RESUMEN
BACKGROUND: Recent studies have suggested that urgent cholecystectomy is the preferred treatment for acute cholecystitis. However, initial conservative treatment followed by delayed elective surgery is still common practice in many medical centers. OBJECTIVES: To determine the effect of percutaneous cholecystostomy on surgical outcome in patients undergoing delayed elective cholecystectomy. METHODS: We conducted a retrospective analysis of all patients admitted to our medical center with acute cholecystitis who were treated by conservative treatment followed by delayed cholecystectomy between 2004 and 2013. Logistic regression was calculated to assess the association of percutaneous cholecystostomy with patient characteristics, planned surgical procedure, and the clinical and surgical outcomes. RESULTS: We identified 370 patients. Of these, 134 patients (36%) underwent cholecystostomy during the conservative treatment period. Patients who underwent cholecystostomy were older and at higher risk for surgery. Laparoscopic cholecystectomy was offered to 92% of all patients, yet assignment to the open surgical approach was more common in the cholecystostomy group (16% vs. 3%). Cholecystostomy was associated with significantly higher conversion rates to open approach (26% vs. 13%) but was not associated with longer operative time, hemorrhage, surgical infections, or bile duct or organ injuries. CONCLUSIONS: Treatment with cholecystostomy is associated with higher conversion rates but does not include other major operative-related complications or poorer clinical outcome.
Asunto(s)
Colecistectomía Laparoscópica/métodos , Colecistectomía/métodos , Colecistitis Aguda/cirugía , Colecistostomía/métodos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Tratamiento Conservador/métodos , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
After the publication of this work [1], an error was noticed in Fig. 2b, Fig. 3a and Fig. 5b. The Skp1 loading control was accidentally duplicated. We apologize for this error, which did not affect any of the interpretations or conclusions of the article.
RESUMEN
The prognosis and clinical management of patients with cancer is commonly determined by traditional clinical and pathological factors. Nevertheless, patients may present with significantly different clinical outcomes despite similar clinicopathological features. This has prompted intense research to find biological markers that may closely reflect tumor biology and thereby clinical outcome. This article presents the current knowledge on the prognostic significance of p27 expression in cancer and its potential role as a target for future therapy.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/biosíntesis , Neoplasias/terapia , Animales , Ciclo Celular/fisiología , Humanos , Terapia Molecular Dirigida , Neoplasias/diagnóstico , Neoplasias/metabolismo , PronósticoRESUMEN
We have recently shown that Skp2 levels are high in undifferentiated human embryonic stem cells, but decline rapidly following induction of differentiation, thereby leading to accumulation of p27. Changes in Skp2 levels were found to be caused mainly by its rate of degradation. Here we show that the activity of APC/C (Cdh1), the ubiquitin ligase that targets Skp2 for degradation, increases markedly during the differentiation process of human embryonic stem cells. APC/C (Cdh1) is present but inactive in undifferentiated embryonic stem cells and becomes active in the differentiated state. The rise in APC/C (Cdh1) activity with differentiation appears to be due, at least in part, to a dramatic decline in the levels of its inhibitor Emi1. In addition, protein kinase activity also appears to contribute to the suppression of APC/C (Cdh1) activity in undifferentiated stem cells, possibly by inhibitory phosphorylation of Cdh1.
Asunto(s)
Diferenciación Celular/fisiología , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Ciclosoma-Complejo Promotor de la Anafase , Diferenciación Celular/genética , Células Cultivadas , Humanos , Immunoblotting , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Complejos de Ubiquitina-Proteína Ligasa/genéticaRESUMEN
Cks1 is an essential factor in facilitating Skp2-dependent degradation of p27, but its role in salivary malignancies is unknown. Expression of cyclin-dependent kinase subunit 1 (Cks1) was examined in 64 salivary malignancies, compared with p27, S-phase kinase protein 2 (Skp2), Ki-67, p53, and TDT-mediated dutp-biotin nick end labeling (TUNEL) expression, and with THE patient's clinical and pathological parameters. Cks1 expression was markedly increased in 30 patients (47%) and strongly correlated with increased expression of Skp2, Ki-67, p53, and TUNEL, but inversely with p27 levels. High expression of Cks1 WAS strongly associated with lymph node metastases and poor prognosis and survival. Cks1 alterations may have a significant biological role in the pathogenesis of salivary cancer.
Asunto(s)
Proteínas Portadoras/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Neoplasias de las Glándulas Salivales/enzimología , Adenocarcinoma/enzimología , Adenocarcinoma/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Quinasas CDC2-CDC28 , Carcinoma de Células Acinares/enzimología , Carcinoma de Células Acinares/secundario , Carcinoma Mucoepidermoide/enzimología , Carcinoma Mucoepidermoide/secundario , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/secundario , Proteínas Portadoras/genética , Quinasas Ciclina-Dependientes/genética , Femenino , Humanos , Técnicas para Inmunoenzimas , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Neoplasias de las Glándulas Salivales/patología , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/metabolismo , Adulto JovenRESUMEN
INTRODUCTION: Preoperative chemotherapy is often used in patients with locally advanced breast cancer. However, commonly used clinical and pathological parameters are poor predictors of response to this type of therapy. Recent studies have suggested that altered regulation of the cell cycle in cancer may be involved in resistance to chemotherapy. Over-expression of the ubiquitin ligase Skp2 results in loss of the cell cycle inhibitor p27Kip1 and is associated with poor prognosis in early breast cancer. The purpose of the present study was to examine the role of these proteins as predictors of clinical outcome and response to chemotherapy in locally advanced breast cancer. METHODS: The expression levels of Skp2 and p27Kip1 were determined by immunohistochemistry both before and after preoperative chemotherapy in 40 patients with locally advanced breast cancer. All patients were treated with cyclophosphamide/doxorubicin (adriamycin)/5-fluorouracil (CAF) and some patients received additional treatment with docetaxel. Expression data were compared with patients' clinical and pathological features, clinical outcome, and response to chemotherapy. RESULTS: Skp2 expression before preoperative chemotherapy was inversely related to p27Kip1 levels, tumor grade, and expression of estrogen and progesterone receptors. Both Skp2 and p27Kip1 were found to be accurate prognostic markers for disease-free and overall survival. High preoperative expression of Skp2 was associated with resistance to CAF therapy in 94% of patients (P < 0.0001) but not with resistance to docetaxel. CONCLUSION: Skp2 expression may be a useful marker for predicting response to doxorubicin-based preoperative chemotherapy and clinical outcome in patients with locally advanced breast cancer.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Proteínas Quinasas Asociadas a Fase-S/biosíntesis , Proteínas Quinasas Asociadas a Fase-S/genética , Adulto , Anciano , Neoplasias de la Mama/patología , Ciclo Celular , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , PronósticoRESUMEN
PURPOSE: The use of transanal endoscopic microsurgery for local excision of rectal cancer has recently gained wide acceptance as a valid and safe alternative for the surgical treatment of T1 tumors. The adequacy of such treatment for T2 tumors, however, is still controversial. This study was designed to evaluate our results with local excision of T2 cancers. METHODS: Patients with T2 cancer admitted to our hospital between 1995 and 2005 were offered surgery by transanal endoscopic microsurgery if found medically unfit or were unwilling to undergo radical surgery. Patients who were preoperatively staged as T1 tumor but were found to be pathologically T2 also were included. RESULTS: Overall, we performed 59 transanal endoscopic microsurgery operations for rectal cancers, of which 21 were for T2 cancers. In 16 (76 percent) of the T2 patients, the tumors were completely removed with clear margins by transanal endoscopic microsurgery and no additional surgery was performed, except for 2 patients who developed radiation-induced complications. Radical surgery was performed in a second operation in five patients because of involved margins and residual disease was found in two. At a median follow-up of three years, all 12 patients who received local excision and radiotherapy remained disease free, whereas a 50 percent recurrence rate was observed in patients who refused adjuvant radiotherapy. CONCLUSIONS: The results of this study support the feasibility of transanal endoscopic microsurgery for the treatment of selected patients with T2 rectal cancer. The addition of radiotherapy may decrease the rates of early local recurrence. However, at present, this treatment strategy should not be routinely considered for patients who may undergo radical procedures.
Asunto(s)
Endoscopía Gastrointestinal/métodos , Microcirugia/métodos , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nariz , Radioterapia Adyuvante/métodos , Neoplasias del Recto/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The expression of Skp2, the ubiquitin ligase subunit that targets p27(Kip1) for degradation, is commonly overexpressed in human cancers. p27(Kip1) is a negative regulator of the cell cycle that plays an important role in tumor suppression. Loss of p27(Kip1) secondary to enhanced ubiquitin-mediated degradation results in uncontrolled proliferation and promotes tumor progression. In the present study the prognostic implications of Skp2 are reviewed and the mechanisms that regulate its expression in different human cancers. A review and analysis of the English literature was undertaken. Overexpression of Skp2 mRNA and protein levels was observed in many aggressive cancers and was commonly associated with down-regulation of p27(Kip1) levels and loss of tumor differentiation. Skp2 is an independent prognostic marker for disease-free and overall survival and may provide additional predictive information to that provided by p27(Kip1) alone. Targeting Skp2 in experimental models resulted in up-regulation of p27(Kip1) and arrested cellular proliferation. Alterations in Skp2 expression have profound effects on cancer progression and may serve as an accurate and independent prognostic marker. Thus, determination of levels of Skp2 and p27(Kip1) by readily available immunohistochemical studies may be a useful tool in the assessment of prognosis, especially in patients with intermediate disease, and may potentially assist in the planning of adjuvant therapy. Skp2 may be an attractive target for the development of novel interventional therapy.
Asunto(s)
Neoplasias/metabolismo , Oncogenes/fisiología , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Ubiquitina/metabolismo , Animales , Humanos , PronósticoRESUMEN
Overexpression of Skp2, the ubiquitin ligase subunit that targets p27 for degradation, is often observed in cancers, and is associated with aggressive tumor proliferation and poor prognosis. As there is no drug at present that specifically targets Skp2, studies were undertaken to examine the effects of commonly used drugs on Skp2 regulation. Doxorubicin is among the most effective antitumor agents used for the management of breast cancer, but its effect on Skp2 expression is unknown. The objective of this study was to examine the effect of doxorubicin on Skp2 expression regulation in breast cancer cell lines. The expression of Skp2 mRNA and the protein levels of Skp2, p27, p21 and cyclin B were examined in doxorubicin-treated MCF-7 and MDA-MB-231 breast cancer cells. The effect of doxorubicin on the cell cycle profile was assessed by fluorescence-activated cell sorting analysis. Doxorubicin decreased Skp2 mRNA and protein levels in MCF-7 cells, but had the opposite effect in MDA-MB-231 cells. p27 levels were slightly decreased, whereas p53 and p21 levels were significantly upregulated in doxorubicin-treated MCF-7 cells. In contrast, p27 levels were unaffected by doxorubicin treatment in MDA-MB-231 cells, but cyclin B levels were markedly increased. Doxorubicin arrested MCF-7 cells at G1/S and G2/M checkpoints, whereas MDA-MB-231 cells were arrested at G2/M only. The differential effects of doxorubicin on Skp2 expression in breast cancer cells depend upon the specific cell cycle checkpoints activated by the drug. These changes induced by doxorubicin, however, do not significantly affect p27 expression in these cell lines, suggesting that the potential of a given drug to alter p27 expression through Skp2 modulation might depend on its specific action on cell cycle arrest.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Ciclo Celular/efectos de los fármacos , Doxorrubicina/farmacología , Proteínas Quinasas Asociadas a Fase-S/biosíntesis , Neoplasias de la Mama , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , ARN Mensajero/biosíntesis , Proteínas Quinasas Asociadas a Fase-S/genéticaRESUMEN
PURPOSE: Focused helical CT using rectal contrast material only has emerged recently as an accurate diagnostic tool for the evaluation of suspected acute appendicitis. This study was designed to prospectively compare the efficacy of rectal contrast CT to other commonly used contrast-enhanced and nonenhanced CT techniques for the detection of acute appendicitis. METHODS: A total of 232 patients with clinically suspected appendicitis were randomly assigned to one of three focused helical CT techniques: noncontrast enhanced CT, CT using rectal contrast material only, and dual-contrast CT using both oral and intravenous material. All scans were interpreted by the on-call residents and reported immediately to the surgeon. The sensitivity, specificity, predictive values, and overall accuracy rates were compared between the protocols. RESULTS: One hundred eleven patients (48 percent) had acute appendicitis. The sensitivity and specificity rates of rectal contrast CT were 93 and 95 percent, respectively, with overall accuracy of 94 percent. The sensitivity and specificity rates of dual-contrast CT were 100 and 89 percent, respectively, with overall accuracy of 94 percent. The sensitivity and specificity of noncontrast enhanced CT were 90 and 86 percent, respectively, but the overall accuracy was significantly lower (70 percent) compared with the other studies. CONCLUSIONS: Rectal contrast CT is as accurate, although less sensitive, compared with dual-contrast CT and significantly superior to noncontrast-enhanced CT for the diagnosis of acute appendicitis. Rectal contrast CT may be performed rapidly, saves resources, and may avoid the diagnostic delay and potential allergic reactions associated with oral and intravenous-enhanced studies, and, therefore, may be the preferred initial technique in the diagnostic workup of suspected acute appendicitis.
Asunto(s)
Apendicitis/diagnóstico por imagen , Medios de Contraste/administración & dosificación , Diatrizoato de Meglumina/administración & dosificación , Yopamidol/administración & dosificación , Tomografía Computarizada Espiral/métodos , Administración Oral , Administración Rectal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios ProspectivosRESUMEN
Embryonic stem cells combine the features of robust proliferation with precise differentiation capacity. p27 is a cell cycle inhibitor that is involved in the regulation of proliferation and differentiation in many developing tissues. Recent studies in murine embryonic stem cells have suggested that p27 is involved in the progression of normal differentiation programs in these cells. However, the expression and regulation of p27 and its role in the differentiation of human embryonic stem cells (hESc) has not been previously explored. Herein we show that p27 expression was low in undifferentiated hESc, but increased markedly in differentiated cells. The expression of Skp2, the ubiquitin ligase that targets p27 for degradation, was inversely related to p27 expression. Moreover, embryoid bodies (EBs) with low p27 expression and high Skp2/p27 ratio showed poorer differentiation than those with high p27 expression. Modulation of Skp2 expression is mainly regulated by its rate of degradation. In contrast to somatic cells, which have high levels of Skp2 mainly in S and G2/M, in undifferentiated hESc Skp2 levels were also high in G1. These results point to a potentially important role for p27 regulation in hESc.
Asunto(s)
Ciclo Celular/fisiología , Diferenciación Celular , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Células Madre Embrionarias/metabolismo , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Quinasas Ciclina-Dependientes , Cicloheximida/farmacología , Inhibidores de Cisteína Proteinasa/farmacología , Células Madre Embrionarias/citología , Células Madre Embrionarias/efectos de los fármacos , Citometría de Flujo , Fase G1/fisiología , Fase G2/fisiología , Humanos , Immunoblotting , Leupeptinas/farmacología , Inhibidores de la Síntesis de la Proteína/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fase S/fisiología , Proteínas Quinasas Asociadas a Fase-S/genética , Ubiquitina/metabolismoRESUMEN
The development of lymphedema is the most feared complication shared by breast cancer survivors undergoing hand surgery after prior axillary lymph node dissection (ALND). Traditionally, these patients are advised to avoid any interventional procedures in the ipsilateral upper extremity. However, the appropriateness of some of these precautions was recently challenged by some surgeons claiming that elective hand operations can be safely performed in these patients. The purpose of this study was to evaluate our experience and determine the safety of elective hand operations in breast cancer survivors. The medical records of patients operated for different hand conditions after prior breast surgery and ALND at our institution between 1983 and 2002 were reviewed. The techniques and preventive measures performed, use of antibiotics, and upper extremity complications associated with the operations were analyzed. Overall, we operated on 27 patients after prior ALND performed for breast cancer. Follow-up was available for 25 patients. Four patients had pre-existing lymphedema. The surgical technique used was similar to that performed in patients without prior ALND and antibiotic prophylaxis was not given. Delayed wound healing was observed in one patient and finger joint stiffness in another. Two patients with pre-existing lymphedema developed temporary worsening of their condition. None of the patients developed new lymphedema. The results of the present study support the few previous studies, suggesting that hand surgery can be safely performed in patients with prior ALND. Based on these findings, the appropriateness of the rigorous precautions and prohibitions regarding the care and use of the ipsilateral upper extremity may need to be reconsidered.
Asunto(s)
Brazo/cirugía , Neoplasias de la Mama/cirugía , Procedimientos Quirúrgicos Electivos , Escisión del Ganglio Linfático/efectos adversos , Linfedema/cirugía , Brazo/patología , Axila , Femenino , Humanos , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/cirugía , Linfedema/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Loss of the cell cycle inhibitory protein p27Kip1 in cancer is associated with tumor aggressiveness and poor prognosis in the prostate. The decrease in p27(Kip1) results from increased proteasome dependent degradation, which is mediated by its specific ubiquitin ligase subunits S-phase kinase protein 2 and cyclin dependent kinase subunit 1. S-phase kinase protein 2 was found to be over expressed in aggressive prostate cancers but to our knowledge the role of cyclin dependent kinase subunit 1 in these cancers is unknown. MATERIALS AND METHODS: The expression of cyclin dependent kinase subunit 1, S-phase kinase protein 2 and p27Kip1 was examined by immunohistochemistry in tissue sections from 45 patients with prostate cancer. The expression of cyclin dependent kinase subunit 1 was compared to that of S-phase kinase protein 2 and p27Kip1, and patient clinical and histological characteristics. RESULTS: Cyclin dependent kinase subunit 1 expression was strongly associated with S-phase kinase protein 2 expression (r = 0.666, p = 0.001) and inversely with p27Kip1 expression (r = -0.737, p < 0.001). Cyclin dependent kinase subunit 1 over expression was associated with loss of tumor differentiation (r = 0.631, p = 0.001), high serum prostate specific antigen (r = 0.627, p < 0.001) and metastatic disease (p < 0.001). CONCLUSIONS: These results suggest that cyclin dependent kinase subunit 1 is involved in p27Kip1 down-regulation and it may have an important causative role in the development of aggressive tumor behavior in prostate cancer.
Asunto(s)
Proteínas Portadoras/fisiología , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/fisiología , Quinasas Ciclina-Dependientes/fisiología , Neoplasias de la Próstata/enzimología , Proteínas Quinasas Asociadas a Fase-S/fisiología , Anciano , Anciano de 80 o más Años , Quinasas CDC2-CDC28 , Humanos , Masculino , Persona de Mediana EdadRESUMEN
p27Kip1, an inhibitor of cyclin-dependent kinases, is a negative cell cycle regulator that plays an important role in tumor suppression. Deregulation of p27 is commonly observed in many human cancers secondary to enhanced ubiquitin-mediated degradation, mediated and rate-limited by its specific ubiquitin ligase subunits Skp2 and Cks1. In the present study the prognostic implications of p27 and the mechanisms that down-regulate its expression in colorectal cancer (CRC) are reviewed. A review and analysis of the English literature was conducted. Loss of p27 was strongly associated with aggressive tumor behavior and poor clinical outcome in CRC. Overexpression of Skp2 and Cks1 was observed in aggressive CRC and is responsible for down-regulation of p27 levels. Both Skp2 and Cks1 were found to be independent prognostic markers for survival and provide predictive information additional to that provided by p27 alone. Deregulation of p27 has a profound effect on tumor progression in CRC and was found to be an accurate and independent prognostic marker. Thus, determination of levels of p27 and of its ubiquitin ligase subunits by readily available immunohistochemical studies may be a useful tool in the assessment of prognosis, especially in patients with intermediate disease, and may potentially assist in the planning of adjuvant therapy and development of novel interventional therapy.
Asunto(s)
Neoplasias Colorrectales/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Biomarcadores de Tumor , Neoplasias Colorrectales/patología , Quinasas Ciclina-Dependientes/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Proteínas Quinasas Asociadas a Fase-S/metabolismoRESUMEN
INTRODUCTION: Loss of the cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in breast cancer. The decrease in p27 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S phase kinase protein 2 (Skp2). The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer. Rapamycin was found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression is unknown. METHODS: The expression of Skp2 mRNA and protein levels were examined in rapamycin-treated breast cancer cell lines. The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1. RESULTS: Rapamycin significantly decreased Skp2 mRNA and protein levels in a dose and time-dependent fashion, depending on the sensitivity of the cell line to rapamycin. The decrease in Skp2 levels in the different cell lines was followed by cell growth arrest at G1. In addition, rapamycin enhanced the degradation rate of Skp2 and down-regulated the expression of the APC\C inhibitor Emi1. CONCLUSION: These results suggest that Skp2, an important oncogene in the development and progression of breast cancer, may be a novel target for rapamycin treatment.
Asunto(s)
Neoplasias de la Mama/metabolismo , Inhibidores Enzimáticos/farmacología , Proteínas Quinasas/metabolismo , Proteínas Quinasas Asociadas a Fase-S/biosíntesis , Sirolimus/farmacología , Ubiquitina/metabolismo , Neoplasias de la Mama/fisiopatología , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Humanos , Ligasas , Serina-Treonina Quinasas TORRESUMEN
BACKGROUND AND OBJECTIVES: More than half the breast cancer patients with positive sentinel lymph nodes (SLN) do not harbor additional metastases in non-sentinel nodes (NSN). The aim of this study was to identify a subgroup of patients with positive SLNs and negative NSNs, on the basis of tumor involvement patterns in multiple radioactive nodes. METHODS: Between 2000 and 2004, 290 patients with primary invasive breast cancer and clinically negative axillary nodes had a SLN biopsy in our breast unit. Radiotracer was identified intraoperatively in the axilla. All radioactive nodes were removed and radioactivity was measured in each node extracorporeally. Nodes were ranked according to radioactivity, constituting a "Sentinel Chain", and the histopathological status of each node was reported. The different metastatic involvement patterns of the Sentinel Chain were correlated with the metastatic status of the NSNs after axillary dissection. Information was charted in a prospective database. RESULTS: Of 290 patients, 216 (74.5%) had multiple radioactive nodes. Ninety patients (31%) had SLN metastases. Fifty patients had multiple ranked radioactive nodes and positive SLNs. Twenty-five of these patients had a sequential involvement pattern, with tumor-bearing high radioactivity nodes, and uninvolved low-radioactivity nodes. In the 23 of these 25 patients who had axillary dissection, NSN involvement was detected in only one patient (4.3%), whereas in 24 patients with other involvement patterns of the Sentinel Chain, NSN involvement reached 54.2% (p<0.001). CONCLUSION: Tumor-free status of NSN may be predicted using the Sentinel Chain concept in some breast cancer patients with positive SLNs.
Asunto(s)
Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Axila , Neoplasias de la Mama/diagnóstico por imagen , Colorantes , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática , Valor Predictivo de las Pruebas , Cintigrafía , Colorantes de Rosanilina , TecnecioRESUMEN
BACKGROUND: The management of penetrating abdominal stab wounds has been the subject of continued reappraisal and controversy. In the present study a novel method which combines the use of diagnostic laparoscopy and DPL, termed laparoscopic diagnostic peritoneal lavage (L-DPL) is described METHOD: Five trauma patients with penetrating injuries to the lower chest or abdomen were included. Standard videoscopic equipment is utilized for the laparoscopic trauma evaluation of the injured patient. When no significant injury is detected, the videoscope is withdrawn and 1000 mL of normal saline is infused through the abdominal trochar into the peritoneal cavity, and the effluent fluid studied for RBCs, WBC, amylase debry, bile as it is uced in regular diagnostic peritoneal lavage RESULTS: Laparoscopic peritoneal lavage (L-DPL) was then performed and proved to be negative in all 5 patients. RBC lavage counts above 100,000/mcrl were not considered as a positive lavage result, because the bleeding source was directly observed and controlled laparoscopically. All patients recovered uneventfully and were released within 3 days. This procedure combines the visual advantages of laparoscopy together with the sensitivity and specificty of DPL for the diagnosis of significant penetrating intra-abdominal injury, when the diagnostic strategy of selective consevatism for abdominal stab wounds is adopted. CONCLUSION: A method of laparoscopic diagnostic peritoneal lavage (L-DPL) in hemodynamically stable patients with penetrating lower thoracic or abdominal stab wounds is described. The method is especially applicable for trauma surgeons with only basic experience in laparoscopic technique. This procedure is used to obtain conclusive evidence of significant intra-abdominal injury, confirm peritoneal penetration, control intra-abdominal bleeding, and repair lacerations to the diaphragm and abdominal wall. The combination of laparoscopy and DPL afforded by the L-DPL method adds to the sensitivity and specificity of DPL, and avoids under or over sesitivty, that have limited the use of DPL in the hemodynamically stable trauma patients with suspicious or proven peritoneal penetration.
RESUMEN
BACKGROUND: We sought to determine the incidence of positive sentinel lymph nodes in thin melanoma (
Asunto(s)
Ganglios Linfáticos/patología , Melanoma/secundario , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Precoz , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Melanoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias Cutáneas/cirugía , Azufre Coloidal Tecnecio Tc 99mRESUMEN
INTRODUCTION: Loss of the cell-cycle inhibitory protein p27Kip1 is associated with a poor prognosis in breast cancer. The decrease in the levels of this protein is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1). Skp2 was recently found to be overexpressed in breast cancers, but the role of Cks1 in these cancers is unknown. The present study was undertaken to examine the role of Cks1 expression in breast cancer and its relation to p27Kip1 and Skp2 expression and to tumor aggressiveness. METHODS: The expressions of Cks1, Skp2, and p27Kip1 were examined immunohistochemically on formalin-fixed, paraffin-wax-embedded tissue sections from 50 patients with breast cancer and by immunoblot analysis on breast cancer cell lines. The relation between Cks1 levels and patients' clinical and histological parameters were examined by Cox regression and the Kaplan-Meier method. RESULTS: The expression of Cks1 was strongly associated with Skp2 expression (r = 0.477; P = 0.001) and inversely with p27Kip1 (r = -0.726; P < 0.0001). Overexpression of Cks1 was associated with loss of tumor differentiation, young age, lack of expression of estrogen receptors and of progesterone receptors, and decreased disease-free (P = 0.0007) and overall (P = 0.041) survival. In addition, Cks1 and Skp2 expression were increased by estradiol in estrogen-dependent cell lines but were down-regulated by tamoxifen. CONCLUSION: These results suggest that Cks1 is involved in p27Kip1 down-regulation and may have an important role in the development of aggressive tumor behavior in breast cancer.
Asunto(s)
Neoplasias de la Mama/enzimología , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Quinasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quinasas CDC2-CDC28 , Línea Celular Tumoral , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Quinasas Ciclina-Dependientes , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica/métodos , Subunidades de Proteína/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Transanal endoscopic microsurgery has recently gained acceptance as an alternative minimally invasive surgical technique for the curative management of large rectal adenomas and selected early rectal carcinomas. OBJECTIVES: To analyze our 8 year experience using TEM for the management of rectal cancer. METHODS: Local resection by TEM was performed in patients with benign tumors and early rectal cancer. In addition, selected patients with T2 and T3 rectal cancers who were either medically unfit or unwilling to undergo radical surgery were also treated with this modality. Radical surgery was offered to all patients with incomplete tumor excision by TEM. RESULTS: Overall, 116 TEM operations for rectal tumors were carried out between 1995 and 2003, including 74 patients with rectal adenomas and 42 patients with rectal carcinomas. In 25 patients, TEM successfully removed all T1 tumors with clear tumor margins. Fourteen patients had T2 cancer and 3 of them (21%) required additional radical surgery due to incomplete excision. Local recurrence was observed in one patient with T2 cancer. There was no mortality. Major surgery or radiotherapy-related complications requiring additional surgical intervention was needed in five patients with T2 cancer. CONCLUSIONS: Local excision by TEM is a safe surgical procedure and should be offered to highly selected patients with early rectal cancer.