 (p <0.05). Overall, this study provides a comprehensive and integrated characterization of non-metastatic RC cases as a new insight to deliver a personalized therapeutic approach.

Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer.

Locally advanced rectal cancer (LARC) remains a medical challenge. Reliable biomarkers to predict which patients will significantly respond to neoadjuvant chemoradiotherapy (nCRT) have not been identified. We evaluated baseline genomic and transcriptomic features to detect differences that may help predict response to nCRT. Eligible LARC patients received nCRT (3D-LCRT 50.4 Gy plus capecitabine 825 mg/m2/bid), preceded by three cycles of CAPOX in high systemic-relapse risk tumors, and subsequent surgery. Frozen tumor biopsies at diagnosis were sequenced using a colorectal cancer panel. Transcriptomic data was used for pathway and cell deconvolution inferential algorithms, coupled with immunohistochemical validation. Clinical and molecular data were analyzed according to nCRT outcome. Pathways related to DNA repair and proliferation (p < 0.005), and co-occurrence of RAS and TP53 mutations (p = 0.001) were associated with poor response. Enrichment of expression signatures related to enhanced immune response, particularly B cells and interferon signaling (p < 0.005), was detected in good responders. Immunohistochemical analysis of CD20+ cells validated the association of good response with B cell infiltration (p = 0.047). Findings indicate that the presence of B cells is associated with successful tumor regression following nCRT in LARC. The prevalence of simultaneous RAS and TP53 mutations along with a proficient DNA repair system that may counteract chemoradio-induced DNA damage was associated with poor response.

A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy.

PURPOSE: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy ("Watch-and-Wait"). EXPERIMENTAL DESIGN: Biopsies from two independent cohorts (n 1 = 131, n 2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. RESULTS: ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06-0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the "Watch-and-Wait" cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). CONCLUSIONS: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.

Helicobacter pylori and corpus gastric pathology are associated with lower serum ghrelin.

AIM: To evaluate the association of Helicobacter pylori (H. pylori), cagA genotype, and type of gastric pathology with ghrelin, leptin and nutritional status. METHODS: Fasted dyspeptic adults (18-70 years) referred for an upper digestive endoscopy were enrolled in this cross-sectional study. Height and weight were assessed for body mass index (BMI) calculation. A sociodemographic survey was administered and nutrient intake was evaluated with 24 h dietary recalls. Serum total ghrelin and leptin levels were analyzed by enzyme-linked immunosorbent assay. 13C-Urea Breath Test was performed and four gastric biopsies were obtained during endoscopy for histopathology and H. pylori DNA amplification and genotyping. Data analysis was performed using χ2, Mann-Whitney U, Kruskal-Wallis tests, Spearman's correlation and linear regression. RESULTS: One hundred and sixty-three patients (40.8 ± 14.0 years), 98/65 females/males, were included. Overall, persistent H. pylori prevalence was 53.4% (95%CI: 45.7%-65.8%). Neither nutrient intake nor BMI differed significantly between H. pylori positive and negative groups. Serum ghrelin was significantly lower in infected patients [median 311.0 pg/mL (IQR 230.0-385.5)] than in uninfected ones [median 355.0 pg/mL (IQR 253.8-547.8)] (P = 0.025), even after adjusting for BMI and gender (P = 0.03). Ghrelin levels tended to be lower in patients carrying cagA positive strains both in the antrum and the corpus; however, differences with those carrying cagA negative strains did not reach statistical significance (P = 0.50 and P = 0.49, respectively). In addition, the type and severity of gastric pathology in the corpus was associated with lower serum ghrelin (P = 0.04), independently of H. pylori status. Conversely, leptin levels did not differ significantly between infected and uninfected patients [median 1.84 ng/mL (0.80-4.85) vs 1.84 ng/mL (0.50-5.09), (P = 0.51)]. CONCLUSION: H. pylori infection and severity of gastric corpus pathology are associated with lower serum ghrelin. Further studies could confirm a lower ghrelin prevalence in cagA-positive patients.

Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model.

BACKGROUND: Intestinal transplantation (ITx) faces many challenges due to the complexity of surgery and to the multiple immunological reactions that lead to the necessity of rigorous follow-up for early detection of acute cellular rejection (ACR). Our aim was to determine the kinetics of ACR using an experimental ITx model, with emphasis in the characterization of the process using different approaches, including the use of functional assays of absorptive and barrier function. METHODS: ITx in rats conducting serial sampling was performed. Clinical monitoring, graft histology, proinflammatory gene expression, and nitrosative stress determination were performed. Also, glucose absorption, barrier function using ovalbumin translocation, and contractile function were analyzed. RESULTS: The model used reproduced the different stages of ACR. Allogeneic ITx recipients showed signs of rejection from postoperative day (POD) 5, with increasing severity until 12 POD. Histological evaluation showed mild rejection in early sampling and severe rejection at late stages, with alterations in all graft layers. IL-6, CXCL 10, IFNg, and nitrite plasmas levels showed behavior coincident with histopathology. Remarkably, allogeneic grafts showed a marked alteration of glucose absorptive capacity from POD 5 that was sustained until endpoint. Coincidently, barrier function alteration was evidenced by luminal ovalbumin translocation to serum. Contractile function was progressively impaired along ACR. CONCLUSIONS: Glucose absorption and barrier function are altered at early stages of ACR when histological alterations or gene expression changes were much subtle. This observation may provide simple evaluation tools that could be eventually translated to the clinics to contribute to early ACR diagnosis.

Bifidobacterium infantis NLS Super Strain Reduces the Expression of α-Defensin-5, a Marker of Innate Immunity, in the Mucosa of Active Celiac Disease Patients.

BACKGROUND: We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity. GOALS: To investigate the potential mechanisms of a probiotic B. infantis Natren Life Start super strain on the mucosal expression of innate immune markers in adult patients with active untreated CD compared with those treated with B. infantis×6 weeks and after 1 year of gluten-free diet (GFD). METHODS: Numbers of macrophages and Paneth cells and α-defensin-5 expression were assessed by immunohistochemistry in duodenal biopsies. RESULTS: We showed that GFD decreases duodenal macrophage counts in CD patients more effectively than B. infantis. In contrast, B. infantis decreases Paneth cell counts and expression of α-defensin-5 in CD (P<0.001). CONCLUSIONS: The results identify differential innate immune effects of treatment with B. infantis compared with 1 year of GFD. Further studies are needed to investigate synergistic effects of GFD and B. infantis supplementation in CD.

Utility of Aminotransferase/Platelet Ratio Index to Predict Liver Fibrosis in Intestinal Failure-Associated Liver Disease in Pediatric Patients.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) is a frequent indication for intestinal transplantation. Liver biopsy (LBX) is the gold standard test for its diagnosis. Identifying noninvasive markers of fibrosis progression would be of considerable clinical use. Aspartate aminotransferase/platelet ratio index (APRI) has a good correlation in adult patients with chronic liver disease; few studies have been performed in children with IFALD. AIM: To evaluate APRI in a cohort of children with IFALD. MATERIALS AND METHODS: Retrospective analysis of a prospective database of patients <18 years with severe intestinal failure and at least 1 LBX, registered in our unit from March 2006 to December 2014. RESULTS: Forty-nine LBX were done on 36 patients: 20 were male, and 31 had short gut. Fibrosis was found in 71% of LBX. Biopsies were grouped according to the fibrosis stage (METAVIR [M]): (1) group 1 (G1) LBX with M 0, 1, 2 (n = 33) and (2) group 2 (G2) LBX with M 3, 4 (n = 16). The median APRI score was 0.92 (interquartile range [IQR] 0.63-1.50) for G1 and 2.50 (IQR 1.81-5.82) for G2 ( P = .001) The c statistic of the receiving operating characteristic curve was 0.79 (95% CI 0.64-0.94; P < .001). The analyses allowed identifying a cutoff value for APRI of 1.6 as the point with the best sensitivity (81%) and specificity (76%) to predict advanced fibrosis. CONCLUSIONS: APRI in this cohort of patients shows that a score >1.6 correlates with advanced fibrosis.

Observational study of patients with gastroenteropancreatic and bronchial neuroendocrine tumors in Argentina: Results from the large database of a multidisciplinary group clinical multicenter study.

Neuroendocrine tumors (NET) include a spectrum of malignancies arising from neuroendocrine cells throughout the body. The objective of this clinical investigation of retrospectively and prospectively collected data was to describe the prevalence, demographic data, clinical symptoms and methods of diagnosis of NET and the treatment and long-term follow-up of patients with NET. Data were provided by the participating centers and assessed for consistency by internal reviewers. All the cases were centrally evaluated (when necessary) by the pathologists in our group. The tissue samples were reviewed by hematoxylin and eosin and immunohistochemical staining techniques to confirm the diagnosis of NET. In total, 532 cases were documented: 461 gastroenteropancreatic-NET (GEP-NET) and 71 bronchial NET (BNET). All the tumors were immunohistochemically defined according to the World Health Organization (WHO) and European Neuroendocrine Tumor Society criteria. The most common initial symptoms in GEP-NET were abdominal pain, diarrhea, bowel obstruction, flushing, gastrointestinal bleeding and weight loss. The most common tumor types were carcinoid (58.0%), non-functional pancreatic tumor (23.0%), metastatic NET of unknown primary (16.0%) and functional pancreatic tumor (3.0%). Of the BNET, 89.0% were typical and 11.0% atypical carcinoids. Of the patients with GEP-NET, 59.2% had distant metastasis at diagnosis. The locations of the primary tumors in GEP-NET were the small bowel (26.9%), pancreas (25.2%), colon-rectum (12.4%), appendix (7.6%), stomach (6.9%), esophagus (2.8%), duodenum (2.0%) and unknown primary (16.3%). The histological subtypes based on the WHO classification were well-differentiated NET (20.1%), well-differentiated neuroendocrine carcinomas (66.5%) and poorly differentiated neuroendocrine carcinomas (10.3%). Overall, 67.3% of the patients underwent surgery, 41.2% with curative intent and 26.1% for palliative purposes. The 5-year survival rates were 65.1% (95% confidence interval, 58.0-71.4%) in GEP-NET and 100.0% in typical carcinoid of the lung. This observational, non-interventional, longitudinal study aimed to accumulate relevant information regarding the epidemiology, clinical presentation and current practices in the treatment of NET patients in Argentina, providing insight into regional differences and patterns of care in this heterogeneous disease.

Sclerosing peritonitis, a rare complication after intestinal transplant. Report of one case successfully treated with adjustment of immunosuppression.

Sclerosing peritonitis is a complication described in different clinical situations, such as patients that underwent prolonged peritoneal dialysis or renal transplantation with previous history of peritoneal dialysis. The origin of this entity is unclear so far and it is believed that several mechanisms may contribute to its development. The hallmark of sclerosing peritonitis is the continuous accumulation of fibrocollagenous deposits in the intestinal wall and mesenteries causing progressive adhesion of the intestinal loops and mesenteric retraction resulting in intestinal obstruction. Also, it has been described as a rare complication after intestinal transplant that might lead to graft failure. In this report, we describe a case of sclerosing peritonitis after intestinal transplantation that was successfully treated with modifications in the immunosuppressive regime allowing restitution of gastrointestinal transit and intestinal autonomy.

A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer.

OBJECTIVE: Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. DESIGN: We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤ 50 years old (n=188), a group of sporadic CRC >50 years (MSS n=89; MSI n=46), and a group of Lynch syndrome CRCs (n=20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. RESULTS: Mean LINE-1 methylation levels (± SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥ 65% LINE-1 methylation had significantly better overall survival (p=0.026, log rank test). CONCLUSIONS: LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.

[Partial external biliary diversion: a therapeutic alternative for Alagille syndrome. First case in Argentina]. / Derivación biliar externa parcial: alternativa terapéutica en el síndrome de Alagille. Primer caso en la Argentina.

BACKGROUND: Alagille 's syndrome is the main syndromic chronic intrahepatic cholestasis characterized by hypoplasia of the intrahepatic bile ducts. It is a multisystem disorder of autosomal dominant inheritance with involvement of multiple organs. Usually it becomes apparent in the neonatal period, presenting as subclinical cases or severe degrees of the disease with the consequent development of liver cirrhosis and subsequent liver failure associated with multiple abnormalities: defects in the vertebral arches, typical facies, pulmonary stenosis, mental retardation and hypogonadism. OBJECTIVE: To present the first case of partial external biliary diversion in Argentina, showing the surgical technique and the improvement in the quality of life, as an alternative to be considered in patients with Alagille's syndrome before the development of cirrhosis. RESULTS: It has been shown that partial external biliary diversion can stop the process of liver fibrogenesis, halting the progression of the disease and avoiding the need for transplantation in some types of intrahepatic cholestasis when cirrhosis has not been established. DISCUSSION: This surgical technique can improve the quality of life and morbidity associated with hypercholesterolemia in patients with Alagille's syndrome, delaying and maybe avoiding the need for liver transplantation.

Celiac disease serology in patients with different pretest probabilities: is biopsy avoidable?

AIM: To establish the diagnostic performance of several serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential serological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.

Visceral Kaposi's sarcoma remission after intestinal transplant. First case report and systematic literature review.

BACKGROUND: Kaposi's sarcoma (KS) is an infrequent vascular neoplasm commonly diagnosed as an isolated cutaneous lesion that can involve other organs. So far, there are no data in the literature about the development of KS after intestinal transplant. METHODS: In this study, the authors describe a case of "visceral KS" with pulmonary and intestinal involvement and perform a systematic literature review of case reports and single-center series identified in MEDLINE. RESULTS: This case was a 42-year-old man, diagnosed with visceral KS 9 months after receiving an isolated intestinal transplant. He was successfully treated with a combination of sirolimus and liposomal doxorubicin and achieved an 18-month disease-free survival. A total of 54 cases from 27 manuscripts and the present case were analyzed in this study. The mean time from transplant to diagnosis was 17.2 months. Lungs and gastrointestinal tract were the main organs involved. Immunosuppressants were discontinued in two of the three (66.7%) cases, and sirolimus was added in eight cases. Doxorubicin was used in 12 cases. In a univariate analysis, the use of Tacrolimus, type of transplant, and presence of cutaneous KS seem to be the significant predictors of response to therapy and survival; the addition of doxorubicin showed a reduction in graft loss. CONCLUSIONS: Treatment of KS in posttransplant patients should be designed aiming to obtain a complete response, irrespective of the organ affected. Only recipients who are able to achieve a sustained response would be able to obtain long-term disease-free survival.

Diferencias clínicas y quirúrgicas entre pacientes con tuberculosis abdominal con y sin infección por el virus de inmunodeficiencia humana / Clinical and surgical differences in patients with abdominal tuberculosis infected and non infected by human immunodeficiency virus patient

La tuberculosis abdominal (TBa) ocurre en el 1 al 2,5 % del total de la tuberculosis diagnosticadas. Objetivos: Analizar las diferencias entre las características clínicas y quirúrgicas de la TBa en pacientes VIH positivos y VIH negativos. Materiales y métodos: Estudio descriptivo-analítico retrospectivo entre dos poblaciones asistidas entre los años 1989-2009 con diagnóstico de TBa. Once pacientes eran VIH positivos y 60 VIH negativos. Se analizaron variables clínicas, humorales, hallazgos quirúrgicos, procedimientos diagnósticos utilizados y los diferentes órganos abdominales afectados. En el análisis estadístico se utilizó la prueba del Chi cuadrado o el test de Fischer. También se calcularon el ODDS Ratio (OR) e intervalo de confianza al 95 %. Resultados: se diagosticaron 71 casos de TBa de los cuales 11 (15,5 %) fueron VIH positivos. de los 71 casos la edad media fue de 38 años, los síntomas más frecuentes observados fueron pérdida de peso 90,1 %, dolor abdominal 81,4 %, hipertermia 91,6 %, entre otros. el 8,5 % de los pacientes fallecieron. Al comparar ambas poblaciones, se observaron diferencias estadísticamente significativas en la población VIH positiva quienes fueron más jóvenes, más frecuentemente de género masculino, con menor tiempo de duración de los síntomas, presentando en menor frecuencia hipertermia y disminución de peso y más frecuentemente masa abdominal palpable y adenopatías en la cavidad abdominal. La mortalidad fue también mayor en este grupo. Conclusiones: La población presentó variables estadísticamente significativas para la edad, el género, tiempo de evolución de los síntomas, entre otras variaables que pueden ser de utilidad en su diagnóstico diferencial.

Abdominal tuberculosis (TBA) occurs in 1 to 2,5 % of total tuberculosis diagnosed. Objective: To analyze the differences between clinical and surgical characteristics of the TBA in HIV patients and HIV non-reactive reagents. Materials and Methods: A retrospective descriptive-analyticstudy of two groups assisted in the years 1989-2009 with a diagnosis of TBA. Eleven patients were HIV positive and 60 HIV-negative. We analyzed the clinical, laboratory findings and surgical findings, the diagnostic procedures used and the abdominal organs affected. Statistical analysis used Chi square test or Fischer test. Also calculated the Odds Ratio (OR) and confidence interval 95 %. Results: We diagnosed 71 cases of TBA of which 11 (15,5%) were HIV positive. Of the 71 cases the average age was 38 years, the most common symptoms observed were weight loss (90,1 %), abdominal pain (81,4 %), hyperthermia (91,6 %). 8,5 % of the patients died. HIV positive and negative were compared finding statistically significant differences in the HIV who were younger, more often male, with shorter duration of symptoms. In this population weight reduction and hyperthermia was less frequently in contrast with frequently palpable abdominal mass and lymphadenopathy in the abdominal cavity. Mortality was higher in among HIV positive patients. Conclusions: the present population statistically significnt variables for age, gender and time in the presence of sympotoms, among other variable that may be useful in the differential diagnosis.

[Image-guided percutaneous biopsy of gastric lesions with suspicion of malignancy and negative endoscopic biopsies: report of our experience and revision of the literature]. / Biopsia percutánea guiada por imágenes de lesiones gástricas sospechosas de malignidad y biopsias endoscópicas negativas: reporte de nuestra experiencia y revisión de la literatura.

BACKGROUND: Endoscopic biopsy is the most efficient way to obtain a biopsy specimen from neoplastic lesions located in the stomach. Therefore, it is the procedure of choice to obtain a histologic diagnosis of gastric cancer. Image guided percutaneous biopsy is an alternative method to obtain histologic material for definitive diagnosis when the biopsies are negative for neoplastic cells in several endoscopies. OBJECTIVE: The purpose of this study was to evaluate the efficacy, complications, and histologic results of image guided percutaneous biopsies of gastric lesions in our center. MATERIALS AND METHODS: Between March 2004 and March 2007, 6 patients with strong suspicion of gastric cancer and negative endoscopic biopsies were referred for image guided percutaneous biopsy of gastric lesions (5 were guided by ultrasonography and 1 by CT scan). RESULTS: A histologic diagnosis was made in 5 patients: poorly differentated signet-ring cell carcinoma 3, B-cell non-Hodgkin's lymphoma 2. One patient suffered a perforation during the procedure and the final histologic diagnosis was obtained after the consequent surgery (B-cell non-Hodgkin's lymphoma). CONCLUSION: Despite of the scant published series, image guided percutaneous biopsy of gastric lesions is an useful, safe and effective technique to obtain a histologic diagnosis in patients with strong suspicion of gastric cancer and negative endoscopic biopsies.

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.

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.

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.

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.