RESUMO
BACKGROUND: The optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type 1-associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database. METHODS: A multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups: those with multiple endocrine neoplasia type 1 versus those with sporadic disease. Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed. Propensity score matching was used to reduce bias. RESULTS: Of 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606 sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors were more common in younger patients and associated with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in either cohort, disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when patients who underwent subtotal and total pancreatectomy were excluded. CONCLUSION: Multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors are more common in younger patients and are associated with multifocality and higher T-stage. Survival for patients with multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine tumors, even in the absence of radical pancreatectomy. Consideration should be given to parenchymal-sparing surgery to preserve pancreatic function.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1 , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Estudos de Coortes , Humanos , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/patologia , Neoplasia Endócrina Múltipla Tipo 1/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , PancreatectomiaRESUMO
Liver metastases are commonly detected in a range of malignancies including colorectal cancer (CRC), pancreatic cancer, melanoma, lung cancer and breast cancer, although CRC is the most common primary cancer that metastasizes to the liver. Interactions between tumour cells and the tumour microenvironment play an important part in the engraftment, survival and progression of the metastases. Various cells including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, parenchymal hepatocytes, dendritic cells, resident natural killer cells as well as other immune cells such as monocytes, macrophages and neutrophils are implicated in promoting and sustaining metastases in the liver. Four key phases (microvascular, pre-angiogenic, angiogenic and growth phases) have been identified in the process of liver metastasis. Imaging modalities such as ultrasonography, CT, MRI and PET scans are typically used for the diagnosis of liver metastases. Surgical resection remains the main potentially curative treatment among patients with resectable liver metastases. The role of liver transplantation in the management of liver metastasis remains controversial. Systemic therapies, newer biologic agents (for example, bevacizumab and cetuximab) and immunotherapeutic agents have revolutionized the treatment options for liver metastases. Moving forward, incorporation of genetic tests can provide more accurate information to guide clinical decision-making and predict prognosis among patients with liver metastases.
Assuntos
Células Endoteliais , Neoplasias Hepáticas , Bevacizumab , Humanos , Neoplasias Hepáticas/diagnóstico , Microambiente Tumoral , UltrassonografiaRESUMO
IMPORTANCE: While laparoscopic pancreaticoduodenectomy (LPD) is being adopted with increasing enthusiasm worldwide, it is still challenging for both technical and anatomical reasons. Currently, there is no consensus on the technical standards for LPD. OBJECTIVE: The aim of this consensus statement is to guide the continued safe progression and adoption of LPD. EVIDENCE REVIEW: An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy. Statements were produced upon reviewing the literature and assessed by the members of the expert panel. The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019. The Web of Science, Medline, and Cochrane Library and Clinical Trials databases were searched, The search strategy included, but was not limited to, the terms 'laparoscopic', 'pancreaticoduodenectomy, 'pancreatoduodenectomy', 'Whipple's operation', and 'minimally invasive surgery'. Reference lists from the included articles were manually checked for any additional studies, which were included when appropriate. Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements. The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan, China. FINDINGS: Twenty-eight international experts from 8 countries constructed the expert panel. Sixteen statements were produced by the members of the expert panel. At least 80% of responders agreed with the majority (80%) of statements. Other than three randomized controlled trials published to date, most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument. CONCLUSIONS AND RELEVANCE: The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LPD. LPD is currently in its development and exploration stages, as defined by the international IDEAL framework for surgical innovation. More robust randomized controlled trial and registry study are essential to proceed with the assessment of LPD.
RESUMO
BACKGROUND: BDI is the most common serious complication of laparoscopic cholecystectomy. To address this problem, a multi-society consensus conference was held to develop evidenced-based recommendations for safe cholecystectomy and prevention of BDI. METHODS: Literature reviews were conducted for 18 key questions across 6 broad topics around cholecystectomy directed by a steering group and subject experts from 5 surgical societies (Society of Gastrointestinal and Endoscopic Surgeons, Americas Hepato-Pancreato-Biliary Association, International Hepato-Pancreato-Biliary Association, Society for Surgery of the Alimentary Tract, and European Association for Endoscopic Surgery). Evidence-based recommendations were formulated using the grading of recommendations assessment, development, and evaluation methodology. When evidence-based recommendations could not be made, expert opinion was documented. A number of recommendations for future research were also documented. Recommendations were presented at a consensus meeting in October 2018 and were voted on by an international panel of 25 experts with greater than 80% agreement considered consensus. RESULTS: Consensus was reached on 17 of 18 questions by the guideline development group and expert panel with high concordance from audience participation. Most recommendations were conditional due to low certainty of evidence. Strong recommendations were made for (1) use of intraoperative biliary imaging for uncertainty of anatomy or suspicion of biliary injury; and (2) referral of patients with confirmed or suspected BDI to an experienced surgeon/multispecialty hepatobiliary team. CONCLUSIONS: These consensus recommendations should provide guidance to surgeons, training programs, hospitals, and professional societies for strategies that have the potential to reduce BDIs and positively impact patient outcomes. Development of clinical and educational research initiatives based on these recommendations may drive further improvement in the quality of surgical care for patients undergoing cholecystectomy.
Assuntos
Ductos Biliares/lesões , Colecistectomia Laparoscópica/normas , Doença Iatrogênica/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Humanos , Fatores de RiscoRESUMO
BACKGROUND: In 2017, the WHO updated their 2010 classification of pancreatic neuroendocrine tumors, introducing a well-differentiated, highly proliferative grade 3 tumor, distinct from neuroendocrine carcinomas. The aim of this study was to investigate the clinical significance of this update in a large cohort of resected tumors. METHODS: Using a multicenter, international dataset of patients with pancreatic neuroendocrine lesions, patients were classified both according to the WHO 2010 and 2017 schema. Multivariable survival analyses were performed, and the models were evaluated for discrimination ability and goodness of fit. RESULTS: Excluding patients with a known germline MEN1 mutation and incomplete data, 544 patients were analyzed. The performance of the WHO 2010 and 2017 models was similar, however surgically resected grade 3 tumors behaved very similarly to neuroendocrine carcinomas. CONCLUSION: The addition of a grade 3 NET classification may be of limited utility in surgically resected patients, as these lesions have similar postoperative survival compared to carcinomas. While the addition may allow for a more granular evaluation of novel treatment strategies, surgical intervention for high grade tumors should be considered judiciously.
Assuntos
Carcinoma Neuroendócrino , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Compostos Orgânicos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Organização Mundial da SaúdeRESUMO
BACKGROUND: The most hazardous complication to pancreatic surgery is the development of a post-operative pancreatic fistula (POPF). Appropriate understanding of the underlying pathophysiology, risk factors and perioperative mechanisms may allow for better management and use of preventive measures. METHODS: Systematic literature search using the English PubMed literature up to April 2019, with emphasis on the past 5 years. RESULTS: Several risk scores have been developed but none are perfect in predicting POPF risk. A conceptual framework of factors that contribute to the pathophysiology of pancreatic fistulae is still developing but incomplete. Recognized factors include those related to the patient, the pathology and the perioperative care. Interventions such as use of drains, stents and various drugs to mediate risk is still debated. Emerging data suggest that both the microbiome and the inflammation in the post-operative phase may play important roles in risk for POPF. Available risk scores allow for stratification of risk and mitigation strategies tailored to reduce this. However, accurate estimation of risk remains a challenge and mechanisms are only partially understood. CONCLUSIONS: The pathophysiology of POPF remains poorly understood. Current models only partially explain risks or associated mechanisms. Novel areas of investigation need to be explored for better prediction.
Assuntos
Pâncreas/cirurgia , Fístula Pancreática/etiologia , Complicações Pós-Operatórias , Humanos , Medição de Risco , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Minimally invasive surgical necrosectomy and endoscopic necrosectomy, compared with open necrosectomy, might improve outcomes in necrotising pancreatitis, especially in critically ill patients. Evidence from large comparative studies is lacking. DESIGN: We combined original and newly collected data from 15 published and unpublished patient cohorts (51 hospitals; 8 countries) on pancreatic necrosectomy for necrotising pancreatitis. Death rates were compared in patients undergoing open necrosectomy versus minimally invasive surgical or endoscopic necrosectomy. To adjust for confounding and to study effect modification by clinical severity, we performed two types of analyses: logistic multivariable regression and propensity score matching with stratification according to predicted risk of death at baseline (low: <5%; intermediate: ≥5% to <15%; high: ≥15% to <35%; and very high: ≥35%). RESULTS: Among 1980 patients with necrotising pancreatitis, 1167 underwent open necrosectomy and 813 underwent minimally invasive surgical (n=467) or endoscopic (n=346) necrosectomy. There was a lower risk of death for minimally invasive surgical necrosectomy (OR, 0.53; 95% CI 0.34 to 0.84; p=0.006) and endoscopic necrosectomy (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). After propensity score matching with risk stratification, minimally invasive surgical necrosectomy remained associated with a lower risk of death than open necrosectomy in the very high-risk group (42/111 vs 59/111; risk ratio, 0.70; 95% CI 0.52 to 0.95; p=0.02). Endoscopic necrosectomy was associated with a lower risk of death than open necrosectomy in the high-risk group (3/40 vs 12/40; risk ratio, 0.27; 95% CI 0.08 to 0.88; p=0.03) and in the very high-risk group (12/57 vs 28/57; risk ratio, 0.43; 95% CI 0.24 to 0.77; p=0.005). CONCLUSION: In high-risk patients with necrotising pancreatitis, minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy.
Assuntos
Desbridamento , Drenagem , Duodenoscopia , Pâncreas/patologia , Pancreatite Necrosante Aguda/cirurgia , Adulto , Idoso , Brasil , Canadá , Desbridamento/métodos , Drenagem/métodos , Duodenoscopia/métodos , Feminino , Alemanha , Hospitais , Humanos , Hungria , Índia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Necrose , Países Baixos , Pancreatite Necrosante Aguda/mortalidade , Pancreatite Necrosante Aguda/patologia , Estudos Prospectivos , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVES: Liver metastasis from a neuroendocrine tumour (NET) represents a significant clinical entity. A multidisciplinary group of experts was convened to develop state-of-the-art recommendations for its management. METHODS: Peer-reviewed published reports on intra-arterial therapies for NET hepatic metastases were reviewed and the findings presented to a jury of peers. The therapies reviewed included transarterial embolization (TAE), transarterial chemoembolization (TACE) and radioembolization (RE). Two systems were used to evaluate the level of evidence in each publication: (i) the US National Cancer Institute (NCI) system, and (ii) the GRADE system. RESULTS: Eighteen publications were reviewed. These comprised 11 reports on TAE or TACE and seven on RE. Four questions posed to the panel were answered and recommendations offered. CONCLUSIONS: Studies of moderate quality support the use of TAE, TACE and RE in hepatic metastases of NETs. The quality and strength of the reports available do not allow any modality to be determined as superior in terms of imaging response, symptomatic response or impact on survival. Radioembolization may have advantages over TAE and TACE because it causes fewer side-effects and requires fewer treatments. Based on current European Neuroendocrine Tumor Society (ENETS) Consensus Guidelines, RE can be substituted for TAE or TACE in patients with either liver-only disease or those with limited extrahepatic metastases.
Assuntos
Quimioembolização Terapêutica/normas , Embolização Terapêutica/normas , Artéria Hepática , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/terapia , Compostos Radiofarmacêuticos/administração & dosagem , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Quimioembolização Terapêutica/mortalidade , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Embolização Terapêutica/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Tumores Neuroendócrinos/mortalidade , Seleção de Pacientes , Compostos Radiofarmacêuticos/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Previous results of the EORTC intergroup trial 40983 showed that perioperative chemotherapy with FOLFOX4 (folinic acid, fluorouracil, and oxaliplatin) increases progression-free survival (PFS) compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Here we present overall survival data after long-term follow-up. METHODS: This randomised, controlled, parallel-group, phase 3 study recruited patients from 78 hospitals across Europe, Australia, and Hong Kong. Eligible patients aged 18-80 years who had histologically proven colorectal cancer and up to four liver metastases were randomly assigned (1:1) to either perioperative FOLFOX4 or surgery alone. Perioperative FOLFOX4 consisted of six 14-day cycles of oxaliplatin 85mg/m(2), folinic acid 200 mg/m(2) (DL form) or 100 mg/m(2) (L form) on days 1-2 plus bolus, and fluorouracil 400 mg/m(2) (bolus) and 600 mg/m(2) (continuous 22 h infusion), before and after surgery. Patients were centrally randomised by minimisation, adjusting for centre and risk score and previous adjuvant chemotherapy to primary surgery for colorectal cancer, and the trial was open label. Analysis of overall survival was by intention to treat in all randomly assigned patients. FINDINGS: Between Oct 10, 2000, and July 5, 2004, 364 patients were randomly assigned to a treatment group (182 patients in each group, of which 171 per group were eligible and 152 per group underwent resection). At a median follow-up of 8·5 years (IQR 7·6-9·5), 107 (59%) patients in the perioperative chemotherapy group had died versus 114 (63%) in the surgery-only group (HR 0·88, 95% CI 0·68-1·14; p=0·34). In all randomly assigned patients, median overall survival was 61·3 months (95% CI 51·0-83·4) in the perioperative chemotherapy group and 54·3 months (41·9-79·4) in the surgery alone group. 5-year overall survival was 51·2% (95% CI 43·6-58·3) in the perioperative chemotherapy group versus 47·8% (40·3-55·0) in the surgery-only group. Two patients in the perioperative chemotherapy group and three in the surgery-only group died from complications of protocol surgery, and one patient in the perioperative chemotherapy group died possibly as a result of toxicity of protocol treatment. INTERPRETATION: We found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable liver metastases from colorectal cancer. However, the previously observed benefit in PFS means that perioperative chemotherapy with FOLFOX4 should remain the reference treatment for this population of patients. FUNDING: Norwegian and Swedish Cancer Societies, Cancer Research UK, Ligue Nationale Contre Cancer, US National Cancer Institute, Sanofi-Aventis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Terapia Neoadjuvante , Adulto , Idoso , Austrália , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Feminino , Fluoruracila/administração & dosagem , Hong Kong , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: This study aimed to determine the effect of LP229v on intestinal permeability and tumour necrosis factor (TNF) p55 receptor concentrations in patients with obstructive jaundice undergoing biliary drainage. PATIENTS AND METHODS: Patients undergoing biliary drainage were recruited and randomized into three groups to receive Lactobacillus plantarum 299v (LP299v), inactivated LP299v (placebo) or water. These were administered daily at noon until 7 days after biliary drainage. Intestinal permeability was measured using the lactulose/mannitol (L/M) dual sugar absorption test on admission, the day before biliary drainage and on days 1 and 7 after biliary drainage. Blood and urine were collected to determine the L/M ratio and the TNF p55 receptor levels at each time point. RESULTS: A total of 25 patients were recruited; 12 had choledocholithiasis and nine had a periampullary tumour. Open surgical biliary drainage was performed in nine patients, endoscopic retrograde cholangiopancreatography in 12 and percutaneous transhepatic cholangiography in two. Five patients received LP299v, five received placebo and seven, water. The median L/M ratio was 0.035 (0.018-0.065) at baseline. No difference existed between the groups on admission, before drainage and on day 7 after drainage (P=0.59, 0.175 and 0.61, respectively). The L/M ratio was lower in the LP299v group on day 1 after drainage [0.01 (0.01) vs. 0.18 (0.03-0.3) and 0.11 (0.07-0.14); P=0.37]. Although the TNF p55 receptor levels were lower on day 1 after drainage in the LP299v group (15.3 vs. 30.9 vs. 82.7 ng/ml; P=0.43), the concentration at the four time points was similar (P=0.24, 0.96, 0.43 and 0.68). CONCLUSION: Pretreatment with probiotic LP299v improves intestinal permeability after biliary drainage and attenuates the inflammatory response. However, a larger multicentre trial is required to determine the effect on clinical outcome.
Assuntos
Absorção Intestinal/fisiologia , Icterícia Obstrutiva/terapia , Lactobacillus plantarum , Probióticos/uso terapêutico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Coledocolitíase/complicações , Método Duplo-Cego , Drenagem , Feminino , Humanos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/metabolismo , Icterícia Obstrutiva/fisiopatologia , Lactulose/urina , Masculino , Manitol/urina , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Permeabilidade , Projetos Piloto , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/urina , Fatores Sexuais , Resultado do Tratamento , Receptores Chamariz do Fator de Necrose Tumoral/sangue , Receptores Chamariz do Fator de Necrose Tumoral/urinaRESUMO
BACKGROUND & AIMS: Protocols for enhanced recovery provide comprehensive and evidence-based guidelines for best perioperative care. Protocol implementation may reduce complication rates and enhance functional recovery and, as a result of this, also reduce length-of-stay in hospital. There is no comprehensive framework available for pancreaticoduodenectomy. METHODS: An international working group constructed within the Enhanced Recovery After Surgery (ERAS®) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group. The quality of evidence was rated "high", "moderate", "low" or "very low". Recommendations were graded as "strong" or "weak". RESULTS: Comprehensive guidelines are presented. Available evidence is summarised and recommendations given for 27 care items. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSIONS: The present evidence-based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy. A unified protocol allows for comparison between centres and across national borders. It facilitates multi-institutional prospective cohort registries and adequately powered randomised trials.
Assuntos
Pâncreas/cirurgia , Pancreaticoduodenectomia/métodos , Assistência Perioperatória/métodos , Consenso , Medicina Baseada em Evidências , Humanos , Tempo de Internação , Metanálise como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: The aim of this prospective study was to investigate the implementation of an enhanced recovery after surgery (ERAS) programme following pancreaticoduodenectomy (PD). METHODS: Patients undergoing PD were managed according to an ERAS protocol. Outcome measures included postoperative mortality, morbidity, hospitalization and 30-day readmission rate. Key protocol targets were: nasogastric tube (NGT) removal [postoperative day (PoD) 1]; resumption of oral fluids (PoD 1); urinary catheter removal (PoD 3); high-dependency unit (HDU) discharge (PoD 3); tolerating diet (PoD 4); drain removal (PoD 5), and hospital discharge (PoD 6). RESULTS: Data were collected for 50 patients (24 male; median age 67 years). Rates of mortality, morbidity and readmission were 4%, 46% and 4%, respectively. The median length of postoperative hospitalization was 10 days. The proportions of patients achieving key targets were: 78% for NGT removal; 82% for resumption of oral fluids; 48% for urinary catheter removal; 82% for HDU discharge; 86% for tolerating diet; 84% for meeting mobility targets, and 72% for drain removal. One patient was discharged by PoD 6, eight patients by PoD 7, 15 patients by PoD 8 and 26 patients (52%) by PoD 10. Discharge was delayed in 16 patients for social or transport-related reasons. CONCLUSIONS: The ERAS protocol was implemented safely. Achieving certain targets was challenging. Non-medical causes remain a significant factor in delayed discharge following PD.
Assuntos
Pancreaticoduodenectomia , Idoso , Analgésicos/uso terapêutico , Remoção de Dispositivo , Dieta , Drenagem/instrumentação , Feminino , Mortalidade Hospitalar , Humanos , Intubação Gastrointestinal/instrumentação , Tempo de Internação , Masculino , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Alta do Paciente , Readmissão do Paciente , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Cateterismo Urinário/instrumentação , Cateteres UrináriosRESUMO
OBJECTIVES: Excessive blood loss during liver surgery contributes to postoperative morbidity and mortality and the minimizing of blood loss improves outcomes. This study examines pre- and intraoperative factors contributing to blood loss and identifies areas for improvement. METHODS: All patients who underwent elective hepatic resection between June 2007 and June 2009 were identified. Detailed information on the pre- and perioperative clinical course was analysed. Univariate and multivariate analyses were used to identify factors associated with intraoperative blood loss. RESULTS: A total of 175 patients were studied, of whom 95 (54%) underwent resection of three or more segments. Median blood loss was 782 ml. Greater blood loss occurred during major resections and prolonged surgery and was associated with an increase in postoperative complications (P= 0.026). Peak central venous pressure (CVP) of >10 cm H(2)O was associated with increased blood loss (P= 0.01). Although no differences in case mix were identified, blood loss varied significantly among anaesthetists, as did intraoperative volumes of i.v. fluids and transfusion practices. CONCLUSIONS: This study confirms a relationship between CVP and blood loss in hepatic resection. Intraoperative CVP values were higher than those described in other studies. There was variation in the intraoperative management of patients. Collaboration between surgical and anaesthesia teams is required to minimize blood loss and the standardization of intraoperative anaesthesia practice may improve outcomes following liver surgery.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/efeitos adversos , Pressão Venosa Central , Distribuição de Qui-Quadrado , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Assistência Perioperatória , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Escócia , Reação Transfusional , Adulto JovemRESUMO
OBJECTIVE: In EORTC study 40983, perioperative FOLFOX increased progression-free survival (PFS) compared with surgery alone for patients with initially 1 to 4 resectable liver metastases from colorectal cancer (CRC). We conducted an exploratory retrospective analysis to identify baseline factors possibly predictive for a benefit of perioperative FOLFOX on PFS. METHODS: The analysis was based on 237 events from 342 eligible patients. Cox proportional hazards regression models with a significance level of 0.1 were used to build up univariate and multivariate models. RESULTS: After adjustment for identified prognostic factors, moderately (5.1-30 ng/mL) and highly (>30 ng/mL) elevated carcinoembryonic antigen (CEA) serum levels were both predictive for the benefit of perioperative chemotherapy (interaction P = 0.07; hazard ratio [HR] = 0.58 and HR = 0.52 for treatment benefit). For patients with moderately or highly elevated CEA (>5 ng/mL), the 3-year PFS was 35% with perioperative chemotherapy compared to 20% with surgery alone. Performance status (PS) 0 and BMI lower than 30 were also predictive for the benefit of perioperative chemotherapy (interaction P = 0.04 and P = 0.02). However, the number of patients with PS 1 and BMI 30 or higher were limited. The benefit of perioperative therapy was not influenced by the number of metastatic lesions (1 vs 2-4, interaction HR = 0.98). CONCLUSIONS: Perioperative FOLFOX seems to benefit in particular patients with resectable liver metastases from CRC when CEA is elevated and when PS is unaffected, regardless of the number of metastatic lesions.ClinicalTrials.gov number NCT00006479.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Assistência Perioperatória , Terapia Combinada , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Two novel antiendotoxin peptides, P6 and C1, may reduce the inflammatory response. This study aimed to determine the effect of endotoxin on hepatic cytokine response and to assess P6 and C1-related attenuation of the proinflammatory response to endotoxemia, in experimental biliary obstruction. MATERIALS AND METHODS: 15 Male Wistar rats were randomized to one of three groups: bile duct ligation (BDL)+P6 (n=5), BDL+C1 (n=5), and BDL+no peptide (n=5). Rats were weighed and underwent BDL surgery on day 1. On day 8, the rats were reweighed and isolated hepatic perfusion was carried out. P6 or C1 peptide (10 µmol/l) was preincubated with 300 ml of endotoxin-containing Krebs perfusate. After perfusion of 10 min with endotoxin-free perfusate, the livers were perfused for another 10 min with 300 ml of perfusate-containing endotoxin on its own or endotoxin plus peptide. This was followed by a further 100 min of perfusion with endotoxin-free perfusate. Effluent perfusate was collected at 20-min intervals for subsequent biochemical and cytokine analyses. RESULTS: Perfusion with endotoxin+P6 or endotoxin+C1 resulted in no significant difference in weight loss, or interleukin-6 response compared with perfusion with endotoxin alone. However, perfusion with endotoxin+P6 or endotoxin+C1 significantly reduced the tumor necrosis factor-α response to portal endotoxemia compared with perfusion with endotoxin alone. CONCLUSION: This study demonstrates that novel antiendotoxin peptides may attenuate the hepatic inflammatory response in portal endotoxemia. In obstructive jaundice, preoperative peptide administration may reduce endotoxin-related postoperative complications.
Assuntos
Endotoxemia/tratamento farmacológico , Icterícia Obstrutiva/complicações , Proteínas de Membrana/uso terapêutico , Animais , Bilirrubina/sangue , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Endotoxemia/etiologia , Endotoxemia/metabolismo , Endotoxinas/administração & dosagem , Endotoxinas/antagonistas & inibidores , Endotoxinas/farmacologia , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Icterícia Obstrutiva/metabolismo , Masculino , Fragmentos de Peptídeos/uso terapêutico , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: An exaggerated proinflammatory response to endotoxaemia can occur in obstructive jaundice. The aims of this study were to determine the hepatic proinflammatory and anti-inflammatory cytokine response to endotoxaemia in experimental biliary obstruction and to determine the source of interleukin-6 (IL-6) using immunohistochemistry. METHODOLOGY: Male Wistar rats were randomized into three groups: bile duct ligation (BDL), sham operation, and control groups. They were weighed before surgery and after 1 week. On day 8, hepatic perfusion was performed with endotoxin (Escherichia coli 0111:B4). Serial samples of blood, effluent, and influent perfusate were analyzed for proinflammatory and anti-inflammatory cytokines. Ultrastructural assessment of sections of the liver was performed. RESULTS: BDL animals lost weight in the first week compared with the sham and the control animals that gained weight. Liver function tests were elevated in the BDL group. Effluent biochemistry did not reveal liver injury as a result of perfusion. Ultrastructurally, there was no evidence of liver injury, with only active Kupffer cells, preservation of liver architecture, and minimal liver injury being detected. Serum tumor necrosis factor-α was not detected in any group before perfusion; however, serum IL-6 was higher in the BDL group. Portal endotoxaemia resulted in an increase in tumor necrosis factor-α, IL-6, and IL-10 in the BDL group. Fluorescence immunohistochemistry demonstrated IL-6 in the sinusoidal spaces and the cytoplasm of Kupffer cells. CONCLUSION: There is an exaggerated proinflammatory and anti-inflammatory cytokine response to portal endotoxaemia in animals with jaundice compared with the sham group.
Assuntos
Citocinas/metabolismo , Endotoxemia/metabolismo , Icterícia Obstrutiva/metabolismo , Animais , Peso Corporal/fisiologia , Modelos Animais de Doenças , Endotoxemia/complicações , Endotoxemia/patologia , Mediadores da Inflamação/metabolismo , Interleucinas/metabolismo , Icterícia Obstrutiva/complicações , Icterícia Obstrutiva/patologia , Fígado/metabolismo , Fígado/ultraestrutura , Masculino , Microscopia Eletrônica , Ativação de Neutrófilo , Neutrófilos , Ratos , Ratos Wistar , Explosão Respiratória/fisiologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Concomitant injury to the bile duct and hepatic artery is an increasingly recognized complication of laparoscopic cholecystectomy (LC). The impact of a concomitant arterial injury in patients with a bile duct injury (BDI) remains debatable. Early reports described a high incidence of septic complications, difficulty of biliary repair, and increased the risk of recurrent stricture. DATA SOURCES: A literature search on the clinical significance and management of a concomitant hepatic artery injury (HAI) to the outcome of biliary-enteric reconstruction following BDI was reviewed. Relevant articles were extracted through MEDLINE, with secondary references obtained from key articles. CONCLUSIONS: The association between failure of biliary repair and concomitant arterial injuries is not confirmed by the largest studies, which showed no difference in anastomotic stricture rate between patients who had an isolated BDI and those who had a combined HAI and BDI. However, right arterial injury associated with liver necrosis or damage to the right hepatic duct may require right hepatectomy.