RESUMO
BACKGROUND: Compassionate drug use (CDU) provides early access to not yet authorised medicines and is funded by pharmaceutical companies. The observational retrospective study Compass-O monitored the CDU of onco-haematological drugs, managed by seven Italian units for cytotoxic drug preparations (Unità Farmaci Antiblastici [UFA]), between 1 January, 2016 and 31 December, 2021. OBJECTIVE: We aimed to evaluate the CDU of onco-haematological drugs managed by seven Italian UFA, between 2016 and 2021. METHODS: The seven UFA provided anonymised data concerning CDU approved in the study period. The early access and potential cost savings for the National Health System (Servizio Sanitario Nazionale [SSN]) were analysed for CDU concerning drug-therapeutic indication combinations with complete data and reimbursed by SSN up to December 2023 (date of study execution), according to the executive decision of the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]). Both analyses distinguished solid/liquid tumours and categorised the combinations as innovative (fully/conditionally) or non-innovative based on AIFA assessments. RESULTS: Compass-O collected 783 CDU authorisations, with 572 (73.1%) analysable in terms of early access and cost savings. On average, early access amounted to 514 days and the total cost savings was 376,115,801. Compassionate drug use approvals involved mainly solid tumours (93.7% vs 6.3% for liquid tumours), and the combination of trastuzumab emtansine-breast cancer was the most dispensed (n = 73; early access = 426 days; potential cost savings: 610,388). Out of 572 CDU approvals, 200 (35%) were innovative drug-therapeutic indication combinations, with 598 days of early access and a total potential saving of 113,124,069. CONCLUSIONS: The study Compass-O showed a significant economic burden of CDU and a relevant need for early access, particularly for innovative drugs. However, there is currently no structured monitoring of CDU in Italy, suggesting the need for a national observatory, of which Compass-O can be the pilot phase.
RESUMO
BACKGROUND/OBJECTIVES: Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. METHODS: 312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). RESULTS: One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15-379) µg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 µg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15-340) to 202 (40-387) µg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. CONCLUSION: The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.
Assuntos
Pancreatite Autoimune , Insuficiência Pancreática Exócrina , Humanos , Pancreatite Autoimune/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Insuficiência Pancreática Exócrina/tratamento farmacológico , Pâncreas Exócrino/efeitos dos fármacos , Adulto , Esteroides/uso terapêutico , Elastase PancreáticaRESUMO
BACKGROUND: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. METHODS: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). RESULTS: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. CONCLUSIONS: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Pancreatite , Humanos , Bicarbonatos/metabolismo , Cloretos , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Mutação , Pancreatite/genética , Pancreatite/metabolismo , QuinolonasRESUMO
OBJECTIVES: Type 2 is a rare form of autoimmune pancreatitis (AIP). Despite being considered a benign disease, only few studies with limited sample size and short follow-up have been published on type 2 AIP. The aim of this observational study was to evaluate long-term outcomes, such as the risk of relapse, pancreatic insufficiency and cancer in a large type 2 AIP cohort with long follow-up. METHODS: Patients with definitive or probable diagnosis of type 2 AIP by International Consensus Diagnostic Criteria (ICDC) present in our prospectively maintained database since 1995 at 31.12.2021 were identified. All patients were clinically evaluated during the year 2022. Clinical, radiological, serological, and pathological data were evaluated. RESULTS: Eighty-eight out of 420 patients present in the database (21%) were diagnosed with type 2 AIP (mean age 33.5 ± 13.5 years). According to the ICDC, 21 patients (23.8%) had a definitive and 67 (76.2%) a probable diagnosis of type 2 AIP. The mean follow-up was 9.2 ± 7.1 years (range 1-27 years). No differences were observed when comparing patients with definitive and probable type 2 AIP diagnosis. Concomitant IBD was reported in 77 patients (87.5%). The probability of disease relapse was lower in patients treated with steroids versus surgery (at 5 years 13% vs. 33%; p = 0.038) but this difference was not statistically significant at multivariable analysis. The risk of endocrine or severe exocrine insufficiency was low (5% and 25%). Four extra-pancreatic malignancies (5%) were diagnosed, none pancreatic. One patient died in a car accident. CONCLUSIONS: Type 2 AIP has benign long-term clinical outcomes. Mortality and cancer rates are low and no specific follow-up is needed after radiological remission.
Assuntos
Doenças Autoimunes , Pancreatite Autoimune , Pancreatite , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Pancreatite Autoimune/diagnóstico , Pancreatite/diagnóstico , Pancreatite/epidemiologia , Pancreatite/terapia , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Recidiva Local de Neoplasia , Doença Crônica , RecidivaRESUMO
INTRODUCTION: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before. METHODS: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). RESULTS: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported. DISCUSSION: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.
Assuntos
Carcinoma Ductal Pancreático , Carcinoma , Neoplasias Pancreáticas , Humanos , Adolescente , Estudos Prospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/epidemiologia , Pâncreas/patologia , Imageamento por Ressonância Magnética , Carcinoma Ductal Pancreático/patologiaRESUMO
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.
RESUMO
INTRODUCTION: Autoimmune pancreatitis (AIP) is a fibroinflammatory disease of the pancreas. Type 1 AIP is the pancreatic manifestation of a systemic IgG4-related disease and is associated with serum elevation of IgG4, tissue infiltration of IgG4-positive plasma cells, and multiorgan involvement. Although serum IgG4 elevation is considered a useful diagnostic tool, the concomitant presence of more diagnostic criteria is needed to achieve diagnosis. No other biomarkers have been approved in clinical practice in type 1 AIP. Type 2 AIP is a pancreatic-specific disease associated with inflammatory bowel disease. No specific biomarkers for type 2 AIP have been identified. AREAS COVERED: The role of serum IgG4 in the diagnosis, management and follow-up of patients with type 1 AIP. Moreover, data on other emerging biomarkers for type 1 and 2 AIP have been reported. EXPERT OPINION: The diagnosis of AIP is challenging in clinical practice, especially for focal forms without multiorgan involvement, where distinction from pancreatic cancer can be difficult. Despite the strong association with type 1 AIP, serum IgG4 should only be measured when the suspicion for the disease is high, considering its limited sensitivity. New biomarkers with high diagnostic yield for both type 1 and type 2 AIP are needed.
Assuntos
Doenças Autoimunes , Pancreatite Autoimune , Pancreatite , Humanos , Pancreatite Autoimune/diagnóstico , Pancreatite/diagnóstico , Pancreatite/terapia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Imunoglobulina G , Biomarcadores , Diagnóstico DiferencialRESUMO
BACKGROUND/OBJECTIVES: Autoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. In our study, we aimed to investigate HLA alleles in a large European cohort of autoimmune pancreatitis (AIP) patients. METHODS: Hundred patients with AIP, diagnosed and classified according to the International Consensus Diagnostic Criteria (ICDC), were prospectively enrolled in the study. Forty-four patients with chronic pancreatitis (CP) and 254 healthy subjects served as control groups. DNA was isolated from blood samples and two-digit HLA typing was performed with sequence-specific primer (SSP-) PCR. HLA allele association strength to AIP was calculated as odds ratio. RESULTS: We uncovered a strong enrichment of HLA-DQB1 homozygosity in type 1 and type 2 AIP patients. Moreover, a significantly increased incidence of the HLA-DRB1∗16 and HLA-DQB1∗05 alleles and a concomitant lack of the HLA-DRB1∗13 allele was detected in AIP type 1 and type 2 patients. In contrast, the HLA-DQB1∗02 allele was underrepresented in the 'not otherwise specified' (NOS) AIP subtype. We detected no significant difference in the HLA-DRB3, HLA-DRB4 and HLA-DRB5 allele frequency in our cohort. CONCLUSIONS: Although AIP type 1 and type 2 are characterized by distinct histopathological characteristics, both subtypes are associated with the same HLA alleles, indicating that the disease might rely on similar immunogenic mechanisms. However, AIP NOS represented another subclass of AIP.
Assuntos
Pancreatite Autoimune , Alelos , Frequência do Gene , Predisposição Genética para Doença , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB4/genética , Haplótipos , HumanosRESUMO
BACKGROUND: The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period. METHODS: To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period. RESULTS: Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P < 0.001 and 37 versus 349, P < 0.001, respectively) and 2018 (117 versus 389, P < 0.001 and 37 versus 282, P < 0.001, respectively). Eighty-two among 98 rare disease experts completed the questionnaire. Diagnostic success (95%), access to diagnosis (80%) and follow-up (72%), lack of Personal Protective Equipment (60%), lack of Covid-19 guidelines (50%) and the need for home therapy (78%) were the most important issues raised during Covid-19 outbreak. CONCLUSIONS: This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.
Assuntos
COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste para COVID-19 , Atenção à Saúde , Surtos de Doenças , Humanos , Pandemias , Doenças Raras/diagnóstico , Doenças Raras/epidemiologia , Sistema de Registros , Estudos RetrospectivosRESUMO
Background & Aims: Type 1 autoimmune pancreatitis (AIP) is an IgG4-related disease whose diagnosis is challenging. The aim of this study was to investigate the diagnostic value of circulating total and IgG4+ plasmablasts in differentiating this condition from the other main pancreatic diseases. Methods: Patients with type 1 AIP (n = 19) were prospectively enrolled in a tertiary center together with patients suffering from type 2 or not otherwise specified (NOS) AIP (n = 10), pancreatic adenocarcinoma (n = 17), chronic pancreatitis (n = 20), and intraductal papillary mucinous neoplasia or chronic asymptomatic pancreatic hyperenzymemia (n = 21) as control groups. Flow cytometry was used to measure the total plasmablast and IgG4+ plasmablast number by gating peripheral blood CD45+CD19+CD38hiCD20-CD24-CD27+ and CD45+CD19+CD38hiCD20-CD24-CD27+IgG4+ cells, respectively. In patients with AIP, these cell populations were also evaluated after 1 month of therapy, after 2-4 months from the end of treatment, and after 1 year from the enrollment. The study was approved by the local ethics committee (protocol number: 59133, 30/11/2017). Results: Total plasmablast quantification was capable of discriminating type 1 AIP from all the other pancreatic disorders with a sensitivity of 47% and a specificity of 81%, according to a cutoff of 4500 cells/mL (AUC = 0.738), whereas IgG4+ plasmablast count distinguished type 1 AIP from all the other pancreatic disorders with a sensitivity of 80% and a specificity of 97% when applying a cutoff of 210 IgG4+ cells/mL (AUC = 0.879). The basal IgG4+ plasmablast number was significantly higher (P = .0001) in type 1 AIP than in type 2/NOS AIP, decreased after steroid therapy, and increased at disease relapse. Conclusion: IgG4+ plasmablast count represents a potentially useful biomarker to differentiate type 1 from type 2/NOS AIP and from other pancreatic diseases.
RESUMO
OBJECTIVES: Type 1 autoimmune pancreatitis (AIP) is a manifestation of immunoglobulin G4-related diseases (IgG4-RD). To evaluate the activity of the disease, the IgG4-RD responder index (RI) has been created. This study evaluated the IgG4-RD RI as prognostic factor of 1-year disease relapse. METHODS: Patients diagnosed with type 1 AIP between January 2012 and December 2016, with available magnetic resonance imaging and IgG4 dosage, were enrolled. Immunoglobulin G4-RD RI was calculated at baseline (time 0), and at 3 to 6 and 12 to 18 months after the end of steroid therapy (time 1 and time 2, respectively). RESULTS: Thirty-three patients were included in the study. Immunoglobulin G4-RD RI was 8.9 (standard deviation [SD], 3.8) at time 0, 2.4 (SD, 3.1) at time 1 (P < 0.0001 vs time 0), and 4.2 (SD, 3.9) at time 2 (P = 0.02 vs time 1). Fourteen patients who relapsed within 1 year showed a higher mean value of IgG4-RD RI at time 0 (10.9; SD, 4.3) versus 19 who did not (7.4; SD, 2.6; P = 0.012). This difference was observed also at time 2 (6.8 vs 2.1; P = 0.002). CONCLUSIONS: Immunoglobulin G4-RD RI correlates with type 1 AIP disease activity, and it predicts disease relapse within 1 year.
Assuntos
Pancreatite Autoimune/diagnóstico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Pâncreas/patologia , Índice de Gravidade de Doença , Adulto , Idoso , Pancreatite Autoimune/tratamento farmacológico , Pancreatite Autoimune/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/imunologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Esteroides/uso terapêutico , Fatores de TempoRESUMO
OBJECTIVE: Rituximab (RTX) has been proposed for the induction of remission and maintenance therapy in relapsing type 1 autoimmune pancreatitis (AIP). The aim of the study was to describe the use of RTX as maintenance therapy for patients with type 1 AIP. METHODS: Patients with type 1 AIP based on the International Consensus Diagnostic Criteria and treated with RTX were selected from our database. Two doses of RTX (1000 mg each) were administered 15 days apart and repeated after 6 months. RESULTS: Eighteen patients were treated with RTX as maintenance therapy. Of these, the involvement of other organs was observed in 16 patients (89%). Eight of the 18 patients (44%) relapsed during follow-up. Median time to relapse after the last infusion was 30 months (range, 12-35 months). No disease relapse was observed in the first year after the last infusion. Probability of disease relapse was 80% between 1 and 3 years from initial treatment. No adverse effects were observed. CONCLUSIONS: Rituximab seems be safe and effective for maintenance therapy of type 1 AIP during the first year after completing RTX infusion. However, the probability of disease relapse is high within 1 and 3 years from the last infusion.
Assuntos
Poliendocrinopatias Autoimunes/tratamento farmacológico , Rituximab/farmacologia , Adulto , Feminino , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Poliendocrinopatias Autoimunes/epidemiologia , Indução de Remissão/métodos , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Painless chronic pancreatitis (CP) is a rare form of the disease. AIM: To evaluate the prevalence and the characteristics of this overlooked form of pancreatitis. METHODS: Patients with a diagnosis of CP and absence of pain were selected, excluding patients suffering from autoimmune pancreatitis. Clinical data, imaging features, and exocrine and endocrine function were therefore analyzed. RESULTS: Among 781 patients observed between 2010 and 2016, 74 patients with painless CP (9.5%) were selected. Mean age at diagnosis was 60.8 (SD 10.8) years. 38(51%) individuals did not report any symptom, 36(49%) were affected by symptoms other than pain. Pancreatic calcifications were diagnosed in 70 patients (95%), main pancreatic duct dilation in 55(74%), and pancreatic atrophy in 39(53%).Thirty-six patients (55%) had severe exocrine pancreatic insufficiency(EPI). Diabetes was observed in 34 out of 72 patients (47%). During a mean follow-up of 2.9 (SD 2.8) years, only a mild pancreatitis was diagnosed in a 71-year old female. No patient underwent endoscopic treatment or surgery, developed pancreatic cancer or died. CONCLUSIONS: In a tertiary center painless CP is observed in 10% of cases, and it is frequently associated with EPI. The probability of onset of pain is very low in a short-term follow-up.
Assuntos
Calcinose/etiologia , Insuficiência Pancreática Exócrina/etiologia , Pancreatite Crônica/complicações , Pancreatite Crônica/fisiopatologia , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcinose/diagnóstico por imagem , Calcinose/epidemiologia , Colangiopancreatografia Retrógrada Endoscópica , Diabetes Mellitus/epidemiologia , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/epidemiologia , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Itália , Masculino , Pessoa de Meia-Idade , Medição da Dor , Índice de Gravidade de Doença , Centros de Atenção Terciária , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Hypertriglyceridemic acute pancreatitis is an emerging issue in gastroenterology, frequently underdiagnosed in clinical practice. Despite the rarity of the disease, hypertriglyceridemia should be considered as a leading cause of acute pancreatitis, especially in defined subsets of patients. Primary and secondary forms of hypertriglyceridemia need to be considered and excluded during the diagnostic work-up of all patients with acute pancreatitis. An accurate diagnosis is crucial to establish an appropriate treatment and to reduce the risk of recurrences. The aim of the present article is to briefly review epidemiology, etiology, diagnosis and therapy of hypertriglyceridemic acute pancreatitis, based on a clinical and practical point of view.
Assuntos
Hipertrigliceridemia/complicações , Pancreatite/etiologia , Doença Aguda , Humanos , Hipertrigliceridemia/etiologia , Pancreatite/diagnóstico , Pancreatite/epidemiologia , Pancreatite/terapia , Prognóstico , RecidivaRESUMO
INTRODUCTION: A prospective survey to evaluate the diagnostic workup of cystic pancreatic neoplasms (CPNs) according to the Italian guidelines. METHODS: An online data sheet was built. RESULTS: Fifteen of the 1385 patients (1.1%) had non cystic neoplastic lesions. Forty percent (518/1295) had at least one 1st degree relative affected by a solid tumor of the digestive and extra-digestive organs. Symptoms/signs associated with the cystic lesion were present in 24.5% of the patients. The cysts were localized in the head of the pancreas in 38.5% of patients. Of the 2370 examinations (1.7 examinations per patient) which were carried out for the diagnosis, magnetic resonance imaging was performed as a single test in 48.4% of patients and in combination with endoscopic ultrasound in 27% of the cases. Of the 1370 patients having CPNs, 89.9% had an intraductal papillary mucinous neoplasm (IPMN) (70.1% a branch duct IPMN, 6.2% a mixed type IPMN and 4.6% a main duct IPMN), 12.7% had a serous cystadenoma, 2.8% a mucinous cystadenoma, 1.5% a non-functioning cystic neuroendocrine neoplasm, 0.7% a solid-pseudopapillary cystic neoplasm, 0.3% a cystic adenocarcinoma, and 1.2% an undetermined cystic neoplasm. Seventy-eight (5.7%) patients were operated upon after the initial work-up. CONCLUSIONS: This prospective study offers a reliable real-life picture of the diagnostic work-up CPN.
Assuntos
Cistadenoma Mucinoso/epidemiologia , Cistadenoma Seroso/epidemiologia , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/epidemiologia , Adenocarcinoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Endossonografia , Feminino , Humanos , Itália/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/epidemiologia , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Scores predicting postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) mainly use intraoperative predictors. The aim of this study is to investigate the role of pancreatic exocrine function expressed by fecal elastase (FE-1) as preoperative predictor of POPF. METHODS: Patients scheduled for PD at the Department of General and Pancreatic Surgery, University of Verona Hospital, from April 2017 to July 2018 were prospectively enrolled. FE-1 was measured in a preoperative stool sample through an ELISA test. RESULTS: The study population consisted of 105 patients. The POPF rate was 17.1%. Patients developing POPF showed high values of FE-1 (454 vs 155 mcg/g; p < 0.01), and FE-1 was an independent predictor of POPF (OR 1.008, CI 95% 1.003-1.014; p < 0.01), even considering only patients with a "soft" texture. A cut-off value of 260 mcg/g presented 100% sensitivity and 64.3% specificity (AUC 0.83) in predicting POPF. Approximately 30% of patients with a "soft" pancreatic texture presented with FE-1 < 260 mcg/g and did not develop POPF. CONCLUSION: FE-1 is a promising tool to preoperatively assess the risk of POPF after PD. Further studies with larger populations are needed to potentially incorporate FE-1 into risk scores for PD with better stratification.
Assuntos
Fezes/química , Elastase Pancreática/metabolismo , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Projetos Piloto , Complicações Pós-Operatórias/metabolismo , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Fatores de RiscoRESUMO
OBJECTIVES: Chronic asymptomatic pancreatic hyperenzymemia (CAPH) was described as a benign disease. However, we already described clinically relevant findings requiring surgery or follow-up in half of the subjects. The aim of this study was to evaluate the long-term outcome of CAPH in terms of symptoms and evolution toward chronic pancreatitis. METHODS: Subjects previously enrolled in the first phase of the study (from 2005 to 2010) were reinvestigated from December 2013 to January 2017 with a phone call ± magnetic resonance cholangiopancreatography with secretin stimulation. RESULTS: A total of 133 subjects were eligible for the follow-up study (75 males, 58 females; age, 48.4 [standard deviation {SD}, 14] years); 24 (18%) of them dropped out. During a mean follow-up of 9.3 (SD, 5.2) years after the first diagnosis of CAPH, no episode of acute pancreatitis or abdominal pain was reported. Sixty-three subjects (58%) of 109 underwent magnetic resonance cholangiopancreatography with secretin stimulation with a mean follow-up of 5.7 [SD, 3.1] years (range, 1-11 years). Secretin stimulation-MRCP resulted unchanged in 54 (90%) of 60 subjects, worsened in 3 (5%) and improved in 3 (5%). Two subjects died from causes unrelated to pancreatic disease. CONCLUSIONS: Excluding subjects with a pancreatic disease at index magnetic resonance imaging, CAPH is a benign condition.
Assuntos
Amilases/sangue , Colangiopancreatografia por Ressonância Magnética/métodos , Lipase/sangue , Pâncreas/diagnóstico por imagem , Pancreatopatias/diagnóstico por imagem , Pancreatite Crônica/diagnóstico por imagem , Adulto , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/enzimologia , Pâncreas/patologia , Pancreatopatias/sangue , Pancreatopatias/enzimologia , Pancreatite Crônica/sangue , Pancreatite Crônica/enzimologia , Fatores de TempoRESUMO
Ablation treatments have been increasingly applied as an alternative treatment for unresectable locally advanced pancreatic cancer (LAPC). The goal of LAPC therapy is surgical resection with negative margins (R0); however, that can be achieved only in a minority of patients and only following neoadjuvant treatment. Ablation might be useful for those patients with unresectable LAPC that do not progress towards metastatic stage and do not experience a true downstaging. Indeed, some LAPC that tend to grow locally, might be the subgroup of tumors that could benefit from ablation. Experience is necessary to select patients and the technique to adopt, since serious or fatal complications can occur. This review aims to discuss the role of ablation treatments in LAPC, with a unique focus on radiofrequency ablation and irreversible electroporation.
Assuntos
Neoplasias Pancreáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Eletroquimioterapia/métodos , Eletroporação/métodos , Humanos , Terapia a Laser/métodos , Micro-Ondas/uso terapêutico , Neoplasias Pancreáticas/patologia , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/métodos , Terapia por Radiofrequência/métodosRESUMO
Autoimmune pancreatitis (AIP) is a rare disorder whose association with coeliac disease (CD) has never been investigated, although CD patients display a high prevalence of both endocrine and exocrine pancreatic affections. Therefore, we sought to evaluate the frequency of CD in patients with AIP and in further medical pancreatic disorders. The screening for CD was carried out through the detection of tissue transglutaminase (tTG) autoantibodies in sera of patients retrospectively enrolled and divided in four groups: AIP, chronic pancreatitis, chronic asymptomatic pancreatic hyperenzymemia (CAPH), and control subjects with functional dyspepsia. The search for anti-endomysium autoantibodies was performed in those cases with borderline or positive anti-tTG values. Duodenal biopsy was offered to all cases showing positive results. One patient out of 72 (1.4%) with AIP had already been diagnosed with CD and was following a gluten-free diet, while one case out of 71 (1.4%) with chronic pancreatitis and one out of 92 (1.1%) control subjects were diagnosed with de novo CD. No cases of CD were detected in the CAPH group. By contrast, a high prevalence of cases with ulcerative colitis was found in the AIP group (13.8%). Despite a mutual association between CD and several autoimmune disorders, our data do not support the serologic screening for CD in AIP. Further studies will clarify the usefulness of CD serologic screening in other pancreatic disorders.