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1.
Nat Commun ; 12(1): 4039, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193867

RESUMO

The controlled assembly of nanomaterials into desired architectures presents many opportunities; however, current preparations lack spatial precision and versatility in developing complex nano-architectures. Inspired by the amphiphilic nature of surfactants, we develop a facile approach to guide nanomaterial integration - spatial organization and distribution - in metal-organic frameworks (MOFs). Named surfactant tunable spatial architecture (STAR), the technology leverages the varied interactions of surfactants with nanoparticles and MOF constituents, respectively, to direct nanoparticle arrangement while molding the growing framework. By surfactant matching, the approach achieves not only tunable and precise integration of diverse nanomaterials in different MOF structures, but also fast and aqueous synthesis, in solution and on solid substrates. Employing the approach, we develop a dual-probe STAR that comprises peripheral working probes and central reference probes to achieve differential responsiveness to biomarkers. When applied for the direct profiling of clinical ascites, STAR reveals glycosylation signatures of extracellular vesicles and differentiates cancer patient prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais/métodos , Neoplasias Colorretais/diagnóstico , Vesículas Extracelulares/metabolismo , Estruturas Metalorgânicas/química , Nanoestruturas/química , Tensoativos/química , Ascite/metabolismo , Neoplasias Colorretais/metabolismo , Glicosilação , Humanos , Prognóstico
2.
Clin Cancer Res ; 27(7): 1875-1881, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33148667

RESUMO

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel laparoscopic, intraperitoneal chemotherapy delivery technique aiming to improve drug distribution and tissue penetration to treat peritoneal metastases. Thus far, PIPAC oxaliplatin is conducted at an arbitrary dose of 92 mg/m2. We conducted a phase I study to establish safety and tolerability. PATIENTS AND METHODS: We used a 3+3 dose-escalation design of PIPAC oxaliplatin for patients with peritoneal metastases from gastrointestinal tumors, after failure of at least first-line chemotherapy. Dose levels were planned at 45, 60, 90, and 120 mg/m2. RESULTS: This study included 16 patients with 24 PIPAC procedures (8 gastric; 5 colorectal; and 1 gallbladder, pancreas, and appendix cancer each). Median age and peritoneal cancer index (PCI) score were 62 years and 17, respectively. Two patients developed pancreatitis (grade 2 and 3) at 45 mg/m2, necessitating cohort expansion. Another patient developed grade 2 pancreatitis at 90 mg/m2. There were no other dose-limiting toxicities, and the highest-dose cohort (120 mg/m2) tolerated PIPAC well. Pharmacokinetic analyses demonstrated good linearity between dose and maximum concentration (r 2 = 0.95) and AUC (r 2 = 0.99). On the basis of RECIST, 62.5% and 50% had stable disease after one and two PIPAC procedures, respectively. A total of 8 patients underwent two PIPAC procedures, with improvement of median PCI and peritoneal regression grade score from 15 to 12 and 2.5 to 2.0, respectively. CONCLUSIONS: The recommended phase II dose is 120 mg/m2. Future studies should further delineate the efficacy and role of PIPAC oxaliplatin for peritoneal metastases.See related commentary by de Jong et al., p. 1830.

3.
Value Health ; 23(9): 1171-1179, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32940235

RESUMO

OBJECTIVES: To evaluate cost-effectiveness of a novel screening strategy using a microRNA (miRNA) blood test as a screen, followed by endoscopy for diagnosis confirmation in a 3-yearly population screening program for gastric cancer. METHODS: A Markov cohort model has been developed in Microsoft Excel 2016 for the population identified to be at intermediate risk (Singaporean men, aged 50-75 years with Chinese ethnicity). The interventions compared were (1) initial screening using miRNA test followed by endoscopy for test-positive individuals and a 3-yearly follow-up screening for test-negative individuals (proposed strategy), and (2) no screening with gastric cancer being diagnosed clinically (current practice). The model was evaluated for 25 years with a healthcare perspective and accounted for test characteristics, compliance, disease progression, cancer recurrence, costs, utilities, and mortality. The outcomes measured included incremental cost-effectiveness ratios, cancer stage at diagnosis, and thresholds for significant variables. RESULTS: The miRNA-based screening was found to be cost-effective with an incremental cost-effectiveness ratio of $40 971/quality-adjusted life-year. Key drivers included test costs, test accuracy, cancer incidence, and recurrence risk. Threshold analysis highlights the need for high accuracy of miRNA tests (threshold sensitivity: 68%; threshold specificity: 77%). A perfect compliance to screening would double the cancer diagnosis in early stages compared to the current practice. Probabilistic sensitivity analysis reported the miRNA-based screening to be cost-effective in >95% of iterations for a willingness to pay of $70 000/quality-adjusted life-year (approximately equivalent to 1 gross domestic product/capita) CONCLUSIONS: The miRNA-based screening intervention was found to be cost-effective and is expected to contribute immensely in early diagnosis of cancer by improving screening compliance.


Assuntos
Detecção Precoce de Câncer/economia , Endoscopia/economia , Programas de Rastreamento/economia , MicroRNAs/economia , Neoplasias Gástricas/diagnóstico , Idoso , Grupo com Ancestrais do Continente Asiático , Análise Custo-Benefício , Detecção Precoce de Câncer/métodos , Humanos , Estudos Longitudinais , Masculino , Programas de Rastreamento/estatística & dados numéricos , MicroRNAs/sangue , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Medição de Risco , Sensibilidade e Especificidade , Singapura/epidemiologia , Neoplasias Gástricas/epidemiologia
4.
J Gastric Cancer ; 20(2): 115-126, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32595996

RESUMO

Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.

5.
Sci Adv ; 6(19): eaba2556, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32494726

RESUMO

Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis-through simultaneous biophysical and biomolecular evaluation of the same vesicles-directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.

6.
Pleura Peritoneum ; 5(2): 20200102, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32566726

RESUMO

Intraperitoneal chemotherapy has shown promising results for the treatment of peritoneal carcinomatosis in gastric cancer. However, the implantation of an intraperitoneal chemotherapy port may be associated with catheter-related complications. The authors describe a case of cutaneous port-site recurrence secondary to tumour seeding from an intraperitoneal chemotherapy access port.

7.
Surg Endosc ; 34(8): 3292-3297, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32394175

RESUMO

BACKGROUND: The COVID-19 pandemic has resulted in significant changes to surgical practice across the worlds. Some countries are seeing a tailing down of cases, while others are still having persistent and sustained community spread. These evolving disease patterns call for a customized and dynamic approach to the selection, screening, planning, and for the conduct of surgery for these patients. METHODS: The current literature and various international society guidelines were reviewed and a set of recommendations were drafted. These were circulated to the Governors of the Endoscopic and Laparoscopic Surgeons of Asia (ELSA) for expert comments and discussion. The results of these were compiled and are presented in this paper. RESULTS: The recommendations include guidance for selection and screening of patients in times of active community spread, limited community spread, during times of sporadic cases or recovery and the transition between phases. Personal protective equipment requirements are also reviewed for each phase as minimum requirements. Capability management for the re-opening of services is also discussed. The choice between open and laparoscopic surgery is patient based, and the relative advantages of laparoscopic surgery with regard to complications, and respiratory recovery after major surgery has to be weighed against the lack of safety data for laparoscopic surgery in COVID-19 positive patients. We provide recommendations on the operating room set up and conduct of general surgery. If laparoscopic surgery is to be performed, we describe circuit modifications to assist in reducing plume generation and aerosolization. CONCLUSION: The COVID-19 pandemic requires every surgical unit to have clear guidelines to ensure both patient and staff safety. These guidelines may assist in providing guidance to units developing their own protocols. A judicious approach must be adopted as surgical units look to re-open services as the pandemic evolves.


Assuntos
Infecções por Coronavirus/epidemiologia , Controle de Infecções/métodos , Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pandemias , Pneumonia Viral/epidemiologia , Ásia/epidemiologia , Betacoronavirus , COVID-19 , Humanos , Salas Cirúrgicas , Seleção de Pacientes , Equipamento de Proteção Individual , SARS-CoV-2 , Cirurgiões
8.
Ann Thorac Surg ; 108(1): e57-e59, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30872101

RESUMO

Despite the high incidence of reflux esophagitis, there are few reports of antireflux modifications for minimally invasive Ivor-Lewis esophagectomy. We present the case of a 63-year-old man with mid-thoracic esophageal squamous cell carcinoma who underwent minimally invasive Ivor-Lewis esophagectomy after neoadjuvant chemoradiotherapy. Laparoscopic dissection, gastric tube creation, and mobilization was performed. Thoracoscopic esophageal dissection, subcarinal, paraesophageal and diaphragmatic lymphadenectomy were performed, followed by esophagogastric anastomosis with double seromuscular flap reconstruction to recreate the lower esophageal sphincter. The operation was completed in 618 minutes with 200 mL blood loss and the patient recovered uneventfully. A morphologic sphincter was seen on postoperative contrast study.


Assuntos
Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Retalhos Cirúrgicos , Anastomose Cirúrgica , Esofagite Péptica/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle
9.
Gastric Cancer ; 22(3): 423-434, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30805742

RESUMO

INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols have been successfully integrated into peri-operative management of different cancer surgeries such as colorectal cancer. Their value for gastric cancer surgery, however, remains uncertain. METHODS: A search for randomized and observational studies comparing ERAS versus conventional care in gastric cancer surgery was performed according to PRISMA guidelines. Random-effects meta-analyses with inverse variance weighting were conducted, and quality of included studies was assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa scale (PROSPERO: CRD42017080888). RESULTS: Twenty-three studies involving 2686 patients were included. ERAS was associated with reduced length of hospital stay (WMD-2.47 days, 95% CI - 3.06 to - 1.89, P < 0.00001), time to flatus (WMD-0.70 days, 95% CI - 1.02 to - 0.37, P < 0.0001), and hospitalization costs (WMD-USD$ 4400, 95% CI - USD$ 5580 to - USD$ 3210, P < 0.00001), with consistent results across open and laparoscopic surgery. Postoperative morbidity and 30-day mortality were similar, although a higher rate of readmission was observed in the ERAS group (RR = 1.95, 95% CI 1.03-3.67, P = 0.04). Patients in the ERAS arm had significantly attenuated C-reactive protein levels on days 3/4 and 7, interleukin-6 levels on days 1, and 3/4, and tumor necrosis factor-α levels on days 3/4 postoperatively. CONCLUSION: Compared to conventional care, ERAS reduces hospital stay, costs, surgical stress response and time to return of gut function, without increasing post-operative morbidity in gastric cancer surgery. However, precaution is necessary to reduce the increased risk of hospital readmission when adopting ERAS.


Assuntos
Gastrectomia/mortalidade , Laparoscopia/mortalidade , Tempo de Internação/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias , Padrão de Cuidado , Neoplasias Gástricas/cirurgia , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Taxa de Sobrevida
10.
Cancer Med ; 8(4): 1447-1458, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30790469

RESUMO

To evaluate the response and quality of life of palliative gastric radiotherapy in patients with symptomatic locally advanced gastric cancer. Patients with bleeding, pain or obstruction and were treated with palliative gastric radiotherapy to a dose of 36 Gy in 12 daily fractions. The primary outcomes were symptom response rates. Secondary outcomes included overall survival, adverse events and proportion of patients with ≥10-point absolute improvement in the fatigue, nausea/vomiting and pain subscales in the EORTC Qualify of Life Questionnaire C30 (EORTC QLQ-C30) and dysphagia/pain subscales in the gastric specific module (STO22) at the end of RT and 1 month after the completion of radiotherapy. Fifty patients were accrued. Median survival duration was 85 days. 40/50 patients (80%) with bleeding, 2/2 (100%) patients with obstruction and 1/1 (100%) patient with pain responded to radiotherapy. Improvements fatigue, nausea/vomiting and pain subscales of the EORTC QLQ-C30 was seen in 50%, 28% and 44% of patients at the end of RT and in 63%, 31% and 50% of patients 1 month after RT. Improvements in dysphagia/pain subscales of the STO22 was seen in 42% and 28% of patients at then end of RT and 44% and 19% of patients 1 month after RT. Two patients (5%) had grade 3 anorexia and gastritis. Palliative gastric radiotherapy was effective, well tolerated and resulted in improvement in fatigue, dysphagia and pain at the end of radiotherapy and 1 month after the completion of radiotherapy in a significant proportion of patients.


Assuntos
Qualidade de Vida/psicologia , Neoplasias Gástricas/radioterapia , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Radioterapia/efeitos adversos , Neoplasias Gástricas/psicologia , Análise de Sobrevida , Resultado do Tratamento
11.
J Gastrointest Surg ; 23(3): 445-450, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30187324

RESUMO

BACKGROUND: Changes in body composition after bariatric surgery such as a sustained loss of body fat are often associated with an inevitable loss of fat free mass. This can contribute to an undesirable disturbance in resting metabolic rate and weight maintenance. Our aim was to study changes in body composition in a multiethnic Asian cohort following bariatric surgery and to identify differences between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. METHODS: A retrospective review of prospectively collected data on 295 patients who underwent either laparoscopic sleeve gastrectomy (256 patients) or laparoscopic Roux-en-Y gastric bypass (39 patients) was performed. Body composition variables were measured with the analyzer, GAIA 359 PLUS, which included the parameters; total body weight, body mass index, excess weight, basal metabolic rate, fat-free mass, fat mass, and total body water. RESULTS: There were no statistical differences in gender, ethnicity, age, weight, height, and body mass index between laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass. At each time point (6, 12, 24, and 36 months) post-operation, there was no significant differences in % total body weight loss, basal metabolic rate, fat mass, fat percentage, and total body water between sleeve gastrectomy and bypass patients. There was significant difference (p < 0.05) in fat free mass only at 3 years post-operation, with sleeve gastrectomy patients having 9.79 kg less fat-free mass than bypass patients. However, after multivariate analysis, we found no statistically significant differences. CONCLUSION: Sleeve gastrectomy and gastric bypass seemed to give similar changes to body composition.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Gastrectomia , Derivação Gástrica , Laparoscopia , Obesidade Mórbida/etnologia , Obesidade Mórbida/cirurgia , Tecido Adiposo , Adulto , Composição Corporal , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Singapura , Perda de Peso
13.
Obes Surg ; 27(12): 3075-3081, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28674840

RESUMO

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly performed procedures for the treatment of obesity. Patients with obesity are more prone to experience opioid-related adverse events (ORAE). OBJECTIVES: The objective of this study is to determine if a multimodal analgesia protocol (MAP) reduces ORAE and provides effective pain relief for patients after LSG. SETTING: This study was conducted at University Hospital, Singapore. METHODS: The MAP consists of mandatory pre-operative etoricoxib, intra-operative acetaminophen, and post-operative acetaminophen with optional post-operative tramadol. We identified and collected data for patients who underwent LSG between May 2010 and November 2015 and compared patients before and after the implementation of the MAP. RESULTS: One hundred fifty-eight patients were included and 68 patients were treated with the MAP. There were no differences in age, gender, body mass index, ethnicity, or comorbidities between the two groups except for the incidence of hypertension (p = 0.015). There was a significant reduction in the incidence of ORAE from 33.3 to 8.8% (p < 0.001) after the implementation of the MAP. There was also a significant reduction in the use of opioids intra-operatively from 58.2 to 43.6 mg (p < 0.001) and post-operatively from 23.7 to 0.7 mg (p < 0.001). Pain scores were similar at 1, 6, and 48 post-operatively, while pain scores were significantly reduced at 12 (p = 0.033) and 24 h (p = 0.02) post-operatively. Multivariate analysis showed that these results remained significant. CONCLUSION: Our study suggests that a MAP reduces ORAE and provides effective pain relief for patients undergoing LSG.


Assuntos
Analgesia/métodos , Analgésicos Opioides/efeitos adversos , Analgésicos/uso terapêutico , Gastrectomia , Obesidade Mórbida/cirurgia , Dor Pós-Operatória/prevenção & controle , Adulto , Analgesia/efeitos adversos , Analgesia/economia , Analgésicos/economia , Índice de Massa Corporal , Custos de Medicamentos , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Dor Pós-Operatória/economia , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Período Pós-Operatório , Singapura/epidemiologia
14.
Oncotarget ; 7(18): 25391-407, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27058427

RESUMO

In gastric cancer (GC), the main subtypes (diffuse and intestinal types) differ in pathological characteristics, with diffuse GC exhibiting early disseminative and invasive behaviour. A distinctive feature of diffuse GC is loss of intercellular adhesion. Although widely attributed to mutations in the CDH1 gene encoding E-cadherin, a significant percentage of diffuse GC do not harbor CDH1 mutations. We found that the expression of the actin-modulating cytoskeletal protein, gelsolin, is significantly higher in diffuse-type compared to intestinal-type GCs, using immunohistochemical and microarray analysis. Furthermore, in GCs with wild-type CDH1, gelsolin expression correlated inversely with CDH1 gene expression. Downregulating gelsolin using siRNA in GC cells enhanced intercellular adhesion and E-cadherin expression, and reduced invasive capacity. Interestingly, hepatocyte growth factor (HGF) induced increased gelsolin expression, and gelsolin was essential for HGF-medicated cell scattering and E-cadherin transcriptional repression through Snail, Twist and Zeb2. The HGF-dependent effect on E-cadherin was found to be mediated by interactions between gelsolin and PI3K-Akt signaling. This study reveals for the first time a function of gelsolin in the HGF/cMet oncogenic pathway, which leads to E-cadherin repression and cell scattering in gastric cancer. Our study highlights gelsolin as an important pro-disseminative factor contributing to the aggressive phenotype of diffuse GC.


Assuntos
Carcinoma/patologia , Gelsolina/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Transdução de Sinais/fisiologia , Neoplasias Gástricas/patologia , Antígenos CD , Caderinas/metabolismo , Carcinoma/metabolismo , Humanos , Invasividade Neoplásica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo
15.
Surg Obes Relat Dis ; 12(3): 518-521, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26944549

RESUMO

BACKGROUND: The aim of our study is to determine if a goal-directed program improves weight loss after sleeve gastrectomy. METHODS: Our goal-directed program involves setting excess weight loss targets at fixed intervals after sleeve gastrectomy. We identified patients in 3 bariatric centers between April 2010 and July 2013 and compared the center that has a goal-directed weight loss program (goal-directed program) with the other 2 centers (standard program). RESULTS: A total of 211 patients were included, with 129 patients in the goal-directed weight loss program. The 2 groups were similar in terms of gender distribution, ethnicity distribution, age, and preoperative weight, preoperative body mass index, and surgical technique. The follow-up rates at 3, 6, 9, and 12 months for patients in the goal-directed program was 84.5%, 75.2%, 59.7%, and 82.2%, respectively, compared with 65.9%, 68.3%, 51.2%, and 68.3% for the standard program. The percentage total weight loss at 3, 6, 9, and 12 months was 17.1%, 23.3%, 26.8%, and 28.6%, respectively, for the goal-directed program, compared with 15.3%, 21.8%, 24.4%, and 25.4%, respectively, for the standard program. The mean excess weight loss at 3, 6, 9, and 12 months were 40%, 54%, 62%, and 67%, respectively, for the goal-directed program group, and 36%, 50%, 54%, and 55%, respectively, for the standard program, where statistical significance (P<.005) was achieved at 12 months. CONCLUSION: Our results suggest that a goal-directed protocol may improve weight loss outcomes after laparoscopic sleeve gastrectomy.


Assuntos
Gastrectomia/métodos , Obesidade Mórbida/cirurgia , Perda de Peso/fisiologia , Adulto , Cirurgia Bariátrica/métodos , Estudos de Casos e Controles , Feminino , Objetivos , Humanos , Masculino , Resultado do Tratamento
16.
Obes Surg ; 26(9): 2156-2160, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26780361

RESUMO

BACKGROUND: The preoperative use of gastroscopy for patients undergoing bariatric surgery remains controversial. We aim to evaluate the diagnostic yield of gastroscopy and the clinical significance in asymptomatic individuals undergoing bariatric surgery in Asia. METHODS: We retrospectively reviewed the medical records of all patients undergoing gastroscopy prior to bariatric surgery at the National University Hospital and Khoo Teck Puat Hospital, Singapore, between Jan 2006 and June 2013. Gastroscopy findings were classified into four groups: group 1 (normal study), group 2 (abnormal findings that do not modify surgical approach), group 3 (abnormal findings that modify surgical approach) and group 4 (absolute contraindications to immediate surgery). RESULTS: During the study period, 208 asymptomatic individuals were evaluated by gastroscopy prior to bariatric surgery. Gastroscopy was normal in 70 (33.6 %). Group 2 comprised 67 (32.2 %) patients with mild gastritis or oesophagitis. Group 3 included 69 (33.2 %) patients diagnosed with erosive gastritis or oesophagitis, peptic ulcer disease, hiatal hernia or mass lesions. There were 2 patients (1.0 %) in group 4. One patient had a gastro-oesophageal junction adenocarcinoma, and 1 had a gastrointestinal stroma tumour. In group 3, modification of surgical approach included concurrent hiatal hernia repair, institution of medical therapy with delay in surgery, further evaluation of mass lesions and change in choice of surgical procedures. CONCLUSIONS: Routine gastroscopy for asymptomatic bariatric patients has a high diagnostic yield. Given the high percentage of patients with clinically important lesions, our current experience supports the use of routine preoperative gastroscopy prior to bariatric surgery in Singapore.


Assuntos
Cirurgia Bariátrica/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Gastroscopia/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Singapura , Adulto Jovem
17.
Cell Rep ; 12(2): 272-85, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26146084

RESUMO

Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H(+) leakage, and the fusion might contribute to invasiveness once a cell is transformed.


Assuntos
Claudinas/genética , Proteínas Ativadoras de GTPase/genética , Proteínas de Fusão Oncogênica/metabolismo , Neoplasias Gástricas/patologia , Sequência de Aminoácidos , Animais , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Clatrina/farmacologia , Claudinas/metabolismo , Cães , Endocitose/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Proteínas Ativadoras de GTPase/metabolismo , Células HeLa , Humanos , Células MCF-7 , Células Madin Darby de Rim Canino , Dados de Sequência Molecular , Proteínas de Fusão Oncogênica/genética , Fenótipo , Neoplasias Gástricas/metabolismo , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/metabolismo
20.
Eur Radiol ; 24(12): 3105-14, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25038858

RESUMO

OBJECTIVES: We evaluated the feasibility of performing CT volumetry of gastric carcinoma (GC) and its correlation with TNM stage. METHODS: This institutional review board-approved retrospective study was performed on 153 patients who underwent a staging CT study for histologically confirmed GC. CT volumetry was performed by drawing regions of interest including abnormal thickening of the stomach wall. Reproducibility of tumour volume (Tvol) between two readers was assessed. Correlation between Tvol and TNM/peritoneal staging derived from histology/surgical findings was evaluated using ROC analysis and compared with CT evaluation of TNM/peritoneal staging. RESULTS: Tvol was successfully performed in all patients. Reproducibility among readers was excellent (r = 0.97; P = 0.0001). The median Tvol of GC showed an incremental trend with T-stage (T1 = 27 ml; T2 = 32 ml; T3 = 53 ml and T4 = 121 ml, P < 0.01). Tvol predicted with good accuracy T-stage (≥T2:0.95; ≥T3:0.89 and T4:0.83, P = 0.0001), M-stage (0.87, P = 0.0001), peritoneal metastases (0.87, P = 0.0001) and final stage (≥stage 2:0.89; ≥stage 3:0.86 and stage 4:0.87, P = 0.0001), with moderate accuracy for N-stage (≥N1:0.75; ≥N2:0.74 and N3:0.75, P = 0.0001). Tvol was significantly (P < 0.05) more accurate than standard CT staging for prediction of T-stage, N3-stage, M-stage and peritoneal metastases. CONCLUSION: CT volumetry may provide useful adjunct information for preoperative staging of GC. KEY POINTS: CT volumetry of gastric carcinoma is feasible and reproducible. Tumour volume <19.4 ml predicts T1-stage gastric cancer with 91% sensitivity and 100% specificity (P = 0.0001). Tumour volume >95.7 ml predicts metastatic gastric cancer with 87% sensitivity and 78.5% specificity (P = 0.0001). CT volumetry may be a useful adjunct for staging gastric carcinoma.


Assuntos
Neoplasias Gástricas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomografia Computadorizada de Feixe Cônico/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/secundário , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/patologia , Adulto Jovem
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