Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study.

Early-stage colorectal carcinoma (CRC)-pT1-is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5-2%. Among these cases, approximately 6-16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/µL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management.

Dielectric Characterization of Breast Biopsied Tissues as Pre-Pathological Aid in Early Cancer Detection: A Blinded Feasibility Study.

Dielectric characterization has significant potential in several medical applications, providing valuable insights into the electromagnetic properties of biological tissues for disease diagnosis, treatment planning, and monitoring of therapeutic interventions. This work presents the use of a custom-designed electromagnetic characterization system, based on an open-ended coaxial probe, for discriminating between benign and malignant breast tissues in a clinical setting. The probe's development involved a well-balanced compromise between physical feasibility and its combined use with a reconstruction algorithm known as the virtual transmission line model (VTLM). Immediately following the biopsy procedure, the dielectric properties of the breast tissues were reconstructed, enabling tissue discrimination based on a rule-of-thumb using the obtained dielectric parameters. A comparative analysis was then performed by analyzing the outcomes of the dielectric investigation with respect to conventional histological results. The experimental procedure took place at Complejo Hospitalario Universitario de Toledo-Hospital Virgen de la Salud, Spain, where excised breast tissues were collected and subsequently analyzed using the dielectric characterization system. A comprehensive statistical evaluation of the probe's performance was carried out, obtaining a sensitivity, specificity, and accuracy of 81.6%, 61.5%, and 73.4%, respectively, compared to conventional histological assessment, considered as the gold standard in this investigation.

Primary Ewing's sarcoma of the small intestine.

17 year old female teenager with abdominal pain secondary to pelvic mass of 12 x 10 cm, which seems to depend on ovary. Surgery is scheduled for removal of the tumor, during which it is observed that the lesion originates in the ileum. The histopathological study shows a neoplasm of small round cells with nucleoli and scant cytoplasm. The tumor cells are immunoreactive to CD99 and ERG, being negative for cytokeratins, FLI1, WT1, DOG1 and lymphoid markers. By means of FISH, a rearrangement of the EWSR1 gene was demonstrated. By integrating these molecular and immunohistochemical findings with the morphology, it was diagnosed as Ewing's sarcoma. This aggressive and infrequent tumor originates from neuroectodermal cells and usually develops in the long bones of pediatric and young adult patients, although exceptionally it can occur in other locations. At the intestinal level, it mainly affects the ileum, with a non-specific pain and fatigue clinic. The treatment of choice is surgery for resection of the affected loop, followed by chemotherapy.

Effective treatment of autoimmune hepatitis-primary biliary cholangitis overlap syndrome with obeticholic acid

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Effective treatment of autoimmune hepatitis-primary biliary cholangitis overlap syndrome with obeticholic acid.

There is no consensus treatment for patients with autoimmune hepatitis (AIH) - primary biliary cholangitis (PBC) overlap syndrome who are not responding to conventional therapy. We present a case of a 43-yr-old woman with AIH-PBC overlap syndrome treated with obeticholic acid (OCA). The patient showed a reduction in liver enzymes and no fibrosis progression during 15 months of follow up.

Características y supervivencia del carcinoma hepatocelular en hígado no cirrótico / Characteristics and survival of hepatocellular carcinoma in non-cirrhotic liver

Introducción: las características, cribado, y supervivencia del carcinoma hepatocelular (CHC) en pacientes sin cirrosis están menos definidas. Pacientes y métodos: se recogieron retrospectivamente (enero 2004-octubre 2018) los pacientes con CHC diagnosticados citohistológicamente sin cirrosis. Analizamos sus características, tratamiento y supervivencia. Resultados: de los 332 pacientes con CHC, 25 cumplían los criterios de inclusión (7,5%). Varones: 76%. Mediana de edad: 69,9 años. El virus de la hepatitis B (VHB) fue el principal agente etiológico de hepatopatía: 32%, seguido de la esteatohepatitis no alcohólica (EHNA): 20%. La fibrosis fue leve (0-1) en el 44%. El nódulo se descubrió por ecografía de seguimiento en el 32%, en el 60% fue casual, y 8% por síntomas. El estadio de Barcelona Clinic Liver Cancer (BCLC) fue 0 en 4%, A 88%, B 4%, y C 4%. El tratamiento inicial mayoritario fue la resección quirúrgica (76%), 8% rechazaron tratamiento, y se realizó etanolización, quimioembolización, sorafenib y tratamiento sintomático en el 4% para cada uno. El 21% de los pacientes operados presentó complicaciones, la mitad severas. La mediana de seguimiento fue 22,2 (2,9-150,6) meses, con remisión en el 56%. Mediana de supervivencia global: 57,4 +/- 29,8 meses. Supervivencia acumulada: 84% al año, 61,6% a los 3 años y 47,9% a los 5 años. Conclusión: el 7,5% de los CHC se desarrollaron sin cirrosis. El grado de fibrosis fue leve en casi la mitad. El VHB fue la causa principal, seguida de EHNA. El estadio de BCLC principal al diagnóstico fue el precoz. La cirugía fue el tratamiento más habitual. La supervivencia a los 5 años fue cercana al 50%

Introduction: the characteristics, screening, and survival of hepatocellular carcinoma (HCC) for patients without cirrhosis have not been fully studied. Methods: A retrospective cohort study was performed in non-cirrhotic patients with histological HCC, between January 2004 and October 2018. Their characteristics, treatment, follow-up and overall survival were described. Results: 25 of the 332 patients with HCC met the inclusion criteria (7.5%), 76% were males and the median age was 69.9 years. The main etiology of liver disease was the hepatitis B virus (HBV) (32%), followed by non-alcoholic steatohepatitis (NASH) (20%). Liver fibrosis was mild (0-1) in 44% of cases. The nodule was diagnosed by ultrasonography in 32% of cases, 60% were found incidentally and 8% due to clinical symptoms. The Barcelona Clinic Liver Cancer (BCLC) staging was 0 in 4% of cases, A in 88%, B in 4% and C in 4%. The main initial treatment was surgical resection (76%) and 8% refused to be treated. Percutaneous ethanol injection, chemoembolization, sorafenib and palliative care were each performed in 4% of cases. There were some complications in 21% of patients treated with surgery, half of them were severe. The median follow-up was 22.2 (2.9-150.6) months and 56% were in remission and the median overall survival was 57.4 +/- 29.8 months. The overall cumulative survival at 1, 3 and 5 years was 84%, 61.6% and 47.9%, respectively. Conclusion: 7.5% of HCC presented without cirrhosis and almost half of patients had mild fibrosis. HBV was the main cause of HCC, followed by NASH. The most frequent BCLC stage at diagnosis was early stage and surgery was the most common treatment. Overall cumulative survival at 5 years was almost 50%

Characteristics and survival of hepatocellular carcinoma in non-cirrhotic liver.

INTRODUCTION: the characteristics, screening, and survival of hepatocellular carcinoma (HCC) for patients without cirrhosis have not been fully studied. METHODS: A retrospective cohort study was performed in non-cirrhotic patients with histological HCC, between January 2004 and October 2018. Their characteristics, treatment, follow-up and overall survival were described. RESULTS: 25 of the 332 patients with HCC met the inclusion criteria (7.5%), 76% were males and the median age was 69.9 years. The main etiology of liver disease was the hepatitis B virus (HBV) (32%), followed by non-alcoholic steatohepatitis (NASH) (20%). Liver fibrosis was mild (0-1) in 44% of cases. The nodule was diagnosed by ultrasonography in 32% of cases, 60% were found incidentally and 8% due to clinical symptoms. The Barcelona Clinic Liver Cancer (BCLC) staging was 0 in 4% of cases, A in 88%, B in 4% and C in 4%. The main initial treatment was surgical resection (76%) and 8% refused to be treated. Percutaneous ethanol injection, chemoembolization, sorafenib and palliative care were each performed in 4% of cases. There were some complications in 21% of patients treated with surgery, half of them were severe. The median follow-up was 22.2 (2.9-150.6) months and 56% were in remission and the median overall survival was 57.4 ± 29.8 months. The overall cumulative survival at 1, 3 and 5 years was 84%, 61.6% and 47.9%, respectively. CONCLUSION: 7.5% of HCC presented without cirrhosis and almost half of patients had mild fibrosis. HBV was the main cause of HCC, followed by NASH. The most frequent BCLC stage at diagnosis was early stage and surgery was the most common treatment. Overall cumulative survival at 5 years was almost 50%.

Diagnostic value of halo sign in young women (aged 45 to 49 years) in a breast screening programme with synthesized 2D mammography.

OBJECTIVE:: To assess the clinical performance of the halo sign in tomosynthesis and synthesized 2D mammography, and to identify age groups where its diagnostic value may be greater. METHODS:: 183 patients with nodules were recalled from the breast screening programme (with tomosynthesis and 2D synthesized mammograms). The patients were separated into two groups, 45-49 years and 50-69 years, and depending on the presence or not of halo sign. We calculated the predictive values for the different age groups. RESULTS:: In 45-49 years group, 86 nodular lesions were recalled, 66 (76.7%) with positive halo sign and 20 (23.3%) with negative halo sign. In positive halo sign group, biopsy was considered in 23 (34.8%), with histological features of benignity. In 50-69 years group, 98 nodular lesions from 97 patients were recalled, 51 (52%) with positive halo sign and 47 (48%) with negative halo sign. In positive halo sign group, biopsy was considered in 13 (25.5%); four (30.8%) were malignant and nine (69.2%) were benign. CONCLUSION:: Halo sign could be considered as a marker of benign lesion in females < 50 years. In females ≥ 50 years, other breast imaging techniques should be considered, with or without histological studies, to rule out malignancy. ADVANCES IN KNOWLEDGE:: The trend of a positive halo sign to act as a marker of benign lesion could be improve the recall rate and positive predictive values in the breast screening programme with tomosynthesis and synthesized 2D mammography, especially in young females.

Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases.

BACKGROUND: Diagnosis of celiac disease is difficult when the combined results of serology and histology are inconclusive. Studies using flow cytometry of intraepithelial lymphocytes (IELs) have found that celiac patients have increased numbers of γδ IELs, along with a decrease in CD3-CD103 + IELs. OBJECTIVE: The objective of this article is to assess the role of flow cytometric analysis of IELs in the diagnosis of celiac disease in difficult cases. METHODS: A total of 312 patients with suspicion of celiac disease were included in the study. Duodenal biopsy samples were used for histological assessment and for flow cytometric analysis of IELs. RESULTS: In 46 out of 312 cases (14.7%) the combination of serology and histology did not allow the confirmation or exclusion of celiac disease. HLA typing had been performed in 42 of these difficult cases. Taking into account HLA typing and the response to a gluten-free diet, celiac disease was excluded in 30 of these cases and confirmed in the remaining 12. Flow cytometric analysis of IELs allowed a correct diagnosis in 39 out of 42 difficult cases (92.8%) and had a sensitivity of 91.7% (95% CI: 61.5% to 99.8%) and a specificity of 93.3% (95% CI: 77.9% to 99.2%) for the diagnosis of celiac disease in this setting. CONCLUSION: Flow cytometric analysis of IELs is useful for the diagnosis of celiac disease in difficult cases.

Three molecular classifications surrogate to four immunohistochemical markers in 374 invasive breast carcinomas with long follow-up: which is better?

In the early 21st century, a new way to classify breast cancer appeared, based on their gene expression profiles. Various classifications have been proposed in an attempt to subrogate these molecular groups to an immunohistochemical expression of estrogen and progesterone receptors, HER2 and Ki67. We compared the three major molecular classifications (MCs) of 374 infiltrating breast carcinomas with the assumption that one is better than the others to discriminate the prognosis of patients that are classified by it. We found that [1] there was a significant statistical association with tumor grade and presence of associated HG-DCIS, but with differences in kappa indices [2]; MC3 showed a significant relationship with pathological tumor stage (p=0.012, CI95% of 0.012-0.017); [3] only MC3 showed convincingly that the observed differences in OS were not due to chance in the univariate analysis (p=0.04); [4] only MC3 is an independent prognostic factor of OS. In conclusion, these three classifications are not interchangeable; MC3, the only one that includes Ki67 expression in their defining criteria, is better in predicting prognosis than the others.

Resultados asistenciales de una unidad especializada en tabaquismo / Care Results in a Specialist Stop-Smoking Unit

IntroducciónEl objetivo del presente artículo es presentar los resultados asistenciales y de gasto farmacéutico de una unidad especializada en tabaquismo (UET).Pacientes y métodosSe aplicaron 2 protocolos asistenciales: individual y grupal. En ambos casos se oferta una combinación de tratamiento farmacológico y psicológico en 10 consultas, a lo largo de 12 meses de seguimiento. Como tratamiento farmacológico se emplea: tratamiento sustitutivo con nicotina, bupropión o vareniclina, o una combinación de ellos. El tratamiento psicológico contempla: realización de autorregistros, identificación de situaciones de alto riesgo, técnicas de afrontamiento, técnicas cognitivo-conductuales y apoyo intratratamiento. En todos los casos el tratamiento fue gratuito.ResultadosSe han realizado 21.418 consultas sanitarias a un total de 3.920 fumadores (un 49% varones). Se analiza una muestra constituida por 1.850 fumadores que acudieron consecutivamente a la UET entre enero de 2004 y marzo de 2007. Su edad media (± desviación estándar) era de 47,83±11,03 años, y la puntuación media del test de Fagerström, 6,56±2,41. El 55,9% recibió tratamiento sustitutivo con nicotina, el 22,8% bupropión, el 18,9% vareniclina y un 2,4% no recibió tratamiento farmacológico. La abstinencia continua a los 6 y 12 meses de seguimiento fue del 58,5 y el 54,9%, respectivamente. Estas cifras fueron del 42 y el 35% a los 36 y 57 meses de seguimiento.El coste en fármacos por paciente atendido fue de 118 €, y el coste por fumador atendido que consiguió mantenerse abstinente a los 6; 12; 36, y 57 meses fue de 202; 215; 281, y 338 €, respectivamente.ConclusionesUna UET obtiene buenos resultados asistenciales y económicos a corto, medio y largo plazo(AU)

Background and objectiveTo present the short, medium and long-term results of a stop-smoking clinic after 5 years of experience. The clinic was designed following the SEPAR Recommendations.Patients and methodsTwo types of clinic protocols have been applied: individual and group. Both included the offer of a combination of psychological intervention and pharmacological treatment. The programme included 10 visits over 12 months. The pharmacological treatment consisted of: nicotine replacement therapy (NRT) or bupropion or varenicline or a combination. The psychological intervention consisted of: self-monitoring, copying skills, cognitive-behavioural therapy and social intra-treatment support. The treatment was always offered for free.ResultsA total of 3920 patients were seen in the clinic. These patients made 21,418 clinic visits. The analysis was performed on the 1850 smokers who attended the clinic consecutively. Their mean age was 47.83 (±11.03) and the mean fagerström test for nicotine dependence (FTND)-score was 6.56 (±2.41). 55.9% patients received NRT, 22.8% bupropion, 18.9% varenicline and 2.4% did not receive any pharmacological treatment. Continuous abstinence rates at 6 and 12 months follow up were 58.5% and 54.9%, respectively. These abstinence rates at 36 and 57 months follow up were 42% and 35%, respectively. The cost in medication for each patient was 118 euros and the cost in medication for a successful abstainer at 6, 12, 36, and 57 months of follow up were 202, 215, 281 and 338 euros, respectively.ConclusionsA stop-smoking clinic that is designed according to SEPAR Recommendations is effective and has a good cost/effective ratio(AU)

[Care results in a specialist stop-smoking unit]. / Resultados asistenciales de una unidad especializada en tabaquismo.

BACKGROUND AND OBJECTIVE: To present the short, medium and long-term results of a stop-smoking clinic after 5 years of experience. The clinic was designed following the SEPAR Recommendations. PATIENTS AND METHODS: Two types of clinic protocols have been applied: individual and group. Both included the offer of a combination of psychological intervention and pharmacological treatment. The programme included 10 visits over 12 months. The pharmacological treatment consisted of: nicotine replacement therapy (NRT) or bupropion or varenicline or a combination. The psychological intervention consisted of: self-monitoring, copying skills, cognitive-behavioural therapy and social intra-treatment support. The treatment was always offered for free. RESULTS: A total of 3920 patients were seen in the clinic. These patients made 21,418 clinic visits. The analysis was performed on the 1850 smokers who attended the clinic consecutively. Their mean age was 47.83 (+/-11.03) and the mean fagerström test for nicotine dependence (FTND)-score was 6.56 (+/-2.41). 55.9% patients received NRT, 22.8% bupropion, 18.9% varenicline and 2.4% did not receive any pharmacological treatment. Continuous abstinence rates at 6 and 12 months follow up were 58.5% and 54.9%, respectively. These abstinence rates at 36 and 57 months follow up were 42% and 35%, respectively. The cost in medication for each patient was 118 euros and the cost in medication for a successful abstainer at 6, 12, 36, and 57 months of follow up were 202, 215, 281 and 338 euros, respectively. CONCLUSIONS: A stop-smoking clinic that is designed according to SEPAR Recommendations is effective and has a good cost/effective ratio.