Validation of a novel integral disease index for evaluating the grade of activity in Mexican patients with ulcerative colitis: A prospective cohort study. / Validación de un nuevo índice integral de enfermedad para evaluar el grado de actividad en pacientes mexicanos con colitis ulcerosa: un estudio de cohorte prospectivo.

INTRODUCTION AND AIM: Ulcerative colitis is a chronic condition characterized by inflammation affecting the colon. To objectively and integrally measure disease activity in patients with ulcerative colitis and thus optimize pharmacologic treatment, a novel integral disease index was created that includes the clinical, biochemical, endoscopic, and histologic characteristics necessary for achieving that task. The aim of the present study was to validate the novel integral disease index in patients with ulcerative colitis. MATERIALS AND METHODS: A cohort study on a total of 222 patients with histologic confirmations of ulcerative colitis diagnosis was conducted. The variables included in the disease index were: number of bowel movements per day; values for hemoglobin, high-sensitivity C-reactive protein, and serum albumin; and endoscopic and histologic findings measured through the subscales of the Mayo and Riley scores, respectively. The data analysis was performed utilizing the STATA SE 11.1 statistics program. RESULTS: The correlation of the novel disease index was very good (r=0.817, p <.001 with the Truelove and Witts criteria and r=0.957, p <.0001 with the Mayo score, respectively). Good internal consistency was found with a Cronbach's alpha coefficient of 0.78 and an acceptable mean inter-item correlation (r=0.47, p <.05). The total efficacy of the novel index was 87.2% correctly classified patients, with an AUC according to the three scenarios described of 0.93, 0.92, and 0.96, respectively. CONCLUSIONS: The novel integral disease index (Yamamoto-Furusho Index) provides an integral view of disease activity in patients with ulcerative colitis and is useful for optimizing pharmacologic treatment.

El epitelio seminal en biopsia prostática puede semejar lesiones prostáticas malignas y premalignas / Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions

Objetivos: En la mayoría de las biopsias prostáticas el epitelio seminal se reconoce fácilmente, ya que muestra criterios histológicos característicos. Sin embargo, algunas biopsias pueden semejar lesiones prostáticas malignas o premalignas. Los propósitos de este estudio son analizar el aspecto histológico de las biopsias que simularon adenocarcinomas o lesiones prostáticas preneoplásicas; comentar su diagnóstico diferencial y conocer la frecuencia de epitelio seminal en biopsias prostáticas. Métodos: Revisamos 500 biopsias prostáticas consecutivas por punción obtenidas por el método de sextantes, y seleccionamos aquellos casos en los que observamos epitelio seminal de vesículas seminales o conductos eyaculatorios. En las biopsias en las que el epitelio seminal semejó lesiones malignas o premalignas se emplearon estudios inmunohistoquímicos que incluyeron antígeno prostático específico y MUC6. Se anotaron los datos clínicos de mayor importancia. Resultados: Treinta y seis (7,2%) biopsias mostraron epitelio seminal y 7 de ellas (1,4%) semejaron diversas lesiones prostáticas, incluyendo neoplasia intraepitelial prostática de alto grado, proliferaciones acinares atípicas, adenocarcinomas con patrón papilar y carcinoma poco diferenciado. El epitelio seminal semejó lesiones prostáticas cuando el depósito de lipofuscina, las vacuolas perinucleares o las pseudoinclusiones nucleares fueron poco aparentes o estuvieron ausentes. Cinco de las 7 biopsias mostraron atipia celular leve o moderada con núcleos pequeños e hipercromáticos y solos 2 pleomorfismo celular. Los pacientes se encontraban vivos y asintomáticos después de 6 años de evolución en promedio. Conclusiones: El epitelio seminal semeja neoplasia intraepitelial prostática, proliferaciones acinares atípicas y diversos tipos de adenocarcinomas prostáticos en aproximadamente el 1,4% de las biopsias prostáticas

Objectives: In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. Methods: We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Results: Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. Conclusions: The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies

Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

OBJECTIVES: In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. METHODS: We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. RESULTS: Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. CONCLUSIONS: The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies.

KCNH1 potassium channels are expressed in cervical cytologies from pregnant patients and are regulated by progesterone.

Potassium voltage-gated channel, subfamily H (eag-related), member 1 (KCNH1) potassium channels are potential tumour markers and cancer therapeutic targets and are up-regulated by oestrogens and human papilloma virus (HPV) oncogenes. However, the role of KCNH1 in normal tissues is poorly understood, and its expression in pregnancy is unknown. We wondered whether KCNH1 channels are expressed in cervical cells from pregnant patients and whether progesterone (P4) regulates KCNH1. The association with HPV was also investigated. KCNH1 protein expression was studied by immunocytochemistry in liquid-based cervical cytologies; 93 samples were obtained from pregnant patients at different trimesters, and 15 samples were obtained from non-pregnant women (controls). The presence of HPV was studied by PCR with direct sequencing and nested multiplex PCR. HeLa cervical cancer cells were transfected with human progesterone receptor-B (PR-B) and treated with P4. KCNH1 mRNA expression in these cultures was studied by real-time PCR. KCNH1 protein was detected in 100% of the pregnancy samples and in 26% of the controls. We found 18 pregnant patients infected with HPV and detected 14 types of HPV. There was no association between the percentage of cells expressing KCNH1 and either the presence or type of HPV. P4 induced KCNH1 mRNA and protein expression in cells transfected with human PR-B. No regulation of KCNH1 by P4 was observed in non-transfected cells. We show for the first time the expression of an ion channel during human pregnancy at different trimesters and KCNH1 regulation by P4 in human cells. These data raise a new research field for KCNH1 channels in human tissues.

[Intelukin-10 expression with immunorreglatory function in the mucosa of patients with ulcerative colitis]. / Expresión de la interleucina (IL-10) con función inmunorreguladora en mucosa de pacientes con colitis ulcerosa crónica idiopática.

BACKGROUND: Interleukin-10 (IL-10) is an important immunoregulatory cytokine that acts on antigen presenting cells by the inhibiting both the synthesis of cytokines, co-stimulatory and HLA class II molecules. OBJECTIVE: To study the gene and protein expression of IL-10 in the mucosa from patients with ulcerative colitis (UC). METHODS: We studied 40 patients with UC and 18 controls without endoscopic evidence of intestinal inflammation. From rectal biopsies was determined the gene expression of IL- 10 by real time polymerase chain reaction (PCR). The detection of the protein in tissue was performed by immunohistochemistry. RESULTS: patients with UC in remission had significantly higher expression of il-10 gene in mucosa compared to the group of patients with active UC (p = 0.01) and the control group (p = 0.05). All patients with active UC had pancolitis, while patients in remission from distal inflammation, 16 had extra-intestinal manifestations and 23 had mild to moderate inflammation with less than one relapse within a year. Patients with UC in remission had significantly higher expression of IL-10 gene in mucosa compared with the group of patients with active UC (p = 0.01) or the control group (p = 0.05). CONCLUSIONS: The expression of IL-10 gene is increased in colonic mucosa from patients with UC in remission, confirming that it is an immunoregulatory cytokine that promotes remission in patients with UC.

[Pseudohyperplastic carcinoma with xanthomatous changes: a neoplasm mimicking glandular hyperplasia of the prostate]. / Carcinoma pseudohiperplásico con cambios xantomatosos: una neoplasia que semeja hiperplasia glandular de la próstata.

INTRODUCTION AND OBJECTIVES: Varieties of prostatic adenocarcinoma whose architectural and cytological appearance mimicked benign lesions have been reported in recent decades. Such neoplasms include xanthomatous (foamy) carcinoma and pseudohyperplastic carcinoma. We recently studied five carcinomas showing a cytoarchitectural combination of both neoplasms which were confused with benign glandular proliferations. METHODS: Five cases (1.8%) of pseudohyperplastic carcinoma showing xanthomatous changes were selected from a total of 280 biopsies showing prostate carcinoma. Glandular prostatic hyperplasia was originally diagnosed in four of such cases. RESULTS: Patient age ranged from 54 and 78 years (mean, 64 years). All patients had high prostate-specific antigen levels, and digital rectal examination showed abnormalities in four of them. Neoplasms showed minimal atypia and consisted of mid- to large-sized glands arranged in nests resembling hyperplastic nodules. Glands showed papillary projections, infoldings, and undulations. Most nuclei were basal, small and hyperchromatic, and nucleomegaly was only seen in two biopsies in isolated histological fields. Several useful criteria for diagnosis of acinar carcinoma, such as perineural infiltration, mitosis, crystalloids, blue secretions, and prostatic intraepithelial neoplasm, were absent. CONCLUSIONS: Prostatic carcinoma with a pseudohyperplastic pattern and xanthomatous changes mimics hyperplastic glands. Timely detection is critical to avoid treatment delay.

Prevalence and clinical features of indeterminate colitis in Mexico: a 17-year study.

BACKGROUND: Indeterminate Colitis (IC) is diagnosed after colectomy when macroscopic and microscopic features were not sufficient to allow a definite diagnosis of either the classical types of Ulcerative Colitis (UC) or Crohn's disease (CD). Epidemiological data from some series have reported that IC is diagnosed in between 9% and 20% of colectomy specimens. AIM: To determine the prevalence of IC in Mexican patients and to describe their clinical features. MATERIAL AND METHODS: We carried out a retrospective database analysis of all patients diagnosed with inflammatory bowel disease (IBD) who underwent colectomy between January of 1990 and December of 2006. Demographic data, clinical, laboratory, and histopathological results were analyzed. RESULTS: We found 80 patients in the database who had undergone total colectomy whose average age was 44.8 years. IC was found in 7 patients (8.7%) from colectomy specimens among Mexican patients with IBD, with a mean age at diagnosis of 33.6 years. Subgroup analysis showed that a younger age at diagnosis and toxic megacolon were factors of statistical significance associated with IC. CONCLUSIONS: The prevalence of IC was 8.7% in our group. A younger age of onset and toxic megacolon were the most important associated factors in patients with IC.

Carcinoma pseudohiperplásico con cambios xantomatosos: una neoplasia que semeja hiperplasia glandular de la próstata / Pseudohyperplastic carcinoma with xanthomatous changes: A neoplasm mimicking glandular hyperplasia of the prostate

Introducción y objetivos: En las últimas décadas se han descrito variedades de adenocarcinoma prostático que por su arquitectura y su aspecto citológico semejan lesiones benignas. Estas neoplasias incluyen al carcinoma xantomatoso (espumoso) y al carcinoma pseudohiperplásico. Recientemente hemos estudiado cinco carcinomas que mostraron una combinación citoarquitectónica de ambas neoplasias y fueron confundidas con proliferaciones glandulares benignas. Métodos: De un total de 280 biopsias con carcinoma prostático se seleccionaron cinco casos (1,8%) de carcinoma pseudohiperplásico que mostraron cambios xantomatosos. Cuatro de ellos fueron diagnosticados originalmente como hiperplasia glandular prostática. Resultados: La edad de los pacientes varió de 54 a 78 años (promedio: 64 años). El antígeno prostático estuvo elevado en todos, y en el examen digital rectal se encontraron alteraciones en cuatro. Las neoplasias mostraron atipia mínima y estuvieron constituidas por glándulas de mediano y gran tamaño que se disponían en nidos semejantes a nódulos hiperplásicos. Las glándulas mostraron proyecciones papilares, plegamientos y ondulaciones. La mayoría de los núcleos fueron basales, pequeños e hipercromáticos, y sólo ocasionalmente se observó nucleomegalia. Varios criterios útiles en el diagnóstico de carcinoma acinar, incluyendo infiltración perineural, mitosis, cristaloides, secreciones azules y neoplasia intraepitelial prostática, estuvieron ausentes. Conclusiones: Los carcinomas prostáticos con patrón pseudohiperplásico y cambios xantomatosos semejan glándulas hiperplásicas. Su reconocimiento oportuno es crucial para evitar retardo en el tratamiento (AU)

Introduction and objectives: Varieties of prostatic adenocarcinoma whose architectural and cytological appearance mimicked benign lesions have been reported in recent decades. Such neoplasms include xanthomatous (foamy) carcinoma and pseudohyperplastic carcinoma. We recently studied five carcinomas showing a cytoarchitectural combination of both neoplasms which were confused with benign glandular proliferations. Methods: Five cases (1.8%) of pseudohyperplastic carcinoma showing xanthomatous changes were selected from a total of 280 biopsies showing prostate carcinoma. Glandular prostatic hyperplasia was originally diagnosed in four of such cases. Results: Patient age ranged from 54 and 78 years (mean, 64 years). All patients had high prostate-specific antigen levels, and digital rectal examination showed abnormalities in four of them. Neoplasms showed minimal atypia and consisted of mid- to large-sized glands arranged in nests resembling hyperplastic nodules. Glands showed papillary projections, infoldings, and undulations. Most nuclei were basal, small and hyperchromatic, and nucleomegaly was only seen in two biopsies in isolated histological fields. Several useful criteria for diagnosis of acinar carcinoma, such as perineural infiltration, mitosis, crystalloids, blue secretions, and prostatic intraepithelial neoplasm, were absent. Conclusions: Prostatic carcinoma with a pseudohyperplastic pattern and xanthomatous changes mimics hyperplastic glands. Timely detection is critical to avoid treatment delay (AU)

[Utility of additional histological sections on prostatic needle biopsies with focal glandular atypia]. / Utilidad de los cortes adicionales múltiples en biopsias prostáticas con atipia glandular focal.

INTRODUCTION: Focal glandular atypia in needle prostatic biopsies consists of scarce glands with architectural and cytological features suggestive but not conclusive of malignancy. Although this is a relatively frequent finding, the advantage of carrying out additional sections has not been extensively explored. The objective of this review is to define the usefulness of performing multiple additional sections in needle biopsies showing areas with focal glandular atypia. METHODS: Thirty-eight patients in whom prostate needle biopsies were performed and showed focal glandular atypia in routine sections were selected for this study. In all biopsies there were atypia only in one isolated microscopic field. Each case originally had three cuts of three microns each per slide. In all cases three additional slides were made with three additional cuts. Thus, each case wound up with a total of 12 cuts (the original 3, and additional 9). RESULTS: The average age of the patients was 65 years old, and the average specific prostate antigen was 8.4 ng/ml. The additional sections made it possible to establish a definitive diagnosis of malignancy in nine (22.5%) of the 38 cases, because they made more apparent the architectural and cytological features of prostatic carcinoma. In the other 29 biopsies the area with glandular atypia was less apparent or disappeared altogether. CONCLUSIONS: The additional sections are useful for the diagnosis of adenocarcinoma in one of every four or five needle biopsies with focal glandular atypia. Making additional cuts in these biopsies is a quick and low-cost method that could be practiced routinely, especially if immunohistochemical studies are not available.

Utilidad de los cortes adicionales múltiples en biopsias prostáticas con atipia glandular focal / Utility of additional histological sections on prostatic needle biopsies with focal glandular atypia

Introducción: La atipia glandular focal en biopsias por punción, esta constituida por escasas glándulas que muestran criterios arquitecturales y citológicos sugestivos, pero no diagnósticos, de malignidad. Aunque éste es un problema relativamente frecuente, la ventaja de realizar niveles adicionales múltiples en estas biopsias ha sido poco estudiada. El objetivo de la presente revisión es definir cual es la utilidad de practicar cortes adicionales múltiples en biopsias por punción que muestran áreas con atipia glandular focal. Metodos: Se seleccionaron 38 pacientes en los que se practicó biopsias por punción de la próstata que mostraron atipia glandular focal en cortes rutinarios. Todas las biopsias mostraron atipia glandular en un campo microscópico aislado. Cada caso contó originalmente con tres cortes de tres micras por laminilla. En todos los casos se practicaron tres niveles adicionales con tres cortes histológicos cada uno. Así, cada caso contó con un total de 12 cortes (3 originales y 9adicionales). Resultados: El promedio de edad fue de 65 años y el promedio del antígeno prostático específico de 8,4 ng/ml. Los niveles adicionales permitieron establecer el diagnóstico concluyente de malignidad en nueve (22,5%) de los 38 casos, ya que hicieron mas aparentes los criterios arquitecturales y citológicos de carcinoma prostático. En las otras 29 biopsias el área con atipia glandular se hizo menos aparente o desapareció. Conclusiones: Los niveles adicionales son útiles para el diagnóstico de malignidad en una de cada cuatro o cinco biopsias con atipia glandular focal. Practicar cortes adicionales en estas biopsias representa un método rápido y a bajo costo que podría practicarse rutinariamente, en particular si no se cuenta con estudios inmunohistoquímicos (AU)

Introduction: Focal glandular atypia in needle prostatic biopsies consists of scarce glands with architectural and cytological features suggestive but not conclusive of malignancy. Although this is a relatively frequent finding, the advantage of carrying out additional sections has not been extensively explored. The objective of this review is to define the usefulness of performing multiple additional sections in needle biopsies showing areas with focal glandular atypia. Methods: Thirty-eight patients in whom prostate needle biopsies were performed and showed focal glandular atypia in routine sections were selected for this study. In all biopsies there were atypia only in one isolated microscopic field. Each case originally had three cuts of three microns each per slide. In all cases three additional slides were made with three additional cuts. Thus, each case wound up with a total of 12 cuts (the original 3, and additional 9). Results: The average age of the patients was 65 years old, and the average specific prostate antigen was 8.4 ng/ml. The additional sections made it possible to establish a definitive diagnosis of malignancy in nine (22.5%) of the 38 cases, because they made more apparent the architectural and cytological features of prostatic carcinoma. In the other 29 biopsies the area with glandular atypia was less apparent or disappeared altogether. Conclusions: The additional sections are useful for the diagnosis of adenocarcinoma in one of every four or five needle biopsies with focal glandular atypia. Making additional cuts in these biopsies is a quick and low-cost method that could be practiced routinely, especially if immunohistochemical studies are not available (AU)