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1.
Gastroenterology ; 150(3): 581-590.e4, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26584601

RESUMEN

BACKGROUND & AIMS: It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS: Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS: Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS: In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.


Asunto(s)
Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/terapia , Eosinófilos/patología , Esofagoscopía , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biopsia , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/patología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Inducción de Remisión , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Suiza , Resultado del Tratamiento , Estados Unidos , Adulto Joven
2.
Am J Gastroenterol ; 110(3): 402-14, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25732414

RESUMEN

OBJECTIVES: There is no "gold standard" for assessing disease activity in patients with eosinophilic esophagitis (EoE). We aimed to compare physicians' judgment of EoE activity with patients' judgment of symptom severity. We also aimed to examine the relative contribution of symptoms as well as endoscopic and histologic findings in shaping physicians' judgment of EoE activity. METHODS: Six gastroenterologists (all EoE experts) assessed EoE-associated symptoms in adult patients. Patients completed a symptom instrument and provided global assessment of EoE symptom severity (PatGA) (Likert scale: 0 (inactive) to 10 (most active)). Following esophagogastroduodenoscopy with biopsy sampling, gastroenterologists provided a global assessment of EoE activity (PhysGA) (Likert scale from 0 to 10) based on patient history and endoscopic and histologic findings. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms and endoscopic and histologic findings explain variations in PhysGA. RESULTS: A total of 149 EoE patients were prospectively included (71.8% male, median age at inclusion 38 years, 71.8% with concomitant allergies). A moderate positive correlation between PhysGA and PatGA (rho=0.442, P<0.001) was observed and the mean difference in the Bland-Altman plot was 1.77. Variations in severity of endoscopic findings, symptoms, and histologic findings alone explained 53%, 49%, and 30%, of the variability in PhysGA, respectively. Together, these findings explained 75% of variability in PhysGA. CONCLUSIONS: Gastroenterologists rate EoE activity mainly on the basis of endoscopic findings and symptoms and, to a lesser extent, on histologic findings.


Asunto(s)
Esofagitis Eosinofílica/diagnóstico , Hipersensibilidad/complicaciones , Anamnesis , Pautas de la Práctica en Medicina , Evaluación de Síntomas , Adulto , Análisis de Varianza , Autoevaluación Diagnóstica , Endoscopía del Sistema Digestivo/métodos , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/fisiopatología , Esófago/patología , Femenino , Humanos , Biopsia Guiada por Imagen/métodos , Masculino , Anamnesis/métodos , Anamnesis/normas , Anamnesis/estadística & datos numéricos , Persona de Mediana Edad , Gravedad del Paciente , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Estadística como Asunto , Suiza , Evaluación de Síntomas/métodos , Evaluación de Síntomas/normas , Evaluación de Síntomas/estadística & datos numéricos , Estados Unidos
3.
Abdom Imaging ; 40(2): 246-50, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25099255

RESUMEN

PURPOSE: To describe the abdominal imaging findings of patients with gastrointestinal Basidiobolus ranarum infection. METHODS: A literature search was performed to compile the abdominal imaging findings of all reported worldwide cases of gastrointestinal basidiobolomycosis (GIB). In addition, a retrospective review at our institution was performed to identify GIB cases that had imaging findings. A radiologist aware of the diagnosis reviewed the imaging findings in detail. Additional information was obtained from the medical records. RESULTS: A total of 73 GIB cases have been published in the medical literature. The most common abdominal imaging findings were masses in the colon, the liver, or multiple sites and bowel wall thickening. Initially, many patients were considered to have either a neoplasm or Crohn disease. We identified 7 proven cases of GIB at our institution, of which 4 had imaging studies (4 computed tomography [CT] examinations, 4 abdominal radiographs, and an upper gastrointestinal study). Imaging studies showed abnormalities in all 4 cases. Three-fourths of our study patients had an abdominal mass at CT. Two of 3 masses involved the kidneys and included urinary obstruction. All masses showed an inflammatory component with adjacent soft tissue stranding, with or without abscess formation. CONCLUSIONS: Radiologists should consider GIB when a patient from an arid climate presents with abdominal pain, weight loss, and an inflammatory abdominal mass on CT. Abdominal masses of the colon or liver, bowel wall thickening, and abscesses are the most common imaging findings.


Asunto(s)
Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/microbiología , Radiografía Abdominal , Tomografía Computarizada por Rayos X , Cigomicosis/diagnóstico , Anciano , Antifúngicos/uso terapéutico , Diagnóstico Diferencial , Entomophthorales/aislamiento & purificación , Enfermedades Gastrointestinales/terapia , Humanos , Intestinos/diagnóstico por imagen , Intestinos/microbiología , Intestinos/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cigomicosis/tratamiento farmacológico , Cigomicosis/cirugía
4.
Abdom Imaging ; 40(4): 760-5, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25542217

RESUMEN

PURPOSE: The purpose of this study was to compare fibrosis seen on liver biopsy to MR elastography (MRE) stiffness measurements in normal controls and patients with abnormal transaminases and chronic liver disease. METHODS: The control group consisted of 22 healthy liver transplant donors who by definition had normal transaminases. The patient group (32 patients) was recruited from the Mayo Clinic Arizona hepatobiliary clinic over a 3-year span. All subjects underwent a liver biopsy as part of their evaluation and agreed to MRE within 35 days of biopsy. Non-parametric tests were used to compare the MRE-predicted liver fibrosis to the fibrosis noted on liver biopsy. RESULTS: Analysis included 54 subjects (32 patients with chronic liver disease and 22 healthy liver donor candidates). MRE median liver stiffness measurements increased per histologic liver fibrosis stage (one-way ANOVA p = 0.001), with significant correlation between increasing fibrosis stage and stiffness values. Median MRE for control group (2.13 kPa; mean = 2.3 ± 0.6 kPa) was significantly lower than for patient group (3.7 kPa; mean = 4.1 ± 2.1 kPa) (p = 0.003). Significantly, lower median stiffness was seen in zero-to-moderate (F0-2, n = 22) vs. severe fibrosis stages (F3-4, n = 10) 2.80 vs. 5.9 kPa, respectively (p < 0.05). Using a 3.7-kPa cut-off value, the predicted sensitivity and specificity for detecting F0-2 from F3-4 were 91% and 80%, respectively. CONCLUSIONS: Our analysis supports previous findings that MRE is a non-invasive and effective method for detection and assessment of liver fibrosis, particularly for discrimination between F0-2 stages and F3-4 stages. MRE may represent a valuable tool to finely discern hepatic fibrosis non-invasively.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática/patología , Imagen por Resonancia Magnética , Adulto , Anciano , Biopsia , Estudios de Cohortes , Femenino , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
5.
Abdom Imaging ; 40(4): 795-802, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25445158

RESUMEN

PURPOSE: The aim of this study was to define liver shear stiffness by magnetic resonance elastography (MRE) that distinguishes normal from abnormal liver biopsy, especially when steatosis ≥20%, among potential live liver donors. METHODS: Baseline clinical, laboratory, imaging, MRE, and liver biopsy results were recorded. Using MRE, hepatic shear stiffness in kilopascals (kPa) was measured and compared to liver biopsy. Comparison between groups was done using χ(2) or Fisher's exact test for categorical variables and Wilcoxon test for continuous variables. Receiver operating characteristic (ROC) curve was calculated to assess diagnostic accuracy. Statistical significance was set at p < 0.05. RESULTS: 38 healthy adults were included. Liver biopsy was normal in 27 and abnormal in 11. ROC curve for MRE defined optimal cutoff at 2.6 kPa (sensitivity 0.72, specificity 0.85, AUC 0.81) to distinguish these 2 groups. Hepatic steatosis ≥20% on biopsy is a contraindication for liver donation in our center. We evaluated the ability of MRE to distinguish this degree of steatosis: 8 persons had steatosis ≥20% and were excluded from donation. ROC curve for MRE defined optimal cutoff at 2.82 kPa (sensitivity 0.88, specificity 1, AUC 0.98) to identify this group. CONCLUSIONS: Liver stiffness measured by MRE, even in the absence of liver fibrosis, can be useful in differentiating normal from abnormal liver histology, and most importantly in patients under evaluation for live liver donation, can very accurately distinguish those with complicated hepatic steatosis ≥20%, our cutoff for donation. In the future, MRE might provide supplementary information to make liver biopsy unnecessary in the donor evaluation process.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Cirrosis Hepática/patología , Hígado/patología , Donadores Vivos , Imagen por Resonancia Magnética/métodos , Adulto , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados
6.
AJR Am J Roentgenol ; 202(2): W140-5, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24450695

RESUMEN

OBJECTIVE: The purpose of this article is to report the CT findings of pathologically proven diaphragm disease in the small bowel. MATERIALS AND METHODS: A retrospective review identified 12 patients with pathologically proven small-bowel diaphragm disease who underwent CT within 6 months of surgical resection. Two radiologists, who were unblinded to pathologic and clinical findings, evaluated CT examinations for imaging findings of disease extent, appearance, and location. Clinical history and postoperative follow-up were also performed. RESULTS: The most common presenting symptoms were abdominal pain (7/12 [58%]) and anemia (5/12 [42%]). Long-term use of nonsteroidal antiinflammatory drugs was documented in 58% (7/12) of patients. The most common location of small-bowel diaphragms was the ileum (8/12 [67%]). The CT findings were abnormal in 92% (11/12) of patients. The most common CT findings were small-bowel strictures (11/12 [92%]) and focal (median length, 1 cm) bowel wall thickening (8/12 [67%]). Other less common CT findings included mucosal hyperenhancement (6/12 [50%]), small-bowel dilatation (5/12 [42%]), and video capsule retention (6/9 [67%]). Postoperative follow-up in 11 patients found recurrent symptoms in four patients. CONCLUSION: Small-bowel diaphragm disease should be considered in patients with a history of long-term use of nonsteroidal antiinflammatory drugs, chronic abdominal pain, and anemia who present with CT findings of short, symmetric ileal strictures and focal bowel wall thickening.


Asunto(s)
Diafragma/diagnóstico por imagen , Enfermedades Intestinales/diagnóstico por imagen , Intestino Delgado/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Endoscopía Capsular , Diafragma/irrigación sanguínea , Diafragma/patología , Femenino , Humanos , Enfermedades Intestinales/patología , Intestino Delgado/irrigación sanguínea , Intestino Delgado/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
7.
J Clin Gastroenterol ; 47(3): 239-41, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23391868

RESUMEN

GOALS: To underscore the utility of DNA fingerprinting for clarifying disparate results from endoscopic pathologic specimens. BACKGROUND: Occasionally, serially obtained gastrointestinal biopsies may yield inconsistent results. These discrepancies pose a dilemma for gastroenterologists and their patients, especially when malignancy is a consideration. STUDY: Patients referred to our tertiary care center from outside institutions had undergone endoscopically obtained esophageal biopsies showing malignancy, verified by pathologists at both our site and from the referring center. Repeat endoscopic biopsies at our center did not show malignancy. To verify that different sets of biopsies came from the same patient, we performed a polymerase chain reaction-based analysis comparing the 2 specimens. This analysis, called DNA fingerprinting, can show a high degree of certainty whether 2 specimens came from the same patient. RESULTS: In each case, DNA fingerprinting verified a match, laying the groundwork for intervention. One patient underwent endoscopic radiofrequency ablation to the esophageal mucosa involved. Another underwent esophagectomy with partial gastrectomy. Both are doing well clinically and remain cancer-free on follow-up. CONCLUSIONS: DNA fingerprinting is a powerful and a relatively inexpensive tool. Usually, only small amounts of tissue are required, and even degraded or archival tissue is adequate. DNA fingerprinting can be an important tool in the gastroenterologist's arsenal to help clarify conflicting results, allowing the patient and physician to move forward with the management.


Asunto(s)
Dermatoglifia del ADN/métodos , Endoscopía Gastrointestinal/métodos , Neoplasias Gastrointestinales/diagnóstico , Biopsia , Ablación por Catéter/métodos , Esofagectomía/métodos , Estudios de Seguimiento , Gastrectomía/métodos , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/cirugía , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Derivación y Consulta
8.
Clin Infect Dis ; 54(12): 1685-91, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22441651

RESUMEN

BACKGROUND: We examined the epidemiology, clinical manifestations, histopathology, management, and outcomes of gastrointestinal basidiobolomycosis, an uncommon manifestation of infection caused by the fungus Basidiobolus ranarum. METHODS: In this retrospective observational cohort study, cases of gastrointestinal basidiobolomycosis in the United States were identified by reviewing medical records from Mayo Clinic Hospital (Phoenix, AZ) and contacting local infectious diseases specialists, pathologists, gastroenterologists, the Arizona Department of Health Services, health departments of adjacent states, the Armed Forces Institute of Pathology, and the US Centers for Disease Control and Prevention. A comprehensive literature review identified additional cases worldwide. RESULTS: Of 44 patients (mean age, 37 years [range, 2-81 years]) with gastrointestinal basidiobolomycosis, most were from the United States (19 patients [43%], of whom 17 [89%] were from Arizona) or Saudi Arabia (11 [25%]). Most (28 [64%]) were previously healthy. Common chronic medical conditions among 15 patients (34%) were diabetes mellitus (8 patients [18%]) and gastric disorders (7 [16%]). Common findings were abdominal pain (37 patients [84%]) and a palpable abdominal mass (19 [43%]). Intraabdominal malignancy was the leading provisional diagnosis (19 patients [43%]). The large bowel was involved in 36 (82%), the small intestine in 16 (36%), and the liver or gallbladder in 13 (30%). Characteristic histopathologic findings were observed in 43 (98%). Eight patients (18%) died. Combined surgical intervention and antifungal therapy was the preferred treatment. CONCLUSIONS: Gastrointestinal basidiobolomycosis is an emerging invasive fungal infection in desert regions of the US Southwest. Clinical findings mimic malignancy and inflammatory bowel disease. Surgical excision and prolonged antifungal therapy are associated with favorable outcomes.


Asunto(s)
Entomophthorales/aislamiento & purificación , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/microbiología , Cigomicosis/epidemiología , Cigomicosis/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Arizona/epidemiología , Niño , Preescolar , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/microbiología , Enfermedades Transmisibles Emergentes/terapia , Clima Desértico , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven , Cigomicosis/diagnóstico , Cigomicosis/terapia
9.
Cancer ; 118(21): 5234-44, 2012 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-22605513

RESUMEN

BACKGROUND: One in 4 patients with lymph node-negative, invasive colorectal carcinoma (CRC) develops recurrent disease after undergoing curative surgery, and most die of advanced disease. Predicting which patients will develop a recurrence is a significantly growing, unmet medical need. METHODS: Archival formalin-fixed, paraffin-embedded (FFPE) primary adenocarcinoma tissues obtained at surgery were retrieved from 74 patients with CRC (15 with stage I disease and 59 with stage II disease) for Training/Test Sets. In addition, FFPE tissues were retrieved from 49 patients with stage I CRC and 215 patients with stage II colon cancer for an External Validation (EV) Set (n = 264) from 18 hospitals in 4 countries. No patients had received neoadjuvant/adjuvant therapy. Proprietary genetic programming analysis of expression profiles for 225 prespecified tumor genes was used to create a 36-month recurrence risk signature. RESULTS: Using reverse transcriptase-polymerase chain reaction, a 5-gene rule correctly classified 62 of 92 recurrent patients and 87 of 172 nonrecurrent patients in the EV Set (sensitivity, 0.67; specificity, 0.51). "High-risk" patients had a greater probability of 36-month recurrence (42%) than "low-risk" patients (26%; hazard ratio, 1.80; 95% confidence interval, 1.19-2.71; P = .007; Cox regression) independent of T-classification, the number of lymph nodes examined, histologic grade/subtype, anatomic location, age, sex, or race. The rule outperformed (P = .021) current National Comprehensive Cancer Network Guidelines (hazard ratio, 0.897). The same rule also differentiated the risk of recurrence (hazard ratio, 1.63; P = .031) in a subset of patients from the EV Set who had stage I/II colon cancer only (n = 251). CONCLUSIONS: To the authors' knowledge, the 5-gene rule (OncoDefender-CRC) is the first molecular prognostic that has been validated in both stage I CRC and stage II colon cancer. It outperforms standard clinicopathologic prognostic criteria and obviates the need to retrieve ≥12 lymph nodes for accurate prognostication. It identifies those patients most likely to develop recurrent disease within 3 years after curative surgery and, thus, those most likely to benefit from adjuvant treatment.


Asunto(s)
Adenocarcinoma/genética , Neoplasias Colorrectales/genética , Transcriptoma , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Sensibilidad y Especificidad
10.
Dis Colon Rectum ; 55(11): 1111-6, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23044670

RESUMEN

BACKGROUND: Colonoscopy has an established role in reducing the burden of colorectal cancer through early detection and removal of polyps. For endoscopically unresectable polyps, colectomy is generally indicated to prevent malignant transformation or to remove cancer already present. OBJECTIVE: This study aimed to determine the incidence of malignancy and the factors predictive of malignancy in surgically resected benign polyps. DESIGN/PATIENTS/SETTING: This study was a retrospective chart review of patients undergoing a colectomy for a colonic polyp (no preoperative diagnosis of cancer) in 4 hospitals within the Mayo Clinic Health System. MAIN OUTCOME MEASURES: Patient characteristics, endoscopic location and size, and preoperative and operative polyp pathology were tabulated. Correlations between these features and the finding of invasive carcinoma on surgical pathology were assessed. RESULTS: A total of 750 patients met our inclusion criteria. Patients were predominantly male (55.2%) with an average age of 69.4 ± 9.8 years. A majority of polyps were located in the right colon (70.9%). Invasive cancer was identified in 133 patients (17.7%). Multivariate analysis revealed polyps in the left colon (adjusted OR 2.13, 95% CI (1.22-3.72)), and those with high-grade dysplasia (adjusted OR 4.60, 95% CI (2.91-7.27)) were more likely to harbor carcinoma. Age, sex, polyp dimension, and villous features were not predictive of malignancy. Of the patients with cancer, 31 (23.3%) had nodal disease. LIMITATIONS: This study is limited by its retrospective nature, the change in terminology and technique over time, and the partially subjective nature of an endoscopically unresectable polyp. CONCLUSIONS: The finding that polyp size and villous features do not strongly predict malignancy differs from previous endoscopic studies. This study confirms that polyps located in the left colon or with high-grade dysplasia are more likely to harbor cancer. The results of this study suggest that endoscopically unresectable polyps are best treated by radical oncologic resection.


Asunto(s)
Adenoma/patología , Carcinoma/patología , Neoplasias del Colon/patología , Pólipos del Colon/patología , Adenoma/cirugía , Anciano , Carcinoma/cirugía , Colectomía , Colon Descendente/patología , Neoplasias del Colon/cirugía , Pólipos del Colon/cirugía , Colonoscopía , Intervalos de Confianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Invasividad Neoplásica , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo
11.
J Immunol ; 182(1): 216-24, 2009 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-19109152

RESUMEN

With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRAS(G12D) mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E(2) and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer.


Asunto(s)
Adenocarcinoma/enzimología , Adenocarcinoma/prevención & control , Vacunas contra el Cáncer/administración & dosificación , Carcinoma Ductal Pancreático/enzimología , Carcinoma Ductal Pancreático/prevención & control , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/prevención & control , Adenocarcinoma/patología , Animales , Anticuerpos/sangre , Vacunas contra el Cáncer/inmunología , Carcinoma Ductal Pancreático/patología , Celecoxib , Ciclooxigenasa 2/metabolismo , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Ratones , Ratones Transgénicos , Mucina-1/administración & dosificación , Mucina-1/inmunología , Neoplasias Pancreáticas/patología , Pirazoles/administración & dosificación , Sulfonamidas/administración & dosificación , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/inmunología , Gemcitabina
12.
JOP ; 12(3): 297-305, 2011 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-21546713

RESUMEN

Autoimmune pancreatitis is the pancreatic manifestation of a novel clinicopathological disorder called systemic IgG4-related sclerosing disease. Beside the pancreas, this entity affects other sites (salivary glands, orbit, lung, thyroid, gallbladder, biliary tree system, kidney, abdominal aorta, retroperitoneum, prostate, and lymph node) by infiltration with IgG4-positive plasma cells. Several case reports and small case series have demonstrated the utility of integrated positron emission tomography/computed tomography (PET/CT) in monitoring therapy and documenting relapse and flare-up of autoimmune pancreatitis. However, there are no reports on the usefulness of PET/CT in selecting extrapancreatic sites for tissue sampling. We herein demonstrate the clinical utility of integrated PET/CT in 3 cases of systemic IgG4-related sclerosing disease for targeting extrapancreatic biopsy sites.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Inmunoglobulina G/inmunología , Pancreatitis/inmunología , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Enfermedades Autoinmunes/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Inmunoglobulina G/análisis , Masculino , Persona de Mediana Edad , Páncreas/inmunología , Páncreas/patología , Pancreatitis/diagnóstico , Esclerosis , Sensibilidad y Especificidad
13.
Ann Diagn Pathol ; 15(5): 342-6, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21723760

RESUMEN

Radiographic identification of an abnormal lesion in the esophagus routinely occurs during workup of patients with symptomatic dysphagia. Leiomyoma is the most common benign finding; however, plexiform leiomyoma, a distinctive but rare variant, follows an unusual pattern of growth which can be a challenging surgical resection. A review of indexed literature identified a single previous report. We contribute a second case of plexiform leiomyoma with a discussion of the clinical, radiographic, and pathologic characteristics, as well as the differential diagnosis for plexiform lesions.


Asunto(s)
Neoplasias Esofágicas/diagnóstico , Leiomioma/diagnóstico , Adulto , Diagnóstico Diferencial , Endoscopía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagoscopía , Humanos , Leiomioma/patología , Leiomioma/cirugía , Masculino
15.
Cancers (Basel) ; 12(9)2020 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-32917028

RESUMEN

Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced "dysplastic-like" features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions.

16.
Clin Gastroenterol Hepatol ; 7(7): 749-755.e11, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19345285

RESUMEN

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is characterized by medically/surgically-resistant gastroesophageal reflux symptoms and dense squamous eosinophilia. Studies suggest that histologic assessment of esophageal eosinophilia alone cannot reliably separate patients with EoE from those with gastroesophageal reflux disease (GERD). Our goal was to develop an assay to identify EoE patients and perhaps differentiate EoE from other causes of esophageal eosinophilia. METHODS: A monoclonal antibody specific for an eosinophil secondary granule protein (eosinophil peroxidase [EPX]) was developed and shown to specifically identify intact eosinophils and detect eosinophil degranulation in formalin-fixed specimens. A histopathologic scoring algorithm was developed to analyze data from patient evaluations; the utility of this algorithm was assessed by using archived esophageal tissues from patients with known diagnoses of EoE and GERD as well as controls from 2 tertiary care centers. RESULTS: Intraobserver/interobserver blinded evaluations demonstrated a significant difference (P < .001) between scores of samples taken from control subjects, from patients with esophageal eosinophilia who had a diagnosis of EoE, and from patients with GERD (P < .001). This algorithm also was able to identify patients whose clinical course was suggestive of a diagnosis of EoE, but that nonetheless failed to reach the critical threshold number of > or =15 eosinophils in a high-power (40x) microscopy field. CONCLUSIONS: A novel immunohistochemical scoring system was developed to address an unmet medical need to differentiate histologic specimens from patients with EoE relative to those with GERD. The availability of a unique anti-EPX-specific monoclonal antibody, combined with the ease/rapidity of this staining method and scoring system, will provide a valuable strategy for the assessment of esophageal eosinophilia.


Asunto(s)
Biopsia , Eosinofilia/diagnóstico , Eosinofilia/patología , Esofagitis/diagnóstico , Esofagitis/patología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Animales , Niño , Preescolar , Diagnóstico Diferencial , Eosinofilia/inmunología , Esofagitis/inmunología , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/patología , Humanos , Inmunohistoquímica/métodos , Lactante , Ratones , Persona de Mediana Edad , Coloración y Etiquetado
17.
Liver Transpl ; 15(12): 1872-81, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19938138

RESUMEN

Our aim was to assess long-term survival in patients transplanted for HCV-related end-stage liver disease (ESLD) and evaluate potentially modifiable predictors of survival. We performed a retrospective analysis of adult liver transplants (LT) at our institution for HCV-related ESLD since the program's inception. Pertinent demographic, clinical, and biochemical information was retrieved from electronic medical records and histological data from 990 per-protocol liver biopsies were collected. Three hundred eighty LT were performed at our institution during the study period, 206 patients were transplanted for HCV-related ESLD; 6 died within 30 days of transplantation and were not included. The remaining 200 recipients (DDLT 168 LDLT 32) constituted the evaluable population. The demographics were as follows: 150 males, median age 53 years; median donor age 39 years; hepatocellular carcinoma (HCC) in 26%. Overall 1-, 5-, and 7-year survival: 95%, 81%, and 79%; median survival 43 months, mortality 15%. Significant HCV recurrence (HAI >or=6 and/or fibrosis >or=2) was present in 49%, "early recurrence" (within 1 year of LT) in 30.5% and biopsy-proven acute rejection was present in 27%. Factors with a significant negative impact on patient survival included: fibrosis stage >or=2 at 12-month biopsy, advanced donor age, history of HCC and early acute rejection. Survival was similar regardless of the donor type (DDLT vs. LDLT). Early and aggressive HCV recurrence has a very heavy toll on patient survival. Prompt recognition and treatment of "rapid fibrosers" may impart benefit. As has been described before, avoidance of rejection and selection of young donors for HCV-positive recipients will also improve survival in this population. On the basis of our findings, LDLT is a good option for HCV-positive recipients.


Asunto(s)
Rechazo de Injerto/virología , Hepatitis C/cirugía , Cirrosis Hepática/cirugía , Fallo Hepático/cirugía , Trasplante de Hígado/efectos adversos , Enfermedad Aguda , Adulto , Biopsia , Progresión de la Enfermedad , Femenino , Rechazo de Injerto/mortalidad , Hepatitis C/complicaciones , Hepatitis C/mortalidad , Hepatitis C/patología , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/mortalidad , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Fallo Hepático/mortalidad , Fallo Hepático/patología , Fallo Hepático/virología , Trasplante de Hígado/mortalidad , Donadores Vivos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
18.
Pathol Res Pract ; 215(10): 152561, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31358481

RESUMEN

Nephrogenic adenoma is a common diagnosis in urological pathology that may be challenging for general pathologists. Due to its polymorphic appearance under the microscope, some cases can be misdiagnosed as malignancy and then unnecessarily overtreated. Aside from the typical tubules, cysts and papillae, nephrogenic adenoma may display a broad spectrum of histologic appearances and locations, some of them atypical or unexpected. These unusual and concerning features will have special consideration in this description. The goal of the review is to increase awareness of general pathologists of the varied histology of nephrogenic adenoma.


Asunto(s)
Adenoma/patología , Neoplasias Renales/patología , Riñón/patología , Humanos
19.
Am J Clin Pathol ; 130(4): 518-25, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18794043

RESUMEN

Diaphragm disease (DD) is an uncommon gastrointestinal abnormality typical of nonsteroidal anti-inflammatory drug (NSAID)-induced injury. DD of the small intestine is well defined in its gross appearance (multiple circumferential stenosing lesions); however, its histologic features have been studied in few cases. To better define and update the histologic features of DD, we describe 10 cases in which patients underwent resection of portions of small intestine for DD. Selected gross features and 12 microscopic features were assessed. The typical gross appearance of DD was associated with focal chronic injury of the mucosa with mild to moderate inflammatory infiltrate. A wide array of additional abnormalities was found: eosinophilic enteritis (3 cases), inflammatory fibroid polyp (1 case), enteritis cystica profunda (1 case), villous atrophy (1 case), and neuromuscular and vascular hamartoma-like changes (9 cases). DD and, therefore, NSAID-related injury, should be considered in the differential diagnosis of several conditions affecting the small intestine.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Intestino Delgado/efectos de los fármacos , Intestino Delgado/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
Gastrointest Endosc ; 68(1): 174-80, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18513723

RESUMEN

BACKGROUND: Retention of the video capsule is the most significant complication associated with capsule endoscopy (CE). There are limited data on incidence, risk factors, and outcomes of capsule retention. OBJECTIVE: We aimed to determine the incidence of capsule retention and to investigate the causes and clinical outcomes of capsule retention. SETTING: Single tertiary referral medical center. PATIENTS: All patients who underwent CE for suspected small bowel disease from June 2002 to March 2006. METHODS: Retrospective case series. RESULTS: Capsule retention occurred in 1.4% of our patients (14/1000). Eleven patients failed to pass the capsule because of nonsteroidal anti-inflammatory drug (NSAID) enteropathy (diaphragm disease). One patient had capsule retention from an obstructing carcinoid tumor. Metastatic ovarian cancer with invasion of the ileum was the cause of retention in another patient. One patient who did not have surgical removal of the capsule because of loss of follow-up had retention caused by a small-bowel tumor suspicious for carcinoid tumor on CT enterography. All patients remained "asymptomatic" from the retained capsules. Thirteen patients underwent elective partial small-bowel resection and capsule removal. No deaths were associated with these surgeries. Eleven patients recovered promptly, whereas 2 patients had mild postoperative ileus. LIMITATION: Retrospective study. CONCLUSION: Retention of the capsule endoscope appears to be infrequent. The most common cause is diaphragm disease resulting from NSAIDs in this study population. In most cases, capsule retention is asymptomatic, and it usually leads to surgical removal, which appears safe and also identifies and treats the underlying small-bowel condition.


Asunto(s)
Endoscopios en Cápsulas/efectos adversos , Endoscopía Capsular/efectos adversos , Remoción de Dispositivos/métodos , Obstrucción Intestinal/epidemiología , Adulto , Anciano , Endoscopía Capsular/métodos , Estudios de Cohortes , Endoscopía Gastrointestinal/efectos adversos , Endoscopía Gastrointestinal/métodos , Falla de Equipo , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Obstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Medición de Riesgo
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