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1.
HPB (Oxford) ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38853075

RESUMO

BACKGROUND: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP. METHODS: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed. RESULTS: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA ≥ III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA ≥ III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion. CONCLUSION: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA ≥ III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage.

2.
Transpl Int ; 37: 12732, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38773987

RESUMO

Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.


Assuntos
Acessibilidade aos Serviços de Saúde , Transplante de Fígado , Sistema de Registros , Listas de Espera , Humanos , Feminino , Transplante de Fígado/estatística & dados numéricos , Pessoa de Meia-Idade , Masculino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Idoso , Espanha , Doença Hepática Terminal/cirurgia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Fatores Sexuais , Adulto , Estados Unidos , Índice de Gravidade de Doença , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia
3.
Surg Endosc ; 37(11): 8384-8393, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37715084

RESUMO

BACKGROUND: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30. METHODS: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias. RESULTS: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD. CONCLUSIONS: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Pancreatectomia , Resultado do Tratamento , Laparoscopia/efeitos adversos , Duração da Cirurgia , Tempo de Internação , Estudos Retrospectivos
4.
Cancers (Basel) ; 15(7)2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37046783

RESUMO

BACKGROUND: Transarterial radioembolization in HCC for LT as downstaging/bridging has been increasing in recent years but some indication criteria are still unclear. METHODS: We conducted a systematic literature search of primary research publications conducted in PubMed, Scopus and ScienceDirect databases until November 2022. Relevant data about patient selection, HCC features and oncological outcomes after TARE for downstaging or bridging in LT were analyzed. RESULTS: A total of 14 studies were included (7 downstaging, 3 bridging and 4 mixed downstaging and bridging). The proportion of whole liver TARE was between 0 and 1.6%. Multiple TARE interventions were necessary for 16.7% up to 28% of the patients. A total of 55 of 204 patients across all included studies undergoing TARE for downstaging were finally transplanted. The only RCT included presents a higher tumor response with the downstaging rate for LT of TARE than TACE (9/32 vs. 4/34, respectively). Grade 3 or 4 adverse effects rate were detected between 15 and 30% of patients. CONCLUSIONS: TARE is a safe therapeutic option with potential advantages in its capacity to necrotize and reduce the size of the HCC for downstaging or bridging in LT.

5.
Langenbecks Arch Surg ; 408(1): 45, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662260

RESUMO

BACKGROUND: The physiological changes of pregnancy increase the risk of gallstone formation and choledocholithiasis. Traditionally, endoscopic retrograde cholangiopancreatography (ERCP) has been the main approach for managing choledocholithiasis during pregnancy, but recent progress in laparoscopic bile duct exploration (LBDE) has demonstrated this technique as a safe and effective alternative option. METHODS: A retrospective multicenter study of all patients who underwent LBDE during pregnancy from five centers with proven experience in LBDE between January 2010 and June 2020 was performed. The primary endpoint was to analyze the role of LBDE during pregnancy and to further characterize its position as a safe and effective alternative for the management of choledocholithiasis. A systematic review of the published literature relating to LBDE during pregnancy until February 2022 was also performed. RESULTS: Five institutions reported performing LBDE during pregnancy in 8 patients. Median surgical time was 75 min (range: 60-140 min). The bile duct was cleared successfully in all patients, and the median hospital stay was 2 days (range: 1-3 days). The literature review identified a total of 7 patients with a successful CBD clearance rate of 86%. There were no major maternal, fetal, or pregnancy-related complications in any of the total 15 patients included. The symptomatic common bile duct lithiasis with deranged liver function tests was the most frequent indication (n=7). CONCLUSION: LBDE during pregnancy appears to be safe and effective. More evidence reporting outcomes of LBDE during pregnancy is needed before any strong recommendations can be made.


Assuntos
Colecistectomia Laparoscópica , Coledocolitíase , Laparoscopia , Humanos , Gravidez , Feminino , Coledocolitíase/cirurgia , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Laparoscopia/métodos , Ductos Biliares , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudos Retrospectivos , Estudos Multicêntricos como Assunto
6.
Surgery ; 173(4): 1072-1078, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36549975

RESUMO

BACKGROUND: Postoperative complications of surgical incisions are frequent in liver transplantation. However, evidence justifying the use of incisional negative pressure wound therapy to improve surgical wound outcomes remains limited. METHODS: Participating patients were randomly assigned to receive incisional negative pressure wound therapy or standard surgical dressing on the closed surgical incision of the liver transplantation. The primary endpoint was surgical site infection incidence 30 days postoperatively. The secondary endpoints included surgical site events (ie, surgical site infection, dehiscence, hematoma, and seroma) and wound quality of life. RESULTS: Between December 2018 and September 2021, 108 patients (54 in the incisional negative pressure wound therapy group and 54 in the control group) were enrolled in this study. The incidence of surgical site infection at 30 days postoperatively was 7.4% in the treatment group and 13% in the control group (P = .34). The rate of surgical site events was similar in the treatment in the and control group (27.8% vs 29.6%, P = .83). In relation to wound quality of life, the mean score was 75.20 ± 7.27 in the incisional negative pressure wound therapy group and 72.82 ± 10.57 in the control group (P = .23). CONCLUSION: The prophylactic use of negative pressure wound therapy on primarily closed incisions did not significantly reduce incisional surgical site infection and surgical site event rates after liver transplantation compared with standard surgical dressings.


Assuntos
Transplante de Fígado , Tratamento de Ferimentos com Pressão Negativa , Ferida Cirúrgica , Humanos , Ferida Cirúrgica/terapia , Infecção da Ferida Cirúrgica/epidemiologia , Qualidade de Vida
9.
J Hepatobiliary Pancreat Sci ; 29(12): 1283-1291, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35122406

RESUMO

BACKGROUND: Recently there has been a growing interest in the laparoscopic management of common bile duct stones with gallbladder in situ (LBDE), which is favoring the expansion of this technique. Our study identified the standardization factors of LBDE and its implementation in the single-stage management of choledocholithiasis. METHODS: A retrospective multi-institutional study among 17 centers with proven experience in LBDE was performed. A cross-sectional survey consisting of a semi-structured pretested questionnaire was distributed covering the main aspects on the use of LBDE in the management of choledocholithiasis. RESULTS: A total of 3950 LBDEs were analyzed. The most frequent indication was jaundice (58.8%). LBDEs were performed after failed ERCP in 15.2%. The most common approach used was the transcystic (63.11%). The overall series failure rate of LBDE was 4% and the median rate for each center was 6% (IQR, 4.5-12.5). Median operative time ranged between 60-120 min (70.6%). Overall morbidity rate was 14.6%, with a postoperative bile leak and complications ≥3a rate of 4.5% and 2.5%, respectively. The operative time decreased with experience (P = .03) and length of hospital stay was longer in the presence of a biliary leak (P = .04). Current training of LBDE was defined as poor or very poor by 82.4%. CONCLUSION: Based on this multicenter survey, LBDE is a safe and effective approach when performed by experienced teams. The generalization of LBDE will be based on developing training programs.


Assuntos
Colecistectomia Laparoscópica , Coledocolitíase , Laparoscopia , Humanos , Coledocolitíase/cirurgia , Estudos Retrospectivos , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Estudos Transversais , Laparoscopia/métodos , Ductos Biliares
10.
Ann Surg ; 276(5): e536-e543, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33177356

RESUMO

OBJECTIVE: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. BACKGROUND: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. METHODS: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60).Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. RESULTS: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18-12.16, P = 0.026), age (OR 1.07, 95% CI 1.01-1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64-53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56-5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25-9.90, P = 0.017) were associated with major complications. CONCLUSION: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.


Assuntos
Procedimentos Cirúrgicos Eletivos , Pancreatectomia , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
11.
Transplant Proc ; 53(9): 2659-2662, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34602295

RESUMO

BACKGROUND: Donation after circulatory death (DCD) is related to a warm ischemia time and more complications compared with traditional donors (donation after brain death [DBD]). METHODS: This study included biopsy samples retrospectively collected from November 2014 to December 2018 to compare histologic and biological markers of DCD and DBD liver grafts. The analysis includes marker of early apoptosis (p21), senescence (telomerase reverse transcriptase [TERT]), cell damage (caspase-3 active), endothelial damage (vascular endothelial growth factor), stem cell (CD90), hypoxia (HIF1A), inflammatory activation (COX-2), and cross-organ allograft rejection (CD44). A propensity score matching (PSM) was used to match patients receiving DCD livers to those receiving DBD livers. We analyzed the immunohistochemical initial liver damage-related warm ischemia time. RESULTS: Positive staining expression of liver damage biomarkers (COX-2, CD44, TERT, HIF1A, and CD90) was found, but no significant differences were found between DCD and DBD and with ischemic cholangiopathy. After PSM, there was a significant relationship between CD90 and male donors (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.07-0.91), TERT with donor sodium (OR, 1.11; 95% CI, 1.02-1.2), HIF1A with steatosis (OR, 0.33; 95% CI, 0.13-0.83), and CD44 with donor vasoactive drugs (OR, 0.36; 95% CI, 0.13-1) and glutamic oxaloacetic transaminase 1 week increase (OR, 1.01; 95% CI, 1-1.03). CONCLUSIONS: DCD immunohistochemical initial liver damage was found to behave similarly to DBD. The increase in complications and cholangiopathy associated with warm ischemia could be related to a different later phenomenon.


Assuntos
Morte Encefálica , Fator A de Crescimento do Endotélio Vascular , Biomarcadores , Sobrevivência de Enxerto , Humanos , Fígado , Masculino , Pontuação de Propensão , Estudos Retrospectivos
12.
Front Immunol ; 12: 672829, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381445

RESUMO

Background: Although proteomics has been employed in the study of several models of liver injury, proteomic methods have only recently been applied not only to biomarker discovery and validation but also to improve understanding of the molecular mechanisms involved in transplantation. Methods: The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and the guidelines for performing systematic literature reviews in bioinformatics (BiSLR). The PubMed, ScienceDirect, and Scopus databases were searched for publications through April 2020. Proteomics studies designed to understand liver transplant outcomes, including ischemia-reperfusion injury (IRI), rejection, or operational tolerance in human or rat samples that applied methodologies for differential expression analysis were considered. Results: The analysis included 22 studies after application of the inclusion and exclusion criteria. Among the 497 proteins annotated, 68 were shared between species and 10 were shared between sample sources. Among the types of studies analyzed, IRI and rejection shared a higher number of proteins. The most enriched pathway for liver biopsy samples, IRI, and rejection was metabolism, compared to cytokine-cytokine receptor interactions for tolerance. Conclusions: Proteomics is a promising technique to detect large numbers of proteins. However, our study shows that several technical issues such as the identification of proteoforms or the dynamic range of protein concentration in clinical samples hinder the successful identification of biomarkers in liver transplantation. In addition, there is a need to minimize the experimental variability between studies, increase the sample size and remove high-abundance plasma proteins.


Assuntos
Biomarcadores/metabolismo , Transplante de Fígado , Proteômica/métodos , Animais , Biologia Computacional/métodos , Humanos
13.
Surgery ; 170(3): 910-916, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33875253

RESUMO

BACKGROUND: Annual hospital volume of pancreatoduodenectomies could influence postoperative outcomes. The aim of this study is to establish with a non-arbitrary method the minimum threshold of yearly performed pancreatoduodenectomies in order to improve several postoperative quality outcomes. METHOD: Prospective follow-up of patients submitted to pancreatoduodenectomy in participating hospitals during 1 year. The influence of hospital volume on quality outcomes was analyzed by univariable and multivariable models. The minimum threshold of yearly performed pancreatoduodenectomies to improve outcomes was established by Akaike's information criteria. RESULTS: Data from 877 patients operated in 74 hospitals were analyzed. Of 12 quality outcomes, 9 were influenced by hospital pancreatoduodenectomy volume on multivariable analysis. To decrease the risk of complications and the risk of retrieving an insufficient number of lymph nodes at least 31 pancreatoduodenectomies per year should be performed. To decrease the risk of prolonged length of stay, postoperative death, and affected surgical margins, at least 37, 6, and 14 pancreatoduodenectomies per year should be performed, respectively. CONCLUSION: Several postoperative quality outcomes are influenced by the number of yearly performed pancreatoduodenectomies and could be improved by establishing a minimum threshold of procedures. Number of procedures needed to improve quality outcomes has been established by a non-arbitrary method.


Assuntos
Hospitais/estatística & dados numéricos , Pancreaticoduodenectomia/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais/normas , Humanos , Tempo de Internação/estatística & dados numéricos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/estatística & dados numéricos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/normas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Qualidade da Assistência à Saúde/normas , Fatores de Risco , Espanha/epidemiologia , Adulto Jovem
14.
Obes Surg ; 31(3): 1214-1222, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33225408

RESUMO

BACKGROUND: Obesity-related non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are two main causes of end-stage liver disease requiring a liver transplantation. Studies exploring bariatric surgery in the liver transplantation setting have increased in recent years; however, a systematic analysis of the topic is lacking to date. This meta-analysis was conducted to explore the perioperative and long-term outcomes of bariatric surgery in obese patients undergoing liver transplantation. METHODS: Electronic databases were systematically searched for studies reporting bariatric surgery in patients undergoing liver transplantation. The primary outcomes were postoperative complications and mortality. We also extracted data about excess weight loss, body mass index, and improvement of comorbidities after bariatric surgery. RESULTS: A total of 96 patients from 8 articles were included. Bariatric surgery-related morbidity and mortality rates were 37% (95% CI 0.27-0.47) and 0.6% (95% CI 0.02-0.13), respectively. Body mass index at 24 months was 31.02 (95% CI 25.96-36.09) with a percentage excess weight loss at 12 and 24 months of 44.08 (95% CI 27.90-60.26) and 49.2 (95% CI 31.89-66.66), respectively. After bariatric surgery, rates of improvement of arterial hypertension and diabetes mellitus were 61% (95% CI 0.45-0.75) and 45% (95% CI 0.25-0.66), respectively. In most patients, bariatric surgery was performed after liver transplant and the most frequent technique was sleeve gastrectomy. CONCLUSIONS: Bariatric surgery can be performed safely in the setting of liver transplantation resulting in improvement of obesity-related comorbidities. The optimal timing and technique require further studies.


Assuntos
Cirurgia Bariátrica , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Gastrectomia , Humanos , Hepatopatia Gordurosa não Alcoólica/cirurgia , Obesidade Mórbida/cirurgia , Resultado do Tratamento , Redução de Peso
15.
Rev Esp Enferm Dig ; 111(10): 798-801, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31526011

RESUMO

We present the case of a male diagnosed with a giant hepatic artery aneurysm, which first presented with pain and hemorrhage due to a partial rupture of the aneurysm. After discarding treatment with a stent or surgery due to the wide extension, we chose to embolize the hepatic artery with coils. However, the progress was unfavorable after the procedure, with the appearance of liver failure that was resolved by an urgent liver transplantation. Giant hepatic artery pseudoaneurysms are an infrequent entity and their management is a great challenge. The diagnosis is usually delayed due to non-specific clinical signs and the life of the patient may be threatened in the case of rupture. Thus, endovascular or surgical treatment is recommended. Aneurysm embolization or ligation has been described in the literature as a valid treatment option in cases where revascularization by stent or bypass is not possible, as it preserves the viability of the liver due to the portal flow and collateral arteries. However, in the case of the failure of these treatments, liver transplantation is a rescue option.


Assuntos
Falso Aneurisma/terapia , Embolização Terapêutica/métodos , Artéria Hepática , Falência Hepática/cirurgia , Transplante de Fígado , Terapia de Salvação/métodos , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/cirurgia , Embolização Terapêutica/instrumentação , Emergências , Vesícula Biliar/irrigação sanguínea , Hemoperitônio/diagnóstico , Hemoperitônio/etiologia , Artéria Hepática/diagnóstico por imagem , Humanos , Isquemia/etiologia , Isquemia/patologia , Fígado/irrigação sanguínea , Falência Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Falha de Tratamento
16.
Cir Esp (Engl Ed) ; 97(7): 377-384, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31164217

RESUMO

INTRODUCTION: Total pancreatectomy (TP) is an uncommon operation, with indications that have not been clearly defined and non-standardized postoperative results. We present a national multicentric study on TP and a comparison with the existing literature METHODS: A prospective observational study using data from the national registry of patients after pancreaticoduodenectomy and TP performed for any indication during the study period: January 1 to December 31, 2015 RESULTS: 1016 patients were included from 73 hospitals, 112 of whom had undergone TP. The percentage of TP from the total number of cases was 11%. The mean age was 63.5 years, and 57.2% were males. The most frequently suspected radiological diagnosis was pancreatic cancer (58/112 cases). The most common TP technique was "mesentery artery first" (43/112 cases). Venous resections were performed in 23 patients (20.5%). The percentage of postoperative complications within 90 days was 50%, but major complications (>IIIA) were only 20.7%. The overall 90-day mortality was 8% (9 patients). The average stay was 20.7 days. The 3most frequent definitive histological diagnoses were: adenocarcinoma of the pancreas, intraductal papillary mucinous neoplasm and chronic pancreatitis. The R0 rate was 67.8%. CONCLUSIONS: This study shows that the morbidity and mortality results of TP in Spain are similar or superior to previous publications. More precise TP studies are necessary, focused on specific complications such as endocrine insufficiency.


Assuntos
Pancreatectomia/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/epidemiologia , Adenocarcinoma/cirurgia , Idoso , Feminino , Humanos , Masculino , Artérias Mesentéricas/cirurgia , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/epidemiologia , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/cirurgia , Pancreatite Crônica/diagnóstico por imagem , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros , Espanha/epidemiologia
17.
Cancer Cell ; 35(4): 573-587.e6, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30975481

RESUMO

Five-year survival for pancreatic ductal adenocarcinoma (PDAC) patients remains below 7% due to the lack of effective treatments. Here, we report that combined ablation of EGFR and c-RAF expression results in complete regression of a significant percentage of PDAC tumors driven by Kras/Trp53 mutations in genetically engineered mice. Moreover, systemic elimination of these targets induces toxicities that are well tolerated. Response to this targeted therapy correlates with transcriptional profiles that resemble those observed in human PDACs. Finally, inhibition of EGFR and c-RAF expression effectively blocked tumor progression in nine independent patient-derived xenografts carrying KRAS and TP53 mutations. These results open the door to the development of targeted therapies for PDAC patients.


Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/farmacologia , Gefitinibe/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-raf/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Carcinoma Ductal Pancreático/enzimologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas c-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Proc Natl Acad Sci U S A ; 115(6): E1147-E1156, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29351990

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα+ CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties. We report that the most differentially expressed gene, Saa3, a member of the serum amyloid A (SAA) apolipoprotein family, is a key mediator of the protumorigenic activity of PDGFRα+ CAFs. Whereas Saa3-competent CAFs stimulate the growth of tumor cells in an orthotopic model, Saa3-null CAFs inhibit tumor growth. Saa3 also plays a role in the cross talk between CAFs and tumor cells. Ablation of Saa3 in pancreatic tumor cells makes them insensitive to the inhibitory effect of Saa3-null CAFs. As a consequence, germline ablation of Saa3 does not prevent PDAC development in mice. The protumorigenic activity of Saa3 in CAFs is mediated by Mpp6, a member of the palmitoylated membrane protein subfamily of the peripheral membrane-associated guanylate kinases (MAGUK). Finally, we interrogated whether these observations could be translated to a human scenario. Indeed, SAA1, the ortholog of murine Saa3, is overexpressed in human CAFs. Moreover, high levels of SAA1 in the stromal component correlate with worse survival. These findings support the concept that selective inhibition of SAA1 in CAFs may provide potential therapeutic benefit to PDAC patients.


Assuntos
Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Proteína Amiloide A Sérica/metabolismo , Proteína Amiloide A Sérica/fisiologia , Células Estromais/patologia , Animais , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pâncreas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteína Amiloide A Sérica/genética , Células Estromais/metabolismo , Microambiente Tumoral
19.
Cir Esp ; 94(9): 511-517, 2016 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27712835

RESUMO

INTRODUCTION: In pancreatic ductal adenocarcinoma (PDA), surgical resection is the only curative treatment, but due to its late clinical presentation only 15-25% patients are candidates for curative resection. The aim of this prospective, single-center study is to determine the diagnostic utility of preoperative PET-CT for early detection of PDA and early panIN lesions. METHODS: We studied the histopathological features of PDA and different panIN lesions in 139 surgical samples from patients undergoing pancreatic resection (from 2010-2014), comparing these results with preoperative PET-CT and MDCT study. For tumor diagnosis in PET-CT maximum standard SUV 2.5 was used. Pancreatic baseline SUVmax is the maximum uptake of the radiotracer 18-2FDG on the ROI curve determined for the area of the normal pancreas after pathological reassessment with areas not affected by tumours or preneoplastic lesions. Tumour Uptake Index is the ratio between the tumour SUVmax and pancreatic baseline SUVmax. RESULTS: Using an standard maximum SUV value of 2.5, PET-CT sensitivity was 77.7% (108 of the 139 cases) against 75.5% (105 of the 139 cases) of MDCT. But when we combined this value with maximum SUV of normal pancreatic tissue from each patient, PET-CT sensitivity improved its value to 94.9%. CONCLUSION: A combination of studies of PET-CT in tumor and non-tumor tissue of each patient might be a very useful diagnostic tool not only for preoperative diagnosis of PDA, but also for early panIN lesions.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Detecção Precoce de Câncer/métodos , Fluordesoxiglucose F18 , Pâncreas Exócrino , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos
20.
Cir Esp ; 94(8): 473-80, 2016 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27450270

RESUMO

INTRODUCTION: The aim of this study was to analyze prognostic factors for survival and recurrence in patients with resected pancreatic neuroendocrine tumors (PNT). METHODS: Medical records of 95 patients with resected PNT were retrospectively reviewed. The variables studied were: age, sex, form of presentation (sporadic/familial tumors), functionality, type of tumor, localization, type of surgery, tumor size, multifocal tumors and recurrent rate. The new WHO classification (2010) was used. RESULTS: There were 45 men and 50 women. Mean age was 46.8 years. Regarding the mode of presentation, it was sporadic in 66 patients (69.8%) and 29 cases were familial neuroendocrine tumors (30.2%) in association with MEN 1 syndrome. The 59% of patients suffered from non-functional tumors and 41% were functional: 20 insulinoma, 16 gastrinoma, and 3 glucagonoma. Distal pancreatectomy was the most common surgical procedure, followed by tumor enucleation in 19 patients. According to the WHO classification, 59 patients had a PNT G1, 24 PNT G2 and 12 with a poorly-differentiated carcinoma, respectively. The 5-year survival in well-differentiated tumors was 100%, regardless of the functionality. Sporadic PNT are more commonly unifocal (P<0.001), associating liver metastasis. Survival and recurrence rates after a mean follow-up of 85.3 months were 65.8 and 24%, respectively. CONCLUSIONS: In our experience, WHO classification was an independent prognostic factor in PNT survival.


Assuntos
Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
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