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1.
HPB (Oxford) ; 24(6): 901-909, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34836755

RESUMO

BACKGROUND: Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. METHODS: Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2-4 h thereafter. RESULTS: Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P < 0.01) in the microdialysate already in the first postoperative samples. Glycerol concentrations >400 µmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. CONCLUSION: High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559).


Assuntos
Fístula Anastomótica , Pancreaticoduodenectomia , Idoso , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Catéteres , Glucose , Glicerol , Humanos , Inflamação , Ácido Láctico , Microdiálise , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Ácido Pirúvico
2.
Trials ; 22(1): 642, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544470

RESUMO

BACKGROUND: Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver. METHODS: The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines. DISCUSSION: The ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT03326791 . Registered on 31 October 2017.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Aspirina/efeitos adversos , Neoplasias Colorretais/prevenção & controle , Método Duplo-Cego , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/prevenção & controle , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Prevenção Secundária
3.
Mol Oncol ; 15(4): 830-845, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33325154

RESUMO

Hepatic resection is potentially curative for patients with colorectal liver metastases, but the treatment benefit varies. KRAS/NRAS (RAS)/TP53 co-mutations are associated with a poor prognosis after resection, but there is large variation in patient outcome within the mutation groups, and genetic testing is currently not used to evaluate benefit from surgery. We have investigated the potential for improved prognostic stratification by combined biomarker analysis with DNA copy number aberrations (CNAs), and taking tumor heterogeneity into account. We determined the mutation status of RAS, BRAFV600 , and TP53 in 441 liver lesions from 171 patients treated by partial hepatectomy for metastatic colorectal cancer. CNAs were profiled in 232 tumors from 67 of the patients. Mutations and high-level amplifications of cancer-critical genes, the latter including ERBB2 and EGFR, were predominantly homogeneous within patients. RAS/BRAFV600E and TP53 co-mutations were associated with a poor patient outcome (hazard ratio, HR, 3.9, 95% confidence interval, CI, 1.3-11.1, P = 0.012) in multivariable analyses with clinicopathological variables. The genome-wide CNA burden and intrapatient intermetastatic CNA heterogeneity varied within the mutation groups, and the CNA burden had prognostic associations in univariable analysis. Combined prognostic analyses of RAS/BRAFV600E /TP53 mutations and CNAs, either as a high CNA burden or high intermetastatic CNA heterogeneity, identified patients with a particularly poor outcome (co-mutation/high CNA burden: HR 2.7, 95% CI 1.2-5.9, P = 0.013; co-mutation/high CNA heterogeneity: HR 2.5, 95% CI 1.1-5.6, P = 0.022). In conclusion, DNA copy number profiling identified genomic and prognostic heterogeneity among patients with resectable colorectal liver metastases with co-mutated RAS/BRAFV600E /TP53.


Assuntos
Neoplasias Colorretais/genética , Genes ras , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteína Supressora de Tumor p53/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Variações do Número de Cópias de DNA , GTP Fosfo-Hidrolases/genética , Genômica , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Proteínas de Membrana/genética , Instabilidade de Microssatélites , Mutação , Noruega , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
4.
Clin Cancer Res ; 26(15): 4107-4119, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32299813

RESUMO

PURPOSE: Molecular tumor heterogeneity may have important implications for the efficacy of targeted therapies in metastatic cancers. Inter-metastatic heterogeneity of sensitivity to anticancer agents has not been well explored in colorectal cancer. EXPERIMENTAL DESIGN: We established a platform for ex vivo pharmacogenomic profiling of patient-derived organoids (PDO) from resected colorectal cancer liver metastases. Drug sensitivity testing (n = 40 clinically relevant agents) and gene expression profiling were performed on 39 metastases from 22 patients. RESULTS: Three drug-response clusters were identified among the colorectal cancer metastases, based primarily on sensitivities to EGFR and/or MDM2 inhibition, and corresponding with RAS mutations and TP53 activity. Potentially effective therapies, including off-label use of drugs approved for other cancer types, could be nominated for eighteen patients (82%). Antimetabolites and targeted agents lacking a decisive genomic marker had stronger differential activity than most approved chemotherapies. We found limited intra-patient drug sensitivity heterogeneity between PDOs from multiple (2-5) liver metastases from each of ten patients. This was recapitulated at the gene expression level, with a highly proportional degree of transcriptomic and pharmacological variation. One PDO with a multi-drug resistance profile, including resistance to EGFR inhibition in a RAS-mutant background, showed sensitivity to MEK plus mTOR/AKT inhibition, corresponding with low-level PTEN expression. CONCLUSIONS: Intra-patient inter-metastatic pharmacological heterogeneity was not pronounced and ex vivo drug screening may identify novel treatment options for metastatic colorectal cancer. Variation in drug sensitivities was reflected at the transcriptomic level, suggesting potential to develop gene expression-based predictive signatures to guide experimental therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais/terapia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Variação Biológica Individual , Quimioterapia Adjuvante , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Hepatectomia , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Organoides , Variantes Farmacogenômicos , Medicina de Precisão/métodos , Cultura Primária de Células/métodos , Células Tumorais Cultivadas
5.
Clin Colorectal Cancer ; 19(1): e26-e47, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31982351

RESUMO

BACKGROUND: The prevalence and clinical implications of genetic heterogeneity in patients with multiple colorectal liver metastases remain largely unknown. In a prospective series of patients undergoing resection of colorectal liver metastases, the aim was to investigate the inter-metastatic and primary-to-metastatic heterogeneity of mutations in KRAS, NRAS, BRAF, and PIK3CA and their prognostic impact. PATIENTS AND METHODS: We analyzed the mutation status among 372 liver metastases and 78 primary tumors from 106 patients by methods used in clinical routine testing, by Sanger sequencing, by next-generation sequencing (NGS), and/or by droplet digital polymerase chain reaction. The 3-year cancer-specific survival (CSS) was analyzed using the Kaplan-Meier method. RESULTS: Although Sanger sequencing indicated inter-metastatic mutation heterogeneity in 14 of 97 patients (14%), almost all cases were refuted by high-sensitive NGS. Also, heterogeneity among metastatic deposits was concluded only for PIK3CA in 2 patients. Similarly, primary-to-metastatic heterogeneity was indicated in 8 of 78 patients (10%) using Sanger sequencing but for only 2 patients after NGS, showing the emergence of 1 KRAS and 1 PIK3CA mutation in the metastatic lesions. KRAS mutations were present in 53 of 106 patients (50%) and were associated with poorer 3-year CSS after liver resection (37% vs. 61% for KRAS wild-type; P = .004). Poor prognostic associations were found also for the combination of KRAS/NRAS/BRAF mutations compared with triple wild-type (P = .002). CONCLUSION: Intra-patient mutation heterogeneity was virtually undetected, both between the primary tumor and the liver metastases and among the metastatic deposits. KRAS mutations separately, and KRAS/NRAS/BRAF mutations combined, were associated with poor patient survival after partial liver resection.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Heterogeneidade Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Noruega/epidemiologia , Prognóstico , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto Jovem
6.
Ann Surg ; 271(2): 212-218, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31188200

RESUMO

OBJECTIVE: To determine overall survival and disease-free survival in selected patients with nonresectable liver-only colorectal cancer receiving liver transplantation. BACKGROUND: Patients with nonresectable colorectal cancer receiving palliative chemotherapy has a 5-year overall survival of about 10%. Liver transplantation provided an overall survival of 60% in a previous study (SECA-I). Risk factors for death were carcinoembryonic antigen (CEA) >80 µg/L, progressive disease on chemotherapy, size of largest lesion>5.5 cm, and less than 2 years from resection of the primary tumor to transplantation. METHODS: In this prospective (SECA-II) study, we included colorectal cancer patients with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography scans and at least 10% response to chemotherapy. Time from diagnosis to liver transplant was required to be more than 1 year. RESULTS: At a median follow-up of 36 months, Kaplan-Meier overall survival at 1, 3, and 5 years were 100%, 83%, and 83%, respectively. Disease-free survival at 1, 2, and 3 years were 53%, 44%, and 35%, respectively. Overall survival from time of relapse at 1, 2, and 4 years were 100%, 73%, and 73%, respectively. Recurrence was mainly slow growing pulmonary metastases amenable to curative resection. Fong Clinical Risk Score of 1 to 2 at the time of diagnosis resulted in longer disease-free survival than score 3 to 4 (P = 0.044). Patients included in the present study had significantly better prognostic factors than the previous SECA-I study. CONCLUSION: Liver transplantation provides the longest overall survival reported in colorectal cancer patient with nonresectable liver metastases. Improved selection criteria give patients with nonresectable colorectal liver metastases a 5-year overall survival comparable to other indications for liver transplantation.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/análise , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida
7.
World J Surg Oncol ; 17(1): 156, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484583

RESUMO

BACKGROUND: Liver resection is a treatment of choice for colorectal and neuroendocrine liver metastases, and laparoscopy is an accepted approach for surgical treatment of these patients. The role of liver resection for patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM), however, is still disputable. Outcomes of laparoscopic liver resection for this group of patients have not been analyzed. MATERIAL AND METHODS: In this retrospective study, patients who underwent laparoscopic liver resection for NCNNLM at Oslo University Hospital between April 2000 and January 2018 were analyzed. Perioperative and oncologic data of these patients were examined. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. Median follow-up was 26 (IQR, 12-41) months. RESULTS: Fifty-one patients were identified from a prospectively collected database. The histology of primary tumors was classified as adenocarcinoma (n = 16), sarcoma (n = 4), squamous cell carcinoma (n = 4), melanoma (n = 16), gastrointestinal stromal tumor (n = 9), and adrenocortical carcinoma (n = 2). The median operative time was 147 (IQR, 95-225) min, while the median blood loss was 200 (IQR, 50-500) ml. Nine (18%) patients experienced postoperative complications. There was no 90-day mortality in this study. Thirty-five (68%) patients developed disease recurrence or progression. Seven (14%) patients underwent repeat surgical procedure for recurrent liver metastases. One-, three-, and five-year overall survival rates were 85%, 52%, and 38%, respectively. The median overall survival was 37 (95%CI, 25 to 49) months. CONCLUSION: Laparoscopic liver resection for NCNNLM results in good outcomes and should be considered in patients selected for surgical treatment.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma Adrenocortical/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Hepatectomia/mortalidade , Laparoscopia/mortalidade , Neoplasias Hepáticas/mortalidade , Melanoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Assistência Perioperatória , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Sarcoma/cirurgia , Taxa de Sobrevida
8.
Eur J Surg Oncol ; 45(12): 2340-2346, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31350075

RESUMO

INTRODUCTION: Surgery combined with perioperative chemotherapy has become standard of care in patients with resectable colorectal liver metastases. However, poor outcome is expected for a significant subgroup. The clinical implications of inter-metastatic heterogeneity remain largely unknown. In a prospective, population-based series of patients undergoing resection of multiple colorectal liver metastases, the aim was to investigate the prevalence and prognostic impact of heterogeneous response to neoadjuvant chemotherapy. MATERIALS AND METHODS: Radiological response to treatment was evaluated in a lesion-specific manner in 2-5 metastases per patient. Change of lesion diameter was evaluated and response/progression was classified according to three different size thresholds; 3, 4 and 5 mm. A heterogeneous response was defined as progression and response of different metastases in the same patient. RESULTS: In total, 142 patients with 585 liver metastases were examined with the same radiological method (MRI or CT) before and after neoadjuvant treatment. Heterogeneous response to treatment was seen in 16 patients (11%) using the 3 mm size change threshold, and this group had a 5-year cancer-specific survival of 19% compared to 49% for patients with response in all lesions (p = 0.003). Cut-off values of 4-5 mm were less sensitive for detecting a heterogeneous response, but the survival difference was similar and significant. CONCLUSION: A subgroup of patients with multiple colorectal liver metastases had heterogeneous radiological response to neoadjuvant chemotherapy and poor prognosis. The evaluation of response pattern is easy to perform, feasible in clinical practice and, if validated, a promising biomarker for treatment decisions.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Noruega , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
9.
HPB (Oxford) ; 21(11): 1485-1490, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30962136

RESUMO

BACKGROUND: Laparoscopic liver resection in the posterosuperior segments is technically challenging. This study aimed to compare the perioperative outcomes for laparoscopic and open resection of colorectal liver metastases located in the posterosuperior segments. METHODS: This was a subgroup analysis of the OSLO-COMET randomized controlled trial, where 280 patients were randomly assigned to open or laparoscopic parenchyma-sparing liver resections of colorectal metastases. Patients with tumors in the posterosuperior segments were identified, and perioperative outcomes and health related quality of life (HRQoL) were compared. RESULTS: We identified a total of 136 patients, 62 in the laparoscopic and 74 in the open group. The postoperative complication rate was 26% in the laparoscopic and 31% in the open group. The blood loss was less in the open group (500 vs. 250 ml, P = 0.006), but the perioperative transfusion rate was similar. The operative time was similar, while postoperative hospital stay was shorter in the laparoscopic group (2 vs. 4 days, P < 0.001). HRQoL was significantly better after laparoscopy at 1 month. CONCLUSION: In patients undergoing laparoscopic or open liver resection of colorectal liver metastases in the posterosuperior segments, laparoscopic surgery was associated with shorter hospital stay and comparable perioperative outcomes.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Noruega , Duração da Cirurgia , Complicações Pós-Operatórias , Qualidade de Vida
11.
J Gastrointest Surg ; 23(3): 556-562, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30465187

RESUMO

BACKGROUND: Portal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8 weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks. METHODS: Patients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) < 30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy. RESULTS: Forty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (± 4), compared to 1.5 (± 2) between the first and second CT (p < 0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (± 4) the first week, compared to 4.3 (± 2) for patients who failed to reach a sufficient volume (p = 0.4). During the interval between the first and second CT, the KGR was 2.2 (± 2), respectively (± 0.1) (p = 0.017). DISCUSSION: The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Veia Porta/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Ligadura/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Masculino , Metástase Neoplásica , Período Pós-Operatório , Fatores de Tempo , Tomografia Computadorizada por Raios X
12.
Hepatobiliary Surg Nutr ; 7(4): 234-241, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30221151

RESUMO

BACKGROUND: The aim of the current study was to investigate survival after resection of colorectal liver metastases (CLM) in octogenarians. The survival of octogenarian patients was compared to the survival of the national population of octogenarians and the survival of sexagenarians, the latter representing the average-age patient undergoing resection of CLM. METHODS: Octogenarian and sexagenarian were defined as person 80-89 and 60-69 years of age, respectively. Survival analyses of patients who underwent resection of CLM between 2002 and 2014 were performed. Data from Statistics Norway were used to estimate the survival of the age-matched national population of octogenarians (ageM-Octo) and the age-matched national population of sexagenarians (ageM-Sexa). RESULTS: During the study period, 59 octogenarians underwent resection of CLM. The majority of patients underwent a minor liver resection (n=50). In octogenarians, the 5-year survival was 32.5% and 66.3% [difference, 33.8 percentage points (pp)] in patients and ageM-Octo, respectively. The 10-year survival was 14.1% and 31.2% (difference, 17.1 pp) in patients and ageM-Octo, respectively. In sexagenarians, the 5-year survival was 50.9% and 96.2% (difference, 45.3 pp) in patients and ageM-Sexa, respectively. The 10-year survival was 35.7% and 90.3% (difference, 54.6 pp) in patients and ageM-Sexa, respectively. The 5-year cancer-specific survival and 5-year recurrence-free survival (RFS) after resection of CLM in octogenarians were 43.1% and 32.9%, respectively. CONCLUSIONS: After resection of CLM, the survival was poorer in octogenarians than in sexagenarians. However, the difference between the survival curves of patients and their age-matched population was smaller in octogenarians. In practice, this finding may indicate a greater benefit of resection in the elderly than the survival rates alone would suggest.

13.
Radiol Oncol ; 52(1): 36-41, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29520204

RESUMO

BACKGROUND: Laparoscopic liver resection (LLR) of colorectal liver metastases (CLM) is increasingly performed in specialized centers. While there is a trend towards a parenchyma-sparing strategy in multimodal treatment for CLM, its role is yet unclear. In this study we present short- and long-term outcomes of laparoscopic parenchyma-sparing liver resection (LPSLR) at a single center. PATIENTS AND METHODS: LLR were performed in 951 procedures between August 1998 and March 2017 at Oslo University Hospital, Oslo, Norway. Patients who primarily underwent LPSLR for CLM were included in the study. LPSLR was defined as non-anatomic hence the patients who underwent hemihepatectomy and sectionectomy were excluded. Perioperative and oncologic outcomes were analyzed. The Accordion classification was used to grade postoperative complications. The median follow-up was 40 months. RESULTS: 296 patients underwent primary LPSLR for CLM. A single specimen was resected in 204 cases, multiple resections were performed in 92 cases. 5 laparoscopic operations were converted to open. The median operative time was 134 minutes, blood loss was 200 ml and hospital stay was 3 days. There was no 90-day mortality in this study. The postoperative complication rate was 14.5%. 189 patients developed disease recurrence. Recurrence in the liver occurred in 146 patients (49%), of whom 85 patients underwent repeated surgical treatment (liver resection [n = 69], ablation [n = 14] and liver transplantation [n = 2]). Five-year overall survival was 48%, median overall survival was 56 months. CONCLUSIONS: LPSLR of CLM can be performed safely with the good surgical and oncological results. The technique facilitates repeated surgical treatment, which may improve survival for patients with CLM.

14.
Surg Endosc ; 32(3): 1470-1477, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28916919

RESUMO

BACKGROUND: Stage IV metastatic melanoma carries a poor prognosis. In the case of melanoma liver metastasis (MLM), surgical resection may improve survival and represents a therapeutic option, with varying levels of success. Laparoscopic liver resection (LLR) for metastatic melanoma is poorly studied. The aim of this study was to analyze the outcomes of LLR in patients with MLM. MATERIALS AND METHODS: Between April 2000 and August 2013, 11 (1 cutaneous, 9 ocular and 1 unknown primary) patients underwent LLR for MLM at Oslo University Hospital-Rikshospitalet and 13 procedures in total were carried out. Perioperative and oncologic outcomes were analyzed. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. RESULTS: A total of 23 liver specimens were resected. The median operative time was 137 (65-470) min, while the median blood loss was less than 50 (<50-900) ml. No intraoperative unfavorable incidents and 30-day mortality occurred. Median follow-up was 33 (9-92) months. Ten patients (91%) developed recurrence within a median of 5 months (2-18 months) and two patients underwent repeat LLR for recurrent liver metastases. One-, three-, and five-year overall survival rates were 82, 45 and 9%, respectively. The median overall survival was 30 (9-92) months. CONCLUSION: Perioperative morbidity and long-term survival after LLR for MLM seems to be comparable to open liver resection. Thus, LLR may be preferred over open liver resection due to the well-known advantages of laparoscopy, such as reduced pain and improved possibility for repeated resections.


Assuntos
Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Melanoma/secundário , Melanoma/cirurgia , Neoplasias Cutâneas/patologia , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
15.
Ann Surg ; 267(2): 199-207, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28657937

RESUMO

OBJECTIVE: To perform the first randomized controlled trial to compare laparoscopic and open liver resection. SUMMARY BACKGROUND DATA: Laparoscopic liver resection is increasingly used for the surgical treatment of liver tumors. However, high-level evidence to conclude that laparoscopic liver resection is superior to open liver resection is lacking. METHODS: Explanatory, assessor-blinded, single center, randomized superiority trial recruiting patients from Oslo University Hospital, Oslo, Norway from February 2012 to January 2016. A total of 280 patients with resectable liver metastases from colorectal cancer were randomly assigned to undergo laparoscopic (n = 133) or open (n = 147) parenchyma-sparing liver resection. The primary outcome was postoperative complications within 30 days (Accordion grade 2 or higher). Secondary outcomes included cost-effectiveness, postoperative hospital stay, blood loss, operation time, and resection margins. RESULTS: The postoperative complication rate was 19% in the laparoscopic-surgery group and 31% in the open-surgery group (12 percentage points difference [95% confidence interval 1.67-21.8; P = 0.021]). The postoperative hospital stay was shorter for laparoscopic surgery (53 vs 96 hours, P < 0.001), whereas there were no differences in blood loss, operation time, and resection margins. Mortality at 90 days did not differ significantly from the laparoscopic group (0 patients) to the open group (1 patient). In a 4-month perspective, the costs were equal, whereas patients in the laparoscopic-surgery group gained 0.011 quality-adjusted life years compared to patients in the open-surgery group (P = 0.001). CONCLUSIONS: In patients undergoing parenchyma-sparing liver resection for colorectal metastases, laparoscopic surgery was associated with significantly less postoperative complications compared to open surgery. Laparoscopic resection was cost-effective compared to open resection with a 67% probability. The rate of free resection margins was the same in both groups. Our results support the continued implementation of laparoscopic liver resection.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Método Simples-Cego , Resultado do Tratamento
18.
J Clin Oncol ; 34(21): 2501-8, 2016 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-27247217

RESUMO

PURPOSE: Regular use of aspirin (acetylsalicylic acid) is associated with reduced incidence and mortality of colorectal cancer (CRC). However, aspirin as primary prevention is debated because of the risk of hemorrhagic adverse effects. Aspirin as secondary prevention may be more justified from a risk-benefit perspective. We have examined the association between aspirin use after the diagnosis of CRC with CRC-specific survival (CSS) and overall survival (OS). MATERIALS AND METHODS: An observational, population-based, retrospective cohort study was conducted by linking patients diagnosed with CRC from 2004 through 2011 (Cancer Registry of Norway) with data on their aspirin use (The Norwegian Prescription Database). These registries cover more than 99% of the Norwegian population and include all patients in an unselected and consecutive manner. Exposure to aspirin was defined as receipt of aspirin prescriptions for more than 6 months after the diagnosis of CRC. Multivariable Cox-proportional hazard analyses were used to model survival. The main outcome measures of the study were CSS and OS. RESULTS: A total of 23,162 patients diagnosed with CRC were included, 6,102 of whom were exposed to aspirin after the diagnosis of CRC (26.3%). The median follow-up time was 3.0 years. A total of 2,071 deaths (32.9%, all causes) occurred among aspirin-exposed patients, of which 1,158 (19.0%) were CRC specific. Among unexposed patients (n = 17,060), there were 7,218 deaths (42.3%), of which 5,375 (31.5%) were CRC specific. In multivariable analysis, aspirin exposure after the diagnosis of CRC was independently associated with improved CSS (hazard ratio [HR], 0.85; 95% CI, 0.79 to 0.92) and OS (HR, 0.95; 95% CI, 0.90 to 1.01). CONCLUSION: Aspirin use after the diagnosis of CRC is independently associated with improved CSS and OS.


Assuntos
Aspirina/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Prevenção Secundária , Idoso , Idoso de 80 Anos ou mais , Viés , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
19.
Case Rep Oncol Med ; 2016: 8946471, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27034867

RESUMO

Background. Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) indicates a poor prognosis. Surgery is considered the only curative option for selected patients with HCC recurrence following LT. Traditionally, the preference is given to the open approach. Methods. In this report, we present two cases of laparoscopic resections (LR) for recurrent HCC after LT, performed at Oslo University Hospital, Rikshospitalet. Results. Both procedures were executed without intraoperative and postoperative adverse events. Whereas one of the patients had a recurrence one year after LR, the other patient did not have any sign of disease during 3-year follow-up. Conclusions. We argue that, in selected cases, patients with HCC recurrence following LT may benefit from LR due to its limited tissue trauma and timely start of subsequent treatment if curative resection cannot be obtained. In patients with relatively favorable prognosis, LR facilitates postoperative recovery course and avoids unnecessary laparotomy.

20.
Surgery ; 159(5): 1279-86, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26606881

RESUMO

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has emerged as an additional tool to increase the size of the future liver remnant (FLR) in the settings of advanced tumor burden in the liver. Initial reports have indicated high feasibility but also high mortality and morbidity. The aim of this study was to assess the initial experience with ALPPS in Scandinavia regarding feasibility, morbidity, and mortality. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients who underwent ALPPS since its introduction at 3 Scandinavian hepatobiliary centers. RESULTS: Thirty-six patients were identified, 21 male and 15 female. Median age was 67 years (22-83). Colorectal liver metastases (n = 25) were the most common indication for ALPPS followed by hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 4), and other (n = 3). Median growth of the FLR between the operations was 67% (-17 to 238) in 6 (5-13) days. All patients completed the second operation, and 71% of the resections were R0. Although the total percentage of patients with complication(s) was 92%, only 4 patients (11%) had a grade 3b complication according to the Clavien-Dindo classification, and no other severe complications were noted. There was no in-hospital mortality, but 1 (2.8%) patient died within 90 days of operation. CONCLUSION: ALPPS is a highly feasible method to stimulate FLR growth in patients with colorectal liver metastases as well as primary hepatobiliary malignancies. The treatment can be carried out with relative safety.


Assuntos
Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Fígado/cirurgia , Veia Porta/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Colangiocarcinoma/mortalidade , Neoplasias Colorretais/patologia , Estudos de Viabilidade , Feminino , Hepatectomia/mortalidade , Humanos , Ligadura , Fígado/fisiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Noruega , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Suécia , Resultado do Tratamento
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