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1.
BMC Cancer ; 18(1): 567, 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769057

RESUMO

BACKGROUND: Management of squamous cell carcinoma of the anus (SCCA) is becoming more relevant, as its incidence increases. The purpose of this study was to investigate possible differences in patient population and care delivery for SCCA between academic and community cancer programs in the United States. METHODS: A review of available data from the American College of Surgeons Committee on Cancer National Cancer DataBase focused on gender, age, race, type of health insurance, comorbidity score, distance traveled for care, stage at diagnosis, and therapy utilization (surgery, chemotherapy, and radiation therapy) as first course of treatment (FCT). The analysis included 38,766 patients treated for SCCA. Of them, 14,422 patients received treatment at Academic Cancer Programs (ACPs), while 24,344 were treated at Community Cancer Programs (CCPs) between the years 2003 and 2013. RESULTS: Over the 11-year study period, ACPs had significantly more male patients, of younger age, a greater non-white race population, with more Medicaid or no insurance coverage, who traveled farther for cancer center care (p < 0.001). There was no difference between ACPs and CCPs with respect to Charlson co-morbidity score and stage of SCCA at diagnosis. For stage 0 patients, use of chemotherapy was 8% for ACPs, 9% for CCPs, and use of radiotherapy was 10% for ACPs and 14% for CCPs. The incidence of stage unknown was identical at both ACPs and CCPs (11.5%). CCPs had a greater overall utilization of radiation therapy as FCT for stage 0, I, II and IV patients (p < 0.001). CONCLUSIONS: Our study indicates that gender, demographic and socio-economic differences exist in the patient population with SCCA accessing different cancer programs in the US. The high incidence of stage unknown patients reflects ongoing challenges in the pre-treatment phase. A significant percentage of stage 0 patients received systemic chemotherapy and/or radiotherapy, rather than surgery alone. Despite comparable stage at diagnosis and comorbidity scores between ACPs and CCPs, there appear to be variations in treatment choices, especially with the use of radiotherapy, with associated cost and toxicity risks. Further analysis and monitoring of SCCA management in the US may lead to improved compliance with NCCN guidelines.


Assuntos
Centros Médicos Acadêmicos/organização & administração , Neoplasias do Ânus/terapia , Institutos de Câncer/organização & administração , Carcinoma de Células Escamosas/terapia , Centros Comunitários de Saúde/organização & administração , Padrões de Prática Médica/estatística & dados numéricos , Centros Médicos Acadêmicos/normas , Centros Médicos Acadêmicos/estatística & dados numéricos , Fatores Etários , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/patologia , Institutos de Câncer/normas , Institutos de Câncer/estatística & dados numéricos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Terapia Combinada/economia , Terapia Combinada/métodos , Terapia Combinada/estatística & dados numéricos , Centros Comunitários de Saúde/normas , Centros Comunitários de Saúde/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Estudos Retrospectivos , Fatores Sexuais , Fatores Socioeconômicos , Estados Unidos
2.
J Minim Access Surg ; 13(3): 219-221, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28607291

RESUMO

This technical note describes a novel technique, not previously found in the surgical or endoscopic literature: A combined endoscopic and surgical approach to perform a full-thickness excision of a colonic tumour. At the time of colonoscopy via stoma, a large sessile polyp in the descending colon was detected but could not be safely resected endoscopically. The lesion was exteriorised by prolapsing the distal colon through the colostomy, then excised surgically with adequate margins in a full-thickness fashion. This approach was more complete than an endoscopic approach and less invasive than a segmental colectomy and redo colostomy. It may prove useful to surgical endoscopists facing a similar clinical situation in their practice.

3.
J Clin Gastroenterol ; 50(6): 498-500, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26859123

RESUMO

Solitary rectal ulcer syndrome is a well-known clinical entity, likely secondary to a defecatory dysfunction. In patients who have undergone restorative proctocolectomy with ileoanal reservoir, it is conceivable that a similar pathophysiology may lead to "solitary pouch ulcer," but such a syndrome has not been reported to date. This article reports 2 such cases and clinical success with lasting symptomatic relief through local therapy and behavior modification rather than anti-inflammatory.


Assuntos
Bolsas Cólicas/patologia , Doenças do Íleo/diagnóstico , Úlcera/diagnóstico , Adulto , Feminino , Humanos , Doenças do Íleo/patologia , Pessoa de Meia-Idade , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Úlcera/patologia
4.
Dig Surg ; 27(3): 185-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20571264

RESUMO

BACKGROUND: The purpose of our study was to assess the impact of distal margin length on outcome in patients with rectal cancer treated with neoadjuvant chemoradiation therapy (CRT) followed by radical resection. METHODS: Fifty-three consecutive patients were evaluated. The selection criteria included: adenocarcinoma of the mid- or distal rectum, locally advanced stage, absence of distant metastases, and preoperative CRT followed by proctectomy with total mesorectal excision. The operations included low anterior resection in 33 patients (62%) and abdominoperineal resection in 20 (38%). The outcome measures were: tumor regression, complete pathologic response, length of distal resection margins, status of radial margins and recurrence rate. RESULTS: Forty-eight patients (91%) had tumor regression, and 11 (21%) had a complete pathologic response. Distal resection margins were tumor-free in all patients, ranging in length from 0.1 to 7.4 cm (mean = 2.2). Follow-up (mean = 48.8 months) was current in 50 of 53 patients (94%). There was no locoregional recurrence. CONCLUSIONS: Distal resection margins shorter than 1-2 cm appear to be equivalent to longer margins in patients who undergo CRT followed by proctectomy with total mesorectal excision. These findings may lead to greater utilization of sphincter-saving procedures in rectal cancer.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Retais/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos
5.
Am J Clin Oncol ; 43(2): 133-138, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31764018

RESUMO

OBJECTIVES: National Comprehensive Cancer Network (NCCN) guidelines for stage III colon cancer define low-risk versus high-risk patients based on T (1 to 3 vs. 4) and N (1 vs. 2) status, with some variations in treatment. This study analyzes the impact of tumor deposits (TDs), T and N status, poor differentiation (PD), perineural invasion (PNI), and lymphovascular invasion (LVI) on survival. MATERIALS AND METHODS: A retrospective analysis (2010-2015) of the National Cancer Database of stage III colon cancer patients treated with both surgery and chemotherapy was conducted. Data was extracted on sex, race, age at diagnosis, Charlson-Deyo Score, histopathologic variables, and survival rates. Statistical analysis used the test of proportions, log-rank test for Kaplan-Meier curves, and Cox proportional hazard models. RESULTS: For the 42,901 patients analyzed, 5-year survival rates were similar for LNTD (59.8%) and LNTD (58.2%), but significantly worse for LNTD (41.5%) (P<0.001). The presence of LNTD was more often associated with T4 (36.9%), N2 (55.1%), PD (37.4%), PNI (34.5%), and LVI (69.1%), than LNTD or LNTD (P<0.001). The hazard ratios for each variable were: TD: 1.34; T4: 1.71; N2: 1.44; PD: 1.37; PNI: 1.11; LVI: 1.18. LN patients with ≥3 TD (N1c) had worse overall survival than those with 1 to 2 TD (P<0.01), but similar to ≥4 LNTD (N2) and 1 to 3 LNTD (N1a-b). In our model, 5-year survival ranged from 23.4% for high-risk to 78.1% for low-risk patients (P<0.001). CONCLUSION: This National Cancer Database (NCDB) analysis offers greater risk stratification and may prompt consideration of changes in American Joint Committee on Cancer (AJCC) classification (N2c, in addition to N1c) to reflect the different prognosis and guide management, as well as survivorship strategies, for TD stage III colon cancer patients.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Extensão Extranodal/patologia , Linfonodos/patologia , Adenocarcinoma/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Taxa de Sobrevida , Adulto Jovem
7.
Am J Clin Oncol ; 41(7): 662-666, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28169842

RESUMO

BACKGROUND: Management of squamous cell carcinoma of the anus (SCCA) is becoming more relevant, as its incidence continues to increase. The purpose of this study was to evaluate regional and national data to assess trends in epidemiology, access to cancer center care, and overall management strategies in SCCA. STUDY DESIGN: A review of available data from the American College of Surgeons Committee on Cancer National Cancer Data Base focused on incidence, sex, age, stage at diagnosis, distance traveled for care, and utilization of therapy as first course of treatment (FCT). The analysis included 40,817 patients treated for SCCA at 1513 cancer centers in the United States, of which 2347 patients were treated at 109 cancer centers in New England, between the years 2003 and 2013. RESULTS: Over the 11-year period, incidence of SCCA increased by 76% in the United States and by 83.8% in New England. Stage was unknown in 11.7% of all US cases, significantly higher than more common cancers, for example, breast (4.3%), prostate (6%), or colon (7.8%) (P<0.001). Patients in southern New England, compared with northern New England, traveled <10 miles more often (53.4% vs. 38.1%) (P<0.001), and>25 miles less often (14.3% vs. 28.7%) (P<0.001). Cases of early stage SCCA (0, I) were more frequent in southern New England (29.2%) than northern New England (21.7%) (P=0.0025), whereas more advanced stage (II to IV) cases occurred less frequently in southern New England (60.1%) than northern New England (72%) (P<0.001). Overall, the most common FCT was chemoradiotherapy, utilized in 49.3% of cases, followed by chemoradiotherapy plus surgery in 19.4% of cases. Stage unknown patients were treated with chemoradiotherapy in 34.6% of cases, with surgery alone in 20.2%, and with chemoradiotherapy plus surgery in 15.4% of cases. CONCLUSIONS: The incidence of SCCA is steadily increasing. Its frequency of stage unknown is significantly higher than other common cancer sites. Travel distance and stage at diagnosis data may reflect regional differences in cancer center care access. Although chemoradiotherapy remains the most commonly utilized FCT, challenges in accurate staging and inconsistent use of additional prognostic variables may affect optimal treatment.


Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Bases de Dados Factuais , Neoplasias do Ânus/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Terapia Combinada , Gerenciamento Clínico , Humanos , Incidência , New England/epidemiologia , Prognóstico , Estados Unidos/epidemiologia
8.
Int J Surg ; 27: 88-91, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26808325

RESUMO

OBJECTIVES: The study purpose was to investigate the ability of Emergency Department CT scan to predict the need for operative intervention in patients hospitalized for small bowel obstruction (SBO) likely secondary to adhesions (ASBO) and initially managed nonoperatively. DESIGN: Retrospective case series. Statistical analysis was done with independent-samples t-test and chi-square to identify correlation between variables and outcome of nonoperative management. SETTING: Tertiary care academic medical center. PATIENTS AND METHODS: Of 200 consecutive patients hospitalized for SBO, 108 were included in the study with a diagnosis of ASBO and received initial nonoperative management. Exclusion criteria were need for emergency surgery (e.g. peritonitis) or other diagnoses (e.g. neoplasms, hernias, Crohn's disease). CT findings such as transition point, small bowel faeces, high grade obstruction, and abnormal vascular course were correlated with failure of nonoperative management. RESULTS: Only 18 patients (16.7%) required operative intervention, while the other 90 (83.3%) were successfully discharged after nonoperative care. There was no correlation between CT scan findings and treatment outcome. CONCLUSIONS: Emergency Department CT scan findings do not significantly alter management decisions in patients admitted for ASBO and managed initially with nonoperative care.


Assuntos
Obstrução Intestinal/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência , Feminino , Humanos , Obstrução Intestinal/etiologia , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Aderências Teciduais/complicações , Aderências Teciduais/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
9.
Clin Cancer Res ; 10(9): 3069-75, 2004 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15131045

RESUMO

PURPOSE: Through the use of molecular markers, it may be possible to identify aggressive tumor phenotypes and tailor therapies to treat them. This approach would be particularly useful for stage II colon cancer. The purpose of this study was to define the prognostic value of epidermal growth factor receptor (EGFR), c-MET, beta-catenin, and p53 protein expression in TNM stage II colon cancer using tissue microarray technology. EXPERIMENTAL DESIGN: In this study, we retrospectively analyzed, resected, and otherwise untreated paraffin-embedded specimens from 134 consecutive patients with Tumor-Node-Metastasis stage II colonic carcinomas for EGFR, c-MET, beta-catenin, and p53 protein expression by immunohistochemistry. RESULTS: Thirty-five percent, 77, and 65% of tumors exhibited strong (+2 and +3 immunopositivity) expression of EGFR, c-MET, and beta-catenin, respectively. Fifty-four percent exhibited nuclear staining for p53 in >10% of the tumor cells. Univariate analysis revealed that increased nuclear p53 expression (P = 0.001), strong membranous EGFR expression (P = 0.04), and lymphovascular invasion (P = 0.01) were significantly related to disease recurrence and that p53 (P = 0.02) and EGFR (P = 0.05) expression were associated with decreased survival. Increased nuclear p53 expression also correlated with the presence of distal metastasis (P = 0.027). No significant association was seen between c-MET expression and prognosis, whereas a strong trend was detected between loss of beta-catenin (P = 0.065) expression and poor outcome. Multivariate analysis indicated that p53 (P = 0.04), EGFR (P = 0.05), and lymphovascular invasion (P = 0.03) were independent predictors of recurrence and that p53 (P = 0.02) and EGFR (P = 0.01) expression were both associated with poor survival. CONCLUSIONS: This retrospective tumor microarray study, restricted to Tumor-Node-Metastasis stage II colon cancer patients who did not undergo adjuvant therapy, supports the use of EGFR and p53 as biological markers, which may assist in predicting disease recurrence and survival.


Assuntos
Biomarcadores/análise , Neoplasias do Colo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/metabolismo , Proteínas do Citoesqueleto/análise , Intervalo Livre de Doença , Receptores ErbB/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-met/análise , Fixação de Tecidos/métodos , Transativadores/análise , Proteína Supressora de Tumor p53/análise , beta Catenina
10.
Curr Surg ; 62(2): 214-9, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15796943

RESUMO

OBJECTIVE: The purpose of this study was to use an experimental design to determine the effect of selected aspects of dress on the professional image of physicians in an adult outpatient setting by those who use the health care services the most (55+), the least (18 to 22), and other physicians on whom we depend for referrals. METHODS: Ten slides of physicians representing a variety of ages; ethnic and religious affiliations were shown to 3 populations across the United States and Canada. Set 1 (N = 216) was shown to undergraduates and rated on 10 attributes of professional image. Two slides were altered and retested in a rotated order (Set 2). Set 1 was then tested with groups of elderly and surgeons (N = 277). RESULTS: Significant differences were found between Set 1 and Set 2 for the altered physician slides. There was high correlation of professionalism with the identified attributes for all 3 rater populations. The nonverbal attributes chosen for this study did accurately assess "professionalism." Gender of the rater or physician did not have any effect. Although the most "professional" surgeon was the oldest in the study, the second most "professional" was the youngest. CONCLUSIONS: It is clear that a surgeon's image is a mirror of competence, trust, expertise, and compassion. The variables described in this study may easily be implemented to reflect a more positive professional image with our peers and patients than simply adding a white coat. No one goes to see a surgeon to establish a casual relationship, and because it is difficult to counteract initial impressions, attention to these variables is important.


Assuntos
Atitude Frente a Saúde , Vestuário , Médicos , Competência Profissional , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Relações Médico-Paciente , Grupos Raciais , Fatores Sexuais
12.
Arch Surg ; 137(4): 439-45; discussion 445-6, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11926949

RESUMO

HYPOTHESIS: Interleukin 1 beta (IL-1 beta) levels are elevated in the colonic mucosa of patients with ulcerative colitis (UC). We propose that IL-1 beta may also be elevated in the circular muscle layer of the colon and may be partially responsible for the motility dysfunction observed in patients with UC. DESIGN: Cohort analytic study. SETTING: Research laboratory in a tertiary academic medical center. PARTICIPANTS: Normal smooth muscle was obtained from the disease-free margins of human sigmoid colon specimens resected from patients with cancer and compared with specimens from patients with UC. INTERVENTIONS: An enzyme-linked immunosorbent assay was used to measure IL-l beta. Standard muscle chambers were used to measure force changes. Single muscle cells were isolated by enzymatic digestion, and cell shortening in response to neurokinin A (NKA) and thapsigargin was measured under a microscope. Cytosolic Ca(2+) (calcium) concentrations were measured by standard techniques. MAIN OUTCOME MEASURE: Effects of IL-1 beta on smooth muscle function in normal and UC colons. RESULTS: In patients with UC, IL-1 beta was elevated in the muscularis propria, and sigmoid circular smooth muscle contractions in response to NKA and thapsigargin were significantly reduced. In fura-2-loaded cells from patients with UC, the NKA-induced Ca(2+) signal was also significantly reduced in Ca(2+)-free medium, indicating the reduced intracellular Ca(2+) stores after UC. Exposure of normal cells to IL-1 beta mimicked the changes observed in patients with UC. An IL-1 beta-induced reduction in contraction and release of intracellular Ca(2+) in response to NKA was partially restored by the hydrogen peroxide scavenger catalase. CONCLUSION: In patients with UC, IL-1 beta was increased in colonic circular muscles and may contribute to motor dysfunction after UC through production of hydrogen peroxide.


Assuntos
Colite Ulcerativa/fisiopatologia , Colo/fisiopatologia , Motilidade Gastrointestinal , Interleucina-1/fisiologia , Trifosfato de Adenosina/antagonistas & inibidores , Cálcio/metabolismo , Colite Ulcerativa/metabolismo , Colo Sigmoide/efeitos dos fármacos , Colo Sigmoide/metabolismo , Colo Sigmoide/fisiopatologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/fisiopatologia , Citosol/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Peróxido de Hidrogênio/metabolismo , Técnicas In Vitro , Interleucina-1/análise , Interleucina-1/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Músculo Liso/fisiopatologia , Neurocinina A/farmacologia , Tapsigargina/farmacologia
14.
J Am Coll Surg ; 218(6): 1163-74, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24755190

RESUMO

BACKGROUND: Surgery remains the most effective intervention for obesity and its comorbidities. However, the long-term efficacy of bariatric procedures is rarely reported. This study addresses operative trends, efficiency, and long-term outcomes from a large bariatric program. STUDY DESIGN: Data were prospectively collected on 3,460 patients undergoing 3,503 operations from January 2004 to March 2013. Primary procedures included Roux-en-Y gastric bypass (RY; n = 2,966), adjustable band (AB; n = 352), and sleeve gastrectomy (SG; n = 118). There were 67 revisional procedures (RP). Mean operative time, hospital length of stay, major 30-day morbidity/mortality, follow-up compliance, and weight loss per procedure at follow-up were recorded. RESULTS: Mean operative times decreased to the following: RY, 53 minutes; AB, 35 minutes; SG, 46 minutes; and RP, 71 minutes. Mean length of stay was reduced to the following: RY, 1.53 days; AB, 0.97 days; SG, 2.12 days; and RP, 2.68 days. Major complications were mortality, 0.09%; leak, 0.51%; bleed, 2.37%; pneumonia, 0.63%; venous thromboembolism, 0.40%; and reoperation, 2.34%. The complication rate was lowest for AB and highest for SG (p < 0.05). Adjustable band was the initial procedure in 73% of cases requiring RP. Follow-up compliance was 93% at 1 year, 79% at 3 years, 71% at 5 years, and 33% at 9 years. Adjustable band offered significant weight loss at 1 and 3 years (p < 0.0001), but less than RY or SG (p < 0.0001). Excess weight loss was not significantly different between RY and SG at 1 year. Significant weight loss with RY persisted at 7 to 9 years (p < 0.0001). CONCLUSIONS: Our bariatric program experienced an increase in SG and RP and a decrease in AB. Optimization of care reduced operative time and length of stay. All procedures achieved significant weight loss in the first year. Adjusted band had the lowest morbidity, but inferior weight loss and greater need for revision. Long-term weight-loss data are only available for RY.


Assuntos
Cirurgia Bariátrica/tendências , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Redução de Peso , Adulto Jovem
15.
18.
Am J Surg ; 195(4): 526-7, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18304500

RESUMO

Colonic and rectal anastomotic strictures occur with an incidence ranging from 3% to 30%. Several factors, such as defunctionalization, anastomotic leak, ischemia, radiation, and neoplasms, have been implicated in their pathogenesis. Management of large bowel strictures is generally based on their cause, location, and appearance. Various methods have been described, including endoscopic techniques (eg, balloon dilatation and/or stents) and operative revision. Postoperative rectal strictures usually respond well to direct dilatation, without the need for endoscopic balloons. If surgical revision is necessary, morbidity can be significant, as in any reoperative procedure. We hereby present a novel surgical method of revision for a complete anastomotic obstruction, which proved effective and avoided extensive operative dissection, mobilization, and re-resection.


Assuntos
Colectomia , Colo/patologia , Colo/cirurgia , Reto/patologia , Reto/cirurgia , Grampeamento Cirúrgico , Anastomose Cirúrgica , Colectomia/efeitos adversos , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Humanos , Laparotomia , Reoperação/instrumentação , Reoperação/métodos , Sigmoidoscópios , Resultado do Tratamento
19.
Am J Physiol Gastrointest Liver Physiol ; 292(6): G1641-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17307729

RESUMO

Muscle cells from human gallbladders (GB) with cholesterol stones (ChS) exhibit a defective contraction, excess cholesterol (Ch) in the plasma membrane, and lower binding of CCK-1 receptors. These abnormalities improved after muscle cells were incubated with Ch-free liposomes that remove the excess Ch from the plasma membrane. The present studies were designed to investigate the role of caveolin-3 proteins (Cav-3) in the pathogenesis of these abnormalities. Muscle cells from GB with ChS exhibit higher Ch levels in the plasma membrane that were mostly localized in caveolae and associated with parallel increases in the expression of Cav-3 in the caveolae compared with that in GB with pigment stones (PS). The overall number of CCK-1 receptors in the plasma membrane was not different between muscle cells from GB with ChS and PS, but they were increased in the caveolae in muscle cells from GB with ChS. Treatment of muscle cells from GB with ChS with a Galpha(i3) protein fragment increased the total binding of CCK-1 receptors (from 8.3 to 11.2%) and muscle contraction induced by CCK-8 (from 11.2 to 17.3% shortening). However, Galpha(q/11) protein fragment had no such effect. Moreover, neither fragment had any effect on muscle cells from GB with PS. We conclude that the defective contraction of muscle cells with excessive Ch levels in the plasma membrane is due to an increased expression of Cav-3 that results in the sequestration of CCK-1 receptors in the caveolae, probably by inhibiting the functions of Galpha(i3) proteins.


Assuntos
Cavéolas/metabolismo , Colecistolitíase/metabolismo , Colesterol/metabolismo , Vesícula Biliar/metabolismo , Cálculos Biliares/metabolismo , Contração Muscular , Músculo Liso/metabolismo , Animais , Pigmentos Biliares/metabolismo , Caveolina 3/metabolismo , Colecistolitíase/fisiopatologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Vesícula Biliar/fisiopatologia , Cobaias , Humanos , Técnicas In Vitro , Lipossomos/metabolismo , Masculino , Músculo Liso/fisiopatologia , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Receptor de Colecistocinina A/metabolismo , Receptores da Colecistocinina/metabolismo , Sincalida/metabolismo
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