Chronic pancreatitis for the clinician. Complications and special forms of the disease. Interdisciplinary position paper of the Catalan Society of Digestology (SCD) and the Catalan Pancreatic Society (SCPanc).

Chronic pancreatitis tends to develop a number of complications that may constitute the form of presentation of the disease. Some societies have issued guidelines for diagnosis and treatment of chronic pancreatitis complications, but the level of evidence for any topic is usually low and recommendations tend to be weak. We aimed at providing defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The goal was to propose defined terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 14 sections related to complications and special forms of chronic pancreatitis (early chronic, groove and autoimmune pancreatitis) were reviewed by 21 specialists from 6 different fields to generate 32 statements. Featured statements assert common bile duct stenosis does not require invasive treatment (endoscopic or surgical) unless cholestasis, cholangitis, lithiasis or other symptoms develop. Pancreatic duct strictures and calculi should be approached (after ruling out malignancy) if causing pain, pancreatitis, pseudocysts or other complications. Treatment of symptomatic pseudocysts must be individualized, considering associated main duct stenosis, vascular and pericystic complications. Higher risk conditions for pancreatic cancer are advance age, smoking, genetic background, recent diagnosis of chronic pancreatitis or diabetes, and appearance of new symptoms. Groove pancreatitis can initially be treated with conservative measures. Both prednisolone or rituximab can induce remission and maintenance of autoimmune pancreatitis. Internal fistula, vascular complications, bacterial overgrowth, osteoporosis and renal lithiasis require specific therapeutic approaches.

Preclinical testing of oncolytic adenovirus sensitivity in patient-derived tumor organoids.

Patient-derived organoids (PDOs) have shown the potential to reflect patient sensitivity to chemotherapeutic or targeted drugs. Recently, we showed that organoid models can also serve as a platform to screen for selectivity and potency of oncolytic adenoviruses (OAds). In this protocol, we describe the steps for tumor organoid adenoviral infection and functional assessment of patient-specific responses to OAds. We provide methods to determine OAd relative efficacy by evaluation of PDO viability after infection and adenoviral replication within cancer cells. For complete details on the use and execution of this protocol, please refer to Raimondi et al. (2020).

Spectrum of Disease Manifestations in Patients with Selective Immunoglobulin E Deficiency.

BACKGROUND: Selective IgE deficiency (SIgED) has been previously evaluated in selected patients from allergy units. This study investigates the effects of SIgED on the entire population in a hospital setting and sought to delineate in detail the clinical aspects of SIgED. METHODS: A retrospective study of the data obtained from electronic medical records of 52 adult patients (56% female) with a mean age of 43 years and IgE levels of <2.0 kU/L with normal immunoglobulin (Ig) IgG, IgA, and IgM levels, seen at our hospital, without selection bias, from 2010 to 2019. RESULTS: Recurrent upper respiratory infections were recorded in 18 (34.6%) patients, pneumonia was recorded in 16 (30.7%) patients, bronchiectasis was recorded in 16 (30.7%) patients, and asthma was recorded in 10 (19.2%) patients. Eighteen patients (34.6%) suffered autoimmune clinical manifestations either isolated (19%) or combining two or more diseases (15%), Hashimoto's thyroiditis being the most frequent (19%), which was followed by arthritis (10%) and thrombocytopenia and/or neutropenia (5.7%). Other less frequent associations were Graves' disease, primary sclerosing cholangitis, Sjögren's syndrome, and autoimmune hepatitis. Eczematous dermatitis (15.3%), chronic spontaneous urticaria (17.3%), and symptoms of enteropathy (21%) were also highly prevalent. Thirty percent of patients developed malignancies, with non-Hodgkin lymphomas (13.4%) being the most prevalent. CONCLUSIONS: The clinical manifestations of SIgED encompass a variety of infectious, non-infectious complications, and malignancy. Since it cannot be ruled out that some type of selection bias occurred in the routine assessment of IgE serum Ievels, prospective studies are required to better characterize SIgED and to determine whether it should be added to the list of antibody deficiencies.

DYRK1A modulates c-MET in pancreatic ductal adenocarcinoma to drive tumour growth.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumour with a poor prognosis using current treatments. Targeted therapies may offer a new avenue for more effective strategies. Dual-specificity tyrosine regulated kinase 1A (DYRK1A) is a pleiotropic kinase with contradictory roles in different tumours that is uncharacterised in PDAC. Here, we aimed to investigate the role of DYRK1A in pancreatic tumorigenesis. DESIGN: We analysed DYRK1A expression in PDAC genetic mouse models and in patient samples. DYRK1A function was assessed with knockdown experiments in pancreatic tumour cell lines and in PDAC mouse models with genetic reduction of Dyrk1a dosage. Furthermore, we explored a mechanistic model for DYRK1A activity. RESULTS: We showed that DYRK1A was highly expressed in PDAC, and that its protein level positively correlated with that of c-MET. Inhibition of DYRK1A reduced tumour progression by limiting tumour cell proliferation. DYRK1A stabilised the c-MET receptor through SPRY2, leading to prolonged activation of extracellular signal-regulated kinase signalling. CONCLUSIONS: These findings reveal that DYRK1A contributes to tumour growth in PDAC, at least through regulation of c-MET accumulation, suggesting that inhibition of DYRK1A could represent a novel therapeutic target for PDAC.

Zeb1 in Stromal Myofibroblasts Promotes Kras-Driven Development of Pancreatic Cancer.

The transcription factor Zeb1 has been identified as a crucial player in Kras-dependent oncogenesis. In pancreatic ductal adenocarcinoma (PDAC), Zeb1 is highly expressed in myofibroblasts and correlates with poor prognosis. As Kras mutations are key drivers in PDAC, we aimed here to assess the necessity of Zeb1 for Kras-driven PDAC and to define the role of Zeb1-expressing myofibroblasts in PDAC development. Genetically engineered mice with conditional pancreatic KrasG12D and Trp53 mutations (KPC) were crossed with Zeb1 haploinsufficient mice (Z+/-). Extensive PDAC was prominent in all 20-week-old KPC;Z+/+ mice, whereas only low-grade precursor lesions were detected in age-matched KPC;Z+/- littermates, with PDAC developing eventually in KPC;Z+/- aged animals. Zeb1 expression in myofibroblasts occurred early in tumorigenesis and Zeb1 haploinsufficiency retarded native expansion of stromal myofibroblasts during precursor-to-cancer progression. Zeb1 downregulation in mPSC repressed their activated gene profile, impaired their migratory and proliferative activity, and attenuated their tumor-supporting features. Conditioned media from Z+/+ mouse-activated (myofibroblast-like) pancreatic stellate cells (mPSC) boosted Ras activity in pancreatic cancer cells carrying mutant Kras; this effect was not observed when using conditioned media from Z+/- mPSC, revealing a paracrinal cooperative axis between Zeb1-expressing PSC and oncogenic Kras-bearing tumor cells. We conclude that Zeb1-expressing stromal myofibroblasts enable a heterotypic collaboration with the Kras-fated epithelial compartment, thus supporting pancreatic malignancy.Significance: Zeb1 expression in stromal myofibroblasts supports PDAC development via collaboration with the epithelial compartment bearing oncogenic Kras mutations. Cancer Res; 78(10); 2624-37. ©2018 AACR.

Endoscopic ultrasonography can avoid unnecessary laparotomies in patients with pancreatic adenocarcinoma and undetected peritoneal carcinomatosis.

BACKGROUND/OBJECTIVE: To assess the relationship between the presence of ascites detected by endoscopic ultrasonography (EUS) and peritoneal carcinomatosis (PC) in patients with pancreatic adenocarcinoma. METHODS: Consecutive patients who underwent a EUS for preoperative staging of a pancreatic adenocarcinoma between 1998 and 2014 were retrospectively reviewed. The diagnosis of PC was confirmed by histopathology or peritoneal fluid cytology. The main outcome of the study was the relationship of ascites at EUS and PC in patients with pancreatic cancer. Secondarily, to evaluate the relationship between this finding and survival as well as the development of PC during follow-up. RESULTS: A total of 136 patients were included: 30 patients with local unresectable tumor or metastatic disease and 106 potentially-resectable candidates based on CT staging. EUS showed ascites in 27 (20%) patients, of whom 8 (29.6%) had PC. The sensitivity, specificity, PPV, NPV and accuracy of ascites by EUS in the detection of PC in this group of patients were 67%, 85%, 30%, 96% and 83%, respectively. Ascites detected by EUS was the only independent predictive factor of PC with an OR of 11 (CI 95%: 3-40). The detection of ascites by EUS was associated with a shorter survival (median survival time 7,3 months; range 0-60 vs 14.2 months; range 0-140) (p = 0.018) and earlier development of PC during follow-up (median 3.2 months, range 1.4-18.1 vs 12.7 months, range 5.4-54.8; p = 0.003). CONCLUSION: The finding of ascites at EUS in patients with pancreatic adenocarcinoma is highly associated with PC and a poor outcome.

[Recommendations for the diagnosis, staging and treatment of pre-malignant lesions and pancreatic adenocarcinoma]. / Recomendaciones para el diagnóstico, la estadificación y el tratamiento de las lesiones premalignas y el adenocarcinoma de páncreas.

BACKGROUND AND OBJECTIVE: Clinical management of adenocarcinoma of the pancreas is complex, and requires a multidisciplinary approach. The same applies for the premalignant lesions that are increasingly being diagnosed. The current document is an update on the diagnosis and management of premalignant lesions and adenocarcinoma of the pancreas. PATIENTS AND METHODS: A conference to establish the basis of the literature review and manuscript redaction was organized by the Grupo Español Multidisciplinar en Cáncer Digestivo. Experts in the field from different specialties (Gastroenterology, Surgery, Radiology, Pathology, Medical Oncology and Radiation Oncology) met to prepare the present document. RESULTS: The current literature was reviewed and discussed, with subsequent deliberation on the evidence. CONCLUSIONS: Final recommendations were established in view of all the above.

Impact of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration on the management of pancreatic cystic lesions.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are well-recognized techniques for the study of pancreatic cystic lesions (PCLs). However, little evidence exists on their impact on clinical care. The aim of this study is to determine how often EUS and EUS-FNA alter the diagnosis and management of patients with PCLs. PATIENTS AND METHODS: Eight physicians expert in pancreatic diseases were asked to report their diagnoses and management recommendations for 49 different PCLs. Clinical information was sequentially disclosed in a stepwise manner - progressively from clinical data plus computed tomography or MRI (level 1), to EUS (level 2) and EUS-FNA results including cytology, carcinoembryonic antigen, and amylase levels (level 3). RESULTS: EUS led to a change in the diagnosis and management in 30% [95% confidence interval (CI): 26-35%] and 19% (95% CI: 16-23%) of cases, respectively, usually to a more intensive approach (14%; 95% CI: 11-18%). EUS-FNA altered the diagnosis and management in an additional 39% (95% CI: 34-44%) and 21% (95% CI: 17-25%) of the evaluations, respectively. EUS-FNA also increased the consensus in the diagnosis among the specialists that ranged from fair with computed tomography/MRI (κ-index=0.32) to substantial with EUS-FNA (κ-index=0.43). CONCLUSION: EUS and EUS-FNA impact the diagnosis and management of patients with PCLs; therefore, both are necessary in the workup of these patients. EUS-FNA markedly improves the agreement between physicians in terms of diagnosis, but not management. This study highlights the need for more research and standardization in the field.

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery.

OBJECTIVE: To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery. BACKGROUND: EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients. METHODS: Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement. RESULTS: These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement. CONCLUSIONS: EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.

Recomendaciones para el diagnóstico, la estadificación y el tratamiento de las lesiones premalignas y el adenocarcinoma de páncreas / Recommendations for the diagnosis, staging and treatment of pre-malignant lesions and pancreatic adenocarcinoma

Antecedentes y objetivo. El tratamiento del adenocarcinoma de páncreas es complejo y requiere un enfoque multidisciplinar, al igual que sucede con las lesiones premalignas, cuyo diagnóstico es cada vez más frecuente. Este documento constituye una puesta al día sobre el diagnóstico y el tratamiento de las lesiones premalignas y del adenocarcinoma de páncreas. Pacientes y método. Para ello, el Grupo Español Multidisciplinar en Cáncer Digestivo organizó una conferencia en Barcelona durante la cual un panel formado por expertos en esta enfermedad, procedentes de diversas especialidades (Gastroenterología, Cirugía, Radiología, Anatomía Patológica, Oncología Médica y Oncología Radioterápica), estableció las bases para la revisión y la elaboración del manuscrito. Resultados. Se ha revisado la literatura, discutido y, finalmente, deliberado sobre las evidencias. Conclusiones. Con todo ello, se han establecido unas recomendaciones (AU)

Background and objective. Clinical management of adenocarcinoma of the pancreas is complex, and requires a multidisciplinary approach. The same applies for the premalignant lesions that are increasingly being diagnosed. The current document is an update on the diagnosis and management of premalignant lesions and adenocarcinoma of the pancreas. Patients and methods. A conference to establish the basis of the literature review and manuscript redaction was organized by the Grupo Español Multidisciplinar en Cáncer Digestivo. Experts in the field from different specialties (Gastroenterology, Surgery, Radiology, Pathology, Medical Oncology and Radiation Oncology) met to prepare the present document. Results. The current literature was reviewed and discussed, with subsequent deliberation on the evidence. Conclusions. Final recommendations were established in view of all the above (AU)

Pancreatitis autoinmune: un dilema quirúrgico / Autoimmune pancreatitis: a surgical dilemma

La pancreatitis autoinmune (PAI) es una enfermedad fibroinflamatoria benigna del páncreas, se manifiesta frecuentemente como ictericia obstructiva asociada a masa pancreática o lesión obstructiva de la vía biliar y presenta una respuesta excelente a corticoides. Aunque no existen estudios a nivel mundial que definan su epidemiología, la PAI se considera una entidad poco frecuente, con una prevalencia estimada del 2% de los pacientes con pancreatitis crónica. Su frecuente presentación clínica y radiológica en forma de masa pancreática e ictericia similar al cáncer de páncreas y la falta de elementos diagnósticos específicos son causa de un elevado porcentaje de resecciones quirúrgicas pancreáticas por una enfermedad benigna que responde a tratamiento médico. En esta revisión detallamos los acuerdos actuales para el diagnóstico, clasificación y tratamiento de la PAI, enfatizando en las series quirúrgicas y en estrategias para mejorar el diagnóstico diferencial con el cáncer de páncreas y evitar así resecciones pancreáticas innecesarias

Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis that often manifests as obstructive jaundice associated with a pancreatic mass or an obstructive bile duct lesion, and that has an excellent response to corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is considered as a rare entity. The clinical and radiological presentation of AIP can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and obliging the surgeon to balance decision-making between the potential risk presented by the misdiagnosis of a deadly disease against the desire to avoid unnecessary major surgery for a disease that responds effectively to corticosteroid treatment. In this review we detail the current and critical points for the diagnosis, classification and treatment for AIP, with a special emphasis on surgical series and the methods to differentiate between this pathology and bilio-pancreatic cancer

Autoimmune pancreatitis type-1 associated with intraduct papillary mucinous neoplasm: report of two cases.

Chronic pancreatitis lesions usually embrace both intraduct papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC). Patients at genetically-determined high risk of PDAC often harbor IPMN and/or chronic pancreatitis, suggesting IPMN, chronic pancreatitis and PDAC may share pathogenetic mechanisms. Chronic autoimmune pancreatitis (AIP) may also herald PDAC. Concurrent IPMN and AIP have been reported in few patients. Here we describe two patients with IPMN who developed type-1 AIP fulfilling the Honolulu and Boston diagnostic criteria. AIP diffusively affected the whole pancreas, as well as peripancreatic lymph nodes and the gallbladder. Previous pancreatic resection of focal IPMN did not show features of AIP. One of the patients carried a CFTR class-I mutation. Of notice, serum IgG4 levels gradually decreased to normal values after IPMN excision. Common risk factors to IPMN and AIP may facilitate its coincidental generation.

Autoimmune pancreatitis: a surgical dilemma.

Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis that often manifests as obstructive jaundice associated with a pancreatic mass or an obstructive bile duct lesion, and that has an excellent response to corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is considered as a rare entity. The clinical and radiological presentation of AIP can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and obliging the surgeon to balance decision-making between the potential risk presented by the misdiagnosis of a deadly disease against the desire to avoid unnecessary major surgery for a disease that responds effectively to corticosteroid treatment. In this review we detail the current and critical points for the diagnosis, classification and treatment for AIP, with a special emphasis on surgical series and the methods to differentiate between this pathology and bilio-pancreatic cancer.

Recomendaciones del Club Español Pancreático para el diagnóstico y tratamiento de la pancreatitis crónica: parte 2 (tratamiento) / No disponible

La pancreatitis crónica (PC) es una enfermedad compleja, con un amplio espectro de manifestaciones clínicas, que abarca desde pacientes asintomáticos a pacientes con síntomas inhabilitantes o con complicaciones serias. El manejo de la PC frecuentemente difiere entre áreas geográficas e incluso entre centros. Ello se debe a la escasez de estudios de calidad y guías de práctica clínica que aborden el diagnóstico y tratamiento de esta enfermedad. El objetivo del Club Español Pancreático fue elaborar recomendaciones basadas en la evidencia para el manejo de la PC. Dos coordinadores eligieron un panel multidisciplinario de 24 expertos en esta enfermedad. Estos expertos se seleccionaron por su experiencia clínica e investigadora en PC. Se elaboró una lista de preguntas, cada una de las cuales se revisó por 2 panelistas. Con ello se produjo un borrador que se discutió en una reunión presencial por todos los participantes. Los niveles de evidencia se basaron en la clasificación del Oxford Centre for Evidence-Based Medicine. En la segunda parte del consenso se dieron recomendaciones para el manejo del dolor, seudoquistes, estenosis biliar y duodenal, fístula pancreática y ascitis, hipertensión portal izquierda, diabetes mellitus, insuficiencia pancreática exocrina y soporte nutricional en PC (AU)

Chronic pancreatitis (CP) is a complex disease with a wide spectrum of clinical manifestations ranging from asymptomatic disease to disabling forms or serious complications. The management of CP frequently differs among geographical areas and even among centers. These differences are due to the scarcity of high-quality studies and clinical practice guidelines that focus on the diagnosis and treatment of this disease. The aim of the Spanish Pancreatic Club was to create evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. These experts were selected on the basis of their clinical and research experience in CP. A list of questions was drawn up and each question was then reviewed by two panelists. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. Levels of evidence were based on the classification of the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus process, recommendations were established for the management of pain, pseudocysts, biliary and duodenal stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP (AU)

[Recommendations of the Spanish Pancreatic Club on the diagnosis and treatment of chronic pancreatitis: part 2 (treatment)]. / Recomendaciones del Club Español Pancreático para el diagnóstico y tratamiento de la pancreatitis crónica: parte 2 (tratamiento).

Chronic pancreatitis (CP) is a complex disease with a wide spectrum of clinical manifestations ranging from asymptomatic disease to disabling forms or serious complications. The management of CP frequently differs among geographical areas and even among centers. These differences are due to the scarcity of high-quality studies and clinical practice guidelines that focus on the diagnosis and treatment of this disease. The aim of the Spanish Pancreatic Club was to create evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. These experts were selected on the basis of their clinical and research experience in CP. A list of questions was drawn up and each question was then reviewed by two panelists. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. Levels of evidence were based on the classification of the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus process, recommendations were established for the management of pain, pseudocysts, biliary and duodenal stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Recomendaciones del Club Español Pancreático para el diagnóstico y tratamiento de la pancreatitis crónica: parte 1 (diagnóstico) / Recommendations of the Spanish pancreatic club on the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis)

La pancreatitis crónica (PC) es una enfermedad relativamente infrecuente, compleja y muy heterogénea. La ausencia de un patrón oro aplicable a las fases iniciales de la PC hace que su diagnóstico precoz sea difícil. Algunas de sus complicaciones, en particular el dolor crónico, pueden ser difíciles de manejar. Hay mucha variedad en el diagnóstico y tratamiento de la PC y de sus complicaciones entre los diferentes centros y profesionales. El Club Español Pancreático ha desarrollado un consenso sobre el manejo de la PC. Dos coordinadores eligieron un panel multidisciplinario de 24 expertos en esta enfermedad. Se elaboró una lista de preguntas. Cada pregunta fue revisada por 2 expertos. Con ello se elaboró un borrador compartido con todo el panel de expertos y discutido en una reunión presencial. En la primera parte del consenso se aborda el diagnóstico de la PC y de sus complicaciones (AU)

Chronic pancreatitis (CP) is a relatively uncommon, complex and highly heterogeneous disease. There is no clear pattern applicable to the initial stages of CP, which hampers its early diagnosis. Some of the complications of CP, especially chronic pain, can be difficult to manage. There is wide variation in the diagnosis and treatment of CP and its complications among centers and health professionals. The Spanish Pancreatic Club has developed a consensus document on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. A list of questions was drawn up. Each question was reviewed by two experts. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. The first part of the consensus document focusses on the diagnosis of CP and its complications (AU)

[Recommendations of the Spanish Pancreatic Club on the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis)]. / Recomendaciones del Club Español Pancreático para el diagnóstico y tratamiento de la pancreatitis crónica: parte 1 (diagnóstico).

Chronic pancreatitis (CP) is a relatively uncommon, complex and highly heterogeneous disease. There is no clear pattern applicable to the initial stages of CP, which hampers its early diagnosis. Some of the complications of CP, especially chronic pain, can be difficult to manage. There is wide variation in the diagnosis and treatment of CP and its complications among centers and health professionals. The Spanish Pancreatic Club has developed a consensus document on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. A list of questions was drawn up. Each question was reviewed by two experts. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. The first part of the consensus document focusses on the diagnosis of CP and its complications.

Expanding roles of ZEB factors in tumorigenesis and tumor progression.

The ZEB family of transcription factors regulates key factors during embryonic development and cell differentiation but their role in cancer biology has only more recently begun to be recognized. Early evidence showed that ZEB proteins induce an epithelial-to-mesenchymal transition linking their expression with increased aggressiveness and metastasis in mice models and a wide range of primary human carcinomas. Reports over the last few years have found that ZEB proteins also play critical roles in the maintenance of cancer cell stemness, control of replicative senescence, tumor angiogenesis, overcoming of oncogenic addiction and resistance to chemotherapy. These expanding roles in tumorigenesis and tumor progression set ZEB proteins as potential diagnostic, prognostic and therapeutic targets.

En paciente con dolor abdominal e historia de ingesta alcohólica elevada, ¿qué pruebas permiten confirmar o descartar la existencia de una pancreatitis crónica? / In patients with abdominal pain and a history of high alcoholin take, which tests allow the presence of chronic pancreatitis to be confirmedor excluded?

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