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Infecções por Herpesviridae , Doenças dos Cavalos , Carga Viral , Animais , Cavalos , Doenças dos Cavalos/virologia , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Carga Viral/veterinária , Gastropatias/veterinária , Gastropatias/virologia , Feminino , MasculinoRESUMO
Fibroblast activation protein is a promising target for oncologic molecular imaging with radiolabeled fibroblast activation protein inhibitors (FAPI) in a large variety of cancers. However, there are yet no published recommendations on how to set up an optimal imaging protocol for FAPI PET/CT. It is important to optimize the acquisition duration and strive toward an acquisition that is sufficiently short while simultaneously providing sufficient image quality to ensure a reliable diagnosis. The aim of this study was to evaluate the feasibility of reducing the acquisition duration of [68Ga]FAPI-46 imaging while maintaining satisfactory image quality, with certainty that the radiologist's ability to make a clinical diagnosis would not be affected. Methods: [68Ga]FAPI-46 PET/CT imaging was performed on 10 patients scheduled for surgical resection of suspected pancreatic cancer, 60 min after administration of 3.6 ± 0.2 MBq/kg. The acquisition time was 4 min/bed position, and the raw PET data were statistically truncated and reconstructed to represent images with an acquisition duration of 1, 2, and 3 min/bed position, additional to the reference images of 4 min/bed position. Four image quality criteria that focused on the ability to distinguish specific anatomic details, as well as perceived image noise and overall image quality, were scored on a 4-point Likert scale and analyzed with mixed-effects ordinal logistic regression. Results: A trend toward increasing image quality scores with increasing acquisition duration was observed for all criteria. For the overall image quality, there was no significant difference between 3 and 4 min/bed position, whereas 1 and 2 min/bed position were rated significantly (P < 0.05) lower than 4 min/bed position. For the other criteria, all images with a reduced acquisition duration were rated significantly inferior to images obtained at 4 min/bed position. Conclusion: The acquisition duration can be reduced from 4 to 3 min/bed position while maintaining satisfactory image quality. Reducing the acquisition duration to 2 min/bed position or lower is not recommended since it results in inferior-quality images so noisy that clinical interpretation is significantly disrupted.
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The European Pancreatic Club Lifetime Achievement Award is a distinction awarded for research on the pancreas and service to European Pancreatology. It comes with the obligation to submit a review article to our society's journal, Pancreatology. It was awarded to me 2023 and I take this opportunity to highlight my journey with the central organ AKA the pancreas, that is inseparatable from "Pancreas 2000" - an educational program for future pancreatologists, inaugurated by Karolinska Institutet.
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Pâncreas , Humanos , Distinções e Prêmios , Gastroenterologia/história , Gastroenterologia/educação , História do Século XX , História do Século XXIRESUMO
Screening of the general population for cancer is a matter of primary prevention reducing the burden of disease. Whilst this is successful for several cancers including breast, colon and prostate, the situation to screen and hence prevent pancreatic cancer is different. The organ is not as accessible to simple physical exam or biological samples (fecal or blood test). Neither exists a blood test such as PSA that is cost-effective. Reviewing the evidence from screening risk groups for pancreatic cancer, one must conclude that there is no rational at present to screen the general population, for a lack of appropriate tests.
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Detecção Precoce de Câncer , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/prevenção & controle , Detecção Precoce de Câncer/métodos , Predisposição Genética para Doença , Vigilância da População/métodos , Programas de Rastreamento/métodos , Masculino , FemininoRESUMO
BACKGROUND AND AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN. METHODS: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to ≤5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death. RESULTS: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths). CONCLUSIONS: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.
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Neoplasias Gastrointestinais , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Intraductais Pancreáticas/mortalidade , Neoplasias Intraductais Pancreáticas/patologia , Estudos Retrospectivos , Estudos de Casos e Controles , Modelos de Riscos Proporcionais , Idoso de 80 Anos ou mais , Adulto , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Fatores de Risco , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologiaRESUMO
The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM.
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INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur at almost any anatomical site. It often presents as a multiorgan disease that may mimic malignancy, infection, or other immune-mediated conditions. Autoimmune pancreatitis (AIP) type 1 is the most prominent manifestation of IgG4-RD in the digestive tract, with common extra-pancreatic inflammation. We present the first patient with AIP and involvement of the testicles and nasal cavity. PATIENT AND METHODS: A case of a patient with AIP type 1 and other organ involvement (bile ducts, testicles, nasal polyps, and lungs) is described. Additionally, a systematic review of AIP type 1 with testicular and nasal involvement was conducted. RESULTS: The systematic review found two cases of AIP type 1 with testicular involvement and 143 cases with AIP type 1 with nasal cavity involvement. None of them had both testicular and nasal involvement. CONCLUSIONS: This is the first case of AIP type 1 with other organ involvement, including testicular and nasal involvement, to be described. The number of patients with nasal and testicular involvement described in the literature is low. Creating awareness of this rare clinical condition is necessary, especially due to the very effective available treatment with corticosteroids and rituximab.
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Correct and timely diagnosis of pancreatic cancer (PC) is essential for treatment selection but is still clinically challenging. Standard-of-care imaging methods can sometimes not differentiate malignancies from inflammatory lesions or detect malignant transformation in premalignant lesions. This interim analysis of a prospective clinical trial aimed to evaluate the diagnostic accuracy of [68Ga]fibroblast activation protein inhibitor (FAPI)-46 PET/CT for PC and determine the sample size needed to demonstrate whether this imaging technique improves the characterization of equivocal lesions detected by standard-of-care imaging methods. Methods: [68Ga]FAPI-46 PET/CT imaging was performed on 30 patients scheduled for surgical resection of suspected PC. Target lesions were delineated, SUVmax and SUVmean were determined, and the results were compared with those of standard-of-care imaging. Receiver operating characteristics were calculated for the whole cohort and a subcohort of 11 patients with an equivocal clinical imaging work-up preoperatively. Postoperative histopathologic findings served as a reference standard, and the statistical power was determined. Results: Histopathologic examination revealed malignancy in 20 patients and benign lesions in 10 patients. Significantly elevated [68Ga]FAPI-46 uptake was observed in malignant tumors compared with benign lesions (P < 0.001). Receiver-operating-characteristic analyses established optimal cutoffs for both SUVs for differentiation of malignant from nonmalignant pancreatic tumors. The optimal SUVmax cutoff was 10.2 and showed 95% sensitivity and 80% specificity for the whole cohort, as well as 100% diagnostic accuracy when considering the subcohort with equivocal imaging work-up only. For sufficient statistical power, 38 equivocal observations are needed. Conclusion: We conclude that [68Ga]FAPI-46 PET/CT can accurately differentiate malignant from benign pancreatic lesions deemed equivocal by standard-of-care imaging. This trial will therefore continue to recruit a total of 120 patients to reach those 38 equivocal observations needed for sufficient statistical power. On the basis of our findings, we propose that [68Ga]FAPI-46 PET/CT not only can be clinically applied as a complement but also could become a necessary tool when standard-of-care imaging is inconclusive.
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Neoplasias Pancreáticas , Quinolinas , Humanos , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias PancreáticasRESUMO
Sulfur is an essential element of life. Thiol-containing metabolites in all organisms are involved in the regulation of diverse biological processes. Especially, the microbiome produces bioactive metabolites or biological intermediates of this compound class. The analysis of thiol-containing metabolites is challenging due to the lack of specific tools, making these compounds difficult to investigate selectively. We have now developed a new methodology comprising bicyclobutane for chemoselective and irreversible capturing of this metabolite class. We utilized this new chemical biology tool immobilized onto magnetic beads for the investigation of human plasma, fecal samples, and bacterial cultures. Our mass spectrometric investigation detected a broad range of human, dietary and bacterial thiol-containing metabolites and we even captured the reactive sulfur species cysteine persulfide in both fecal and bacterial samples. The described comprehensive methodology represents a new mass spectrometric strategy for the discovery of bioactive thiol-containing metabolites in humans and the microbiome.
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INTRODUCTION: The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is estimated as 2-46% among patients without known pancreatic diseases. An association between NAFPD and non-alcoholic fatty liver disease (NAFLD) has been proposed, as well as an association between NAFPD and pancreatic exocrine insufficiency (PEI). PATIENTS AND METHODS: Patients with histologically confirmed NAFLD were included in the study. The control group consisted of individuals included in a surveillance screening program. Magnetic resonance imaging (MRI) of the pancreas was performed in all patients and fat measurement was made using 2-point Dixon imaging. Fecal elastase-1 (FE-1) was performed to evaluate pancreatic exocrine function. Additionally, a 13C-mixed triglyceride breath test (13 C-MTG-BT) was performed in patients with FE-1 < 200 µg/g. RESULTS: Imaging signs of NAFPD were present in 17 (71%) patients; 11 (85%) from the NAFLD group and 6 (55%) from the control group. FE-1 < 200 µg/g was found in six (25%) patients (four in the NAFLD group and two in the control group); however, none of them had clinical symptoms of PEI. Therefore, in five out of six patients with low FE-1, a 13C-MTG-BT was performed, showing normal results (>20.9%) in all tested patients. Furthermore, the serum nutritional panel was normal in all patients with low FE-1. A systematic review identified five studies relevant to the topic. CONCLUSION: NAFPD was found in 85% of patients with NAFLD and in 55% of control patients. We did not diagnose PEI in either group. A literature review showed PEI in 9-56% of patients with NAFPD.
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Insuficiência Pancreática Exócrina , Hepatopatia Gordurosa não Alcoólica , Pancreatopatias , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Projetos Piloto , Pancreatopatias/diagnóstico , Pancreatopatias/diagnóstico por imagem , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/etiologia , Pâncreas/patologiaRESUMO
INTRODUCTION: Nutritional deficiencies, including fat-soluble vitamins and minerals have been detected in many autoimmune diseases, including those involving the digestive system, but have yet to be assessed in autoimmune pancreatitis (AIP). The aim of the present study was to determine the prevalence of micronutrient deficiencies in patients with AIP as well as to investigate their relationship with relapse. PATIENTS AND METHODS: We retrospectively analysed medical records of patients treated for AIP. Demographic and clinical data were collected. RESULTS: One hundred patients were included in the final analysis. The male-to-female ratio was 2.5:1; median age at diagnosis was 57 years (range 19-85). Median follow-up was 53 months, and during this time, 38% of patients suffered from at least one micronutrient deficiency. The most prevalent micronutrient deficiencies were vitamin D (16.1%) and zinc (25.5%). Relapse was observed in 37% of the AIP patients. Initial analysis showed that AIP relapse was associated with any micronutrient deficiency as well as zinc and vitamin D deficiency, but after stratifying for AIP type 1 and adjusting for PEI and elevated IgG4 levels, the association ceased to be statistically significant. CONCLUSION: Zinc and vitamin D deficiencies may be common in patients with AIP, indicating that these micronutrients might play a role in the natural course of AIP. Importantly, any micronutrient deficiency may be prevalent even in the light of treated PEI, which emphasizes the potential of micronutrients as an additional tool in the workup and follow-up of AIP patients.
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Doenças Autoimunes , Pancreatite Autoimune , Desnutrição , Deficiência de Vitamina D , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Micronutrientes , Estudos Retrospectivos , Vitaminas/uso terapêutico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Zinco/uso terapêutico , RecidivaRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) patients might benefit from a biomarker to more precisely prognosticate their overall survival to make more informed treatment and surveillance decisions. The aim of the study was to assess the circulating biomarker Thymidine kinase (TK) activity in samples from patients with PDAC to improve prognostic precision. MATERIAL AND METHODS: Using the sensitive TK activity (TKa) assay DiviTum®, serum samples from 60 PDAC patients were analyzed. RESULTS: Median TKa value for patients with PDAC was 931 Du/L. TK activity <931 and CA19-9 < 37 was prognostic for a longer survival, compared to patients with any or both TK activity >931 and CA19-9 > 37, with median 41.3 vs 8.6 months from sample to death (p < 0.001), and 3-year survival was 55.6% vs 8.9% (p < 0.001). Hazard ratio was 2.81 if any or both of TK or CA19-9 were above the cut-off value (p < 0.05).TKa in combination with CA19-9 outperforms each marker individually for prediction of survival. Overall survival is longer in patients with both TKa <931 Du/L and CA19-9 < 37. Further studies of TKa levels at different disease stages and correlation to outcome is warranted to find the full potential clinical usage of the TKa marker in PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Prospectivos , Timidina Quinase , Prognóstico , Antígeno CA-19-9 , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Biomarcadores Tumorais , Neoplasias PancreáticasRESUMO
INTRODUCTION: Most patients with chronic pancreatitis (CP) develop pancreatic exocrine insufficiency (PEI) over the course of the disease. PEI may lead to hyperoxaluria and development of urinary oxalate stones. It has been postulated that the patients with CP may be at increased risk of kidney stone formation, but the data is scarce. We aimed to estimate incidence and risk factors for nephrolithiasis in a Swedish cohort of patients with CP. PATIENTS AND METHODS: We performed retrospective analysis of an electronical medical database of patients diagnosed with definite CP during 2003-2020. We excluded patients <18 years of age, those with missing relevant data in medical charts, patients with probable CP (according to the M-ANNHEIM classification system) and those in whom kidney stones were diagnosed before CP diagnosis. RESULTS: Some 632 patients with definite CP were followed over a median of 5.3 (IQR 2.4-6.9) years. There were 41 (6.5%) patients diagnosed with kidney stones, of whom 33 (80.5%) were symptomatic. Comparing to patients without kidney stones, patients with nephrolithiasis were older, with median age of 65 (IQR 51-72) years, and a male predominance (80% vs 63%). Cumulative incidence of kidney stones was 2.1%, 5.7%, 12.4% and 16.1% at 5, 10, 15, and 20 years after CP diagnosis, respectively. Multivariable cause-specific Cox regression analysis revealed PEI as independent risk factor for nephrolithiasis (adjusted HR 4.95, 95%CI 1.65-14.84; p = 0.004). Another risk factors were increase in BMI (aHR 1.16 95% CI 1.04-1.30; p = 0.001 per unit increment), and a male sex (4.51, 95% CI 1.01-20.3, p = 0.049). CONCLUSION: PEI and increase in BMI are risk factors for kidney stone development in patients with CP. Male CP patents are particularly at increased risk of nephrolithiasis. This should be taken into consideration in general clinical approach to raise awareness among patients and medical workers.
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Insuficiência Pancreática Exócrina , Cálculos Renais , Pancreatite Crônica , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Estudos Retrospectivos , Pancreatite Crônica/complicações , Pancreatite Crônica/epidemiologia , Insuficiência Pancreática Exócrina/complicações , Insuficiência Pancreática Exócrina/epidemiologia , Fatores de Risco , Cálculos Renais/complicações , Cálculos Renais/epidemiologiaRESUMO
BACKGROUND: Acute on chronic pancreatitis (ACP) is a relatively common condition, but there are significant gaps in our knowledge on the definition, incidence, diagnosis, treatment and prognosis. METHODS: A systematic review that followed PICO (Population; Intervention; Comparator; Outcome) recommendation for quantitative questions and PICo (Population, Phenomenon of Interest, Context) for qualitative research was done to answer 10 of the most relevant questions about ACP. Quality of evidence was judged by the GRADE criteria (Grades of Recommendation, Assessment, Development and Evaluation). The manuscript was sent for review to 12 international experts from various disciplines and continents using a Delphi process. RESULTS: The quality of evidence, for most statements, was low to very low, which means that the recommendations in general are only conditional. Despite that, it was possible to reach strong levels of agreement by the expert panel for all 10 questions. A new consensus definition of ACP was reached. Although common, the real incidence of ACP is not known, with alcohol as a major risk factor. Although pain dominates, other non-specific symptoms and signs can be present. Serum levels of pancreatic enzymes may be less than 3 times the upper limit of normal and cross-sectional imaging is considered more accurate for the diagnosis in many cases. It appears that it is less severe and with a lower mortality risk than acute pancreatitis. CONCLUSIONS: Although the evidence base is poor, this position statement provides a foundation from which to advance management of ACP.
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Pancreatite Crônica , Humanos , Doença Aguda , Incidência , PrognósticoRESUMO
Preneoplastic high-risk lesions in the pancreas need to be differentiated from low-risk lesions warranting surveillance and eventually surgical intervention. Imaging is used so far; however, certain imaging features are subject to interpretation and hence have their intrinsic flaws. In a recent article, a liquid biopsy with protein and RNA markers demonstrates differentiation based on a blood test. See related article by Zhang et al., p. 1535.
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Neoplasias Intraductais Pancreáticas , Humanos , Neoplasias Intraductais Pancreáticas/patologia , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Diagnóstico por Imagem , Medição de RiscoRESUMO
BACKGROUND: Post-pancreatitis diabetes mellitus (PPDM) is a common consequence of chronic pancreatitis (CP). We aimed to determine the incidence and predictors of PPDM after CP onset, as well as complications and antidiabetic therapy requirements, in a high-volume tertiary center. METHODS: We did a cohort study with retrospectively collected data from patients with definite CP seen at the Karolinska University Hospital between January 1999 and December 2020. Cause-specific Cox regression analysis was used to assess PPDM predictors. To estimate risk of complications and need for therapy the Fine-Gray subdistribution hazard model was employed, accounting for death as a competing risk. RESULTS: We identified 481 patients with CP. The cumulative incidence of PPDM was 5.1%, 13.2%, 27.5% and 38.9% at 5, 10, 15 and 20 years, respectively. Compared to CP patients without diabetes, patients with PPDM were predominantly male (55% vs. 75%), had more frequently alcoholic etiology (44% vs. 62%) and previous acute pancreatitis. The only independent predictor of PPDM was presence of pancreatic calcifications (aHR = 2.45, 95% CI 1.30-4.63). Patients with PPDM had higher rates of microangiopathy (aSHR = 1.59, 95% CI 1.02-2.52) and infection (aSHR = 4.53, 95% CI 2.60-9.09) compared to CP patients who had type 2 diabetes (T2DM). The rate of insulin use was three-fold higher, whereas metformin use rate was two-fold higher in the same comparison. CONCLUSIONS: Patients with PPDM have a higher frequency of clinically significant complications and were more commonly prescribed insulin and metformin, suggesting a more aggressive phenotype than that of T2DM. Greater PPDM awareness is needed to optimize disease management.