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1.
Pancreatology ; 22(7): 1028-1034, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35948507

RESUMO

BACKGROUND AND AIMS: Pancreatic resection is associated with pancreatic exocrine insufficiency (PEI) leading to nutritional consequences. The Pancreatic Nutrition Clinic was established to diagnose and manage PEI through standardised nutritional assessment. In this prospective observational study, we aimed to define the rate of PEI, diabetes mellitus and nutritional abnormalities in patients who underwent pancreatic resection. METHODS: All Pancreatic Nutrition Clinic patients were included for analysis. Clinical data were prospectively obtained at initial assessment. Biochemical data included micronutrient levels, faecal elastase-1 and haemoglobin A1c. Bone mineral density and nutritional assessment were undertaken. RESULTS: Ninety-eight patients were included. Fifty-nine per cent (58/98) had undergone a pancreatoduodenectomy. Ninety-three patients had a faecal elastase-1 result, 65% (60/93) of which had a faecal elastase-1 less than 200 µg/g of faeces. Seventy-five patients (76%) of the total population required PERT, and thirty-nine (40%) were classified as malnourished using the patient-generated subjective global assessment tool. Seventy-two per cent (70/97) had a biochemical deficiency of one or more micronutrients. Thirty-eight people (39%) had diabetes mellitus. Of the seventy-eight patients with a bone mineral density scan available for analysis, 29% (23/78) had osteoporosis and 49% (38/78) osteopenia. CONCLUSIONS: Pancreatic exocrine insufficiency, micronutrient deficiency, bone disease, diabetes mellitus and malnutrition are highly prevalent in patients who have undergone pancreatic resection.


Assuntos
Diabetes Mellitus , Insuficiência Pancreática Exócrina , Desnutrição , Doenças Metabólicas , Humanos , Insuficiência Pancreática Exócrina/diagnóstico , Elastase Pancreática/análise , Micronutrientes
3.
Br J Surg ; 102(12): 1459-72, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26350029

RESUMO

BACKGROUND: R0 resection rates (complete tumour removal with negative resection margins) in pancreatic cancer are 70-80 per cent when a 0-mm margin is used, declining to 15-24 per cent with a 1-mm margin. This review evaluated the R0 resection rates according to different margin definitions and techniques. METHODS: Three databases (MEDLINE from 1946, PubMed from 1946 and Embase from 1949) were searched to mid-October 2014. The search terms included 'pancreatectomy OR pancreaticoduodenectomy' and 'margin'. A meta-analysis was performed with studies in three groups: group 1, axial slicing technique (minimum 1-mm margin); group 2, other slicing techniques (minimum 1-mm margin); and group 3, studies with minimum 0-mm margin. RESULTS: The R0 rates were 29 (95 per cent c.i. 26 to 32) per cent in group 1 (8 studies; 882 patients) and 49 (47 to 52) per cent in group 2 (6 studies; 1568 patients). The combined R0 rate (groups 1 and 2) was 41 (40 to 43) per cent. The R0 rate in group 3 (7 studies; 1926 patients) with a 0-mm margin was 72 (70 to 74) per cent The survival hazard ratios (R1 resection/R0 resection) revealed a reduction in the risk of death of at least 22 per cent in group 1, 12 per cent in group 2 and 23 per cent in group 3 with an R0 compared with an R1 resection. Local recurrence occurred more frequently with an R1 resection in most studies. CONCLUSION: Margin clearance definitions affect R0 resection rates in pancreatic cancer surgery. This review collates individual studies providing an estimate of achievable R0 rates, creating a benchmark for future trials.


Assuntos
Recidiva Local de Neoplasia/epidemiologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Saúde Global , Humanos , Incidência , Prognóstico
4.
Br J Cancer ; 110(2): 313-9, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24263063

RESUMO

BACKGROUND: Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer. METHODS: We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative. RESULTS: The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ≥70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8%; P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27-2.78, P=0.002). CONCLUSION: Patients aged ≥70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Fatores Etários , Idoso , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Metástase Linfática , Masculino , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico
5.
Ann Surg Oncol ; 21(6): 1937-47, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24558067

RESUMO

BACKGROUND: Although pancreatoduodenectomy (PD) with mesenterico-portal vein resection (VR) can be performed safely in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the impact of this approach on long-term survival is controversial. PATIENTS AND METHODS: Analyses of a prospectively collected database revealed 122 consecutive patients with PDAC who underwent PD with (PD+VR) or without (PD-VR) VR between January 2004 and May 2012. Clinical data, operative results, and survival outcomes were analysed. RESULTS: Sixty-four (53 %) patients underwent PD+VR. The majority (84 %) of the venous reconstructions were performed with a primary end-to-end anastomosis. Demographic and postoperative outcomes were similar between the two groups. American Society of Anesthesiologists (ASA) score, duration of operation, intraoperative blood loss, and blood transfusion requirement were significantly greater in the PD+VR group compared with the PD-VR group. Furthermore, the tumor size was larger, and the rates of periuncinate neural invasion and positive resection margin were higher in the PD+VR group compared with the PD-VR group. Histological venous involvement occurred in 47 of 62 (76 %) patients in the PD+VR group. At a median follow-up of 29 months, the median overall survival (OS) was 18 months for the PD+VR group, and 31 months for the PD-VR group (p = 0.016). ASA score, lymph node metastasis, neurovascular invasion, and tumor differentiation were predictive of survival. The need for VR in itself was not prognostic of survival. CONCLUSIONS: PD with VR has similar morbidity but worse OS compared with a PD-VR. Although VR is not predictive of survival, tumors requiring a PD+VR have more adverse biological features.


Assuntos
Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Veias Mesentéricas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Veia Porta/cirurgia , Idoso , Perda Sanguínea Cirúrgica , Vasos Sanguíneos/patologia , Carcinoma Ductal Pancreático/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Neoplasia Residual , Duração da Cirurgia , Neoplasias Pancreáticas/mortalidade , Nervos Periféricos/patologia , Taxa de Sobrevida , Fatores de Tempo , Carga Tumoral
6.
Ann Oncol ; 23(7): 1713-22, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22241899

RESUMO

BACKGROUND: Current staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making are lacking. Despite the availability of the serum marker carbohydrate antigen 19.9 (CA19.9) for over two decades, its precise role in the management of PC is yet to be defined, and as a consequence, it is not widely used. METHODS: We assessed the relationship between perioperative serum CA19.9 levels, survival and adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent operative resection for PC. RESULTS: By specifically assessing the subgroup of patients with detectable CA19.9, we identified potential utility at key clinical decision points. Low postoperative CA19.9 at 3 months (median survival 25.6 vs 14.8 months, P=0.0052) and before adjuvant chemotherapy were independent prognostic factors. Patients with postoperative CA 19.9 levels>90 U/ml did not benefit from adjuvant chemotherapy (P=0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P=0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P=0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%. CONCLUSIONS: Perioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/sangue , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Período Perioperatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
8.
BJS Open ; 3(4): 521-531, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31388645

RESUMO

Background: There are concerns that non-anatomical resection (NAR) worsens perioperative and oncological outcomes compared with those following anatomical resection (AR) for colorectal liver metastases (CRLM). Most previous studies have been biased by the effect of tumour size. The aim of this study was to compare oncological outcomes after NAR versus AR. Methods: This was a retrospective study of consecutive patients who underwent CRLM resection with curative intent from 1999 to 2016. Data were retrieved from a prospectively developed database. Survival and perioperative outcomes for NAR and AR were compared using propensity score analyses. Results: Some 358 patients were included in the study. Median follow-up was 34 (i.q.r. 16-68) months. NAR was associated with significantly less morbidity compared with AR (31·1 versus 44·4 per cent respectively; P = 0·037). Larger (hazard ratio (HR) for lesions 5 cm or greater 1·81, 95 per cent c.i. 1·13 to 2·90; P = 0·035) or multiple (HR 1·48, 1·03 to 2·12; P = 0·035) metastases were associated with poor overall survival (OS). Synchronous (HR 1·33, 1·01 to 1·77; P = 0·045) and multiple (HR 1·51, 1·14 to 2·00; P = 0·004) liver metastases, major complications after liver resection (HR 1·49, 1·05 to 2·11; P = 0·026) or complications after resection of the primary colorectal tumour (HR 1·51, 1·01 to 2·26; P = 0·045) were associated with poor disease-free survival (DFS). AR was prognostic for poor OS only in tumours smaller than 30 mm, and R1 margin status was not prognostic for either OS or DFS. NAR was associated with a higher rate of salvage resection than AR following intrahepatic recurrence. Conclusions: NAR has at least equivalent oncological outcomes to AR while proving to be safer. NAR should therefore be the primary surgical approach to CRLM, especially for lesions smaller than 30 mm.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas , Idoso , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos
9.
Eur J Surg Oncol ; 42(2): 211-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26456791

RESUMO

BACKGROUND: Resection of the involved mesenteric-portal vein (MPV) is increasingly performed in pancreatoduodenectomy. The primary aim of this study is to assess the rate of R0 resection in transverse closure (TC) versus segmental resection with end-to-end (EE) closure and the secondary aims are to assess the short-term morbidity and long-term survival of TC versus EE. METHODS: Patients undergoing pancreatoduodenectomy with MPV resection were identified from a prospectively database. The reconstruction technique were examined and categorized. Clinical, pathological, short-term and long-term survival outcomes were compared between groups. RESULTS: 110 patients underwent PD with MPV resection of which reconstruction was performed with an end-to-end technique in 92 patients (84%) and transverse closure technique in 18 patients (16%). Patients undergoing transverse closure tended to have had a shorter segment of vein resected (≤2 cm) compared to the end-to-end (83% vs. 43%; P = 0.004) with no difference in R0 rate. Short-term morbidity was similar. The median and 5-year survival was 30.0 months and 18% respectively for patients undergoing transverse closure and 28.6 months and 7% respectively for patients undergoing end-to-end reconstruction (P = 0.766). CONCLUSION: Without compromising the R0 rate, transverse closure to reconstruct the mesenteric-portal vein is shown to be feasible and safe in the setting when a short segment of vein resection is required during pancreatoduodenectomy. Synopsis - We describe a vein closure technique, transverse closure, which avoids the need for a graft, or re-implantation of the splenic vein when resection of the mesenteric-portal vein confluence is required during pancreatoduodenectomy.


Assuntos
Carcinoma/cirurgia , Veias Mesentéricas/cirurgia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Veia Porta/cirurgia , Técnicas de Fechamento de Ferimentos , Adenocarcinoma Mucinoso/cirurgia , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Carcinoma Ductal Pancreático/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Tempo de Internação , Masculino , Ilustração Médica , Pessoa de Meia-Idade , Neoplasia Residual , Duração da Cirurgia , Pancreaticoduodenectomia/efeitos adversos , Taxa de Sobrevida , Técnicas de Fechamento de Ferimentos/efeitos adversos
10.
Eur J Surg Oncol ; 42(10): 1576-83, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27378158

RESUMO

BACKGROUND: Hepatocellular cancer (HCC) is a leading cause of mortality worldwide. Liver resection or transplantation offer the best chance of long-term survival. The aim of this study was to perform a survival and prognostic factor analysis on patients who underwent resection of HCC at two major tertiary referral hospitals, and to investigate a pre-operative prediction model for microvascular invasion (MVI). METHODS: Clinico-pathological and survival data were collected from all patients who underwent liver resection for HCC at two tertiary referral centres (Royal North Shore/North Shore Private Hospitals and Westmead Hospital) from 1998 to 2012. An overall and disease-free survival analysis was performed and a predictive model for MVI identified. RESULTS: The total number of patients in this series was 125 and the 5-year overall and disease-free survival rates were 56% and 37%, respectively. MVI was the only factor to be independently associated with a poor prognosis on both overall and disease-free survival. Age ≥64 years, a serum alpha-fetoprotein (AFP) ≥400 ng/ml (×40 above normal) and tumor size ≥50 mm were independently associated with MVI. An MVI prediction model using these three pre-operative factors provides a good assessment of the risk of MVI. CONCLUSION: MVI in the resected specimen of patients with HCC is associated with a poor prognosis. A preoperative MVI prediction model offers a useful way to identify patients at risk of relapse. However, more precise predictive models using molecular and genetic variables are needed to improve selection of patients most suitable for radical surgical treatment.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Resultado do Tratamento
11.
J Clin Endocrinol Metab ; 83(2): 626-31, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9467584

RESUMO

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the s.c. adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.


Assuntos
Tecido Adiposo/metabolismo , Hidrocortisona/sangue , Lipólise/fisiologia , Ácido 3-Hidroxibutírico , Abdome , Tecido Adiposo/irrigação sanguínea , Adulto , Glicemia/metabolismo , Esterificação , Ácidos Graxos não Esterificados/sangue , Feminino , Glicerol/sangue , Glicerol/metabolismo , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/análogos & derivados , Hidroxibutiratos/sangue , Insulina/sangue , Ácido Láctico/sangue , Lipase Lipoproteica/metabolismo , Masculino , Pessoa de Meia-Idade , Esterol Esterase/metabolismo , Triglicerídeos/sangue
12.
J Clin Endocrinol Metab ; 86(8): 3686-91, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11502796

RESUMO

To determine the role of IGF-binding proteins in mediating the direct effects of recombinant human IGF-I on insulin requirements in type 1(insulin-dependent) diabetes mellitus, overnight changes in IGF-I, IGF-II, and IGF-binding protein-1, -2, and -3, collected under euglycemic conditions, were compared in nine subjects after double blind, randomized, sc administration of recombinant human IGF-I (40 microg/kg) or placebo at 1800 h. On both nights a somatostatin analog infusion (300 ng/kg x h) suppressed endogenous GH production, and three timed discrete GH pulses (total, 0.029 IU/kg x night) ensured identical GH levels. After recombinant human IGF-I administration, IGF-I levels and the IGF-I/IGF-binding protein-3 ratio increased [mean +/- SEM:IGF-I, 401 +/- 22 ng/ml; placebo, 256 +/- 20 ng/ml (P = 0.0002); IGF-I, 0.108 +/- 0.006; placebo, 0.074 +/- 0.004 (P = 0.0003), respectively], and insulin requirements decreased (IGF-I, 0.12 +/- 0.03; placebo, 0.23 +/- 0.03 U/kg x min; P = 0.008). The normal within-individual inverse relationships between insulin and IGF-binding protein-1 levels were observed (lag time 2 h: r = -0.34; P < 0.01). Yet despite reduced free insulin levels (8.5 +/- 1.5; placebo, 12.2 +/- 1.2 mU/liter; P = 0.03), IGF-binding protein-1 levels were reduced after recombinant human IGF-I administration (53.7 +/- 6.8; placebo, 82.2 +/- 11.8 ng/ml; P = 0.008). The largest reductions in free insulin levels after recombinant human IGF-I and thus putative improvement in insulin sensitivity occurred in subjects with the smallest increase in the plasma IGF-I/IGF-binding protein-3 ratio (r = 0.7; P = 0.03). Taken together, these data are consistent with the hypothesis that transcapillary movement of IGF-I (perhaps mediated by IGF-binding protein-1), out of the circulation facilitates altered insulin sensitivity. These data have important implications for risk-benefit assessment of recombinant human IGF-I therapy in type 1 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/uso terapêutico , Insulina/uso terapêutico , Adolescente , Adulto , Criança , Método Duplo-Cego , Feminino , Técnica Clamp de Glucose , Hemoglobinas Glicadas/análise , Humanos , Injeções Subcutâneas , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/administração & dosagem , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Placebos , Radioimunoensaio , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Análise de Regressão , Fatores de Tempo
13.
Am J Clin Nutr ; 63(1): 36-41, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8604667

RESUMO

Previous studies have noted the presence of an early postprandial peak in plasma triacylglycerol concentration, particularly when successive meals have been consumed. We tested the hypothesis that fat from a previous meal contributes to this early postprandial lipemia. We investigated the effect of consuming a lunch containing 61 g fat 5 h after a breakfast containing 54 g fat. The predominant fatty acids in the first meal, expressed as % by wt of total fatty acids, were 18:2 (linoleic acid), 68%, and 18:1 (oleic acid), 19%. The main fatty acids in the second meal were 18:1 (75%) and 18:2 (8%). After lunch, the early peak (at 50-60 min) in chylomicron triacylglycerol was found to contain a large proportion of 18:2, the main constituent of the first meal, whereas at later time points the chylomicron triacylglycerol fatty acid profile more closely resembled that of the second meal. Control studies in three subjects showed the complete absence of the early peaks in plasma and chylomicron triacylglycerol concentrations when either the lunch was omitted or the first meal was low in fat. The plasma nonesterified fatty acid profile also showed a corresponding peak in 18:2 at 50-60 min, which may represent the release into the plasma of fatty acids arising from the hydrolysis of chylomicron triacylglycerol by adipose tissue lipoprotein lipase.


Assuntos
Gorduras na Dieta/administração & dosagem , Ingestão de Alimentos , Ácidos Graxos/administração & dosagem , Lipídeos/sangue , Adulto , Análise de Variância , Glicemia/análise , Quilomícrons/sangue , Ingestão de Alimentos/fisiologia , Ingestão de Energia , Ácidos Graxos não Esterificados/sangue , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
14.
Atherosclerosis ; 137(1): 115-23, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9568743

RESUMO

Six, healthy, male volunteers aged 19-48 years received a 4-h infusion of a triacylgycerol emulsion (Intralipid 10%) after an overnight fast. Plasma triacylglycerol (TAG) and low-density lipoprotein (LDL) -TAG, -protein and -phospholipid concentrations all rose significantly during the course of the infusion and remained elevated 90 min after its end. The weight/weight ratio of LDL-TAG to -protein also increased significantly (from 0.43+/-0.14 to 0.79+/-0.30 at 4 h and 0.63+/-0.31 90 min later), indicating TAG-enrichment of LDL particles. There were no significant changes in LDL particle density. Susceptibility of LDL to copper-induced oxidation, as measured by the lag time for conjugated diene formation, was less at the end of and 90 min after the end of the infusion than in the fasting state (59.3+/-16.5, 47.4+/-17.4 and 34.8+/-19.6 min, respectively). Lag time was positively correlated with LDL TAG in the fasting state (rS=0.900, P < 0.0001) and the correlation continued with the post-infusion TAG-enriched LDL (rs=0.886, P < 0.05). Acute hypertriglyceridaemia induced by infusion of Intralipid therefore causes TAG-enrichment and a decrease in the susceptibility to oxidation of LDL. TAG-enrichment of LDL may lead to subsequent potentially atherogenic changes in LDL following TAG hydrolysis.


Assuntos
Emulsões Gordurosas Intravenosas/farmacologia , Lipoproteínas LDL/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Adulto , Emulsões Gordurosas Intravenosas/administração & dosagem , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/induzido quimicamente , Infusões Intravenosas , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Fatores de Tempo , Triglicerídeos/sangue
15.
Atherosclerosis ; 147(1): 11-5, 1999 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-10525119

RESUMO

The insulin resistant state is a major risk factor for coronary artery disease. This increased risk is likely to be due to associated lipid and coagulation abnormalities rather than just abnormalities in glucose metabolism or hyperinsulinaemia alone. Exaggerated postprandial lipaemia is a well-recognised associate of insulin resistance and postprandial hypertriglyceridaemia is particularly important in the development of coronary atheroma. It seems likely that insulin is one of the hormonal regulators of adipose tissue and skeletal muscle blood flow. The reduced blood flow and blunting of the postprandial rise of peripheral blood flow in insulin resistance may decrease chylomicron-triglyceride delivery to muscle in subjects with insulin resistance. This, in turn, will lead to increased production of atherogenic particles. We propose that impaired postprandial vasodilation, already recognised as a key feature of glucose intolerance, is also the cause of impaired lipid metabolism in insulin resistant subjects and predisposes them to cardiovascular disease.


Assuntos
Tecido Adiposo/irrigação sanguínea , Doenças Cardiovasculares/fisiopatologia , Resistência à Insulina , Músculo Esquelético/irrigação sanguínea , Período Pós-Prandial , Vasodilatação , Animais , Glicemia/metabolismo , Doenças Cardiovasculares/etiologia , Humanos , Hipertensão/fisiopatologia , Insulina/fisiologia , Metabolismo dos Lipídeos , Fluxo Sanguíneo Regional , Fatores de Risco
16.
Metabolism ; 47(1): 31-8, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9440474

RESUMO

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/farmacologia , Insulina/administração & dosagem , Adolescente , Adulto , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Método Duplo-Cego , Ácidos Graxos não Esterificados/sangue , Feminino , Glucagon/sangue , Técnica Clamp de Glucose , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/administração & dosagem , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/genética , Cetonas/sangue , Masculino , Octreotida/administração & dosagem , Octreotida/farmacologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia
17.
Obstet Gynecol ; 73(5 Pt 2): 832-4, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2539572

RESUMO

A case is presented of serologically proved parvovirus infection leading to intrauterine death of the hydropic fetus at 20 weeks' gestation. Although serologic studies of the population indicate that 30-50% of women are susceptible to parvovirus infection, the prevalence of parvovirus infection in pregnancy and the consequences of such an infection are not well understood. A review of reported cases in the world literature indicates a high risk to the fetus once the virus crosses the placenta.


Assuntos
Hidropisia Fetal/etiologia , Infecções por Parvoviridae , Complicações Infecciosas na Gravidez , Adulto , Anticorpos Antivirais/análise , Feminino , Monitorização Fetal , Humanos , Hidropisia Fetal/mortalidade , Imunoglobulina M/análise , Parvoviridae/imunologia , Infecções por Parvoviridae/imunologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia
18.
Lipids ; 34(6): 535-41, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10405965

RESUMO

The triacylglycerol emulsion Intralipid was infused into six normal subjects to investigate the metabolism of individual fatty acids in subcutaneous adipose tissue and forearm muscle, by measurement of arteriovenous differences. The composition of plasma nonesterified fatty acids changed steadily after passage through adipose tissue and became similar to that of the emulsion, reflecting hydrolysis of the Intralipidtriacylglycerol by lipoprotein lipase, since endogenous lipolysis (hormone-sensitive lipase activity plus lipoprotein lipase hydrolysis of very low density lipoprotein triacylglycerol) was decreased. There was no significant net release of total or individual fatty acids from forearm muscle although there was a tendency for the composition of the fatty acids in forearm venous plasma to change during passage through the tissue to reflect the composition of the emulsion. This may reflect hydrolysis of emulsion particles by lipoprotein lipase situated in capillaries which drain into the forearm vein. The behavior of stearic acid in the plasma nonesterified fatty acid pool was consistently aberrant, with arterialized concentrations considerably higher than predicted from adipose tissue release, both before and during Intralipid infusion. We conclude that there are no significant differences in the metabolism of specific fatty acids, with the exception of stearic acid.


Assuntos
Ácidos Graxos/metabolismo , Triglicerídeos/administração & dosagem , Tecido Adiposo/metabolismo , Adulto , Emulsões , Ácidos Graxos/sangue , Humanos , Lipólise , Masculino , Esterol Esterase/metabolismo , Triglicerídeos/sangue
19.
Eur J Surg Oncol ; 39(6): 662-5, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23528253

RESUMO

While colorectal cancer is increasingly common in western populations, anatomical concepts regarding the anatomy of resection have remained static. In attempting to maximise the chance of surgical cure, surgeons and pathologists are now focussing upon the quality of oncological resection. Amongst pathological indices of interest, lymph node yield and the apical lymph node specifically are increasingly being shown to be reliable markers of the adequacy of oncologic resection. However, the position of the apical node in particular, is highly subjective and may not always correlate with the anatomical boundaries ultimately defining resection. We argue that the present definition of the apical lymph node is overly subjective and requires re-defining based on fixed anatomical landmarks. We propose that this new definition include a block of tissue inferolateral to the Trunk of Henle (the anatomical apical lymph node compartment).


Assuntos
Colectomia/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Humanos , Metástase Linfática/diagnóstico
20.
Am J Surg ; 206(4): 518-25, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23809671

RESUMO

BACKGROUND: Early inferior pancreaticoduodenal artery (IPDA) ligation reduces intraoperative blood loss during pancreatoduodenectomy, but the impact on oncologic and long-term outcomes remains unknown. The aim of this study was to review the impact of complete pancreatic head devascularization during pancreatoduodenectomy on blood loss, transfusion rates, and clinicopathologic outcomes. METHODS: Clinicopathologic and outcome data were retrieved from a prospective database for all pancreatoduodenectomies performed from April 2004 to November 2010 and compared between early (IPDA+; n = 62) and late (IPDA-; n = 65) IPDA ligation groups. RESULTS: Early IPDA ligation was associated with reduced blood loss (394 ± 21 vs 679 ± 24 ml, P < .001) and perioperative transfusion (P = .031). A trend toward improved R0 resection was seen in patients with pancreatic adenocarcinoma (IPDA+ vs IPDA-, 100% vs 82%; P = .059), but this did not translate to improved 2-year (IPDA+ vs IPDA-, 76% vs 65%; P = .426) or overall (P = .82) survival. CONCLUSIONS: Early IPDA ligation reduces blood loss and transfusion requirements. Despite overall survival being unchanged, a trend toward improved R0 resection is encouraging and justifies further studies to ascertain the true oncologic significance of this technique.


Assuntos
Artérias/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/estatística & dados numéricos , Pâncreas/irrigação sanguínea , Pancreaticoduodenectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/cirurgia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Duração da Cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Prospectivos , Fatores Sexuais
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