Gastric calcinosis ulcer in a renal transplanted patient.

A 53-year-old lady with dysfunctional renal transplant and post-surgical hypoparathyroidism with phosphocalcic metabolism impairment was admitted to hospital because of long-lasting epigastric pain and nausea. An esophagogastroduodenoscopy was performed, visualising a nodular lesion of 1 cm diameter with a depressed and ulcerated base. Microscopically the lesion was in relation with a metastatic calcinosis ulcer. Pantoprazole was initiated and serum phosphocalcic levels adjusted, achieving symptom remission. In the follow-up esophagogastroduodenoscopy, the lesion was healing with a fibrinous base and the histopathological report diagnosed superficial gastritis.

MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer-related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients.

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer.

Pancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability to predict response to treatment of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion. In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. Based on their results, a series of recommendations are made to optimize the determination of these biomarkers and thus help standardize the diagnosis and treatment of these tumours.

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer / Consenso de Expertos de la Sociedad Española de Patología y la Sociedad Española de Oncología Médica sobre la determinación de biomarcadores en el cáncer de páncreas y vías biliares

Pancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability to predict response to treatment of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion. In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. Based on their results, a series of recommendations are made to optimize the determination of these biomarkers and thus help standardize the diagnosis and treatment of these tumours.

El cáncer de páncreas y el de vías biliares son tumores de mal pronóstico. En los últimos años, el desarrollo de nuevas técnicas diagnósticas de biología molecular ha permitido conocer las principales alteraciones génicas implicadas en el desarrollo de estos tumores. Múltiples estudios han evaluado el carácter predictivo de respuesta a tratamiento de determinados biomarcadores, como BRCA en cáncer de páncreas, IDH1 y FGFR2 en tumores de vía biliar; y la inestabilidad de microsatélites y las fusiones de NTRK, para predecir la respuesta al tratamiento. En este consenso, un grupo de expertos seleccionado por la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Anatomía Patológica (SEAP) ha revisado el papel que desempeñan estas mutaciones en el proceso de carcinogénesis y sus implicaciones clínicas. Como resultado, en este artículo se proponen una serie de recomendaciones para optimizar la determinación de estos biomarcadores, con el fin de fomentar la estandarización en el diagnóstico y el tratamiento de estos tumores.(AU)

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer

Pancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion, to predict response to treatment.In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. As a result, this article proposes a series of recommendations to optimize the determination of these biomarkers to help standardize the diagnosis and treatment of these tumours. (AU)

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer.

Pancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion, to predict response to treatment.In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. As a result, this article proposes a series of recommendations to optimize the determination of these biomarkers to help standardize the diagnosis and treatment of these tumours.

Ustekinumab for corticodependent immune-mediated colitis by pembrolizumab, an alternative for patients with concomitant liver injury.

Pembrolizumab, a programmed cell death receptor (PD-1) inhibitor, have improved the prognosis in several types of cancer. Despite the important clinical benefits, checkpoint inhibition have been associated with inflammatory and immune-related side effects (irAE).

Molecular Alterations in Pancreatic Cancer: Transfer to the Clinic.

Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the exocrine pancreas and probably the tumor that has benefited the least from clinical progress in the last three decades. A consensus has been reached regarding the histologic classification of the ductal preneoplastic lesions (pancreatic intra-epithelial neoplasia-PanIN) and the molecular alterations associated with them. Mutations in KRAS and inactivation of CDKN2A, SMAD4 and TP53 are among the most prevalent alterations. Next generation sequencing studies are providing a broad picture of the enormous heterogeneity in this tumor type, describing new mutations less prevalent. These studies have also allowed the characterization of different subtypes with prognostic value. However, all this knowledge has not been translated into a clinical progress. Effective preventive and early diagnostic strategies are essential to improve the survival rates. The main challenge is, indeed, to identify new effective drugs. Despite many years of research and its limited success, gemcitabine is still the first line treatment of PDA. New drug combinations and new concepts to improve drug delivery into the tumor, as well as the development of preclinical predictive assays, are being explored and provide optimism and prospects for better therapies.

Neoplasias quísticas hepáticas: experiencia en un único centro y revisión de la literatura / Cystic liver neoplams: A single centre experience and literature review

INTRODUCCIÓN: La neoplasia quística hepática es una neoplasia poco frecuente, que representa aproximadamente el 5% de las lesiones quísticas del hígado. El diagnóstico preoperatorio es difícil y puede causar confusión. El objetivo del estudio es analizar una serie de casos operados en nuestro centro con diagnóstico anatomopatológico de neoplasia quística hepática y describir la sintomatología, diagnóstico y tratamiento de acuerdo con la actual clasificación. MÉTODOS: Se realizó un análisis retrospectivo de todas las neoplasias quísticas hepáticas operadas entre enero de 2000 y diciembre de 2019. El estudio se basó en los informes de anatomía patológica ya existentes. Los casos anteriores al 2010 fueron reclasificados según la clasificación de la OMS del año 2010. RESULTADOS: La muestra total del estudio resultó en 10 pacientes: 6 fueron neoplasias mucinosas quísticas hepáticas y 4 neoplasias papilares intraductales biliares. La mayoría de los pacientes fueron mujeres (8/10) y la edad media fue de 47 años. En cuanto al tratamiento, hubo 3 hepatectomías y 7 enucleaciones. En ningún caso se realizó una biopsia intraoperatoria de los márgenes quirúrgicos. En un caso se observó atipia celular variable con zonas de adenocarcinoma, por lo que el paciente recibió quimioterapia adyuvante con taxol y carboplatino. En todos los casos los márgenes de resección fueron negativos. CONCLUSIÓN: Las neoplasias quísticas hepáticas son tumores poco frecuentes, que plantean un dilema en el diagnóstico diferencial, por lo que, ante la sospecha radiológica, el tratamiento de elección debería ser la resección completa del tumor para evitar su malignización y la recidiva

INTRODUCTION: The hepatic cystic tumour is a very rare neoplasm, representing about 5% of all cystic liver neoplasms. The preoperative diagnosis is difficult and can lead to confusion. The aim of this study is to analyze a number of cases operated at our centre with an histologic diagnosis of liver cystic neoplasms and also to describe the sintomathology, diagnosis and management as per the recent classification. METHODS: A retrospective analysis was performed including all the cystic liver neoplasms operated between January 2000 and December 2019. The study was performed based on the pre-existing pathology archives. The 2010 previous cases were reclassified following the new 2010 OMS classification. RESULTS: The study sample was of 10 patients, identifying 6 of them as mucinous cystic liver neoplasms, and the other 4 as intraductal papillary biliary neoplasms. The majority of the patients were women (8/10) and the median age was 47 years. Regarding the treatment, 3 hepatectomy and 7 enucleations were performed. Frozen section intraoperatively was not required in any case. In one case, variable cellular atypia with areas of adenocarcinoma was observed, and the patient received neoadyuvant chemotherapy with taxol and carboplatin. In all cases the resection margins were negative. CONCLUSION: Cystic liver neoplasms are infrequent tumours with a difficult differential diagnosis. Therefore, with a high radiological suspicious, the treatment should be a complete resection to avoid recurrences and malignancies

Cystic liver neoplams: A single centre experience and literature review. / Neoplasias quísticas hepáticas: experiencia en un único centro y revisión de la literatura.

INTRODUCTION: The hepatic cystic tumour is a very rare neoplasm, representing about 5% of all cystic liver neoplasms. The preoperative diagnosis is difficult and can lead to confusion. The aim of this study is to analyze a number of cases operated at our centre with an histologic diagnosis of liver cystic neoplasms and also to describe the sintomathology, diagnosis and management as per the recent classification. METHODS: A retrospective analysis was performed including all the cystic liver neoplasms operated between January 2000 and December 2019. The study was performed based on the pre-existing pathology archives. The 2010 previous cases were reclassified following the new 2010 OMS classification. RESULTS: The study sample was of 10 patients, identifying 6 of them as mucinous cystic liver neoplasms, and the other 4 as intraductal papillary biliary neoplasms. The majority of the patients were women (8/10) and the median age was 47 years. Regarding the treatment, 3 hepatectomy and 7 enucleations were performed. Frozen section intraoperatively was not required in any case. In one case, variable cellular atypia with areas of adenocarcinoma was observed, and the patient received neoadyuvant chemotherapy with taxol and carboplatin. In all cases the resection margins were negative. CONCLUSION: Cystic liver neoplasms are infrequent tumours with a difficult differential diagnosis. Therefore, with a high radiological suspicious, the treatment should be a complete resection to avoid recurrences and malignancies.

Switching from endoscopic submucosal dissection to salvage piecemeal knife-assisted snare resection to remove a lesion: a preoperative risk score from the beginning

Background and aims: endoscopic submucosal dissection (ESD) in the Western setting remains a challenge. Therefore, other simplified techniques such as knife-assisted snare resection (KAR) have been reported to overcome this issue. Methods: patients who underwent an ESD for the treatment of gastrointestinal neoplasms were included in a retrospective cross-sectional observational study. Factors associated with the end of ESD as a salvage p-KAR were identified and a logistic regression model was developed. Results: a total of 136 lesions in 133 patients were analyzed. Operator experience of under 50 cases and the combination of lesion size > 30 mm and colorectal location were independent predictive factors for switching to a salvage p-KAR according to the multivariate logistic regression analysis. We developed a risk scoring system based on these four variables (experience, size, location and the combination of size and location) with a receiver operating characteristic curve of 0.81 (95% CI: 0.74-0.89). The diagnostic accuracy of the score for a cut-off point ≥ 5 had a sensitivity of 0.79 (95% CI: 0.66-0.93) and a specificity of 0.71 (95% CI: 0.61-0.80). Conclusion: a simple predictive score system that includes four preoperative factors accurately predicts ESD to finish as a p-KAR. A careful selection of cases considering these variables could be useful to achieve better outcomes in the Western setting

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Switching from endoscopic submucosal dissection to salvage piecemeal knife-assisted snare resection to remove a lesion: A preoperative risk score from the beginning.

BACKGROUND AND AIMS: endoscopic submucosal dissection (ESD) in the Western setting remains a challenge. Therefore, other simplified techniques such as knife-assisted snare resection (KAR) have been reported to overcome this issue. METHODS: patients who underwent an ESD for the treatment of gastrointestinal neoplasms were included in a retrospective cross-sectional observational study. Factors associated with the end of ESD as a salvage p-KAR were identified and a logistic regression model was developed. RESULTS: a total of 136 lesions in 133 patients were analyzed. Operator experience of under 50 cases and the combination of lesion size > 30 mm and colorectal location were independent predictive factors for switching to a salvage p-KAR according to the multivariate logistic regression analysis. We developed a risk scoring system based on these four variables (experience, size, location and the combination of size and location) with a receiver operating characteristic curve of 0.81 (95% CI: 0.74-0.89). The diagnostic accuracy of the score for a cut-off point ≥ 5 had a sensitivity of 0.79 (95% CI: 0.66-0.93) and a specificity of 0.71 (95% CI: 0.61-0.80). CONCLUSION: a simple predictive score system that includes four preoperative factors accurately predicts ESD to finish as a p-KAR. A careful selection of cases considering these variables could be useful to achieve better outcomes in the Western setting.

La papilomatosis biliar difusa puede recidivar después del trasplante hepático en ausencia de focos de carcinoma infiltrante / Tumor recurrence after liver transplantation for diffuse biliary papillomatosis in the absence of invasive carcinoma

La neoplasia papilar intraductal (NPI) o papilomatosis biliar (PB) es una enfermedad recurrente con un alto riesgo de transformación maligna. Cuando la enfermedad afecta de forma difusa a la vía biliar (VB), el trasplante hepático (TH) es la única alternativa terapeútica disponible. Presentamos el caso de un varón de 43 años que debutó con un cuadro de colangitis aguda, siendo diagnosticado de papilomatosis biliopancreática difusa. El paciente fue sometido a una pancreatectomía total en dos tiempos y finalmente, a un TH, descartándose la presencia de focos de carcinoma infiltrante o de afectación ganglionar tanto en el páncreas inicialmente como en el hígado a posteriori. A los dos años de seguimiento, el paciente desarrolló una recidiva hepática multicéntrica cuya biopsia fue compatible con adenocarcinoma de origen biliar. En 2010, Vibert y cols. describieron que en los casos de PB sin presencia de carcinoma infiltrante o afectación ganglionar, el TH era una opción de tratamiento eficaz. Este caso es el primero que describe recidiva de la enfermedad después del TH en ausencia de focos de carcinoma infiltrante y de afectación ganglionar. Cuando la papilomatosis afecta de forma extensa a la VB, es posible que durante el análisis histopatológico pequeños focos de microinfiltración puedan no ser detectados. No obstante, aunque se trata de una enfermedad recidivante, la patogenia es desconocida, y no sabemos si la papilomatosis podría recidivar sobre el injerto después del TH incluso en ausencia de carcinoma infiltrante

Intraductal papillary neoplasm of the bile duct (IPNB) or biliary papillomatosis (BP) is a premalignant entity with high risk of malignant transformation. When the disease extends widely from the intrahepatic to the extrahepatic biliary tree, liver transplantation (LT) is the only option available. We present the case of a 43-year-old male who was admitted in our hospital with an acute cholangitis. He was diagnosed of diffuse biliary and pancreatic papillomatosis. Firstly, we performed a cephalic pancreaticoduodenectomy, then we completed a total pancreatectomy, and finally, after confirming the absence of foci of carcinoma infiltration or lymph nodes involvement, a LT was performed. Foci of carcinoma infiltration or lymph nodes involvement in the liver were not found. After a two-year follow-up the patient developed liver recurrence and the biopsy showed a biliary adenocarcinoma. In 2010, Vibert et al. published a series of three cases concluding that in the absence of invasive carcinoma and positive lymph nodes, LT can be performed with success. The present case is the first to describe recurrence of the disease after LT in the absence of invasive carcinoma and positive lymph nodes in the literature. When the disease affects widely the entire biliary duct, small micro-invasive foci may not be detected. Nevertheless, although we know that it is a recurrent entity, the pathogenesis is unknown, and we do not know if it is possible that papillomatosis recurs over the new liver

Tumor recurrence after liver transplantation for diffuse biliary papillomatosis in the absence of invasive carcinoma.

Intraductal papillary neoplasm of the bile duct (IPNB) or biliary papillomatosis (BP) is a premalignant entity with high risk of malignant transformation. When the disease extends widely from the intrahepatic to the extrahepatic biliary tree, liver transplantation (LT) is the only option available. We present the case of a 43-year-old male who was admitted in our hospital with an acute cholangitis. He was diagnosed of diffuse biliary and pancreatic papillomatosis. Firstly, we performed a cephalic pancreaticoduodenectomy, then we completed a total pancreatectomy, and finally, after confirming the absence of foci of carcinoma infiltration or lymph nodes involvement, a LT was performed. Foci of carcinoma infiltration or lymph nodes involvement in the liver were not found. After a two-year follow-up the patient developed liver recurrence and the biopsy showed a biliary adenocarcinoma. In 2010, Vibert et al. published a series of three cases concluding that in the absence of invasive carcinoma and positive lymph nodes, LT can be performed with success. The present case is the first to describe recurrence of the disease after LT in the absence of invasive carcinoma and positive lymph nodes in the literature. When the disease affects widely the entire biliary duct, small micro-invasive foci may not be detected. Nevertheless, although we know that it is a recurrent entity, the pathogenesis is unknown, and we do not know if it is possible that papillomatosis recurs over the new liver.

Hematemesis como debut de gastroenteritis eosinofílica en lactantes / Hematemesis as debut of eosinophilic gastroenteritis in infants

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