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1.
J Surg Educ ; 79(6): 1363-1378, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35902349

RESUMO

OBJECTIVE: Perceptions are important and can affect efficacy of trainer-trainee interactions. Inherent bias toward other specialties may influence the perceived benefit of a multi-specialty learning environment. The aim of this work was to determine surgical resident perceptions regarding the utility of learning from faculty and with learners from other surgical specialties. DESIGN: We measured surgical residents' perceptions before and after a multi-specialty robotic simulation event. Pre- and post-activity surveys were administered electronically to all residents determining previous experience with robotic surgery, perceptions of learning from faculty in different surgical sub-specialties, and of learning from and with residents in other surgical specialties. SETTING: Robotic simulation laboratory. PARTICIPANTS: General surgery (GS), Obstetrics and gynecology (OBG), and Urology (URO) residents in one academic healthcare program. RESULTS: Prior to the simulation, OBG and URO residents perceived highest utility in learning from faculty within their own specialty. While OBG residents reported high pre-activity agreement that learning from other faculty was useful, more than 50% of GS and URO residents were neutral or disagreed that learning from OBG faculty was useful. Pre-activity, all specialties perceived highest value in learning from and about residents of their own specialty. Following the educational event, all specialties reported increased agreement that learning from faculty of different specialties had utility. Following the simulation, the cohort reported the multi-specialty learning environment improved their knowledge and confidence in robotic surgery. CONCLUSIONS: Participation in a multi-specialty educational event can improve perceptions of surgical residents regarding the utility of being taught by faculty in different specialties. Resident opinion of the benefits of learning with and about learners from other specialties can also be improved. Multi-specialty learning environments are important in developing communities of practice to allow socialization and promotion of positive identity development in our surgical residents, which may ultimately benefit efficacy of learning and patient care.


Assuntos
Internato e Residência , Medicina , Especialidades Cirúrgicas , Humanos , Educação de Pós-Graduação em Medicina , Percepção
2.
Dis Colon Rectum ; 64(3): 313-318, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395140

RESUMO

BACKGROUND: Multimodal, narcotic-sparing analgesic strategies are an important part of enhanced recovery after surgery protocols. Within such protocols, regional anesthetics have proven to be superior to narcotics. OBJECTIVE: This study aimed to evaluate the impact of the transversus abdominis plane block within an enhanced recovery after surgery protocol on length of stay. DESIGN: A retrospective analysis of patients who underwent colorectal surgery in 2015 to 2016 was completed. The primary end points for this analysis were total length of stay and total narcotics consumed during hospitalization. Length of stay and total narcotic use were compared for patients who received a transversus abdominis plane block versus those that did not. DATA SOURCE: The data were obtained from the data warehouse of a university teaching hospital. SETTINGS: This study took place at a university teaching hospital. PATIENTS: The patients were 18 years or older. MAIN OUTCOME MEASURES: The primary outcomes measured were length of stay and the total narcotics used. RESULTS: A total of 347 patients underwent colorectal procedures under the enhanced recovery protocol. Among these, 186 (54%) received a transversus abdominis plane block. Overall, the mean length of stay was 5.8 days (SD ±5.6), and median length of stay was 4 days. These values compare to a mean length of stay of 9.6 days and median length of stay of 7 days before implementing the enhanced recovery protocol. Patients who received a transversus abdominis plane block had a mean length of stay of 5.1 days compared to 6.6 days for those who did not receive one (p < 0.01). Patients who received a transversus abdominis plane block consumed 736.5 morphine milligram equivalents of opioids compared to 1150.3 morphine milligram equivalents of opioid consumed by those without a transversus abdominis plane block (p < 0.05), a 36% decrease in opioid use. When comparing patients who had a mean length of stay of 4 days with those whose length of stay was >4 days, there was an 80% decrease in opioid use. The readmission rate was 7.8%. LIMITATIONS: The lack of randomization of patients was a limitation of this study. CONCLUSION: The use of transversus abdominis plane block in the setting of a well-structured enhanced recovery protocol was associated with a statistically significant decrease in length of stay by 1.5 days and a 36% decrease in narcotic use. See Video Abstract at http://links.lww.com/DCR/B432. IMPACTO DE LA ANESTESIA DEL PLANO MUSCULAR DE LOS TRANSVERSOS ABDOMINALES EN LA ESTADA DENTRO UN PROTOCOLO ERAS: ANTECEDENTES:La estrategia analgésica multimodal que consume poco medicamento de tipo narcótico es parte importante en los protocolos de recuperación mejorada postoperatoria. Dentro de dichos protocolos, los anestésicos regionales han demostrado ser superiores a la administración de medicamentos narcóticos.OBJETIVO:Estudiar el impacto del bloqueo del plano muscular de los transversos del abdomen sobre la duración de la estadía dentro de un protocolo de recuperación mejorada postoperatoria.DISEÑO:Se realizó un análisis retrospectivo de los pacientes que se sometieron a cirugía colorrectal entre 2015-2016. Los criterios principales de valoración en el presente análisis fueron la duración total de la estadía y el total de medicamentos narcóticos consumidos durante la hospitalización. Se comparó la duración de la estadía y el uso total de narcóticos en los pacientes que recibieron un bloqueo anestésico del plano muscular de los transversos del abdomen con los que no lo recibieron.FUENTE DE DATOS:Banco de datos de un hospital universitario docente.AMBIENTE:Hospital Universitario Docente.PACIENTES:Adultos desde los 18 años o mayores.PRINCIPALES MEDIDAS DE RESULTADO:Duración de la estadía, cantidad total de medicamentos narcóticos administrados.RESULTADOS:Un total de 347 pacientes se sometieron a procedimientos colorrectales bajo el protocolo ERAS. Entre ellos, 186 (54%) recibieron un bloqueo del plano muscular de los transversos del abdomen. En la globalidad, la duración media de la estadía fué de 5,8 días (DE ± 5,6) y la duración media de la estadía fué de 4 días. Estos resultados fueron comparados con la estadía media de 9,6 días y una estadía media de 7 días antes de implementar el protocolo ERAS. Los pacientes que recibieron un bloqueo del plano muscular de los transversos del abdomen tuvieron una estadía media de 5,1 días en comparación con los 6,6 días de los que no recibieron el mencionado bloqueo (p <0,01). Los pacientes que recibieron el bloqueo del plano muscular consumieron 736,5 miligramos de morfina o su equivalente en opioides, comparados con los 1150,3 de aquellos sin bloqueo del plano muscular (p <0,05) lo que significó una disminución del 36% en la administración de opioides. Al comparar los pacientes que tuvieron una estadía media de 4 días con aquellos cuya estadía fue mayor a 4 días, se evidenció una disminución en el 80% de la administración de opioides. La tasa de reingreso fue del 7,8%.LIMITACIONES:Estudio sin sin aleatorización de pacientes.CONCLUSIÓN:El bloqueo anestésico del plano muscular de los transversos del abdomen dentro un contexto protocolar tipo ERAS o de recuperación mejorada bien estructurada, se asoció con la disminución estadísticamente significativa de la duración de la estadía en 1,5 días y una disminución del 36% en la administración de medicamentos narcóticos. Consulte Video Resumen en http://links.lww.com/DCR/B432.


Assuntos
Músculos Abdominais/efeitos dos fármacos , Anestesia por Condução/estatística & dados numéricos , Recuperação Pós-Cirúrgica Melhorada/normas , Tempo de Internação/estatística & dados numéricos , Bloqueio Neuromuscular/métodos , Músculos Abdominais/inervação , Adulto , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/farmacologia , Anestesia por Condução/métodos , Estudos de Casos e Controles , Cirurgia Colorretal/estatística & dados numéricos , Cirurgia Colorretal/tendências , Hospitalização/estatística & dados numéricos , Hospitais de Ensino , Humanos , Entorpecentes/provisão & distribuição , Entorpecentes/uso terapêutico , Estudos Retrospectivos
3.
Dis Colon Rectum ; 63(9): 1338-1342, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33952973
4.
Clin Colon Rectal Surg ; 30(1): 63-75, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28144214

RESUMO

Rectoceles are a very common finding in patients, and symptoms most commonly include pelvic pain, pressure, or difficulty with passing stool. However, there are often other associated pelvic floor disorders that accompany rectoceles, making the clinical significance of it in an individual patient often hard to determine. When evaluating a patient with a rectocele, a thorough history and physical exam must be conducted to help delineate other causes of these symptoms. Treatment consists of addressing other defecatory disorders through various methods, with surgery reserved for select cases in which obstructed defecation is well documented.

5.
Dis Colon Rectum ; 59(1): 28-34, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26651109

RESUMO

BACKGROUND: Laparoscopic colorectal resection is an index case for advanced skills training, yet many residents struggle to reach proficiency by graduation. Current methods to reduce the learning curve for residents remain expensive, time consuming, and poorly validated. OBJECTIVE: The purpose of this study was to assess the impact of the addition of a preprocedural instructional video to improve the ability of a general surgery resident to perform laparoscopic right colectomy when compared with standard preparation. DESIGN: This was a single-blinded, randomized control study. SETTINGS: Four university-affiliated teaching hospitals were included in the study. PARTICIPANTS: General surgery residents in postgraduation years 2 through 5 participated. INTERVENTION: Residents were randomly assigned to preparation with a narrated instructional video versus standard preparation. MAIN OUTCOME MEASURES: Resident performance, scored by a previously validated global assessment scale, was measured. RESULTS: Fifty-four residents were included. Half (n = 27) were randomly assigned to view the training video and half (n = 27) to standard preparation. There were no differences between groups in terms of training level or previous operative experience or in patient demographics (all p > 0.05). Groups were similar in the percentage of the case completed by residents (p = 0.39) and operative time (p = 0.74). Residents in the video group scored significantly higher in total score (mean: 46.8 vs 42.3; p = 0.002), as well as subsections directly measuring laparoscopic skill (vascular control mean: 11.3 vs 9.7, p < 0.001; mobilization mean: 7.6 vs. 7.0, p = 0.03) and overall performance score (mean: 4.0 vs 3.1; p < 0.001). Statistical significance persisted across training levels. LIMITATIONS: There is potential for Hawthorne effect, and the study is underpowered at the individual postgraduate year level. CONCLUSIONS: The simple addition of a brief, narrated preprocedural video to general surgery resident case preparation significantly increased trainee ability to successfully perform a laparoscopic right colectomy. In an era of shortened hours and less exposure to cases, incorporating a brief but effective instructional video before surgery may improve the learning curve of trainees and ultimately improve safety.

6.
Carcinogenesis ; 35(6): 1341-51, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24510238

RESUMO

Upregulation of fatty acid synthase (FASN), a key enzyme of de novo lipogenesis, is associated with metastasis in colorectal cancer (CRC). However, the mechanisms of regulation are unknown. Since angiogenesis is crucial for metastasis, we investigated the role of FASN in the neovascularization of CRC. The effect of FASN on tumor vasculature was studied in orthotopic CRCs, the chick embryo chorioallantoic membrane (CAM) and Matrigel plug models using immunohistochemistry, immunofluorescent staining and confocal microscopy. Cell secretion was evaluated by ELISA and antibody arrays. Proliferation, migration and tubulogenesis of endothelial cells (ECs) were assessed in CRC-EC coculture models. In this study, we found that stable knockdown of FASN decreased microvessel density in HT29 and HCT116 orthotopic CRCs and resulted in 'normalization' of tumor vasculature in both orthotopic and CAM models. Furthermore, FASN regulated secretion of pro- and antiangiogenic factors, including vascular endothelial growth factor-A (VEGF-A). Mechanisms associated with the antiangiogenic activity noted with knockdown of FASN included: downregulation of VEGF(189), upregulation of antiangiogenic isoform VEGF(165b) and a decrease in expression and activity of matrix metalloproteinase-9. Furthermore, conditioned medium from FASN knockdown CRC cells inhibited activation of vascular endothelial growth factor receptor-2 and its downstream signaling and decreased proliferation, migration and tubulogenesis of ECs as compared with control medium. Together, these results suggest that cancer cell-associated FASN regulates tumor vasculature through alteration of the profile of secreted angiogenic factors and regulation of their bioavailability. Inhibition of FASN upstream of VEGF-A and other angiogenic pathways can be a novel therapeutic strategy to prevent or inhibit metastasis in CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Células Endoteliais/metabolismo , Ácido Graxo Sintases/genética , Neovascularização Patológica/genética , Animais , Linhagem Celular Tumoral , Embrião de Galinha , Modelos Animais de Doenças , Ácido Graxo Sintases/metabolismo , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
7.
Clin Cancer Res ; 20(5): 1212-22, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24443523

RESUMO

BACKGROUND: The precise involvement of the PI3K/mTOR and RAS/MEK pathways in carcinoid tumors is not well defined. Therefore, the purpose of our study was to evaluate the role these pathways play in carcinoid cell proliferation, apoptosis, and secretion and to determine the effects of combined treatment on carcinoid tumor inhibition. METHODS: The human neuroendocrine cell lines BON (pancreatic carcinoid), NCI-H727 (lung carcinoid), and QGP-1 (somatostatinoma) were treated with either the pan-PI3K inhibitor, BKM120, or the dual PI3K-mTOR inhibitor, BEZ235, alone or in combination with the MEK inhibitor, PD0325901; proliferation, apoptosis, and protein expression were assessed. Peptide secretion was evaluated in BON and QGP-1 cells. The antiproliferative effect of BEZ235, alone or combined with PD0325901, was then tested in vivo. RESULTS: Both BKM120 and BEZ235 decreased proliferation and increased apoptosis; combination with PD0325901 significantly enhanced the antineoplastic effects of either treatment alone. In contrast, neurotensin peptide secretion was markedly stimulated with BKM120 treatment, but not BEZ235. The combination of BEZ235 + PD0325901 significantly inhibited the growth of BON xenografts without systemic toxicity. CONCLUSIONS: Both BKM120 and BEZ235 effectively inhibited neuroendocrine tumor (NET) cell proliferation and stimulated apoptosis. However, inhibition of the PI3K pathway alone with BKM120 significantly stimulated neurotensin peptide secretion; this did not occur with the dual inhibition of both PI3K and mTOR using BEZ235 suggesting that this would be a more effective treatment regimen for NETs. Moreover, the combination of BEZ235 and the MEK inhibitor PD0325901 was a safe and more effective therapy in vivo compared with single agents alone.


Assuntos
Tumores Neuroendócrinos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais/efeitos dos fármacos , Aminopiridinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Difenilamina/análogos & derivados , Difenilamina/farmacologia , Sinergismo Farmacológico , Humanos , Imidazóis/farmacologia , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Morfolinas/farmacologia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Am Surg ; 79(7): 686-92, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23816001

RESUMO

Abdominal operations for rectal prolapse are associated with lower recurrence rates than perineal procedures but presumed higher morbidity. Therefore, perineal procedures are recommended for patients deemed unfit for abdominal repair. Consequently, bias confounds retrospective comparisons of the two approaches. To clarify the impact of operative approach on outcomes, we analyzed abdominal and perineal procedures in a propensity score-matched analysis. We selected patients undergoing surgery for rectal prolapse from the American College of Surgeons National Surgical Quality Improvement Program data set from 2005 to 2010. We grouped procedures as abdominal or perineal. We identified preoperative variables predictive of complications and regressed against operative approach. The resulting propensity score was used to select a matched cohort with similar clinical risk. We identified 2188 patients (848 abdominal [38.8%]; 1340 perineal [61.2%]). Patients undergoing the perineal approach had higher rates of most risk variables. Propensity matching resulted in 563 matched pairs (1126 patients) with similar clinical risk. In this matched cohort, no significant difference was found in the rate of any complication between the operative approaches; mortality was 0.9 per cent in each group (P = 1.0). Relative risk for major morbidity after abdominal approach was 1.39 (95% confidence interval, 0.92 to 2.10; P = 0.15). Although many patients with rectal prolapse are high risk for abdominal surgery, our study indicates that many patients treated by perineal repair could be safely treated with a more durable operation.


Assuntos
Abdome/cirurgia , Segurança do Paciente , Períneo/cirurgia , Prolapso Retal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Pontuação de Propensão , Recidiva , Resultado do Tratamento
9.
J Surg Res ; 185(2): 690-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23890402

RESUMO

BACKGROUND: Small interfering RNA (siRNA) provides a highly selective method to target mutated pathways; however, its use is complicated by specific delivery to tumor cells. The aims of the present study were to develop a novel murine model of portal vein catheterization for the chronic delivery of therapeutic agents to liver metastases, determine the benefits of local delivery of siRNA to liver metastases, and determine the utility of epithelial cell adhesion molecule (EpCAM) as a selective target for siRNA delivery to colorectal cancer (CRC) metastases. MATERIALS AND METHODS: First, portal vein catheterization was performed through a midline laparotomy in 2 mo-old Balb/C mice. Second, the portal venous flow distribution and catheter patency were evaluated using fluorescent-labeled microspheres. Metastatic studies were performed by splenic injection of CT26 murine colon cancer cells. Uptake of DY-547-labeled siRNA was assessed by IVIS imaging, with delivery to the metastases confirmed using fluorescent microscopy. Finally, EpCAM expression was evaluated using immunohistochemical staining of human tissue microarrays. RESULTS: Successful portal vein catheterization was confirmed by saline injection and ultrasound. Fluorescent imaging of microspheres confirmed excellent distribution and catheter patency. Portal venous injection of DY547-labeled siRNA demonstrated a high level of fluorescence throughout the liver, with siRNA also identified within the liver metastases. Also, all primary CRCs and liver metastases stained strongly for EpCAM, with no expression in normal hepatocytes. CONCLUSIONS: Liver-directed therapy can provide the selective delivery of siRNA to CRC metastases. EpCAM expression in CRC, but not normal liver, could further selectively target hepatic metastases of epithelial origin.


Assuntos
Antígenos de Neoplasias/genética , Cateterismo Venoso Central/métodos , Moléculas de Adesão Celular/genética , Neoplasias do Colo/terapia , Terapia Genética/métodos , Neoplasias Hepáticas Experimentais/terapia , Veia Porta , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/secundário , Modelos Animais de Doenças , Molécula de Adesão da Célula Epitelial , Fígado/irrigação sanguínea , Fígado/patologia , Neoplasias Hepáticas Experimentais/secundário , Camundongos , Camundongos Endogâmicos BALB C , Microesferas , Transplante de Neoplasias , Poliestirenos/farmacocinética , RNA Interferente Pequeno/farmacologia
10.
PLoS One ; 8(12): e83693, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24386254

RESUMO

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. METHODS: Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water) for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF), and mesenteric lymph nodes. RESULTS: During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1ß, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. CONCLUSIONS: Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes.


Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Colite/genética , Colite/patologia , Citocinas/genética , Expressão Gênica , Doença Aguda , Animais , Colite/induzido quimicamente , Colite/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Mesentério/metabolismo , Mesentério/patologia , Camundongos , Fatores de Tempo
11.
Surgery ; 152(2): 277-85, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22828149

RESUMO

BACKGROUND: RNA interference has the potential to be more selective than small molecule inhibitors and can be used to target proteins, such as Ras, that are currently undruggable. The purpose of our study was to determine the optimal cotargeting strategy of the commonly mutated PI3K/AKT/mTOR and Ras pathways by a selective RNA interference approach in colorectal cancer cell lines possessing coexistent PIK3CA and KRAS mutations. METHODS: Human colorectal cancer cell lines HCT116 and DLD-1 were treated with a panel of small interfering RNAs directed against the PI3K/AKT/mTOR and Ras pathways; proliferation, apoptosis, and protein expression were assessed. Combined treatment with small interfering RNA and 5-fluorouracil was then evaluated. RESULTS: PIK3CA and KRAS small interfering RNAs were most effective as single treatments; combined treatments with PIK3CA and KRAS small interfering RNA resulted in a more pronounced inhibition of colorectal cancer cell proliferation. Either KRAS small interfering RNA alone or combined PIK3CA and KRAS small interfering RNA treatments increased apoptosis in HCT116 cells but not in the DLD-1 cell line. Inhibition of 4E-BP1 phosphorylation correlated with increased apoptosis. In addition, small interfering RNA treatment combined with 5-fluorouracil further inhibited colorectal cancer cell proliferation. CONCLUSION: Combined PIK3CA and KRAS small interfering RNA treatments offer an effective therapy against colorectal cancer cells with coexisting mutations in both pathways. Decreased 4E-BP1 phosphorylation correlates with increased apoptosis and may provide a biomarker indicative of treatment success. In addition, small interfering RNA directed to PIK3CA and KRAS may be used to enhance the effects of current chemotherapy.


Assuntos
Carcinoma/terapia , Neoplasias Colorretais/terapia , Interferência de RNA , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Apoptose , Carcinoma/genética , Carcinoma/metabolismo , Proteínas de Ciclo Celular , Proliferação de Células/efeitos dos fármacos , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Fluoruracila/farmacologia , Células HCT116 , Humanos , Mutação , Fosfatidilinositol 3-Quinases/genética , Fosfoproteínas/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , RNA Interferente Pequeno , Proteínas ras/genética
12.
Dis Colon Rectum ; 55(4): 429-35, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22426267

RESUMO

BACKGROUND: Previous reports comparing outcomes of laparoscopic colectomy in obese vs nonobese patients from small, single-institution series have included few obese patients and have shown variable results, some suggesting that obesity has no impact on outcomes. OBJECTIVE: We aimed to determine whether any intraoperative or short-term postoperative outcome of laparoscopic colectomy is affected by obesity, independent of other variables. DESIGN: We performed a retrospective study comparing outcomes of patients undergoing laparoscopic colectomy grouped by BMI. PATIENTS: We queried American College of Surgeons National Surgical Quality Improvement Program Participant Use Data Files for patients undergoing nonemergent, laparoscopic colectomy from 2005 through 2008. Cases with a secondary procedure (with the exception of laparoscopic lysis of adhesions, rigid proctosigmoidoscopy, or laparoscopic splenic flexure takedown) were excluded. MAIN OUTCOME MEASURES: We analyzed operative time, length of stay, transfusion requirement, reoperation within 30 days, wound complications, pulmonary complications, sepsis/septic shock, deep venous thrombosis, renal failure/insufficiency, and death. We tested for differences in outcomes using χ tests or analyses of variance, and when differences between BMI classes were found, we performed multivariable regression to adjust for preoperative and intraoperative variables. RESULTS: In an analysis of 9693 patients (30% with BMI ≥30), significant differences were found among BMI classes for length of stay, operative time, and wound complication. Operative time correlated with BMI class independent of other variables; length of stay did not. After adjustment of all available variables, obesity remained an independent risk factor for wound complication, and the odds ratios increased with increasing obesity class. LIMITATIONS: Retrospective design and standardized outcome measures prevent examination of procedure-specific outcomes; therefore, this is not an intention-to-treat analysis. CONCLUSIONS: These data confirm that, in patients undergoing laparoscopic colectomy, obesity is an independent risk factor for wound complications. Although obesity also increases operative time, the effect of obesity on wound complications remains after adjustment for this and other risk factors.


Assuntos
Colectomia/métodos , Laparoscopia/métodos , Obesidade/complicações , Análise de Variância , Transfusão de Sangue/estatística & dados numéricos , Distribuição de Qui-Quadrado , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Análise de Regressão , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
13.
Curr Opin Endocrinol Diabetes Obes ; 18(1): 75-82, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21124211

RESUMO

PURPOSE OF REVIEW: Neurotensin is a 13-amino acid peptide found in the central nervous system central nervous system and the gastrointestinal tract. Since its initial discovery in 1973, neurotensin has been shown to play a role in a wide range of physiologic and pathologic processes throughout the body. Ongoing research efforts continue to clarify the role of neurotensin in various central nervous system and gastrointestinal processes, as well as how disruption of these normal mechanisms may lead to diseases ranging from schizophrenia to colorectal cancer. The goal of this review is to provide an overview of the most recent advances in the field of neurotensin research, in the context of what has been previously published. RECENT FINDINGS: Because of the seemingly unrelated functions of neurotensin in the central nervous system and the periphery, the scope of the articles reviewed is rather broad. Contributions continue to be made to our understanding of the downstream effects of neurotensin signaling and the complex feedback loops between neurotensin and other signaling molecules. By selective targeting or blockade of specific neurotensin receptors, investigators have identified potential drugs for use in the treatment of schizophrenia, alcoholism, chronic pain, or cancer. Neurotensin-based pharmacologic agents are being used successfully in animal models for a number of these conditions. SUMMARY: The review highlights the wide array of biological processes in which neurotensin has a role, and summarizes the most recent advances in various fields of neurotensin research. The knowledge gained through this research has led to the development of first-in-class drugs for the treatment of various medical conditions, and it is clear that in the coming years some of these agents will be ready to move from the bench to the bedside in clinical trials.


Assuntos
Fenômenos Fisiológicos Celulares , Doença/etiologia , Neurotensina/fisiologia , Animais , Fenômenos Fisiológicos Celulares/genética , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiologia , Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/metabolismo , Doença/genética , Gastroenteropatias/etiologia , Gastroenteropatias/genética , Gastroenteropatias/metabolismo , Humanos , Neoplasias/etiologia , Neoplasias/genética , Neoplasias/metabolismo , Neurotensina/genética , Neurotensina/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
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