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1.
Clin Gastroenterol Hepatol ; 22(5): 994-1004.e10, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38184096

RESUMEN

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.


Asunto(s)
Pancreatitis Autoinmune , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Pancreatitis Autoinmune/tratamiento farmacológico , Pancreatitis Autoinmune/diagnóstico , Europa (Continente) , Anciano , Resultado del Tratamiento , Adulto , Esteroides/uso terapéutico , Esteroides/administración & dosificación , Anciano de 80 o más Años
2.
Eur Radiol ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862730

RESUMEN

OBJECTIVES: Imaging features of pancreatic acinar cystic transformation (ACT) have been published. We aimed to describe the clinical and radiological characteristics of patients with a presumed pancreatic ACT diagnosis, reappraising the value of these published imaging criteria. MATERIALS AND METHODS: Single-center retrospective study (2003-2021) of consecutive patients with a presumed diagnosis of ACT as suggested by the local expert multidisciplinary case review board. Patients without available imaging (CT or MRI) for review were excluded. Patients were classified into "certain" ACT (if ≥ 2 imaging criteria and no differential diagnosis) or "uncertain" ACT (if ≥ 1 imaging criteria and suggested differential diagnoses). RESULTS: Sixty-four patients (35 males, [55%]) were included. ACT was considered "certain" for 34 patients (53%) and "uncertain" for 30 patients (47%). The number of ACT criteria did not differ between groups, with 91.2% of patients with ≥ 3 ACT imaging criteria in the "certain" group vs 93.3% in the "uncertain" group (p = 0.88). In the "uncertain" group, the main suggested differentials were branch-duct intraductal papillary mucinous neoplasm (18/30 patients, 60%), calcifying chronic pancreatitis (8/30 patients, 27%), both (three patients, 10%) and serous cystadenoma (one patient, 3%). Calcifications were significantly more frequent in the "uncertain" group (89% vs 63% in the "certain" group, p = 0.02). CONCLUSION: Published ACT imaging criteria are frequently associated with features suggesting differential diagnoses. They appear insufficient to reach a final diagnosis in a subset of patients. CLINICAL RELEVANCE STATEMENT: ACT displays a heterogeneous morphological imaging presentation challenging the non-invasive diagnostic work-up. Physicians' and radiologists' awareness of this entity is important to better understand its natural history and improve non-invasive diagnostic criteria. KEY POINTS: The criteria to help diagnose ACT are frequently associated with features suggestive of differentials. The main alternatives suggested when ACT diagnosis was "uncertain" were branch-duct intraductal papillary mucinous neoplasm and calcifying chronic pancreatitis. Published ACT diagnostic imaging criteria can be insufficient for a definite non-invasive diagnosis.

3.
Surg Endosc ; 38(2): 769-779, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38052888

RESUMEN

BACKGROUND: Three randomized controlled trials have reported improved functional recovery after Laparoscopic pancreatoduodenectomy (LPD), as compared to open pancreatoduodenectomy (OPD). Long-term results regarding quality of life (QoL) are lacking. The aim of this study was to compare long-term QoL of LPD versus OPD. METHODS AND PATIENTS: A monocentric retrospective cross-sectional study was performed among patients < 75 years old who underwent LPD or OPD for a benign or premalignant pathology in a high-volume center (2011-2021). An electronic three-part questionnaire was sent to eligible patients, including two diseases specific QoL questionnaires (the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire for cancer (QLQ-C30) and a pancreatic cancer module (PAN26) and a body image questionnaire. Patient demographics and postoperative data were collected and compared between LPD and OPD. RESULTS: Among 948 patients who underwent PD (137 LPD, 811 OPD), 170 were eligible and 111 responded (58 LPD and 53 OPD). LPD versus OPD showed no difference in mean age (51 vs. 55 years, p = 0.199) and female gender (40% vs. 45%, p = 0.631), but LPD showed lower BMI (24 vs 26; p = 0.028) and higher preoperative pancreatitis (29% vs 13%; p = 0.041). The postoperative outcome showed similar Clavien-Dindo ≥ III morbidity (19% vs. 23%; p = 0.343) and length of stay (24 vs. 21 days, p = 0.963). After a similar median follow-up (3 vs. 3 years; p = 0.122), LPD vs OPD patients reported higher QoL (QLQ-C30: 49.6 vs 56.3; p = 0.07), better pancreas specific health status score (PAN20: 50.5 vs 55.5; p = 0.002), physical functioning (p = 0.002), and activities limitations (p = 0.02). Scar scores were better after LPD regarding esthetics (p = 0.001), satisfaction (p = 0.04), chronic pain at rest (p = 0.036), moving (p = 0.011) or in daily activities (p = 0.02). There was no difference in digestive symptoms (p = 0.995). CONCLUSION: This monocentric study found improved long-term QoL in patients undergoing LPD, as compared to OPD, for benign and premalignant diseases. These results could be considered when choosing the surgical approach in these patients.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Humanos , Femenino , Anciano , Pancreaticoduodenectomía/métodos , Calidad de Vida , Estudios Retrospectivos , Estudios Transversales , Tiempo de Internación , Neoplasias Pancreáticas/cirugía , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía
4.
Surg Endosc ; 38(4): 2169-2179, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38448620

RESUMEN

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPNP) are rare tumors predominantly in young women. We report the largest single-center cohort study comparing resection of SPNP by laparoscopic approach (LA) and the open approach (OA). METHOD: Between 2001 and 2021, 102 patients (84% women, median age: 30) underwent pancreatectomy for SPNP and were retrospectively studied. Demographic, perioperative, pathological, early and the long-term results were evaluated between patients operated by LA and those by OA. RESULTS: Population included 40 LA and 62 OA. There were no significant differences in demographics data between the groups. A preoperative biopsy by endoscopic ultrasound was performed in 45 patients (44%) with no difference between the groups. Pancreatoduodenectomy (PD) was less frequently performed by LA (25 vs 53%, p = 0.004) and distal pancreatectomy (DP) was more frequently performed by LA (40 vs 16%, p = 0.003). In the subgroup analysis by surgical procedure, LA-PD was associated with one mortality, less median blood loss (180 vs 200 ml, p = 0.034) and fewer harvested lymph nodes (11 vs 15, p = 0.02). LA-DP was associated with smaller median tumor size on imaging (40 vs 80mm, p = 0.048), shorter surgery (135 vs 190 min, p = 0.028), and fewer complications according to the median comprehensive complication index score (0 vs 8.7, p = 0.048). LA-Central pancreatectomy was associated with shorter surgery (160 vs 240, p = 0.037), less median blood loss (60 vs 200, p = 0.043), and less harvested lymph nodes (5 vs 2, p = 0.025). After a median follow-up of 60 months, two recurrences (2%) were observed and were unrelated to the approach. CONCLUSIONS: The LA for SPNP appears to be safe, should be applied cautiously in case of PD for large lesion, and was not associated with recurrence.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Humanos , Femenino , Adulto , Masculino , Pancreatectomía/métodos , Estudios de Cohortes , Estudios Retrospectivos , Neoplasias Pancreáticas/patología , Laparoscopía/métodos , Resultado del Tratamiento , Complicaciones Posoperatorias/cirugía
5.
Surg Endosc ; 37(5): 3684-3690, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36639578

RESUMEN

INTRODUCTION: A dilatation of the main pancreatic duct (MPD) is mainly due to obstructive causes (pancreatic tumor, chronic pancreatitis) or intraductal papillary mucinous neoplasm (IPMN). This study aims to assess the risk of pre-malignancy or malignancy in case of MPD dilatation with no visible mass nor obstructive calcification on computed tomography scan (CT-scan) in a population operated for it. PATIENTS AND METHODS: All patients operated on from November 2015 to December 2019 in our center for a significant dilatation of the MPD without visible obstructive cause on CT-scan were included. Preoperative work-up included at least CT-scan, magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). Primary endpoint was the final pathological diagnosis. Secondary endpoints were predictive factors of malignancy. RESULTS: 101 patients were included, mean age 68 years-old. Final pathological data were pancreatic adenocarcinoma (n = 2), IPMN with high-grade dysplasia (n = 37), high-grade Pancreatic Intraepithelial Neoplasia (PanIN) (n = 2) (total of pre-malignant or malignant lesions: n = 41), neuroendocrine tumor (n = 6), IPMN with low-grade dysplasia (n = 45), low-grade PanIN (n = 5), chronic pancreatitis (n = 3), and benign stenosis (n = 1). On preoperative explorations, the median diameter of MPD was 7 mm [3-35]. MRI and/or EUS showed intraductal material, nodule, or cyst in 22, 32, and 52 patients, respectively; 22 patients without nodule visible on MRI or EUS had still a pre-malignant or malignant lesion. In multivariate analysis, predictive factors for pre-malignancy or malignancy were symptoms before surgery (p = 0.01), MPD dilatation without downstream stenosis (p = 0.046), and the presence of nodule (p = 0.009). CONCLUSION: A dilatation of the MPD without detectable mass or obstructive calcification on CT-scan was associated with a pre-malignant or malignant lesion in 41 patients. Symptoms before surgery, MPD dilatation without duct narrowing, and the presence of nodules on MRI/EUS were associated with the risk of  pre-malignancy or malignancy.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Pancreatitis Crónica , Humanos , Anciano , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/etiología , Carcinoma Ductal Pancreático/cirugía , Adenocarcinoma/patología , Constricción Patológica , Dilatación , Estudios Retrospectivos , Conductos Pancreáticos/diagnóstico por imagen , Factores de Riesgo , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/diagnóstico por imagen
6.
Am J Transplant ; 22(12): 3069-3077, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35704274

RESUMEN

Laparoscopic approach was rarely described in recipients for liver transplantation (LT). We report the feasibility and safety of laparoscopic-assisted LT (LA-LT) in patients with unresectable liver metastases of neuroendocrine tumors. Total hepatectomy was performed laparoscopically with graft implantation through an upper midline incision. Liver grafts were retrieved from deceased donors. From July 2019 to July 2021, six patients (4 women, 2 men) underwent LA-LT. Median age and BMI were 46 (29-54) and 24 (19-35) kg/m2 , respectively. Implanted grafts were reduced (n = 3), full (n = 2), and a right split liver (n = 1). Median surgical time was 405 min (390-450) and median blood loss was 425 ml (250-600). Median cold and warm ischemia times were 438 min (360-575) and 35 min (30-40), respectively. Median anhepatic phase was 51 min (40-67) and midline incision was 14 cm (13-20) long. On postoperative day 5, median prothrombin index and serum bilirubin levels were 95% (70-117) and 11 (10-37) µmol/L, respectively. No Clavien-Dindo > III complications were encountered. Median hospital stay was 12 days (10-14). After a median follow-up of 8 (8-32) months, all patients were alive without tumor recurrence or adverse event. This preliminary series suggests that in selected patients, LA-LT is a safe and effective option.


Asunto(s)
Laparoscopía , Trasplante de Hígado , Masculino , Humanos , Femenino , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/etiología , Hepatectomía/efectos adversos
7.
Eur Radiol ; 32(2): 1297-1307, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34374801

RESUMEN

OBJECTIVES: To evaluate the value of MRI in differentiating benign (b-MCN) and malignant (m-MCN) MCN. European guidelines suggest that certain mucinous cystic neoplasms (MCN) of the pancreas can be conservatively managed. METHODS: A retrospective single-center study of consecutive patients with resected MCN. MRIs were independently reviewed by two readers blinded to the pathological results. The authors compared b-MCN (i.e., mucinous-cystadenoma comprising high-grade dysplasia (HGD)) and m-MCN (i.e., cystadenocarcinoma). RESULTS: Sixty-three patients (62 women [98%]) with 63 MCN (6 m-MCN, 2 HGD) were included. m-MCN tumors had a tendency to be larger than b-MCN (median 86 [25-103] vs. 45 [17-130] mm, p = .055). The combination of signal heterogeneity on T2-weighted imaging, wall thickness ≥ 5 mm, the presence of mural nodules ≥ 9 mm, and enhancing septa had an area under the ROC curve of 0.97 (95% CI 0.91-1.00) for the diagnosis of m-MCN. A total of 24 (37%), 20 (32%), 10 (16%), 5 (8%), and 4 (6%) out of 63 MCNs showed 0, 1, 2, 3, and 4 of these features, respectively. The corresponding rate of m-MCN was 0%, 0%, 10%, 20%, and 100%, respectively, with a good-to-excellent inter-reader agreement. Patterns with a high NPV for m-MCN included an absence of enhancing septa or walls (NPV 97% and 100%, respectively), wall thickness < 3 mm (NPV 100%), and no mural nodules (NPV 100%). CONCLUSIONS: A combination of 4 imaging features suggests malignant MCN on MRI. On the other hand, visualization of a thin non-enhancing wall with no mural nodules suggests benign MCN. KEY POINTS: • A heterogenous signal on T2-weighted MRI, a ≥ 5-mm-thick wall, mural nodules ≥ 9 mm, and/or enhancing septa suggest malignant MCNs. • A thin non-enhancing wall with no mural nodules suggests benign MCNs. • MRI should be performed in the pre-therapeutic evaluation of MCN to help determine the therapeutic strategy in these patients.


Asunto(s)
Cistoadenoma Mucinoso , Neoplasias Pancreáticas , Cistoadenoma Mucinoso/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Páncreas , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios Retrospectivos
8.
Pancreatology ; 21(1): 282-290, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33168404

RESUMEN

BACKGROUND/OBJECTIVES: Disconnectedpancreatic duct syndrome (DPDS), a severe complication of acute necrotizing pancreatitis (ANP), may require surgery, usually by distal splenopancreatectomy, thus increasing the risk of diabetes. We describe a new technique reconnecting the distal pancreas to the digestive tract. METHODS: This technique was proposed after failure of non-surgical treatment and at least 3 months after the onset of ANP in non-diabetic or non-insulin dependent diabetic patients with a distal pancreas of at least 5 cm. The ruptured zone was identified and the distal side was anastomosed to the stomach or the jejunum. RESULTS: From 2013 to June 2019, 36 patients (median age = 49 years) with DPDS underwent a "French reconnection" procedure, indicated for chronic pain/recurrent pancreatitis (n = 35; 97%), persistent pancreatic fistula (n = 33; 91%), or digestive compression/fistulisation (n = 9; 25%). Median preoperative weight loss was 10 kg (4-27), the median number of hospitalisations per patient was 5(1-8) and 24(67%) patients had received endoscopic/percutaneous treatment. Surgery was performed in median 279(90-2000) days after ANP, laparoscopically in 9(25%) patients. The remnant pancreas (median length = 70 mm; range = 50-130) was anastomosed to the stomach (n = 30) or the jejunum (n = 6). There were 13(36%) postoperative grade B/C pancreatic fistulas and 3(10%) bleedings including one death (mortality = 3%). The median hospital stay was 18 (7-121) days. After a median follow-up of 24 (4-53) months, all pancreatic fistulas had healed and the clinical success rate was 91%. Median BMI increased from 22 to 25 kg/m2. In patients with normal pancreatic function, postoperative de novo endocrine and severe exocrine insufficiencies were observed in 4/27 (15%) and 7/22 (32%), respectively. CONCLUSIONS: The "French reconnection" procedure, as an alternative to distal splenopancreatectomy for the treatment of DPDS, provides good control of symptoms and decreases the risk of pancreatic insufficiency.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Enfermedades Pancreáticas/cirugía , Conductos Pancreáticos/cirugía , Pancreatitis Aguda Necrotizante/cirugía , Adulto , Anciano , Anastomosis Quirúrgica , Índice de Masa Corporal , Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Endoscopía/métodos , Femenino , Estudios de Seguimiento , Humanos , Yeyuno/cirugía , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rotura/cirugía , Estómago/cirugía , Resultado del Tratamiento , Pérdida de Peso
9.
Pancreatology ; 2021 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-34090806

RESUMEN

BACKGROUND: The efficacy and safety of gemcitabine and nab-paclitaxel (GnP) among elderly patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We aimed to evaluate the safety and efficacy of GnP in this setting. PATIENTS AND METHODS: We retrospectively included all consecutive patients aged ≥65 years with histologically proven PDAC who received at least one cycle of GnP (January 2014 to May 2018) in four academic centers. The primary endpoints were toxicity and overall survival (OS). Secondary endpoints were progression-free survival (PFS) and objective response rate. We compared patients aged ≥ or <75 years. RESULTS: The study included 127 patients; among them 42 (33.1%) were aged ≥ 75 years. Fifty-seven and seventy patients received GnP as the first-line and the second-line treatment or beyond, respectively. Sixty-seven patients had at least one grade 3/4 adverse event, the most frequent being neutropenia and peripheral neuropathy. No deaths were related to toxicity. OS (median, 8.0 months; 95% confidence interval (CI), 5.8-10.2) and PFS (median, 5.5 months; 95% CI, 4.8-6.2) were similar for patients aged <75 or ≥75 years in the whole cohort and among patients receiving GnP as the first-line treatment. Cephalic PDAC, liver metastases, hypoalbuminemia, and GnP received beyond the first-line were associated with a significantly shorter OS on the multivariate analysis. CONCLUSION: GnP is well tolerated and effective in elderly patients with advanced PDAC, even patients aged ≥75 years. The data from daily clinical practice are consistent with the results reported with first-line treatment and highlight the relevance of GnP administration in elderly patients.

10.
Pancreatology ; 20(7): 1354-1367, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32948427

RESUMEN

Since the description of the SPINK1 gene encoding the serine protease inhibitor Kazal type 1 and the CTRC gene encoding the Chymotrypsin C as being involved in chronic pancreatitis, more than 56 SPINK1 and 87 CTRC variants have been reported. Assessing the clinical relevance of SPINK1 and CTRC variants is often complicated in the absence of functional evidence and interpretation of rare variants is not very easy in clinical practice. The aim of this study was to review the different variants identified in these two genes and to classify them according to their degree of damaging effect. This classification was based on the results of in vitro experiments, in silico analysis using different prediction tools, and on population data, in comparing the allelic frequency of each variant in patients with pancreatitis and in unaffected control individuals. This review should help geneticists and clinicians in charge of patient's care and genetic counseling to interpret the results of genetic studies.


Asunto(s)
Quimotripsina/genética , Pancreatitis/genética , Inhibidor de Tripsina Pancreática de Kazal/genética , Simulación por Computador , Frecuencia de los Genes , Variación Genética , Humanos , Valor Predictivo de las Pruebas
11.
Pancreatology ; 20(5): 822-827, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32631791

RESUMEN

BACKGROUND: Chronic pancreatitis (CP) is a complex inflammatory disease with variable presentations and outcomes. This statement is part of the international consensus guidelines on CP, specifically on the diagnostic role of endoscopic ultrasound (EUS). METHODS: An international working group with experts on the role of diagnostic EUS in the management of CP from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated two key statements generated from evidence on two questions deemed to be the most clinically relevant. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus was obtained for both of the following statements [1]. The ideal threshold number of EUS criteria necessary to diagnose CP has not been firmly established, but the presence of 5 or more and 2 or less strongly suggests or refutes the diagnosis, respectively. The Rosemont scoring system standardizes the reporting of EUS signs indicative of chronic pancreatitis, but further studies are needed to demonstrate an overall improvement of its diagnostic accuracy over conventional scoring [2]. Specificity, inter- and intra-observer variability and pre-test probability limit the reliability and utility of EUS to help diagnose CP especially early stages of the disease. CONCLUSIONS: The presence of 5 or more and 2 or less EUS criteria strongly suggests or refutes the diagnosis of CP, respectively. Intra-observer variability still limits the role of EUS in diagnosing CP especially early stage disease.


Asunto(s)
Pancreatitis Crónica/diagnóstico por imagen , Pancreatitis Crónica/terapia , Consenso , Endosonografía , Medicina Basada en la Evidencia , Guías como Asunto , Humanos , Japón , Variaciones Dependientes del Observador , Pancreatitis Crónica/diagnóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estados Unidos
12.
Pancreatology ; 20(5): 910-918, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32624419

RESUMEN

BACKGROUND: Patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer. We present the international consensus guidelines for surveillance of pancreatic cancer in CP. METHODS: The international group evaluated 10 statements generated from evidence on 5 questions relating to pancreatic cancer in CP. The GRADE approach was used to evaluate the level of evidence available per statement. The working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: In the following domains there was strong consensus: (1) the risk of pancreatic cancer in affected individuals with hereditary pancreatitis due to inherited PRSS1 mutations is high enough to justify surveillance; (2) the risk of pancreatic cancer in patients with CP associated with SPINK1 p. N34S is not high enough to justify surveillance; (3) surveillance should be undertaken in pancreatic specialist centers; (4) surveillance should only be introduced after the age of 40 years and stopped when the patient would no longer be suitable for surgical intervention. All patients with CP should be advised to lead a healthy lifestyle aimed at avoiding risk factors for progression of CP and pancreatic cancer. There was only moderate or weak agreement on the best methods of screening and surveillance in other types of environmental, familial and genetic forms of CP. CONCLUSIONS: Patients with inherited PRSS1 mutations should undergo surveillance for pancreatic cancer, but the best methods for cancer detection need further investigation.


Asunto(s)
Neoplasias Pancreáticas , Pancreatitis Crónica , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Consenso , Medicina Basada en la Evidencia , Femenino , Predisposición Genética a la Enfermedad , Guías como Asunto , Humanos , Japón , Estilo de Vida , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Pancreatitis Crónica/epidemiología , Pancreatitis Crónica/genética , Vigilancia de la Población , Factores de Riesgo , Tripsina/genética , Inhibidor de Tripsina Pancreática de Kazal/genética , Estados Unidos
13.
Neuroendocrinology ; 110(11-12): 967-976, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31791037

RESUMEN

INTRODUCTION: The goal of this retrospective study was to investigate the potential link between diabetes mellitus (DM) and the recurrence of pancreatic neuroendocrine tumors (PanNET) following curative intent surgery. METHODS: We included patients who underwent surgical resection of nonmetastatic well-differentiated PanNET. Exacerbation of DM was defined as the postoperative occurrence of DM or worsening of preexisting DM. We explored the variables associated with PanNET recurrence-free survival (RFS). RFS was compared in a subset of patients with and without DM operated on by anatomical resection, after matching for the main prognostic factors. The impact of antidiabetic therapy on RFS was assessed. RESULTS: A total of 268 patients (median age 54.7, 40% men) were included. Most PanNET were sporadic (85%), G1 (61%), pT1/pT2 (79%), and pN0 (76%). Postoperative DM exacerbation occurred in 38 patients (14%), including 27 with new-onset DM. On multivariable analysis, DM exacerbation was independently associated with an increased risk of PanNET recurrence (HR 2.35, 95% CI [1.24-4.47], p = 0.009) after adjustment for age, multiplicity of tumors, grade, pT, and pN stages. Similar results were found when 27 patients with and 48 patients without DM exacerbation, matched for grade, pT stage and pN stage, were compared (HR 3.03, 95% CI [1.05-8.77], p = 0.032). The postoperative use of metformin tended to decrease the risk of recurrence (HR 0.59, 95% CI 0.24-1.47, p = 0.26). CONCLUSION: Patients with postoperative DM exacerbation may have an increased risk of PanNET recurrence. Closer follow-up might be beneficial in these patients. The protective role of metformin should be further explored.


Asunto(s)
Diabetes Mellitus , Recurrencia Local de Neoplasia , Tumores Neuroendocrinos , Pancreatectomía , Neoplasias Pancreáticas , Complicaciones Posoperatorias , Adulto , Anciano , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Diabetes Mellitus/prevención & control , Femenino , Estudios de Seguimiento , Humanos , Hipoglucemiantes/farmacología , Masculino , Metformina/farmacología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Evaluación de Resultado en la Atención de Salud , Pancreatectomía/efectos adversos , Pancreatectomía/estadística & datos numéricos , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/patología , Supervivencia sin Progresión , Estudios Retrospectivos , Brote de los Síntomas
14.
Ann Surg Oncol ; 26(8): 2640-2650, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31025231

RESUMEN

BACKGROUND: The management of intraductal papillary mucinous neoplasms (IPMNs) is mainly based on imaging features and clinical symptoms, and remains challenging. OBJECTIVE: The aim of this study was to assess GNAS, RAS family (KRAS, NRAS and HRAS), BRAF, and PIK3CA mutation status in resected IPMNs and correlate it with clinicopathological characteristics and patient survival. METHODS: Overall, 149 consecutive unselected patients who underwent pancreatectomy for IPMNs were included. After dissection from formalin-fixed and paraffin-embedded tumors, GNAS mutational screening was assessed by allelic discrimination using Taqman® probes and confirmed by SNaPshot analysis. RAS family, BRAF, and PIK3CA mutational screening was assessed by high resolution melt and Sanger sequencing. RESULTS: Gastric- and intestinal-type IPMNs were the most frequent lesions (52% and 41%, respectively). Intestinal-type IPMNs were more frequently associated high-grade dysplasia (49%) and were the only IPMNs associated with colloid-type carcinoma. All pancreatobiliary IPMNs were invasive lesions, located in the main pancreatic duct. GNAS-activating mutations were strongly associated with the intestinal phenotype (p < 10-4), while RAS pathway mutations were not associated with any particular phenotype. Mutations within other members of the epidermal growth factor receptor (EGFR) pathway were very rare (2%). GNAS-mutated IPMNs were rarely invasive (11%) and almost exclusively (83%) of the colloid type. For invasive lesions, multivariate analyses determined that only node negativity was associated with improved cancer-specific survival, but, in univariate analysis, GNAS mutation was associated with prolonged survival. CONCLUSION: In patients selected for surgery, GNAS mutation analysis and tumor phenotype can help to better predict patient prognosis. In the near future, a more precise mutational analysis of IPMNs might help to better tailor their management.


Asunto(s)
Adenocarcinoma Mucinoso/patología , Carcinoma Ductal Pancreático/patología , Cromograninas/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Mutación , Pancreatectomía/mortalidad , Neoplasias Pancreáticas/patología , Proteínas ras/genética , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/cirugía , Anciano , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Fenotipo , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia
15.
Clin Genet ; 96(6): 579-584, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31432501

RESUMEN

The rate of genetic diagnosis of French patients with familial pancreatic ductal adenocarcinoma (PDAC) is not known. We report germline genetic testing data from 133 index cases meeting criteria for familial pancreatic cancer (FPC) as well as 87 'FPC-like' index cases who did not fulfilled strict FPC definition but were evocative for a PDAC predisposition. The overall rate of genetic diagnosis (in BRCA1, BRCA2, CDKN2A, and ATM genes) was 8.3% in FPC patients and 4.6% in FPC-like patients, consistent with the literature in other populations. Genetic variants were also identified in FANCA and BAP1 genes, as well as in the CDKN2A p12 transcript. This pancreas-specific transcript is a known key player in driving pancreatic oncogenesis. This might be the first described case of a PDAC genetic predisposition due to a variant in this specific transcript.


Asunto(s)
Carcinoma/genética , Pruebas Genéticas , Células Germinativas/metabolismo , Neoplasias Pancreáticas/genética , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Adulto Joven
16.
Eur Radiol ; 29(11): 5731-5741, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30972547

RESUMEN

PURPOSE: To evaluate whether pancreatic parenchymal abnormalities on magnetic resonance imaging (MRI) are associated with pancreatic intraepithelial neoplasia (PanIN) on histology. MATERIALS AND METHODS: Retrospective study approved by institutional review board. One hundred patients (48 men, 52 women; mean age, 53.2 ± 16.29 [SD]) underwent MRI before pancreatectomy for pancreatic tumors analyzed by two independent observers blinded to histopathological results for the presence of non-communicating microcysts and pancreatic atrophy (global or focal) beside tumors. MRI findings were compared to histopathological findings of resected specimens. Interobserver agreement was calculated. The association between parenchymal abnormalities and presence of PanIN was assessed by uni- and multivariate analyses. RESULTS: PanIN was present in 65/100 patients (65%). The presence of microcysts on MRI had a sensitivity of 52.3% (34/65 [95%CI, 51.92-52.70%]), a specificity of 77.1% (27/35 [95%CI, 76.70-77.59]), and accuracy of 61% (61/100 95%CI [50.7-70.6]) for the diagnosis of PanIN while global atrophy had a sensitivity of 24.6% (16/6 [95%CI, 24.28-24.95]) and a specificity of 97.1% (34/35 [95%CI, 96.97-97.32%]). In multivariate analysis, the presence of microcysts (OR, 3.37 [95%CI, 1.3-8.76]) (p = 0.0127) and global atrophy (OR, 9.79 [95%CI, 1.21-79.129]) (p = 0.0324) were identified as independent predictors of the presence of PanIN. The combination of these two findings was observed in 10/65 PanIN patients and not in patients without PanIN (p = 0.013 with an OR of infinity [95%CI, 1.3-infinity]) and was not discriminant for PanIN-3 and lower grade (p = 0.22). Interobserver agreement for the presence of microcysts was excellent (kappa = 0.92), and for the presence of global atrophy, it was good (kappa = 0.73). CONCLUSION: The presence of non-communicating microcysts on pre-operative MRI can be a significant predictor of PanIN in patients with pancreatic tumors. KEY POINTS: • In patients with pancreatic tumors who had partial pancreatectomy, MR non-communicating pancreatic microcysts have a 52.3% sensitivity, a 77.1% specificity, and a 61% accuracy for the presence of PanIN with univariate and with an odds ratio of 3.37 with multivariate analyses. • The association of global atrophy and non-communicating microcysts increases the predictive risk of PanIN.


Asunto(s)
Quiste Pancreático/patología , Neoplasias Pancreáticas/patología , Adulto , Anciano , Atrofia/patología , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Detección Precoz del Cáncer , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Páncreas/patología , Pancreatectomía , Quiste Pancreático/cirugía , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios Retrospectivos
17.
Langenbecks Arch Surg ; 404(2): 203-212, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30739172

RESUMEN

INTRODUCTION: Risk factors of postoperative pancreatic fistula (POPF) after laparoscopic distal pancreatectomy (LDP) are not well known and were studied, including the stapler cartridge size and drainage modality. METHODS: Between January 2008 and December 2016, 181 LDP were performed and the pancreas was sectioned by stapler in 130 patients (72%). Patients received white (2.5 mm), blue (3.5 mm), or green (4.1 mm) staplers and the size was not based on any pre or peroperative randomization. As primary analysis of the first 84 patients (28 in each group) showed no effect of stapler size on POPF, we decided to use the white (total = 47) or blue and finally the blue (total = 55) of medium size for standardization. Drainage was obtained by multi-tubular drain (first, 79) and a small suction drain (last, 102). Risk factors of POPF were studied and grades B and C were compared to grade A or no POPF. RESULTS: POPF (n = 66; 36%) was of grade A (n = 25, 14%), grade B (n = 32, 18%), and grade C (n = 9, 5%). The comparison of the three groups of staplers showed that the blue stapler was used more with a small suction drain (85 vs 23%, p < 0.0001), had lower rate of grade B POPF (p = 0.028), and a shorter hospital stay (p = 0.004). On multivariate analysis, only the use of a small suction drain was associated with significant decrease in grades B and C POPF (6 vs 44%, odds ratio 7.385 (1.919-28.418); p = 0.004). CONCLUSION: The occurrence of POPF following LDP is influenced by the type of drainage alone and is significantly decreased with a small suction drain.


Asunto(s)
Drenaje/métodos , Laparoscopía/efectos adversos , Pancreatectomía/efectos adversos , Fístula Pancreática/cirugía , Neoplasias Pancreáticas/cirugía , Engrapadoras Quirúrgicas/efectos adversos , Adulto , Anciano , Análisis de Varianza , Estudios de Cohortes , Supervivencia sin Enfermedad , Drenaje/efectos adversos , Diseño de Equipo , Seguridad de Equipos , Femenino , Humanos , Laparoscopía/métodos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Pancreatectomía/métodos , Fístula Pancreática/etiología , Fístula Pancreática/mortalidad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Grapado Quirúrgico/efectos adversos , Grapado Quirúrgico/métodos , Análisis de Supervivencia , Resultado del Tratamiento
18.
Gut ; 67(10): 1855-1863, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-28754779

RESUMEN

OBJECTIVE: Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus. DESIGN: 1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used. RESULTS: We replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk. CONCLUSION: An inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.


Asunto(s)
Quimotripsina/genética , Pancreatitis Alcohólica , Adulto , Anciano , Europa (Continente)/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis Alcohólica/epidemiología , Pancreatitis Alcohólica/genética , Polimorfismo de Nucleótido Simple
19.
Pancreatology ; 18(1): 114-121, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29146108

RESUMEN

BACKGROUND: Pancreatic incidentalomas (PI) are nowadays common but the benefit-risk balance of surgery remains difficult to determine. METHODS: Monocentric retrospective study of 881 pancreatectomies comparing resected PI with symptomatic lesion. Univariate and multivariate (MV) analyses were done to identify risk factors of malignancy in PI undergoing surgery. RESULTS: Overall, 32% of pancreatectomies were performed for PI. Median size of PI was 30 mm (vs 28 mm; p = 0.15) and 49% were cystic (vs 42%; p = 0.197). Resected PI were mostly located in distal pancreas (61% vs 34%; p < 0.001), less frequently malignant (49% vs 59%; p = 0.004). PNETs were more frequent in PI (50% vs 21%; p < 0.001). Distal pancreatectomy (36% vs 23%; p < 0.001) or parenchyma-sparing surgery (34% vs 13%; p < 0.001) were more frequently performed for PI. Overall mortality (1.1% vs 1.2%) and morbidity (70% vs 68%) were not significantly different between both groups. Severe morbidity was lower for PI (15% vs 22%; p = 0.007). In multivariate analysis, age>55 years (HR 6.14; p < 0.001), size >20 mm (HR:26.7; p < 0.001) and biliary dilatation (HR 29.9; p = 0.027) were independent risk factors of malignancy and, when associated, the likelihood of malignancy was above 90%. CONCLUSIONS: PI represent about 30% of indications for pancreatectomy and when resected after careful selection are malignant in 50% of cases.


Asunto(s)
Pancreatectomía/efectos adversos , Adulto , Anciano , Femenino , Humanos , Hallazgos Incidentales , Masculino , Persona de Mediana Edad , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
20.
Pancreatology ; 18(5): 516-527, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29793839

RESUMEN

BACKGROUND: Chronic pancreatitis (CP) is a progressive inflammatory disorder currently diagnosed by morphologic features. In contrast, an accurate diagnosis of Early CP is not possible using imaging criteria alone. If this were possible and early treatment instituted, the later, irreversible features and complications of CP could possibly be prevented. METHOD: An international working group supported by four major pancreas societies (IAP, APA, JPS, and EPC) and a PancreasFest working group sought to develop a consensus definition and diagnostic criteria for Early CP. Ten statements (S1-10) concerning Early CP were used to gauge consensus on the Early CP concept using anonymous voting with a 9 point Likert scale. Consensus required an alpha ≥0.80. RESULTS: No consensus statement could be developed for a definition of Early-CP or diagnostic criteria. There was consensus on 5 statements: (S2) The word "Early" in early chronic pancreatitis is used to describe disease state, not disease duration. (S4) Early CP defines a stage of CP with preserved pancreatic function and potentially reversible features. (S8) Genetic variants are important risk factors for Early CP and can add specificity to the likely etiology, but they are neither necessary nor sufficient to make a diagnosis. (S9) Environmental risk factors can provide evidence to support the diagnosis of Early CP, but are neither necessary nor sufficient to make a diagnosis. (S10) The differential diagnosis for Early CP includes other disorders with morphological and functional features that overlap with CP. CONCLUSIONS: Morphology based diagnosis of Early CP is not possible without additional information. New approaches to the accurate diagnosis of Early CP will require a mechanistic definition that considers risk factors, biomarkers, clinical context and new models of disease. Such a definition will require prospective validation.

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