Assuntos
Adenoma de Células Hepáticas/complicações , Amiloidose/etiologia , Interleucina-6/metabolismo , Neoplasias Hepáticas/complicações , Fígado/metabolismo , Proteína Amiloide A Sérica/metabolismo , Adenoma de Células Hepáticas/metabolismo , Amiloidose/diagnóstico , Evolução Fatal , Feminino , Expressão Gênica , Humanos , Interleucina-6/genética , Fígado/citologia , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Pessoa de Meia-Idade , Análise de Sequência de RNARESUMO
PURPOSE: In this prospective study, our goal was to emphasize the diagnostic value of combining (11)C-choline and (18)F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease. METHODS: Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death). RESULTS: Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of (11)C-choline, (18)F-FDG and combined (11)C-choline and (18)F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with (18)F-FDG-positive lesions than those with (18)F-FDG-negative lesions (p < 0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with (18)F-FDG-positive lesions than in those with (18)F-FDG-negative lesions (p < 0.05). CONCLUSION: The combined use of (11)C-choline and (18)F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Fluordesoxiglucose F18/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Radioisótopos de Carbono/administração & dosagem , Colina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
BACKGROUND & AIMS: Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is a challenge to determine a patient's prognosis. We aimed to identify new prognostic markers of patients with HCC treated by liver resection. METHODS: We collected 314 HCC samples from patients at Bordeaux (1998-2007) and Créteil (2003-2007) hospitals in France. We analyzed the gene expression patterns of the tumors and compared expression patterns with patient survival times. Using the coefficient and regression formula of the multivariate Cox model, we identified a "5-gene score" associated with survival times. This molecular score was then validated in 2 groups of patients from Europe and the United States (n = 213) and China (n = 221). RESULTS: The 5-gene score, based on combined expression level of HN1, RAN, RAMP3, KRT19, and TAF9, was associated with disease-specific survival times of 189 patients with resected HCC in Bordeaux (hazard ratio = 3.5; 95% confidence interval: 1.9-6.6; P < .0001). The association between the 5-gene score and disease-specific survival was validated in an independent cohort of 125 patients in Créteil (hazard ratio = 2.3; 95% confidence interval: 1.1-4.9; P < .0001). The 5-gene score more accurately predicted patient outcomes than gene expression signatures reported previously. In multivariate analyses, the 5-gene score was associated with disease-specific survival, independent of other clinical and pathology feature of HCC. Disease-specific survival was also predicted by combining data on microvascular invasion, the Barcelona Clinic Liver Cancer classification system, and the 5-gene score in a nomogram. The prognostic accuracy of the 5-gene score was further validated in European and US patients with hepatitis C, cirrhosis, and HCC (overall survival P = .002) and in Asian patients with HCC with hepatitis B (overall survival, P = .02). Combining the 5-gene score with the expression pattern of 186 genes in corresponding cirrhotic tissues increased its prognostic accuracy. CONCLUSIONS: The molecular 5-gene score is associated with outcomes of patients with HCC treated by resection in different clinical settings worldwide. This new biomarker should be tested in clinical trials to stratify patients in therapeutic decisions.
Assuntos
Carcinoma Hepatocelular/genética , Hepatectomia , Neoplasias Hepáticas/genética , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Proteínas de Ciclo Celular , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Proteínas Associadas aos Microtúbulos , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares , Prognóstico , Modelos de Riscos Proporcionais , Proteína 3 Modificadora da Atividade de Receptores/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genética , Proteína ran de Ligação ao GTP/genéticaRESUMO
BACKGROUND & AIMS: Hepatocellular adenomas (HCA) are benign liver tumors mainly related to oral contraception and classified into 4 molecular subgroups: inflammatory (IHCA), HNF1A-inactivated (H-HCA), ß-catenin-activated (bHCA) or unclassified (UHCA). Glycogen storage disease type I (GSD) is a rare hereditary metabolic disease that predisposes to HCA development. The aim of our study was to characterize the molecular profile of GSD-associated HCA. METHODS: We characterized a series of 25 HCAs developed in 15 patients with GSD by gene expression and DNA sequence of HNF1A, CTNNB1, IL6ST, GNAS, and STAT3 genes. Moreover, we searched for glycolysis, gluconeogenesis, and fatty acid synthesis alterations in GSD non-tumor livers and compared our results to those observed in a series of sporadic H-HCA and various non-GSD liver samples. RESULTS: GSD adenomas were classified as IHCA (52%) mutated for IL6ST or GNAS, bHCA (28%) or UHCA (20%). In contrast, no HNF1A inactivation was observed, showing a different molecular subtype distribution in GSD-associated HCA from that observed in sporadic HCA (p = 0.0008). In non-tumor GSD liver samples, we identified glycolysis and fatty acid synthesis activation with gluconeogenesis repression. Interestingly, this gene expression profile was similar to that observed in sporadic H-HCA. CONCLUSIONS: Our study showed a particular molecular profile in GSD-related HCA characterized by a lack of HNF1A inactivation. This exclusion could be explained by similar metabolic defects observed with HNF1A inactivation and glucose-6-phosphatase deficiency. Inversely, the high frequency of ß-catenin mutations could be related to the increased frequency of malignant transformation in hepatocellular carcinoma.
Assuntos
Adenoma de Células Hepáticas/epidemiologia , Adenoma de Células Hepáticas/genética , Perfilação da Expressão Gênica , Doença de Depósito de Glicogênio Tipo I/epidemiologia , Doença de Depósito de Glicogênio Tipo I/genética , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Adenoma de Células Hepáticas/metabolismo , Adolescente , Adulto , Cromograninas , Comorbidade , Receptor gp130 de Citocina/genética , Receptor gp130 de Citocina/metabolismo , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Regulação Neoplásica da Expressão Gênica , Doença de Depósito de Glicogênio Tipo I/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Masculino , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Adulto Jovem , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Liver adenomas are benign tumors at risk of malignant transformation. In a genome-wide search for loss of heterozygosity (LOH) associated with liver adenomas, we found a deletion in chromosome 12q in five of ten adenomas. In most cases, LOH at 12q was the only recurrent genetic alteration observed, suggesting the presence of a tumor-suppressor gene in that region. A minimal common region of deletion was defined in 12q24 that included the gene TCF1 (transcription factor 1), encoding hepatocyte nuclear factor 1 (HNF1; refs 1,2). Heterozygous germline mutations of TCF1 have been identified in individuals affected with maturity-onset diabetes of the young type 3 (MODY3; ref. 3). Bi-allelic inactivation of TCF1 was found in 10 of 16 screened adenomas, and heterozygous germline mutation were present in three affected individuals. Furthermore, 2 well-differentiated hepatocellular carcinomas (HCCs) occurring in normal liver contained somatic bi-allelic mutations of 30 screened HCCs. These results indicate that inactivation of TCF1, whether sporadic or associated with MODY3, is an important genetic event in the occurrence of human liver adenoma, and may be an early step in the development of some HCCs.
Assuntos
Adenoma/genética , Proteínas de Ligação a DNA , Neoplasias Hepáticas/genética , Proteínas Nucleares , Fatores de Transcrição/genética , Adenoma/fisiopatologia , Adulto , Idoso , Cromossomos Humanos Par 12 , Diabetes Mellitus Tipo 2/genética , Feminino , Marcadores Genéticos , Fator 1 Nuclear de Hepatócito , Fator 1-alfa Nuclear de Hepatócito , Fator 1-beta Nuclear de Hepatócito , Humanos , Neoplasias Hepáticas/metabolismo , Perda de Heterozigosidade , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Análise de Sequência de DNARESUMO
BACKGROUND: Researchers have suggested that antibiotics could cure acute appendicitis. We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis. METHODS: In this open-label, non-inferiority, randomised trial, adult patients (aged 18-68 years) with uncomplicated acute appendicitis, as assessed by CT scan, were enrolled at six university hospitals in France. A computer-generated randomisation sequence was used to allocate patients randomly in a 1:1 ratio to receive amoxicillin plus clavulanic acid (3 g per day) for 8-15 days or emergency appendicectomy. The primary endpoint was occurrence of postintervention peritonitis within 30 days of treatment initiation. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10 percentage points. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT00135603. FINDINGS: Of 243 patients randomised, 123 were allocated to the antibiotic group and 120 to the appendicectomy group. Four were excluded from analysis because of early dropout before receiving the intervention, leaving 239 (antibiotic group, 120; appendicectomy group, 119) patients for intention-to-treat analysis. 30-day postintervention peritonitis was significantly more frequent in the antibiotic group (8%, n=9) than in the appendicectomy group (2%, n=2; treatment difference 5·8; 95% CI 0·3-12·1). In the appendicectomy group, despite CT-scan assessment, 21 (18%) of 119 patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis. In the antibiotic group, 14 (12% [7·1-18·6]) of 120 underwent an appendicectomy during the first 30 days and 30 (29% [21·4-38·9]) of 102 underwent appendicectomy between 1 month and 1 year, 26 of whom had acute appendicitis (recurrence rate 26%; 18·0-34·7). INTERPRETATION: Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis. Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment. FUNDING: French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002.
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Apendicectomia , Apendicite/tratamento farmacológico , Apendicite/cirurgia , Ácido Clavulânico/uso terapêutico , Doença Aguda , Adolescente , Adulto , Idoso , Apendicite/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The optimal strategy for resectable synchronous colorectal liver metastases remains controversial. Although some authors advocate a staged treatment, an increasing number of studies have reported that combined colorectal and liver resection is safe. Laparoscopic combined resection in primary colorectal cancer with synchronous liver metastases has been reported but there are no specific data for major liver resections. In the present study, we evaluated the feasibility of a simultaneous entirely laparoscopic procedure, in the light of the benefits of laparoscopy in both colon and liver surgery, and discussed the benefits of this strategy. METHODS: Two cases are presented of totally laparoscopic major liver resections associated with laparoscopic colorectal resections for synchronous liver metastases with the emphasis on the technical aspects. Duration of surgery, blood loss and post-operative outcome were evaluated. RESULTS: Laparoscopic right hepatectomy or left hepatectomy with simultaneous colon resection for liver metastasis was feasible and safe with only one suprapubic 5-mm trocar added to the usual trocar sites. The mean duration of surgery was 327 min with a mean estimated blood loss of 200 ml. The post-operative course was uneventful. DISCUSSION: In selected patients, laparoscopic major hepatectomies for unilobular synchronous metastases can be safely performed simultaneously with colorectal surgery.
Assuntos
Colectomia/métodos , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Biópsia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Tomografia Computadorizada por Raios XRESUMO
Hepatocyte transplantation has not yet reached therapeutic status, as it has proven difficult to transplant a sufficient number of functional hepatocytes able to integrate and proliferate inside liver plates. It has recently been shown that whole livers can be decellularized by portal infusion of detergents, yielding a decellularized scaffold with a well preserved vascular network and specific liver matrix. Perfusion of different combinations of cells through the portal vein of these scaffolds results in reconstitution of a complete functional organ that can be transplanted in small animals. An auto-constructed human liver could be engineered from exogenous liver scaffolds seeded with various cell populations, including autologous cells derived from induced pluripotent stem cells. Auto-constructed livers might replace conventional liver grafts in future.
Assuntos
Hepatócitos/transplante , Fígado/citologia , Células-Tronco Pluripotentes/citologia , Diferenciação Celular/fisiologia , Matriz Extracelular/fisiologia , Hepatócitos/citologia , Humanos , Transplante de Fígado/métodos , Engenharia Tecidual/métodosRESUMO
UNLABELLED: The feasibility of ex vivo gene therapy as an alternative to liver transplantation for the treatment of liver metabolic diseases needs to be analyzed in large animal models. This approach requires appropriate gene transfer vectors and effective hepatocyte engraftment. Lentiviral vectors have the ability to transduce nondividing differentiated cells, such as hepatocytes, and portal vein occlusion increases hepatocyte engraftment. We investigated whether reversible portal vein embolization combined with ex vivo lentivirus-mediated gene transfer is an effective approach for successful hepatocyte engraftment in nonhuman primates and whether the transgene remains expressed in the long term in transplanted hepatocytes in situ. Simian hepatocytes were isolated after left lobe resection, and the left and right anterior portal branches of animals were embolized with absorbable material. Isolated hepatocytes were labeled with Hoechst dye or transduced in suspension with lentiviruses expressing green fluorescent protein under the control of the human apolipoprotein A-II promoter and transplanted via the inferior mesenteric vein. The whole procedure was well tolerated. The embolized liver was revascularized within 2 weeks. The volume of nonembolized liver increased from 38.7% +/- 0.8% before embolization to 55.9% +/- 1% after embolization and hepatocytes significantly proliferated (10.5% +/- 0.4% on day 3 after embolization). Liver repopulation after transplantation with Hoechst-labeled hepatocytes was 7.4% +/- 1.2%. Liver repopulation was 2.1% +/- 0.2% with transduced hepatocytes, a proportion similar to that obtained with Hoechst-labeled cells, given that the mean transduction efficacy of simian hepatocyte population was 34%. Transgene expression persisted at 16 weeks after transplantation. CONCLUSION: We have developed a new approach to improve hepatocyte engraftment and to express a transgene in the long term in nonhuman primates. This strategy could be suitable for clinical applications.
Assuntos
Apolipoproteína A-II/metabolismo , Transplante de Células/métodos , Embolização Terapêutica/métodos , Hepatócitos/metabolismo , Hepatócitos/transplante , Animais , Apolipoproteína A-II/genética , Proliferação de Células , Regulação da Expressão Gênica , Terapia Genética , Hepatócitos/patologia , Humanos , Lentivirus/genética , Fígado/metabolismo , Fígado/patologia , Fígado/cirurgia , Regeneração Hepática/fisiologia , Macaca mulatta , Modelos Animais , Veia Porta/cirurgia , Transgenes/genéticaRESUMO
BACKGROUND: Laparoscopic major resections remain a challenge for liver surgeons. This video illustrates, step by step, our laparoscopic technique for left hepatectomy. METHODS: The control of vascular inflow and outflow as well as the division of the left hepatic duct were carried out extraparenchymally before liver transection. Between 2002 and 2008, 11 left hepatectomies were performed by laparoscopy: 7 for liver tumor and 4 for localized Caroli's disease. RESULTS: Mean duration of surgery was 248 +/- 25 min. Mean operative blood loss was 129 +/- 42 ml. Intraoperative blood transfusion or conversion to laparotomy were never required. One postoperative biliary collection occurred and was drained percutaneously. None of the patients died. Mean hospital stay was 7.6 +/- 2.2 days. CONCLUSIONS: This technique has proved to be safe and easily reproducible.
Assuntos
Hepatectomia/métodos , Laparoscopia/métodos , Hepatopatias/cirurgia , Hemostasia Cirúrgica , Humanos , Tempo de Internação/estatística & dados numéricos , Fígado/irrigação sanguínea , Fígado/cirurgia , Complicações Pós-Operatórias , Resultado do Tratamento , Gravação em VídeoRESUMO
BACKGROUND: Only a few series have demonstrated the safety of laparoscopic resection for hepatocellular carcinoma (HCC) and the benefits of this approach. Moreover, these studies reported mostly minor and nonanatomic hepatic resections. This report describes the results of a pair-matched comparative study between open and laparoscopic liver resections for HCC in a series of essentially anatomic resections. METHODS: Patients were retrospectively matched in pairs for the following criteria: sex, age, American Society of Anesthesiology (ASA) score, severity of liver disease, tumor size, and type of resection. A total of 42 patients undergoing laparoscopy were compared with patients undergoing laparotomy during the same period. Surgeons from the authors' department not trained in laparoscopy performed open resections. Operative, postoperative, and oncologic outcomes were compared. RESULTS: The mean duration of surgery was similar in the two groups. Significantly less bleeding was observed in the laparoscopic group (364.3 vs. 723.7 ml; p < 0.0001). Transfusion was required for four patients (9.5%) in the laparoscopic group and seven patients (16.7%) in the open surgery group (p = 0.51). Postoperative ascites was less frequent after laparoscopic resections (7.1 vs. 26.1%; p = 0.03). General morbidity was similar in the two groups (9.5 vs. 11.9%; p = 1.00). The mean hospital stay was significantly shorter for the patients undergoing laparoscopy (6.7 vs. 9.6 days; p < 0.0001). The surgical margin and local recurrence adjacent to the liver stump were not affected by laparoscopy. The overall postoperative survival rates in the laparoscopic group were 93.1% at 1 year, 74.4% at 3 years, and 59.5% at 5 years and, respectively, 81.8, 73, and 47.4% in the open surgery group (p = 0.25). The postoperative disease-free survival rates in the laparoscopic group were at 81.6% at 1 year, 60.9% at 3 years, and 45.6% at 5 years, respectively, 70.2, 54.3, and 37.2% in the open surgery group (p = 0.29). CONCLUSIONS: Laparoscopic resection of HCC for selected patients gave a better postoperative outcome without oncologic consequences. Prospective trials are required to confirm these results.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , França/epidemiologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Transplantation of hepatocytes, whether genetically modified or not, has become an alternative to orthotopic liver transplantation for the treatment of patients with metabolic disease. However, more than ten years after the first clinical trial of ex vivo gene therapy to treat patients with Familial Hypercholesterolemia, there are still a number of impediments to these approaches. Numerous animal models are still being developed on the one hand to improve hepatocyte integration within hepatic parenchyma and function, and on the other hand to develop vectors that drive long-term transgene expression in situ. These include large animal models such as non-human primates, which have recently led to significant progress in hepatocyte transplantation. Simultaneous development of lentiviral vectors from different lentivirus species has permitted the transfer of genes into mitotically-quiescent primary cells including differentiated hepatocytes. Particularly third generation vectors derived from HIV-1 lentivirus are the most widely used and have significantly improved the safety and efficiency of these vectors. Given the shortage of organs and problems related to immunosuppression on one hand, and recent progresses in hepatocyte transduction and transplantation on the other hand, ex vivo approach is becoming a real alternative to allogeneic hepatocyte transplantation. We review the present progresses and limits of the ex vivo liver gene therapy approach in different animal models, emphasizing clinically relevant procedures.
Assuntos
Terapia Genética/métodos , Vetores Genéticos/genética , Hepatócitos/transplante , Doenças Metabólicas/terapia , Retroviridae/genética , Animais , Vetores Genéticos/metabolismo , Humanos , Fígado/metabolismo , Hepatopatias/terapia , Retroviridae/metabolismoRESUMO
OBJECTIVE: To analyze the results of 6 international surgical centers performing laparoscopic major liver resections. SUMMARY BACKGROUND DATA: The safety and feasibility of laparoscopy for minor liver resections has been previously demonstrated. Major anatomic liver resections, initially considered to be unsuitable for laparoscopy, are increasingly reported by several centers worldwide. METHODS: Prospective databases of 3 European, 2 U.S., and 1 Australian centers were combined. Between 1997 and 2008, 210 major liver resections were performed: 136 right and 74 left hepatectomies. Results and differences in surgical techniques between the 6 centers are outlined. RESULTS: Surgical duration was 250 minutes (range: 90-655 minutes). Operative blood loss was 300 mL (range: 20-2500 mL). Thirty patients (14.3%) received blood transfusion. Conversion to open surgery was required in 26 patients (12.4%). Portal triad clamping was performed in 24 patients (11.4%). Median tumor size was 5.4 cm (range: 1-25 cm) and surgical margin was 10.5 mm (range: 0-70 mm). Two patients died during the postoperative period from pulmonary embolism and urosepsis. Liver-specific and general complications occurred in 17 (8.1%) and 29 patients (13.8%), respectively. Hospital length of stay was 6 days (range: 1-34 days). A further analysis of early (n = 90) and late (n = 120) experience showed improved surgical and postoperative results in the latter group. CONCLUSIONS: This multicenter study demonstrates that laparoscopic major liver resections are feasible in selected patients and results improve with experience. However, proficiency in both open liver surgery and advanced laparoscopy is compulsory and surgeons must begin with minor laparoscopic resections.
Assuntos
Hepatectomia , Laparoscopia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contraindicações , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Complicações Intraoperatórias , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Neoplasias Hepáticas , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Adulto JovemRESUMO
OBJECTIVE: To evaluate a multicenter, international series on minimally invasive liver resection for colorectal carcinoma (CRC) metastasis. SUMMARY BACKGROUND DATA: Multiple single series have been reported on laparoscopic liver resection for CRC metastasis. We report the first collaborative multicenter, international series to evaluate the safety, feasibility, and oncologic integrity of laparoscopic liver resection for CRC metastasis. METHODS: We retrospectively reviewed all patients who underwent minimally invasive liver resection for CRC metastasis from February 2000 to September 2008 from multiple medical centers from the United States and Europe. The multicenter series of patients were accumulated into a single database. Patient demographics, preoperative, operative, and postoperative characteristics were analyzed. Actuarial overall survival was calculated with Kaplan-Meier analysis. RESULTS: A total of 109 patients underwent minimally invasive liver resection for CRC metastasis. The median age was 63 years (range, 32-88 years) with 51% females. The most common sites of primary colon cancer were sigmoid/rectum (51%), right colon (25%), and left colon (13%). Synchronous liver lesions were present in 11% of patients. For those with metachronous lesions liver lesions, the median time interval from primary colon cancer surgery to liver metastasectomy was 12 months. Preoperative chemotherapy was administered in 68% of cases prior to liver resection. The majority of patients underwent prior abdominal operations (95%). Minimally invasive approaches included totally laparoscopic (56%) and hand-assisted laparoscopic (41%), the latter of which was employed more frequently in the US medical centers (85%) compared with European centers (13%) (P = 0.001). There were 4 conversions to open surgery (3.7%), all due to bleeding. Extents of resection include wedge/segmentectomy (34%), left lateral sectionectomy (27%), right hepatectomy (28%), left hepatectomy (9%), extended right hepatectomy (0.9%), and caudate lobectomy (0.9%). Major liver resections (> or =3 segments) were performed in 45% of patients. Median OR time was 234 minutes (range, 60-555 minutes) and blood loss was 200 mL (range, 20-2500 mL) with 10% receiving a blood transfusion. There were no reported perioperative deaths and a 12% complication rate. Median length of hospital stay for the entire series was 4 days (range, 1-22 days) with a shorter stay in medical centers in the United States (3 days) versus that seen in Europe (6 days) (P = 0.001). Negative margins were achieved in 94.4% of patients. Actuarial overall survivals at 1-, 3-, and 5-year for the entire series were 88%, 69%, and 50%, respectively. Disease-free survivals at 1-, 3-, and 5-year were 65%, 43%, and 43%, respectively. CONCLUSIONS: Minimally invasive liver resection for colorectal metastasis is safe, feasible, and oncologically comparable to open liver resection for both minor and major liver resections, even with prior intra-abdominal operations, in selected patients and when performed by experienced surgeons.
Assuntos
Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
More than 30 years after the first hepatocyte transplant to treat the Gunn rat, the animal model for Crigler-Najjar syndrome, there are still a number of impediments to hepatocyte transplantation. Numerous animal models are still used in work aimed at improving hepatocyte engraftment and/or long-term function. Although other cell sources, particularly hepatic and extrahepatic stem cells, are being explored, adult hepatocytes remain the cells of choice for the treatment of liver diseases by cell therapy. In recent years, diverse approaches have been developed in various animal models to enhance hepatocyte transduction and amplification in vitro and cell engraftment and functionality in vivo. They have led to significant progress in hepatocyte transplantation for the treatment of patients with metabolic diseases and for bridging patients with acute injury until their own livers regenerate. This review presents and considers the results of this work with a special emphasis on procedures that might be clinically applicable.
Assuntos
Hepatócitos/citologia , Animais , Transplante de Células , Terapia Baseada em Transplante de Células e Tecidos , Síndrome de Crigler-Najjar/patologia , Modelos Animais de Doenças , Humanos , Fígado/patologia , Regeneração Hepática , Camundongos , Ratos , Células-Tronco/citologia , Síndrome , Engenharia Tecidual/métodosRESUMO
PURPOSE: In France, the current practice for postoperative care of thyroidectomy is still inpatient care. No series of outpatient thyroidectomy has been reported. The aim of this work was to assess the acceptability, feasibility, and safety of outpatient unilateral thyroid lobectomy in a university hospital. MATERIALS AND METHODS: The procedure was proposed to patients presenting with nodule(s) in one lobe of the thyroid and fulfilling predetermined inclusion criteria. The surgical protocol included no drainage and, progressively, no dressing. Standard anesthetic, analgesic, and antiemetic protocols were used. Unplanned admission, complication, and re-operation rates were evaluated. RESULTS: Among 153 unilateral thyroid lobectomies performed, 95 (62%) were planned for outpatient surgery. The proportion of outpatient unilateral thyroid lobectomies increased during an 8-year period from 36% to 90%. One patient was re-operated because local hemorrhage was diagnosed in the recovery room. He was discharge the next day. Eighteen patients (13.7%) were admitted because of nausea (n = 6), dizziness, and physical discomfort mostly due to anxiety (n = 5). Seventy-seven patients were discharged as planned 6 to 8 h after the operation. No patient was readmitted. CONCLUSIONS: Outpatient unilateral thyroid lobectomy is feasible and safe in the setting of appropriate facilities and management protocol. Strict control of postoperative nausea is essential, and a preoperative education for ambulatory surgery is useful to minimize patient anxiety and increase acceptability.
Assuntos
Procedimentos Cirúrgicos Ambulatórios , Tireoidectomia , Adolescente , Adulto , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Procedimentos Cirúrgicos Ambulatórios/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Cuidados Pós-Operatórios , Complicações Pós-Operatórias , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Adulto JovemRESUMO
No detailed description of nonhuman primate liver anatomy has been reported and little is known about the similarity between such livers and human liver. The cynomolgus monkey (Macaca fascicularis) was used to establish a preclinical model of genetically modified hepatocytes auto transplantation. Here, we report information gleaned from careful observation and notes obtained from 59 female cynomolgus monkeys undergoing 44 anatomical hepatic resections, 12 main portal vein division dissections and selective branch ligations, and 46 portographies. Additionally, three anatomical liver dissections after total resection at autopsy were performed and served to confirm peroperative observations and for photography to provide illustrations. Our results indicate that the cynomolgus monkey liver has four lobes: the median (the largest), the right and left lateral, and the caudate lobes. In 60% (N=20) of individuals the portal bifurcates into right and left portal veins, in the remaining 40% (N=14) the portal vein trifurcates into right anterior, right posterior, and left portal veins. The anatomy and branching pattern of the hepatic artery and bile ducts closely follow those of the portal branches. Functionally, the cynomolgus monkey liver can be divided into eight independent segments. Thus, we report the first detailed description of the hepatic and portal surgical anatomy of the cynomolgus monkey. The cynomolgus monkey liver is more similar to the human liver than are livers of any small or large nonprimate mammals that have been described.
Assuntos
Fígado/anatomia & histologia , Macaca fascicularis/anatomia & histologia , Animais , Ductos Biliares Intra-Hepáticos/anatomia & histologia , Ductos Biliares Intra-Hepáticos/cirurgia , Feminino , Artéria Hepática/anatomia & histologia , Artéria Hepática/cirurgia , Fígado/irrigação sanguínea , Fígado/cirurgia , Macaca fascicularis/cirurgia , Veia Porta/anatomia & histologia , Veia Porta/cirurgiaRESUMO
BACKGROUND: Single, small hepatocarcinomas (HCC) are still an indication for partial liver resection in patients ineligible for transplantation. Anatomical resections are recommended for oncological reasons. The mini-invasive approach of laparoscopy should minimize hepatic and parietal injury, thereby decreasing the risk of liver failure and ascites. However, the oncological results of this approach and its presumed benefits remain undemonstrated. We evaluated the short- and midterm results of laparoscopic liver resections for HCC. METHODS: Between 1999 and 2006, we performed 32 laparoscopic liver resections for HCC. Mean tumor size was 3.8 +/- 2 cm and the mean age of the patients was 65 +/- 11 years. Twenty-two patients had cirrhosis (21 Child A and one Child C). Operative and postoperative results were analyzed, together with recurrence and survival rates. RESULTS: We carried out 13 unisegmentectomies, nine bisegmentectomies, one trisegmentectomy, two right hepatectomies, one left hepatectomy, and six atypical resections. The duration of the operation was 231 +/- 101 minutes. Conversion to laparotomy was required in three patients (9%), none in emergency situations. Mean blood loss was 461 ml, with five patients (15.6%) requiring blood transfusion. The mean surgical margin was 10.4 mm. One cirrhotic patient (Child C) underwent surgery for a partially ruptured tumor and died of liver failure. Two patients had ascites and no transient liver failure occurred in the other 19 cirrhotic patients. Mean hospital stay was 7.1 days. During a mean follow-up of 26 months, 10 patients (31%) presented recurrence within the liver. None of the patients had peritoneal carcinomatosis or trocar site recurrence. Three-year overall and disease-free survival rates were 71.9% and 54.5%, respectively. CONCLUSIONS: Laparoscopic liver resection for HCC is feasible and well tolerated. Midterm survival and recurrence rates are similar to those after laparotomy.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/cirurgia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
OBJECTIVES: The purpose of this work was to evaluate the feasibility and outcome of elective laparoscopic cholecystectomy as a day-case procedure in a French university hospital. METHODS: Since the creation of a surgical day-care centre in 1999, patients without severe chronic disease and anticoagulant therapy were selected for elective laparoscopic cholecystectomy. They were admitted and operated on in the morning hours and discharged after a double check by the surgeon and an anaesthetist 4 to 6 hours later. They were contacted by telephone the day subsequent to surgery and were seen in the outpatient unit 8 to 10 days after. RESULTS: Two hundred eleven laparoscopic cholecystectomies were performed in day-care surgery from January 1999 to December 2005. The proportion of day-case management increased during the six-year period from 32% to 53%. Eighteen percent of patients had an overnight admission. The overall complication rate was 1.8%. None of the patients had an emergency readmission. Incapacity duration went from 1 to 15 days. CONCLUSION: These results suggest that laparoscopic cholecystectomy can be routinely performed as a day-case procedure.