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1.
Future Oncol ; 16(31): 2499-2509, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33048585

RESUMO

The purpose of this research was to investigate the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). We evaluated preoperative cSFRP5 levels in CRC patients and controls (n = 208). We found significantly higher cSFRP5 levels in CRC patients compared with non-CRC controls (p < 0.001). Levels of cSFRP5 were significantly lower in CRC patients with either vascular invasion (p = 0.001) or liver metastasis (p = 0.016). High cSFRP5 levels were associated with longer disease-free survival in both univariate (p = 0.024) and multivariate (p = 0.015) analyses. Analysis of an independent tissue cohort from The Cancer Genome Atlas database revealed significantly lower SFRP5 RNA expression in CRC tumor tissue compared with adjacent normal mucosa (n = 590 vs 47; p < 0.0001). Our findings confirm the role of cSFRP5 as a physiologic tumor suppressor and demonstrate its potential diagnostic and prognostic value in CRC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Biomarcadores Tumorais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Metilação de DNA , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Regiões Promotoras Genéticas , Curva ROC
2.
Obesity (Silver Spring) ; 28(3): 570-580, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32090515

RESUMO

OBJECTIVE: Adipose tissue plays a key role in obesity-related metabolic dysfunction. MicroRNA (miRNA) are gene regulatory molecules involved in intercellular and inter-organ communication. It was hypothesized that miRNA levels in adipose tissue would change after gastric bypass surgery and that this would provide insights into their role in obesity-induced metabolic dysregulation. METHODS: miRNA profiling (Affymetrix GeneChip miRNA 2.0 Array) of omental and subcutaneous adipose (n = 15 females) before and after gastric bypass surgery was performed. RESULTS: One omental and thirteen subcutaneous adipose miRNAs were significantly differentially expressed after gastric bypass, including downregulation of miR-223-3p and its antisense relative miR-223-5p in both adipose tissues. mRNA levels of miR-223-3p targets NLRP3 and GLUT4 were decreased and increased, respectively, following gastric bypass in both adipose tissues. Significantly more NLRP3 protein was observed in omental adipose after gastric bypass (P = 0.02). Significant hypomethlyation of NLRP3 and hypermethylation of miR-223 were observed in both adipose tissues after gastric bypass. In subcutaneous adipose, significant correlations were observed between both miR-223-3p and miR-223-5p and glucose and between NLRP3 mRNA and protein levels and blood lipids. CONCLUSIONS: This is the first report detailing genome-wide miRNA profiling of omental adipose before and after gastric bypass, and it further highlights the association of miR-223-3p and the NLRP3 inflammasome with obesity.


Assuntos
Inflamassomos/metabolismo , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Obesidade/genética , Redução de Peso/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
3.
Clin Proteomics ; 16: 3, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30679934

RESUMO

Biomarkers are urgently required to support current histological staging to provide additional accuracy in stratifying colorectal cancer (CRC) patients according to risk of spread to properly assign adjuvant chemotherapy after surgery. Chemotherapy is given to patients with stage III to reduce the risk of recurrence but is controversial in stage II patients. Up to 25% of stage II patients will relapse within 5 years after tumor removal and when this occurs cure is seldom possible. The aim of this study was to identify protein biomarkers to stratify risk of spread of CRC patients. Laser micro-dissection was used to isolate cancer cells from primary colorectal tumors of stage II patients which did or did not metastasize within 5 years after surgical resection. Protein expression differences between two groups of tumors were profiled by 2D-DIGE with saturation CyDye labeling and identified using MALDI-TOF mass spectrometry. Evaluation of protein candidates was conducted using tissue micro array (TMA) immunohistochemistry on 125 colorectal tumor tissue samples of different stages. A total of 55 differentially expressed proteins were identified. Ten protein biomarkers were chosen based on p value and ratio between non metastasized and metastazised groups and evaluated on 125 tissues using TMA immunohistochemistry. Expression of HLAB, protein 14-3-3ß, LTBP3, ADAMTS2, JAG2 and NME2 on tumour cells was significantly associated with clinical parameters related to tumour progression, invasion and metastasis. Kaplan-Meier survival curve showed strong expression of six proteins was associated with good CRC specific survival. Expression of HLAB, ADAMTS2, LTBP3, JAG2 and NME2 on tumour cells, was associated with tumour progression and invasion, metastasis and CRC specific survival may serve as potential biomarkers to stratify CRC patients into low and high risk of tumour metastasis. Combined methods of laser microdissection, 2D DIGE with saturation labelling and MALDI-TOF MS proved to be resourceful techniques capable of identifying protein biomarkers to predict risk of spread of CRC to liver.

4.
Am J Physiol Endocrinol Metab ; 316(2): E168-E177, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576243

RESUMO

Obesity, particularly visceral adiposity, has been linked to mitochondrial dysfunction and increased oxidative stress, which have been suggested as mechanisms of insulin resistance. The mechanism(s) behind this remains incompletely understood. In this study, we hypothesized that mitochondrial complex II dysfunction plays a role in impaired insulin sensitivity in visceral adipose tissue of subjects with obesity. We obtained subcutaneous and visceral adipose tissue biopsies from 43 subjects with obesity (body mass index ≥ 30 kg/m2) during planned bariatric surgery. Compared with subcutaneous adipose tissue, visceral adipose tissue exhibited decreased complex II activity, which was restored with the reducing agent dithiothreitol (5 mM) ( P < 0.01). A biotin switch assay identified that cysteine oxidative posttranslational modifications (OPTM) in complex II subunit A (succinate dehydrogenase A) were increased in visceral vs. subcutaneous fat ( P < 0.05). Insulin treatment (100 nM) stimulated complex II activity in subcutaneous fat ( P < 0.05). In contrast, insulin treatment of visceral fat led to a decrease in complex II activity ( P < 0.01), which was restored with addition of the mitochondria-specific oxidant scavenger mito-TEMPO (10 µM). In a cohort of 10 subjects with severe obesity, surgical weight loss decreased OPTM and restored complex II activity, exclusively in the visceral depot. Mitochondrial complex II may be an unrecognized and novel mediator of insulin resistance associated with visceral adiposity. The activity of complex II is improved by weight loss, which may contribute to metabolic improvements associated with bariatric surgery.


Assuntos
Complexo II de Transporte de Elétrons/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Processamento de Proteína Pós-Traducional , Adulto , Cirurgia Bariátrica , Cisteína , Feminino , Humanos , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Gordura Intra-Abdominal/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Compostos Organofosforados/farmacologia , Oxirredução , Piperidinas/farmacologia , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/metabolismo
5.
Int J Cancer ; 140(11): 2577-2586, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28233298

RESUMO

The expression of HLA-G by tumour cells is an established mechanism to escape recognition and immune mediated destruction, allowing tumour survival, growth and metastasis. However, the prognostic value of soluble HLA-G (sHLA-G) remains unknown. Mucinous carcinoma (MC) is a distinct form of colorectal cancer (CRC) found in 10 to 15% of patients, which has long been associated with poor response to treatment. To investigate the prognostic value of plasma sHLA-G levels in CRC patients, preoperative plasma sHLA-G levels were determined by ELISA in CRC patients (n = 133). In addition, the local expression of HLA-G in tumour biopsies was assessed using tissue microarray analysis (n = 255). Within the high 33rd percentile of sHLA-G levels (265-890 U/mL; n = 44) we observed higher frequency of MC patients (p = 0.012; Chi-square), and higher sHLA-G levels in patients with vascular invasion (p = 0.035; two-tailed t-test). Moreover, MC patients had significantly higher sHLA-G levels compared to those with adenocarcinoma not otherwise specified (p = 0.036; two-tailed t-test). Surprisingly, while stage II patients showed negative correlation between sHLA-G levels and liver metastasis free survival (LMFS) (p = 0.041; R = -0.321), in stage III patients high sHLA-G levels were associated with significantly longer LMFS (p = 0.002), and sHLA-G levels displayed positive correlation with LMFS (p = 0.006; R = 0.409). High HLA-G expression in tumours was associated with poor cancer specific overall survival in stage II to III (p = 0.01), and with shorter LMFS in stage II patients (p = 0.004). Our findings reveal that sHLA-G levels are associated with distinct progression patterns in consecutive disease stages, indicating a potential value as surrogate marker in the differential prognosis of CRC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Antígenos HLA-G/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Prognóstico
6.
PLoS One ; 10(3): e0119270, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25742416

RESUMO

Type 2 diabetes mellitus (T2DM) results from a combination of progressive insulin resistance and loss of pancreatic beta cell function and/or mass. Insulin signalling occurs through the insulin receptor, (INSR) which is alternatively spliced into two isoforms: INSRA (-exon 11) and INSRB (+exon 11). Because the INSR isoforms have different functional characteristics, their relative expression ratio has been implicated in the pathogenesis of insulin resistance and T2DM. We studied levels of INSR isoform mRNA in liver samples taken from 46 individuals with or without T2DM at Roux-en-Y (RYGB) surgery, and on average 17 (± 5.6) months later in 16 of the same individuals (8 diabetic and non-diabetic patients). INSRA or INSRB was also overexpressed in HepG2 cells to ascertain their effect on AKT phosphorylation and PCK1 expression as markers of insulin-mediated metabolic signalling. We found the INSRB:A isoform ratio was reduced in individuals with T2DM in comparison to those with normal glucose tolerance and normalised with remission of diabetes. The INSRB:A ratio increased due to a reduction in the alternatively spliced INSRA isoform following remission of diabetes. Overexpressing INSRA isoform in HepG2 hepatoma cells reduced inhibition of PCK1 transcription and did not increase AKT phosphorylation in response to insulin load compared to the effect of overexpressing the B isoform. Data presented here revitalizes the role of the INSR isoforms in the pathogenesis of T2DM, and suggests that an abrogated INSRB:A ratio that favours the INSRA isoform may negatively impact insulin-mediated metabolic signalling.


Assuntos
Antígenos CD/genética , Antígenos CD/metabolismo , Diabetes Mellitus Tipo 2/genética , Fígado/metabolismo , Obesidade Mórbida/cirurgia , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Adulto , Processamento Alternativo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Derivação Gástrica/métodos , Células Hep G2 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Fosforilação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
7.
BMC Gastroenterol ; 14: 222, 2014 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-25539584

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive disease resulting from increasing insulin resistance and reduced pancreatic ß-cell insulin secretion. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibits insulin signalling and may contribute to the pathogenesis of T2DM. Others have found elevated ENPP1 levels in muscle, fat, and skin tissues from insulin resistant individuals, but similar data on liver ENPP1 is lacking. The purpose of this study was to compare expression and protein concentrations of ENPP1 in liver between patients with and without T2DM. METHODS: Roux-en-Y gastric bypass surgery (RYGB) results in remission of insulin resistance and T2DM thus presenting an opportunity to examine some critical aspects of these conditions. We measured liver ENPP1 gene and protein expression in individuals with or without T2DM at RYGB and on average 17 (±5.6) months later. RESULTS: We found liver ENPP1 protein abundance was lower in individuals with T2DM than in those with normal glucose tolerance, and increased after RYGB surgery in those individuals who had remission of T2DM. ENPP1 positively correlated with insulin sensitivity at the liver (as measured by HOMA-IR), which is contrary to what others have reported in other insulin target tissues. CONCLUSIONS: Liver ENPP1 expression in T2DM is the reverse of that expected based on expression in other tissues and is likely due to the unique role the liver has in insulin clearance. The work presented here adds another dimension to the role of ENPP1, and supports the hypothesis that ENPP1 may act as a natural modulator of insulin signalling in the liver.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Derivação Gástrica , Fígado/enzimologia , Diester Fosfórico Hidrolases/metabolismo , Pirofosfatases/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Expressão Gênica , Humanos , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Diester Fosfórico Hidrolases/genética , Pirofosfatases/genética , Indução de Remissão
8.
Hum Pathol ; 44(6): 1089-97, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23317546

RESUMO

Aminoacylase 1 (ACY1) is a cytosolic enzyme responsible for amino acid deacylation during intracellular protein degradation. ACY1 has been implicated in a number of human tumor types. However, the exact role of ACY1 in tumor development remains elusive because it was found to be lost in small cell lung cancer and renal cell carcinoma but overexpressed in colorectal cancer (CRC). The present study aims to further clarify the relationship of ACY1 with CRC progression. Immunohistochemical staining was performed in tissue microarrays composed of 120 cases of CRC using a monoclonal anti-ACY1 antibody. Immunoreactivity was analyzed in association with patients' clinicopathologic parameters and survival time. The role of ACY1 in cell proliferation and apoptosis was assessed by silencing its expression in HCT116 cells using a small interfering RNA. Strong expression of ACY1 was found to be significantly associated with more advanced TNM stage, lymph node metastasis, positive vascular invasion, and shorter cancer-specific survival. ACY1 knockdown significantly inhibited cell proliferation and induced apoptosis. We concluded that ACY1 expression in CRC varies with stage and appears to play a role in cell proliferation and apoptosis. Further evaluation of ACY1 as a clinically useful prognostic marker and a potential drug target for CRC would seem worthwhile.


Assuntos
Adenocarcinoma/enzimologia , Amidoidrolases/biossíntese , Biomarcadores Tumorais/análise , Neoplasias Colorretais/enzimologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Amidoidrolases/análise , Apoptose/fisiologia , Proliferação de Células , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Análise Serial de Tecidos
9.
Int J Hepatol ; 2011: 404916, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22164335

RESUMO

Background. Nonresectable neuroendocrine tumour (NET) liver metastases respond poorly to most widely available and used therapies. Selective Internal Radiation Therapy (SIRT) is becoming recognized as a new modality for selectively treating non-resectable liver tumours. This paper presents an experience of 14 patients with non-resectable NET liver metastases treated with SIRT. Methods. Between September 1997 and October 2009 14 patients with extensive NET liver metastases were treated with 2.0 to 3.0 GBq of (90)Yttrium microspheres. Repeat SIRT was undertaken in three patients after 16, 27, and 48 months, respectively. Responses were assessed clinically, biochemically, and with serial CT scans. Survival was measured from initial SIRT. Results. Some response was seen in all 14 patients. Carcinoid syndrome improved or resolved in 10/10 instances. 24-hour urinary 5-HIAA or serum chromogranin A levels fell dramatically in 5/7 patients following SIRT. Serial CT scans revealed partial response or stable disease in all 14 patients. Repeat treatment in three patients experiencing progression was associated with a further response. Median survival after SIRT is 25 months with 6 patients being alive (and 3 patients still asymptomatic), at 19, 22, 23, 23, 58, and 60 months. Conclusions. SIRT is an effective and well-tolerated treatment for non-resectable NET liver metastases capable of both alleviating the carcinoid syndrome and achieving significant tumour regression. Repeat treatment is an option and liver resection after downstaging may also become possible.

10.
J Proteomics ; 75(2): 339-51, 2011 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-21843667

RESUMO

The emergence of laser capture microdissection (LCM) and two-dimensional difference gel electrophoresis (2D-DIGE) has been shown to greatly improve the accuracy and sensitivity of global protein expression analysis. However, their combined use in profiling tumour proteome has rarely been reported. In this study, we applied these techniques to profile the protein expression changes of the late stage colorectal cancer (CRC) and its liver metastases. The study revealed that both the primary and secondary tumours showed a distinct protein expression profile compared to normal tissues, but were indistinguishable from each other. Differential analysis between the primary tumour and patient-matched normal colon mucosa identified a total of 71 proteins to be altered in CRC. Over 40% of these proteins have been previously reported as CRC-related proteins, validating the accuracy of the current analysis. We have also identified many previously unknown changes including overexpression of ACY1, HSC70, HnRNP I, HnRNP A3, SET, ANP32A and TUFM in CRC, which have been further verified by western blotting and immunohistochemistry. This study demonstrated that LCM in combination with 2D-DIGE is a powerful tool to analyse the proteome of tumour tissues and may lead to the identification of potential novel protein markers and therapeutic targets for cancer.


Assuntos
Neoplasias Colorretais/química , Microdissecção e Captura a Laser/métodos , Proteínas de Neoplasias/análise , Proteômica/métodos , Eletroforese em Gel Diferencial Bidimensional/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/química , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal
11.
BMC Cancer ; 8: 187, 2008 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-18590575

RESUMO

BACKGROUND: Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression. METHODS: Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses. RESULTS: We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02). CONCLUSION: Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for tumour progression, encoding at least 13 genes with a putative role in carcinoma development. Thus, we propose that this region of 8p comprises a metastatic susceptibility locus involved in tumour progression whose disruption increases metastatic potential.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/secundário , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Metástase Neoplásica/genética , Adenocarcinoma/metabolismo , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Deleção Cromossômica , Cromossomos Humanos Par 8 , Neoplasias Colorretais/metabolismo , DNA/análise , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Polimorfismo Genético , RNA Mensageiro/análise , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo
12.
Obes Surg ; 16(10): 1298-303, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17059737

RESUMO

BACKGROUND: The placement of a ring circumferentially around the gastric pouch of a vertical gastric bypass has the advantage of permanently fixing the size of the gastric outlet and slowing the passage of food into the jejunum. Opinion remains divided about the use of rings, and the optimal size. METHODS: Since 1990, we have consistently placed a ring at the time of gastric bypass surgery and have an experience with three ring sizes (circumference); 5.5 cm, 6.0 cm and 6.5 cm. Patient data has been recorded prospectively in a computerized database. We have reviewed the outcomes of all patients with at least 12 months follow-up with respect to quality of eating, the need for subsequent ring removal and weight loss. RESULTS: Quality of eating was better in those with the larger rings. Ring removal was undertaken in 7 (14%) of those with a 5.5-cm ring, in 11 (5.1%) with a 6.0 cm ring and in 3 (2%) with a 6.5-cm ring (P<0.05). Ring removal led to a median recorded weight gain of 6.8 kg (-4.13 kg to 32.2 kg). When only those 415 patients in whom the ring was still in situ and there was no known staple-line disruption were considered (5.5 cm - 50, 6 cm - 215, 6.5 cm -150), there was no difference in the weight loss achieved and maintained out to 5 years, although there was a trend for this to be better in those with the larger rings. CONCLUSION: We conclude that the inclusion of a ring placed around the gastric pouch of a vertical gastric bypass is beneficial for maintenance of weight loss, and a ring size of 6.5-cm circumference should be recommended.


Assuntos
Derivação Gástrica/instrumentação , Adulto , Remoção de Dispositivo , Ingestão de Alimentos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Resultado do Tratamento , Redução de Peso
13.
ANZ J Surg ; 76(8): 696-703, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16916386

RESUMO

BACKGROUND: Many patients with colorectal liver metastases die from liver-only disease. Selective internal radiation therapy (SIRT) is an evolving method suitable for treating patients with non-resectable metastatic liver disease. METHODS: One hundred patients with advanced colorectal liver metastases were treated with SIRT. A single dose of between 2.0 and 3.0 GBq of (90)Y microspheres was given into the hepatic artery either by a surgically implanted portacath or a percutaneous femoral catheter. When a port was used (n = 87), SIRT was followed by hepatic arterial chemotherapy with 5-fluorouracil. RESULTS: Treatment-related morbidity occurred in 11 patients. Responses to SIRT were assessed by serial computed tomography scans and carcinoembryonic antigen (CEA) measurement. Median CEA level 3 months after SIRT (expressed as percentage of initial CEA) was 18%. Only 5 of 80 patients (6.25%) scanned at 3 months showed disease progression. Survival was significantly more in those who experienced a good tumour marker response and in those who were slow to develop extrahepatic disease. Survival was independently influenced by the use of ongoing hepatic arterial chemotherapy, the extent of liver involvement and the lymph node status of the original primary tumour. CONCLUSION: Selective internal radiation therapy is a very effective and well-tolerated regional treatment for colorectal liver metastases, which should be considered for those with liver-only metastatic disease.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/sangue , Masculino , Microesferas , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
15.
BMC Nucl Med ; 5: 7, 2005 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-16375764

RESUMO

BACKGROUND: SIRT is an emerging treatment for liver tumours which relies on the selective uptake by tumour of 90Y microspheres following hepatic arterial injection. Response rates of around 90% are reported. Hepatic arterial injection of MAA gives an indication of the expected distribution of 90Y microspheres within the liver. This study sought to determine if the MAA scan could be predictive of subsequent tumour response. METHODS: 58 patients with colorectal hepatic metastases received SIRT. All had pre-treatment MAA planar images and CT scans which were retrospectively reviewed. Tumours were qualitatively considered "cold", "equivocal" or "hot" based on MAA uptake and the ratio of uptake in tumour and normal liver tissue was calculated (TNR). Following SIRT (which included the administration of hepatic arterial Angiotensin 2) tumour response was assessed by CEA changes one to two months after treatment and by serial CT. RESULTS: Uptake was classified as "hot" in 37 patients (Group 1) and "equivocal" or "cold" in 21 (Group 2). CEA levels fell dramatically in over 90% of patients. The falls were not significantly different between the groups. There was no correlation between TNR and tumour response based on CEA changes (r2 = 0.004). CT responses after 3 months were not different in the 2 Groups. CONCLUSION: The pattern of MAA uptake by colorectal liver tumours after arterial injection is not a predictor of tumour response after treatment by SIRT. The results suggest the doses of 90Y microspheres used may be greater than is necessary.

16.
Obes Surg ; 15(4): 474-81, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15946424

RESUMO

BACKGROUND: Gastric bypass has repeatedly been shown to improve and even cure type 2 diabetes by substantially improving insulin resistance. The mechanism by which it achieves this is not currently known, but some have hypothesized that there may be important humoral effects brought about by the bypass of the stomach, duodenum or proximal jejunum. A better understanding of the time course of the changes in insulin resistance after surgery might assist our understanding of potential mechanisms. METHODS: Intravenous glucose tolerance tests (IVGTT) were performed in 26 severely obese patients on the morning of gastric bypass surgery and again 6 days later. In addition insulin resistance was assessed in 71 patients undergoing gastric bypass surgery by the homeostasis model assessment (HOMA) method before surgery, and again at 6 days, 3, 6, 9, and 12 months. Patients were divided into 3 groups for analysis: diabetics, impaired glucose tolerance and normal glucose tolerance. RESULTS: All 3 groups of patients were noted to have insulin resistance prior to surgery. This was greatest in the diabetic patients, as indicated by HOMA. There was marked loss of/improvement in insulin resistance within 6 days of gastric bypass by both IVGTT and HOMA methods in all groups, which was maintained over the 12-month period. The study included 31 diabetic patients, of whom only 3 required medication following hospital discharge. CONCLUSION: The changes in insulin resistance seen after gastric bypass, which are responsible for the resolution or improvement of type 2 diabetes occur within 6 days of the surgery, before any appreciable weight loss has occurred. This finding has implications for our understanding of the mechanism of insulin resistance in severely obese patients and is consistent with a humoral mechanism emanating from the GI tract.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Derivação Gástrica/métodos , Resistência à Insulina/fisiologia , Obesidade Mórbida/cirurgia , Adulto , Idoso , Análise de Variância , Anastomose em-Y de Roux , Área Sob a Curva , Glicemia/análise , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/diagnóstico , Assistência Perioperatória , Estudos Prospectivos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Redução de Peso
17.
Obes Surg ; 15(2): 155-63, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15802056

RESUMO

BACKGROUND: While a great deal has been published regarding the short- and medium-term outcomes of gastric bypass surgery, much less information is available regarding long-term follow-up. Such information would be valuable in changing attitudes towards this surgery. METHODS: 342 severely obese patients underwent gastric bypass between June 1990 and April 2003 by a single surgeon. Careful preoperative documentation and follow-up have been maintained on a computerized database. Where necessary, recent followup information has been gained by mailed questionnaire and blood tests. RESULTS: Follow-up data from within the last 12 months is available for 88% of patients. Follow-up time ranges from 0-14 years, with a median of 48.6 months. Of those lost to follow-up, only 24 (7%) have <12 months follow-up. The series includes 261 females and 81 males. Preoperative BMI ranged from 28-99 (median 44). Before surgery, hypertension was present in 138, type 2 diabetes in 62, and dyslipidemia in 265. There was no 30-day peri-operative mortality. Three life-threatening complications occurred. BMI and % excess weight loss after 1, 2, 5 and 10 years were 28.7 and 89%, 28.3 and 87%, 31.2 and 70% and 31 and 75%, respectively. At most recent follow-up, 62% of those with hypertension before surgery were cured and 25% had improved. 85% of those with type 2 diabetes were cured and 10% had improved. No patients with impaired glucose tolerance had progressed to diabetes. 34% of those with dyslipidemia were cured and 38% had improved. CONCLUSION: The excellent outcomes, in terms of weight loss and improvement in co-morbidities, seen in both the short- and medium-term after gastric bypass, are well maintained into the longer-term.


Assuntos
Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Redução de Peso , Adaptação Fisiológica , Adolescente , Adulto , Distribuição por Idade , Idoso , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Derivação Gástrica/efeitos adversos , Humanos , Hiperlipidemias/diagnóstico , Hiperlipidemias/epidemiologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/diagnóstico , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Fatores de Tempo
18.
Dis Colon Rectum ; 46(4): 454-8; discussion 458-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12682536

RESUMO

PURPOSE: Liver surgeons usually recommend against biopsy of colorectal liver metastases because of the risk of local dissemination. To date, only case reports describing this problem have been published. This study is an attempt to quantify the risk of biopsy-related dissemination. METHODS: A multicenter, retrospective review was undertaken of cases of colorectal liver metastases presenting for surgery that had undergone a preoperative biopsy. RESULTS: Two hundred thirty-one cases of colorectal liver metastases presenting for surgery were identified. Forty-three cases had undergone a preoperative biopsy (18.6 percent). Seven patients had evidence of dissemination related to the biopsy, giving a risk of dissemination of 16 percent (95 percent confidence interval, 7-30 percent). The risk of dissemination was not related to the type of biopsy. Within the follow-up period (median, 21 months), 3 of the 7 cases with evidence of dissemination and 11 of the 35 without dissemination were alive without disease. Twenty-five percent of the 36 cases without dissemination were resected, whereas 6 of the 7 cases with dissemination were resected. CONCLUSIONS: There is a significant risk of local dissemination with biopsy of colorectal liver metastases. In this series this was independent of the type of biopsy. There was no demonstrated effect on resectability or survival, but numbers were small, and the median follow-up was short.


Assuntos
Biópsia/efeitos adversos , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Inoculação de Neoplasia , Idoso , Biópsia por Agulha/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
Obes Surg ; 12(3): 343-8, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12082884

RESUMO

BACKGROUND: The association between insulin resistance (IR) and obesity and its causal relationship with type 2 diabetes is well recognized. The possibility of an association, causal or otherwise, with other obesity-related co-morbidities warrants consideration. METHODS: IR was calculated pre-operatively in 80 patients undergoing gastric bypass surgery for severe obesity, using the homeostasis model assessment (HOMA) method, and again in 70 patients on at least one occasion post-operatively within 12 months. Correlations with weight parameters and pre-existing co-morbidities including diabetes, hypertension, dyslipidemia and hepatic steatosis were made. RESULTS: 78/80 patients had IR pre-operatively which did not correlate with pre-operative weight or BMI. As expected, there were positive correlations between pre-operative IR and abnormal glucose tolerance and diabetes. A positive correlation was also found between IR and hepatic steatosis, but no correlation was noted between IR and hypertension or fasting levels of cholesterol, triglycerides or Chol/HDL cholesterol ratios. Improvement in IR was uniformly seen after gastric bypass, sooner than would be accounted for by weight loss alone. The degree of pre-operative IR was not a predictor of weight loss after gastric bypass in these patients. CONCLUSIONS: While IR is an almost universal accompaniment of severe obesity, it does not correlate with the degree of obesity in this group of patients. A number of important co-morbidities show a clear association with IR, and improvement in these after gastric bypass may well be related to striking and rapid changes in IR.


Assuntos
Resistência à Insulina/fisiologia , Doenças Metabólicas/complicações , Doenças Metabólicas/fisiopatologia , Obesidade Mórbida/complicações , Obesidade Mórbida/fisiopatologia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Feminino , Derivação Gástrica , Homeostase/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Índice de Gravidade de Doença , Redução de Peso/fisiologia
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