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BACKGROUND: Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown. METHODS: Consecutive patients undergoing pancreatic resection (2010-2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN). RESULTS: 415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574). CONCLUSIONS: Invasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN.
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BACKGROUND: The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS: Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS: In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS: Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.
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BACKGROUND: Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival. METHODS: Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed. RESULTS: In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00). CONCLUSION: A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.
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Recurrencia Local de Neoplasia , Pancreatectomía , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Anciano , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Persona de Mediana Edad , Pronóstico , Pancreatectomía/mortalidad , Supervivencia sin Enfermedad , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/mortalidad , Modelos de Riesgos Proporcionales , Neoplasias Intraductales Pancreáticas/cirugía , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Intraductales Pancreáticas/mortalidad , Estudios de Seguimiento , Europa (Continente)/epidemiología , Adenocarcinoma/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Tasa de Supervivencia , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.
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Recurrencia Local de Neoplasia , Pancreatectomía , Neoplasias Pancreáticas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/tratamiento farmacológico , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/cirugía , Quimioterapia Adyuvante , Gemcitabina , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Intraductales Pancreáticas/terapia , Neoplasias Intraductales Pancreáticas/mortalidad , Neoplasias Intraductales Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirugía , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.
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OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.
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Importance: Understanding the learning curve of a new complex surgical technique helps to reduce potential patient harm. Current series on the learning curve of minimally invasive distal pancreatectomy (MIDP) are mostly small, single-center series, thus providing limited data. Objective: To evaluate the length of pooled learning curves of MIDP in experienced centers. Design, Setting, and Participants: This international, multicenter, retrospective cohort study included MIDP procedures performed from January 1, 2006, through June 30, 2019, in 26 European centers from 8 countries that each performed more than 15 distal pancreatectomies annually, with an overall experience exceeding 50 MIDP procedures. Consecutive patients who underwent elective laparoscopic or robotic distal pancreatectomy for all indications were included. Data were analyzed between September 1, 2021, and May 1, 2022. Exposures: The learning curve for MIDP was estimated by pooling data from all centers. Main Outcomes and Measures: The learning curve was assessed for the primary textbook outcome (TBO), which is a composite measure that reflects optimal outcome, and for surgical mastery. Generalized additive models and a 2-piece linear model with a break point were used to estimate the learning curve length of MIDP. Case mix-expected probabilities were plotted and compared with observed outcomes to assess the association of changing case mix with outcomes. The learning curve also was assessed for the secondary outcomes of operation time, intraoperative blood loss, conversion to open rate, and postoperative pancreatic fistula grade B/C. Results: From a total of 2610 MIDP procedures, the learning curve analysis was conducted on 2041 procedures (mean [SD] patient age, 58 [15.3] years; among 2040 with reported sex, 1249 were female [61.2%] and 791 male [38.8%]). The 2-piece model showed an increase and eventually a break point for TBO at 85 procedures (95% CI, 13-157 procedures), with a plateau TBO rate at 70%. The learning-associated loss of TBO rate was estimated at 3.3%. For conversion, a break point was estimated at 40 procedures (95% CI, 11-68 procedures); for operation time, at 56 procedures (95% CI, 35-77 procedures); and for intraoperative blood loss, at 71 procedures (95% CI, 28-114 procedures). For postoperative pancreatic fistula, no break point could be estimated. Conclusion and Relevance: In experienced international centers, the learning curve length of MIDP for TBO was considerable with 85 procedures. These findings suggest that although learning curves for conversion, operation time, and intraoperative blood loss are completed earlier, extensive experience may be needed to master the learning curve of MIDP.
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Laparoscopía , Neoplasias Pancreáticas , Cirujanos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Curva de Aprendizaje , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Resultado del Tratamiento , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugíaRESUMEN
PURPOSE: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. METHODS: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. RESULTS: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. CONCLUSION: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Humanos , Neoplasias Intraductales Pancreáticas/cirugía , Neoplasias Intraductales Pancreáticas/patología , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Mucinoso/patología , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Páncreas/cirugía , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Benchmarking is the process to used assess the best achievable results and compare outcomes with that standard. This study aimed to assess best achievable outcomes in minimally invasive distal pancreatectomy with splenectomy (MIDPS). METHODS: This retrospective study included consecutive patients undergoing MIDPS for any indication, between 2003 and 2019, in 31 European centres. Benchmarks of the main clinical outcomes were calculated according to the Achievable Benchmark of Care (ABC™) method. After identifying independent risk factors for severe morbidity and conversion, risk-adjusted ABCs were calculated for each subgroup of patients at risk. RESULTS: A total of 1595 patients were included. The ABC was 2.5 per cent for conversion and 8.4 per cent for severe morbidity. ABC values were 160â min for duration of operation time, 8.3 per cent for POPF, 1.8 per cent for reoperation, and 0 per cent for mortality. Multivariable analysis showed that conversion was associated with male sex (OR 1.48), BMI exceeding 30â kg/m2 (OR 2.42), multivisceral resection (OR 3.04), and laparoscopy (OR 2.24). Increased risk of severe morbidity was associated with ASA fitness grade above II (OR 1.60), multivisceral resection (OR 1.88), and robotic approach (OR 1.87). CONCLUSION: The benchmark values obtained using the ABC method represent optimal outcomes from best achievable care, including low complication rates and zero mortality. These benchmarks should be used to set standards to improve patient outcomes.
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Laparoscopía , Neoplasias Pancreáticas , Benchmarking , Humanos , Laparoscopía/métodos , Masculino , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Esplenectomía , Resultado del TratamientoRESUMEN
BACKGROUND: Adequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols in patients with AP. METHODS: MEDLINE, Embase, Science Citation Index and clinical trial registries were searched for randomised clinical trials published before May 2020, assessing types of fluids, routes and rates of administration. RESULTS: A total 15 trials (1073 participants) were included. Age ranged from 38 to 73 years; follow-up period ranged from 0.5 to 6 months. Ringer lactate (RL) showed a reduced number of severe adverse events (SAE) when compared to normal saline (NS) (OR 0.48; 95%CI 0.29-0.81, p = 0.006); additionally, NS showed reduced SAE (RR 0.38; 95%IC 0.27-0.54, p < 0.001) and organ failure (RR 0.30; 95%CI 0.21-0.44, p < 0.001) in comparison with hydroxyethyl starch (HES). High fluid rate fluid infusion showed increased mortality (OR 2.88; 95%CI 1.41-5.88, p = 0.004), increased number of SAE (RR 1.42; 95%CI 1.04-1.93, p = 0.030) and higher incidence of sepsis (RR 2.80; 95%CI 1.51-5.19, p = 0.001) compared to moderate fluid rate infusion. CONCLUSIONS: In patients with AP, RL should be preferred over NS and HES should not be recommended. Based on low-certainty evidence, moderate-rate fluid infusion should be preferred over high-rate infusion.
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Pancreatitis , Sepsis , Niño , Preescolar , Humanos , Enfermedad Aguda , Fluidoterapia , Pancreatitis/diagnóstico , Pancreatitis/terapia , Protocolos ClínicosRESUMEN
A 51-year-old man developed burn wounds on both knees after finishing a cement floor. Cement burns are caused by wet cement, which is highly alkaline Initial treatment consists of lavage. Further management can be conservative but in full thickness injuries excision and grafting should be considered.
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Quemaduras Químicas/diagnóstico , Traumatismos de la Rodilla/inducido químicamente , Cemento de Silicato/efectos adversos , Quemaduras Químicas/etiología , Quemaduras Químicas/cirugía , Humanos , Traumatismos de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Apósitos Oclusivos , Cemento de Silicato/química , Trasplante de Piel , Cicatrización de HeridasRESUMEN
BACKGROUND: Early hepatic artery thrombosis (eHAT) after liver transplantation occurs in 3% of adults and 8% of children and often results in retransplantation. eHAT is initially asymptomatic and arterial patency is monitored with percutaneous Doppler ultrasound screening (pDUS). The aim of the study is to analyze the diagnostic accuracy of "continuous" Doppler registration (CONDOR) using an implantable miniature Doppler. METHODS: This prospective observational study was conducted in 102 liver transplant recipients. Hepatic arterial signal is checked by CONDOR at least six times per day for the first 10 days after transplantation with comparison of diagnostic accuracy of CONDOR versus pDUS. RESULTS: Extra investigations were performed after 48 (11%) regular pDUS where arterial patency was questioned: 32 extra pDUS, 14 computed tomography (CT) angiographies, and 2 reoperations. CT scan confirmed eHAT in 4 cases. In 10 cases of pDUS-suspected eHAT, where subsequent CT showed an open artery, the CONDOR signal was clearly pulsatile. In 2 of 4 patients with five eHATs, a weak arterial signal was inadvertently interpreted as an open artery (sensitivity of 60%). The accuracy for detection of eHAT increased from 93% (pDUS) to 99% (CONDOR). Using CONDOR, additional CT angiographies may be prevented in 10% of cases. CONCLUSION: CONDOR is a useful adjunct to pDUS because it reduces the false-positive rate of pDUS. Further development of the technique and analysis of the signal generated by CONDOR are needed to improve the sensitivity before CONDOR can replace pDUS as a reliable screening method for detection of eHAT.
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Arteria Hepática/diagnóstico por imagen , Trasplante de Hígado , Monitoreo Fisiológico/instrumentación , Prótesis e Implantes , Trombosis/diagnóstico por imagen , Ultrasonografía Doppler/instrumentación , Adolescente , Adulto , Anciano , Angiografía/economía , Angiografía/métodos , Niño , Preescolar , Femenino , Costos de la Atención en Salud , Humanos , Lactante , Masculino , Tamizaje Masivo/economía , Tamizaje Masivo/instrumentación , Tamizaje Masivo/métodos , Persona de Mediana Edad , Monitoreo Fisiológico/economía , Monitoreo Fisiológico/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/economía , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía Doppler/economía , Ultrasonografía Doppler/métodos , Adulto JovenRESUMEN
Hepatoblastoma and liver metastasis of Wilms' tumors are rare hepatic tumors in children. Treatment of both tumors consists of a combination of chemotherapy and liver surgery. Radiofrequency ablation (RFA) is frequently used for the treatment of adult liver tumors but is rarely mentioned as a treatment option in pediatric liver tumors. We present a patient with hepatoblastoma and 1 with liver metastasis from a Wilms' tumor. Both patients were treated according to the latest protocols except that surgery included use of RFA. Both are well and recurrence free 8 and 3 years after surgery. Radiofrequency ablation may be a good addition to the existing arsenal of treatment modalities for pediatric liver tumors.
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Ablación por Catéter , Hepatoblastoma/cirugía , Neoplasias Renales/patología , Neoplasias Hepáticas/cirugía , Tumor de Wilms/cirugía , Preescolar , Femenino , Hepatoblastoma/diagnóstico , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Tumor de Wilms/diagnóstico , Tumor de Wilms/secundarioRESUMEN
With 16,000 operations every year, acute appendicitis is one of the most common surgical diagnoses in Dutch emergency rooms. Diagnosis is based on clinical features: history, physical examination and laboratory testing. When the diagnosis is made, surgeons tend to operate quickly to prevent complications. In some cases this means that a healthy appendix is removed. The Dutch College of Surgeons wanted to reduce the number of removed healthy appendixes. This topic is discussed worldwide and the introduction of imaging is widely suggested. Ultrasonography and CT are said to be highly reliable in diagnosing appendicitis. While this may be the case in a research setting, it has been shown that in general hospitals they are not so reliable. Furthermore, the rise in the use of preoperative imaging has not brought down the negative appendectomy rate. We believe that imaging should be reserved for certain groups of patients. In the clear-cut cases it only increases the cost, patient burden and risk of complications; preoperative imaging should not be performed routinely.
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Apendicitis/diagnóstico , Errores Diagnósticos/prevención & control , Guías de Práctica Clínica como Asunto , Enfermedad Aguda , Apendicitis/diagnóstico por imagen , Apéndice/diagnóstico por imagen , Humanos , Radiografía , UltrasonografíaRESUMEN
BACKGROUND & AIMS: The advent of targeted therapies in hepatocellular carcinoma (HCC) has underscored the importance of pathway characterization to identify novel molecular targets for treatment. We evaluated mTOR signaling in human HCC, as well as the antitumoral effect of a dual-level blockade of the mTOR pathway. METHODS: The mTOR pathway was assessed using integrated data from mutation analysis (direct sequencing), DNA copy number changes (SNP-array), messenger RNA levels (quantitative reverse-transcription polymerase chain reaction and gene expression microarray), and protein activation (immunostaining) in 351 human samples [HCC (n = 314) and nontumoral tissue (n = 37)]. Effects of dual blockade of mTOR signaling using a rapamycin analogue (everolimus) and an epidermal/vascular endothelial growth factor receptor inhibitor (AEE788) were evaluated in liver cancer cell lines and in a xenograft model. RESULTS: Aberrant mTOR signaling (p-RPS6) was present in half of the cases, associated with insulin-like growth factor pathway activation, epidermal growth factor up-regulation, and PTEN dysregulation. PTEN and PI3KCA-B mutations were rare events. Chromosomal gains in RICTOR (25% of patients) and positive p-RPS6 staining correlated with recurrence. RICTOR-specific siRNA down-regulation reduced tumor cell viability in vitro. Blockage of mTOR signaling with everolimus in vitro and in a xenograft model decelerated tumor growth and increased survival. This effect was enhanced in vivo after epidermal growth factor blockade. CONCLUSIONS: MTOR signaling has a critical role in the pathogenesis of HCC, with evidence for the role of RICTOR in hepato-oncogenesis. MTOR blockade with everolimus is effective in vivo. These findings establish a rationale for targeting the mTOR pathway in clinical trials in HCC.