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1.
Br J Surg ; 110(10): 1331-1347, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37572099

RESUMO

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.


Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.


Assuntos
Falência Hepática , Neoplasias Hepáticas , Humanos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado , Verde de Indocianina , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia
3.
Ann Surg ; 272(5): 715-722, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833764

RESUMO

OBJECTIVE: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. SUMMARY/BACKGROUND: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. METHODS: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. RESULTS: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. CONCLUSIONS: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.


Assuntos
Neoplasias Colorretais/patologia , Tomada de Decisões , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Consenso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
Ann Surg ; 270(2): 211-218, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30829701

RESUMO

OBJECTIVE: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD). BACKGROUND: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative. METHODS: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches. RESULTS: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases. CONCLUSION: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.


Assuntos
Benchmarking , Pancreatopatias/cirurgia , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Incidência , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
5.
Am J Surg ; 212(4): 715-721, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27712669

RESUMO

BACKGROUND: Irreversible electroporation is increasingly used for treatment of solid tumors, but safety data remain scarce. This study aimed to describe intraoperative adverse events associated with irreversible electroporation in patients undergoing solid tumor ablation. METHODS: We analyzed demographic and intraoperative data for patients (n = 43) undergoing irreversible electroporation for hepato-pancreato-biliary and retroperitoneal malignancies (2012 to 2015). Adverse events were defined as cardiac, surgical, or equipment-related. RESULTS: Adverse events (n = 20, 47%) were primarily cardiac (90%, n = 18), including blood pressure elevation (77%, n = 14/18) and arrhythmia (16%, n = 7/43). All but one was managed medically, 1 patient with arrhythmia required termination of ablation. Bleeding and technical problems with the equipment occurred in 1 patient each. Multivariable analysis revealed previous cardiovascular disease and needle placement close to the celiac trunk associated with increased likelihood for cardiac events. CONCLUSIONS: Intraoperative cardiac adverse events are common during irreversible electroporation but rarely impair completion of the procedure.


Assuntos
Neoplasias do Sistema Digestório/cirurgia , Eletroporação , Complicações Intraoperatórias , Neoplasias Retroperitoneais/cirurgia , Idoso , Arritmias Cardíacas/etiologia , Doenças Cardiovasculares/complicações , Artéria Celíaca , Eletroporação/instrumentação , Feminino , Humanos , Hiperpotassemia/etiologia , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
6.
Dig Surg ; 33(4): 351-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27216160

RESUMO

With the advent of novel and somewhat effective chemotherapy against pancreas cancer, several groups developed a new interest on locally advanced pancreatic cancer (LAPC). Unresectable tumors constitute up to 80% of pancreatic cancer (PC) at the time of diagnosis and are associated with a 5-year overall survival of less than 5%. To control those tumors locally, with perhaps improved patients survival, significant advances were made over the last 2 decades in the development of ablation methods including cryoablation, radiofrequency ablation, microwave ablation, high intensity focused ultrasound and irreversible electroporation (IRE). Many suggested a call for caution for possible severe or lethal complications in using such techniques on the pancreas. Most fears were on the heating or freezing of the pancreas, while non-thermal ablation (IRE) could offer safer approaches. The multimodal therapies along with high-resolution imaging guidance have created some enthusiasm toward ablation for LAPC. The impact of ablation techniques on primarily non-resectable PC remains, however, unclear.


Assuntos
Ablação por Cateter/métodos , Criocirurgia , Neoplasias Pancreáticas/terapia , Quimiorradioterapia Adjuvante , Eletroporação , Humanos , Micro-Ondas/uso terapêutico
7.
Ann Surg ; 262(5): 764-70; discussion 770-1, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26583664

RESUMO

BACKGROUND: Exposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion "Hypothermic Oxygenated PErfusion" (HOPE) in an attempt to improve graft quality before implantation. METHODS: HOPE-treated DCD livers (n = 25) were matched and compared with normally preserved (static cold preservation) DCD liver grafts (n = 50) from 2 well-established European programs. Criteria for matching included duration of warm ischemia and key confounders summarized in the balance of risk score. In a second step, perfused and unperfused DCD livers were compared with liver grafts from standard brain dead donors (n = 50), also matched to the balance of risk score, serving as baseline controls. RESULTS: HOPE treatment of DCD livers significantly decreased graft injury compared with matched cold-stored DCD livers regarding peak alanine-aminotransferase (1239 vs 2065 U/L, P = 0.02), intrahepatic cholangiopathy (0% vs 22%, P = 0.015), biliary complications (20% vs 46%, P = 0.042), and 1-year graft survival (90% vs 69%, P = 0.035). No graft failure due to intrahepatic cholangiopathy or nonfunction occurred in HOPE-treated livers, whereas 18% of unperfused DCD livers needed retransplantation. In addition, HOPE-perfused DCD livers achieved similar results as control donation after brain death livers in all investigated endpoints. CONCLUSIONS: HOPE seems to offer important benefits in preserving higher-risk DCD liver grafts.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Criopreservação , Morte , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
8.
Am J Surg ; 210(4): 694-701, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26212390

RESUMO

BACKGROUND: Perihilar cholangiocarcinoma is usually unresectable at the time of diagnosis. Only few patients are candidates for a potential curative treatment. For those patients, prognosis is strongly related to negative resection margin and lymph node status. Thus, a certain benchmark of lymph node count is necessary to secure relevant lymph node recovery and to avoid understaging. However, the required minimum number of retrieved lymph nodes remains unclear for perihilar cholangiocarcinoma. The 7th American Joint Committee on Cancer tumor, nodes, metastases edition increased the requirement for the histologic examination of lymph nodes in perihilar cholangiocarcinoma patients from 3 to 15. The applicability of such recommendation appears difficult and questionable. Therefore, the purpose of this systematic review is to evaluate the number of retrieved lymph nodes for staging of patients undergoing surgery for perihilar cholangiocarcinoma. METHODS: The MEDLINE, EMBASE, and The Cochrane Library databases were systematically screened up to December 2014. All studies reporting the number of lymph node count in perihilar cholangiocarcinoma were included and assessed for eligibility. RESULTS: A total of 725 abstracts were screened and 20 studies were included for analysis, comprising almost 4,000 patients. The cumulative median lymph node count was 7 (2 to 24). A median lymph node count greater than or equal to 15 was reported in 9% of perihilar cholangiocarcinoma patients and could only be achieved in extended lymphadenectomy. Subgroup analysis revealed a median lymph node count of 7 (range 7 to 9), which was associated with the detection of most lymph node positive patients and showed the lowest risk for understaging patients. Lymph node count greater than or equal to 15 did not increase detection rate of lymph node positive patients. CONCLUSIONS: This systematic analysis suggests that lymph node count greater than or equal to 7 is adequate for prognostic staging, while lymph node count greater than or equal to 15 does not improve detection of patients with positive lymph nodes.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Tumor de Klatskin/patologia , Tumor de Klatskin/cirurgia , Excisão de Linfonodo , Humanos , Estadiamento de Neoplasias , Prognóstico
9.
Praxis (Bern 1994) ; 104(9): 453-60, 2015 Apr 22.
Artigo em Alemão | MEDLINE | ID: mdl-25900693

RESUMO

Pancreatic cancer is the seventh most common cancer in Switzerland associated with a dismal prognosis. Its natural course is fatal with a 3-year survival rate below 3%. Advances in diagnostic tools, tumor staging and multimodal treatment strategies resulted in an improved 5-year survival rate of over 20%. Patients presenting with pancreatic cancer significantly benefit from a multi-disciplinary treatment strategy in an experienced hepato-pancreato-biliary center. Following a comprehensive tumor staging, surgical resection associated with adjuvant chemotherapy is still the only curative therapy option. The role of neoadjuvant chemotherapy is currently investigated in clinical trials. Patients presenting with advanced pancreatic cancer not eligible for curative treatment might benefit from inclusion into innovative clinical trials with novel treatment concepts.


Le cancer du pancréas est le 7ème cancer le plus fréquent en Suisse. Son histoire naturelle est rapidement fatale avec une survie à trois ans inférieure à 3%. Les moyens diagnostiques modernes et des stratégies thérapeutiques multimodales ont permis d'améliorer la survie à cinq ans au-delà de 20%. C'est pourquoi ces patients bénéficient de façon significative d'un traitement multidisciplinaire au sein d'un centre hépato-pancréato-biliaire spécialisé. Après un bilan d'extension précis, la chirurgie associée à une chimiothérapie adjuvante reste le seul traitement à visée curative. Le rôle de la chimiothérapie néoadjuvante est en cours d'évaluation au sein d'essais cliniques. Les patients avec un cancer du pancréas avancé non-résectable peuvent bénéficier de stratégies thérapeutiques nouvelles dans le cadre d'essais cliniques innovants.


Assuntos
Carcinoma Ductal Pancreático/terapia , Neoplasias Pancreáticas/terapia , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Terapia Combinada , Comportamento Cooperativo , Intervalo Livre de Doença , Humanos , Comunicação Interdisciplinar , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Taxa de Sobrevida
10.
Transplantation ; 99(8): 1606-12, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25769076

RESUMO

BACKGROUND: During times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation. METHODS: Cadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay. RESULTS: Ninety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097 (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance. CONCLUSIONS: This first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Anestésicos Intravenosos/uso terapêutico , Transplante de Fígado/métodos , Éteres Metílicos/uso terapêutico , Disfunção Primária do Enxerto/prevenção & controle , Propofol/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Aspartato Aminotransferases/sangue , Bélgica , Biomarcadores/sangue , Brasil , Feminino , Mortalidade Hospitalar , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Éteres Metílicos/efeitos adversos , Pessoa de Meia-Idade , Razão de Chances , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/mortalidade , Propofol/efeitos adversos , Fatores de Risco , Sevoflurano , Suíça , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/mortalidade , Resultado do Tratamento
11.
Gastroenterology ; 148(2): 307-23, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25224524

RESUMO

Liver transplantation (LT) is a highly successful treatment for many patients with nonmalignant and malignant liver diseases. However, there is a worldwide shortage of available organs; many patients deteriorate or die while on waiting lists. We review the important clinical challenges to LT and the best use of the scarce organs. We focus on changes in indications for LT and discuss scoring systems to best match donors with recipients and optimize outcomes, particularly for the sickest patients. We also cover controversial guidelines for the use of LT in patients with hepatocellular carcinoma and cholangiocarcinoma. Strategies to increase the number of functional donor organs involve techniques to perfuse the organs before implantation. Partial LT (living donor and split liver transplantation) techniques might help to overcome organ shortages, and we discuss small-for-size syndrome. Many new developments could increase the success of this procedure, which is already one of the major achievements in medicine during the second part of the 20th century.


Assuntos
Transplante de Fígado/métodos , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Hepatite C/cirurgia , Humanos , Hepatopatias Alcoólicas/cirurgia , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Hepatopatia Gordurosa não Alcoólica/cirurgia , Perfusão
12.
Am J Surg ; 208(4): 563-70, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25124294

RESUMO

Cholangiocarcinoma is a lethal disease with increasing incidence worldwide. Perihilar cholangiocarcinoma represents the most common type of cholangiocarcinoma. Despite major development on surgical strategies over the past 20 years, the 5-year survival rate after surgery has remained below 40%, often in the vicinity of 20%. Most perihilar cholangiocarcinomas, however, are unresectable at the time of the diagnosis. The recent use of aggressive approaches based on better image modality, specific perioperative management, and a multidisciplinary approach have enabled to convert the use of palliative therapies to more radical surgery. This review focuses on the recent advances in surgical treatment for perihilar cholangiocarcinoma including liver transplantation with their respective impact on patient survival.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia , Transplante de Fígado , Humanos
13.
Curr Opin Organ Transplant ; 19(3): 245-52, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24811436

RESUMO

PURPOSE OF REVIEW: Cholangiocarcinoma is a rare tumour with dismal prognosis. Only radical resection offers a chance for cure with reported survivals ranging from 25 to 45% at 5 years. Considering the low rate of resectability and lack of efficacy of other treatments, liver transplantation has emerged as a reasonable approach to cure selective patients with unresectable diseases. The use of liver transplantation, however, is associated with the inherent risk of early tumour recurrence due to the need for immunosuppression and the poor survival rate. This review will focus on the role of liver transplantation in treating patients with cholangiocellular cancer. RECENT FINDINGS: The indication of liver transplantation for cholangiocarcinoma has evolved over time moving from an absolute to a relative contraindication until eventually becoming the best indication for a small group of patients presenting with unresectable perihilar cholangiocarcinoma, when associated with a neoadjuvant chemoradiotherapy. In contrast, the indication of liver transplantation for intrahepatic cholangiocarcinoma is far from being established and should be offered only under protocol, mainly for small tumours in the setting of cirrhosis. SUMMARY: The poor outcome of cholangiocarcinoma, irrespective of the therapy, justifies the search for novel approaches. Only selective patients with perihilar cholangiocarcinoma subjected to a neoadjuvant protocol may qualify for liver transplantation.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Humanos , Neoplasias Hepáticas/patologia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico
14.
World J Surg ; 37(8): 1782-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23674251

RESUMO

Lymph node staging is one of the most important factors in determining the prognosis after resection of pancreatic ductal adenocarcinoma. Despite ongoing efforts to further refine lymph node staging, the debate on the extent of lymphadenectomy during pancreaticoduodenectomy is still open. The purpose of this review was to summarize the evidence about performing standard lymphadenectomy during curative resection of pancreatic cancer. All four prospective randomized controlled trials published concluded that extended lymphadenectomy does not contribute to better oncologic outcome for patients with adenocarcinoma of the pancreatic head. Indeed, one major drawback of extended lymphadenectomy is the higher risk of persistent postoperative diarrhea. No prospective randomized studies could be found on the role of extended lymphadenectomy in patients with adenocarcinoma of the corpus and tail. Based on current evidence there is no indication that extended lymphadenectomy should be performed routinely during resection of pancreatic cancer.


Assuntos
Excisão de Linfonodo/métodos , Neoplasias Pancreáticas/cirurgia , Ensaios Clínicos como Assunto , Humanos , Metástase Linfática , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/patologia
15.
Curr Opin Gastroenterol ; 29(3): 293-8, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23563982

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to evaluate the most current strategies of surgical treatment for cholangiocarcinoma including liver resection and transplantation. RECENT FINDINGS: More aggressive surgical approaches have emerged over the past decade to treat patients previously considered to have unresectable lesions, which include combined hepatectomy with vascular resection, liver mass manipulation, oncological nontouch technique and liver transplantation. SUMMARY: Cholangiocarcinoma can occur anywhere along the biliary system. Its detection rate, and consequently its incidence, has risen possibly because of improvements in diagnostic imaging. Cholangiocarcinomas are presently understood within three distinct categories: intrahepatic, perihilar and distal tumors. The perihilar type is the most common, followed by the distal and intrahepatic types. This division has therapeutic relevance because the type of surgery depends on the anatomical location and extension of the tumor. This review will primarily focus on those circumstances in which a hepatectomy is required, which provides the greatest chance of cure. In this setting, liver transplantation for perihilar cholangiocarcinoma has resurged as an excellent option for a selective group of patients, when associated with a neoadjuvant chemoradiation protocol. Despite more aggressive surgical approaches, many cases remain unresectable with a poor prognosis.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Transplante de Fígado/métodos , Humanos , Prognóstico
16.
Clin Cancer Res ; 18(21): 5902-10, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23087410

RESUMO

PURPOSE: Serotonin is a well-known neurotransmitter and vasoactive substance. Recent research indicates that serotonin contributes to liver regeneration and promotes tumor growth of human hepatocellular cancer. The aim of this study is to investigate the expression of serotonin receptors in hepatocellular cancer and analyze their potential as a cytotoxic target. EXPERIMENTAL DESIGN: Using a tissue microarray and immunohistochemistry, we analyzed the expression of serotonin receptors in the liver from 176 patients with hepatocellular carcinoma, of which nontumor tissue was available in 109 patients. Relevant clinicopathologic parameters were compared with serotonin receptor expression. Two human hepatocellular cancer cell lines, Huh7 and HepG2, were used to test serotonin antagonists as a possible cytotoxic drug. RESULTS: The serotonin receptors 1B and 2B were expressed, respectively, in 32% and 35% of the patients with hepatocellular cancer. Both receptors were associated with an increased proliferation index, and receptor 1B correlated with the size of the tumor. Serotonin antagonists of receptors 1B and 2B consistently decreased viability and proliferation in Huh7 and HepG2 cell lines. CONCLUSION: We identified two serotonin receptors that are often overexpressed in human hepatocellular cancer and may serve as a new cytotoxic target.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Receptores de Serotonina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Expressão Gênica , Células Hep G2 , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Adulto Jovem
17.
Ann Surg ; 254(5): 716-22; discussion 722-3, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22042467

RESUMO

OBJECTIVE: To assess the incidence and impact of biliary complications in recipients transplanted from donors after cardiac death (DCD) at one single large institution. BACKGROUND: Shortage of available cadaveric organs is a significant limiting factor in liver transplantation (LT). The use of DCD offers the potential to increase the organ pool. However, early results with DCD liver grafts were associated with a greater incidence of ischemic cholangiopathy (IC), leading to several programs to abandoning this source of organs. METHODS: A retrospective analysis of a prospective database from April 2001 to 2010 focused on 167 consecutive DCD-LT. Each DCD transplant was matched with 2 brain death donors (DBD) grafts (n = 333) according to the period of transplantation. Primary outcome measures were biliary complications including the severity of complications, graft survival and patient survival. Minimum follow-up was 3 months. RESULTS: Anastomotic stricture was the most common biliary complication (DCD = 30, 19% vs. DBD = 41, 13%). Most were treated endocoscopically (grade IIIa = 72%), whereas hepatico-jejunostomy (grade IIIb) was performed in 22%. Primary IC occurred in 4 (2.5%) recipients from the DCD group and was absent in the DBD group (P = 0.005). However, none of these patients required retransplantation. Patient and graft survival at 1, 3, and 5 years were similar between DCD and DBD groups (P = 0.106, P = 0.138, P = 0.113, respectively). CONCLUSIONS: The encouraging results with DCD-LT are probably due to the selection of DCD grafts and clear definition of warm ischemia.


Assuntos
Doenças Biliares/epidemiologia , Transplante de Fígado , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Morte , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Adulto Jovem
18.
Hepatology ; 53(4): 1363-71, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21480336

RESUMO

Perihilar cholangiocarcinoma is one of the most challenging diseases with poor overall survival. The major problem for anyone trying to convincingly compare studies among centers or over time is the lack of a reliable staging system. The most commonly used system is the Bismuth-Corlette classification of bile duct involvement, which, however, does not include crucial information such as vascular encasement and distant metastases. Other systems are rarely used because they do not provide several key pieces of information guiding therapy. Therefore, we have designed a new system reporting the size of the tumor, the extent of the disease in the biliary system, the involvement of the hepatic artery and portal vein, the involvement of lymph nodes, distant metastases, and the volume of the putative remnant liver after resection. The aim of this system is the standardization of the reporting of perihilar cholangiocarcinoma so that relevant information regarding resectability, indications for liver transplantation, and prognosis can be provided. With this tool, we have created a new registry enabling every center to prospectively enter data on their patients with hilar cholangiocarcinoma (www.cholangioca.org). The availability of such standardized and multicenter data will enable us to identify the critical criteria guiding therapy.


Assuntos
Neoplasias dos Ductos Biliares/classificação , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/classificação , Colangiocarcinoma/patologia , Estadiamento de Neoplasias/métodos , Humanos , Tumor de Klatskin/patologia , Sistema de Registros
19.
Liver Int ; 31(3): 313-21, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21281431

RESUMO

BACKGROUND: New chemotherapy regimens are increasingly used in metastatic colorectal cancer to the liver before surgery. Some clinical observations have suggested that chemotherapy may affect liver regeneration. AIMS: The aim of this study was to evaluate liver damage and liver regeneration after chemotherapy treatment in a model of partial hepatectomy. METHODS: C57BL/6 mice were repeatedly treated with intraperitoneal injections of either saline or different chemotherapy regimens including the drugs 5-fluorouracyl (5-FU), irinotecan, oxaliplatin, gemcitabine and combined treatments with 5-FU/irinotecan, 5-FU/oxaliplatin. A 70% partial hepatectomy was performed 1 week after the last injection. Ki-67 and PCNA immunohistochemistry were performed to assess liver regeneration, serum liver enzymes and histology analysis to evaluate injury. RESULTS: A variety of chemotherapeutic agents used at maximum tolerated doses compatible with survival affected body weight and blood cell levels. However, these regimens did not affect liver injury before and after hepatectomy nor did they impair liver regeneration. Liver histology showed no steatosis, fibrosis or inflammation before hepatectomy. We therefore tested whether chemotherapy in presence of diet-induced steatosis may trigger injury. Even under these conditions, we did not observe histological signs of inflammation or sinusoidal injury. CONCLUSIONS: Liver injury and liver regeneration are not impaired after neoadjuvant chemotherapy with 5-FU, irinotecan, oxaliplatin and gemcitabine in non-tumoural liver parenchyma. In addition, combined treatments disclose no adverse effects on liver regeneration. Chemotherapy alone induces no histological alterations even in the presence of steatosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Modelos Animais de Doenças , Hepatectomia , Regeneração Hepática/efeitos dos fármacos , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Antígeno Ki-67/metabolismo , Fígado/metabolismo , Fígado/patologia , Regeneração Hepática/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Antígeno Nuclear de Célula em Proliferação/metabolismo
20.
Ann Surg ; 252(5): 726-34, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21037427

RESUMO

OBJECTIVE: To develop and validate a simple score to predict postoperative complications by severity after liver resection, using readily available preoperative risk factors. BACKGROUND: Although liver surgery has enjoyed major development with dramatic reduction in mortality rates, the incidence of serious yet nonlethal complications remains high. No scoring system is currently available to identify those patients at higher risk for a complicated course. METHODS: Complications were prospectively assessed in 615 consecutive noncirrhotic patients undergoing liver resection at the same institution. In randomly selected 60% of the population, multivariate-logistic-regression analysis was used to develop a score to predict severe complications defined as complications grades III, IV, and mortality (grade V) (Clavien-Dindo classification). The score was validated by calibration within the remaining 40% of the patients. RESULTS: Grades III to V complications occurred in 159 (26%) of the 615 patients after liver resection, 90 (15%) were grade III, 48 (8%) grade IV, and 21 (3%) grade V. Four preoperative parameters were identified as independent predictors including American Society of Anesthesiologists category, transaminases levels (aspartate aminotransferase), extent of liver resection (>3 vs <3 segments), and the need for an additional hepaticojejunostomy or colon resection. A prediction score was calculated on the basis of 60% of the population (369 patients) using the 4 independent predictors ranging from 0 to 10 points. The risk to develop serious postoperative complications was 16% in "low risk" patients (0-2 points), 37% in "intermediate risk" patients (3-5 points) and 60% in "high risk" patients (6-10 points). The predicted mean for absolute risk for grades III to V complications was 27% in the validation population including 40% of the patients (n = 246), whereas the observed risk was 24%. Predicted and observed risks were similar throughout the different risk categories (P = 0.8). The score was significantly associated with hospital and intensive care unit stays. Costs of the entire procedure doubled among the 3 risk groups. CONCLUSIONS: This novel and simple score accurately predicts postoperative complications and cost in patients undergoing liver resection. This score allows early identification of patients at risk and may impact not only decision making for surgical intervention but also quality assessment and reimbursement.


Assuntos
Hepatectomia , Complicações Pós-Operatórias , Medição de Risco , Idoso , Análise de Variância , Custos e Análise de Custo , Feminino , Hepatectomia/economia , Hepatectomia/mortalidade , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/mortalidade , Valor Preditivo dos Testes , Estudos Prospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Suíça/epidemiologia
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