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1.
Br J Surg ; 101(13): 1758-65, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25329419

RESUMO

BACKGROUND: The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei (PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance. METHODS: Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively. A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2. RESULTS: Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6-66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78-284) and 96 (86-284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume. CONCLUSION: The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10-15 million inhabitants would be ideal.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Competência Clínica/normas , Procedimentos Cirúrgicos de Citorredução/normas , Curva de Aprendizado , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/cirurgia , Quimioterapia do Câncer por Perfusão Regional/métodos , Terapia Combinada/métodos , Procedimentos Cirúrgicos de Citorredução/educação , Feminino , Humanos , Hipertermia Induzida/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/tratamento farmacológico , Pseudomixoma Peritoneal/tratamento farmacológico , Estudos Retrospectivos
2.
Ann Oncol ; 23(6): 1494-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22056853

RESUMO

BACKGROUND: Combined therapy involving cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has been shown to improve survival outcomes for patients with diffuse malignant peritoneal mesothelioma (DMPM). The present study aims to investigate gender as a potential prognostic factor on overall survival. PATIENTS AND METHODS: Over a period of two decades, 294 patients who underwent CRS and perioperative intraperitoneal chemotherapy were selected from a large multi-institutional registry to assess the prognostic significance of gender on overall survival. RESULTS: Female patients were shown to have a significantly improved survival outcome than male patients (P < 0.001). Staging according to a recently proposed tumor-node-metastasis categorization system was significant in both genders. Older female patients had significantly worse survival than younger female patients (P = 0.019), a finding that was absent in male patients. Female patients with low-stage disease were found to have a very favorable long-term outcome after combined treatment. CONCLUSIONS: Gender has demonstrated a significant impact on overall survival for patients with DMPM after CRS and perioperative intraperitoneal chemotherapy. An improved understanding of the role of estrogen in the pathogenesis of DMPM may improve the prognostication of patients and determine the role of adjuvant hormonal treatment in the future.


Assuntos
Mesotelioma/terapia , Neoplasias Peritoneais/terapia , Adulto , Antineoplásicos/administração & dosagem , Terapia Combinada , Feminino , Humanos , Injeções Intraperitoneais , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Mesotelioma/mortalidade , Mesotelioma/secundário , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Prognóstico , Fatores Sexuais , Resultado do Tratamento
3.
Minerva Chir ; 67(4): 309-18, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23022755

RESUMO

Peritoneal carcinomatosis (PC) arising from colorectal cancer (CRC) is generally considered a terminal condition with few treatment options. However, over the past few decades, new chemotherapeutic and biologic agents have improved the median overall survival of patients with unresectable metastatic disease up to 20 months. There has also been emergence of combining cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with PC. The literature supporting such an approach is significant, though not extensive, mainly consisting of small single-institution series, one international multicenter retrospective review, and one single-institution prospective randomized trial. Yet, there is remarkable homogeneity among the reported clinical outcomes, demonstrating 5-year OS rates of approximately 25-40% for patients undergoing a complete cytoreduction. These studies have fueled increasing interest in the use of CS and HIPEC for metastatic colorectal cancer over the past decade. However, despite the publication of a consensus statement on the role of CS and HIPEC for PC from CRC, there is still controversy regarding its appropriateness, effectiveness, safety, and application in this subset of patients. In this review we analyze the currently available scientific evidence supporting the clinical application of CS and HIPEC in the treatment of PC of colorectal origin.


Assuntos
Quimioterapia do Câncer por Perfusão Regional , Neoplasias Colorretais/terapia , Hipertermia Induzida , Neoplasias Colorretais/cirurgia , Humanos
4.
J Surg Oncol ; 102(6): 565-70, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-20976729

RESUMO

BACKGROUND: Evaluation of peritoneal metastases by computed tomography (CT) scans is challenging and has been reported to be inaccurate. METHODS: A multi-institutional prospective observational registry study of patients with peritoneal carcinomatosis from colorectal cancer was conducted and a subset analysis was performed to examine peritoneal cancer index (PCI) based on CT and intraoperative exploration. RESULTS: Fifty-two patients (mean age 52.6 ± 12.4 years) from 16 institutions were included in this study. Inaccuracies of CT-based assessment of lesion sizes were observed in the RUQ (P = 0.004), LLQ (P < 0.0005), RLQ (P = 0.003), distal jejunum (P = 0.004), and distal ileum (P < 0.0005). When CT-PCI was classified based on the extent of carcinomatosis, 17 cases (33%) were underestimations, of which, 11 cases (21%) were upstaged from low to moderate, 4 cases (8%) were upstaged from low to severe, and 2 cases (4%) were upstaged from moderate to severe. Relevant clinical discordance where an upstage occurred to severe carcinomatosis constituted a true inaccuracy and was observed in six cases (12%). CONCLUSIONS: The actual clinical impact of inaccuracies of CT-PCI was modest. CT-PCI will remain as a mandatory imaging tool and may be supplemented with other tools including positron emission tomography scan or diagnostic laparoscopy, in the patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.


Assuntos
Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Neoplasias Colorretais/patologia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/secundário , Tomografia Computadorizada por Raios X , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Humanos , Laparotomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia
5.
Science ; 198(4314): 313-4, 1977 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-910131

RESUMO

Alveolar macrophages from smokers, in contrast to those of non-smokers, release elastase into serum-free culture medium. Since enzymes that digest elastin produce pulmonary emphysema in experimental animals, release of elastase by alveolar macrophages from smokers suggests that these cells are important in the pathogenesis of emphysema of smokers.


Assuntos
Macrófagos/enzimologia , Elastase Pancreática/metabolismo , Alvéolos Pulmonares/enzimologia , Fumar/fisiopatologia , Adulto , Feminino , Glucuronidase/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Masculino , Alvéolos Pulmonares/citologia , Enfisema Pulmonar/etiologia , Fumar/complicações
6.
Eur J Surg Oncol ; 44(9): 1378-1383, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30131104

RESUMO

BACKGROUND: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. OBJECTIVE: To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. MATERIAL AND METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. RESULTS: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. CONCLUSION: Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/secundário , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências
7.
Oncogene ; 17(20): 2629-36, 1998 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-9840926

RESUMO

The MDM2 oncogene product is a regulator of the p53 tumor suppressor. MDM2 is cleaved by Caspase 3 (CPP32) during apoptosis after aspartic acid-361, generating a 60 kd fragment. Here we report that human tumor cell lines often express high levels of a 60 kd MDM2 isoform (p60) in the absence of apoptosis. We demonstrate that p60 is a product of caspase cleavage of full length MDM2 after residue 361. The protease that cleaves MDM2 in non-apoptotic cells appears to be distinct from the apoptosis-specific Caspase 3, since Caspase 3 substrate poly(ADP-ribose) polymerase (PARP) is not cleaved in cells producing p60. The p60 form of MDM2 is a significant fraction of the p53-bound MDM2 protein in certain tumor cells, suggesting that it functions in the regulation of p53. p60 is also detected in breast tumors overexpressing MDM2. These observations suggest that MDM2 is regulated by caspase processing in non-apoptotic cells, and may account for the MDM2 proteins of similar mobility seen in tumors and other cell lines.


Assuntos
Caspases/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares , Isoformas de Proteínas/biossíntese , Precursores de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas/biossíntese , Sequência de Aminoácidos , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Caspase 3 , Inibidores de Caspase , Citosol/metabolismo , Epitopos/imunologia , Feminino , Humanos , Dados de Sequência Molecular , Peso Molecular , Proteínas de Neoplasias/imunologia , Oligonucleotídeos Antissenso/farmacologia , Inibidores de Proteases/farmacologia , Isoformas de Proteínas/imunologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/imunologia , Proteínas Proto-Oncogênicas c-mdm2 , Estaurosporina/farmacologia , Transfecção , Células Tumorais Cultivadas
8.
J Clin Oncol ; 15(10): 3249-57, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9336362

RESUMO

PURPOSE: In addition to tumor size, grade, location, and the presence of metastases, other factors may be useful in prognostication for adults with soft tissue sarcoma (STS). This study examines the relationship of MDR-1 mRNA, p-glycoprotein (P-gp), Ki-67 expression, and DNA content expression to clinical outcome in adults with STS. PATIENTS AND METHODS: Snap-frozen STS specimens from 65 patients were analyzed and compared with clinical outcomes. Immunohistochemistry was performed for the Ki-67 antigen and P-gp. DNA content was determined using the Feulgen reaction and quantitated using image analysis. MDR-1 mRNA expression was determined using a reverse-transcriptase polymerase chain reaction (RT-PCR)-based assay. RESULTS: P-glycoprotein expression was found by immunohistochemistry in 48% of cases with 5-year overall (54% v 14%, P = .07) and disease-free survival rates (32% v 18%, P = .039) higher in high-grade tumors that did not express P-gp. MDR-1 mRNA was detected in 51% of cases and no patient with high levels of MDR-1 mRNA expression was a long-term survivor. Patients with diploid tumors had significantly better survival than those with nondiploid tumors (51% v 31%, P = .03). High levels of Ki-67 were associated with poorer overall survival (46% v 31%, P = .04). On multivariate analysis, American Joint Committee on Cancer (AJCC) staging, DNA content, Ki-67, and P-gp staining were significant prognostic factors for 5-year overall and disease-free survival. CONCLUSION: P-gp expression, high-level Ki-67 expression, and nondiploid DNA content are independent prognostic indicators that correlate with poor outcomes in STS patients. However, MDR-1 mRNA was not found to be predictive of survival. These newer markers are useful additions to AJCC staging for prognostication for patients with STS. Such markers may be useful in selecting high-risk STS patients who could benefit from systemic adjuvant therapy.


Assuntos
Biomarcadores Tumorais/análise , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , DNA de Neoplasias/análise , Intervalo Livre de Doença , Feminino , Genes MDR , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcoma/química , Sarcoma/patologia , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida
9.
J Clin Oncol ; 22(16): 3284-92, 2004 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15310771

RESUMO

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/secundário , Neoplasias Colorretais/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Neoplasias Peritoneais/cirurgia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
10.
Exp Hematol ; 21(11): 1487-91, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8405228

RESUMO

The risks inherent in the use of homologous blood products have increased efforts toward identifying alternatives to transfusion. We have previously shown that the administration of recombinant human erythropoietin (rhEpo) enhances the erythropoietic response to acute blood loss. Recombinant human interleukin-3 (rh-IL-3) is a hematopoietic growth factor that has been shown to act synergistically with rhEpo in accelerating erythropoiesis in vitro. The purpose of this study in a primate model was to determine if the administration of rhIL-3 in combination with rhEpo could augment the erythropoietic response to acute blood loss more than rhEpo therapy alone. Twenty-four adult male baboons were randomized into four groups. The induction of acute normovolemic anemia to a hematocrit of 20% was accomplished via exchange-transfusion with 6% hetastarch. The groups were then treated for 7 consecutive days with the following growth factors: group I (n = 7), no growth factors; group II (n = 5), rhIL-3 alone (100 micrograms/kg/d); group III (n = 6), rhEpo alone (1000 U/kg/d); group IV (n = 6), rhEpo (1000 U/kg/d) plus rhIL-3 (100 micrograms/kg/d). All animals received folate, vitamin B12, and intravenous iron-dextran immediately following the exchange-transfusion. Response to therapy was monitored for 35 days. There were no adverse reactions following growth factor administration. The analysis of erythropoietic rates between study days 1 through 11, as determined via linear regression analysis, revealed that hematocrits increased significantly faster in the groups receiving rhEpo compared to controls. The administration of rhIL-3, however, did not increase the rate of erythropoiesis when compared to controls, nor did it augment response when added to the rhEpo regimen. The results of this study demonstrate that the administration of rhIL-3 alone had no significant effect on erythropoiesis in this setting of acute blood loss. Further, despite promising in vitro data, rhIL-3 provided no additional stimulation of erythropoiesis in animals receiving rhEpo. Nevertheless, the study confirms that the pharmacologic acceleration of erythropoiesis by rhEpo alone remains an attractive alternative to homologous transfusion.


Assuntos
Anemia/sangue , Eritropoese/efeitos dos fármacos , Eritropoetina/farmacologia , Interleucina-3/farmacologia , Doença Aguda , Análise de Variância , Anemia/tratamento farmacológico , Animais , Contagem de Células Sanguíneas/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada , Eritropoetina/uso terapêutico , Interleucina-3/uso terapêutico , Masculino , Papio , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico
11.
Cancer Epidemiol Biomarkers Prev ; 5(4): 293-6, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8722221

RESUMO

Surgical therapy for localized melanoma is highly successful. However, if melanoma spreads beyond its primary site, the results of treatment are poor. Therefore, early detection of circulating melanoma cells in the blood may be important. Currently, circulating melanoma cells are undetectable. Tyrosinase is an enzyme in the melanin synthetic pathway the expression of which is only found in melanin-producing cells. Because melanocytes are not normally found in the peripheral blood, we hypothesize that melanoma cells circulating in the peripheral blood could be detected by amplifying the tyrosinase mRNA using the reverse transcription-PCR (RT-PCR). The purpose of this study was to determine the sensitivity of a RT-PCR-based assay for tyrosinase mRNA from peripheral blood and evaluate correlations with tumor status in melanoma patients. RNA was isolated from the peripheral blood or tissue culture cells, and cDNA was prepared. DNA was amplified using RT-PCR with nested primers for tyrosinase and beta(2)-microglobulin. Serial dilution experiments using cells from the SK-MEL-28 cell line were performed in culture media and in whole blood. Twelve patients with melanoma, 10 healthy controls, and 15 patients with nonmelanoma malignancies were tested for tyrosinase expression in peripheral blood. The sensitivity of this assay was determined to be as low as 1 melanoma cell in 5 ml of whole blood. No tyrosinase was found in healthy subjects or other cancer control patients. Tyrosinase mRNA was detected in the blood of five melanoma patients (one stage II, two stage III, and two stage IV). Three of these tyrosinase-positive patients had biopsy-proven evidence of melanoma, whereas the other two had no clinical evidence of malignant disease after surgical resection. The remaining seven melanoma patients had no evidence of disease and tested negative for tyrosinase mRNA. This study suggests that a RT-PCR-based assay for the detection of tyrosinase mRNA in peripheral blood is feasible. Moreover, the presence of tyrosinase mRNA in the blood seems to correlate with the stage of melanoma. Further study and follow-up are needed to clarify the role of tyrosinase mRNA as a tumor marker for malignant melanoma.


Assuntos
Biomarcadores Tumorais/sangue , Melanoma/enzimologia , Monofenol Mono-Oxigenase/sangue , RNA Mensageiro/sangue , Neoplasias Cutâneas/enzimologia , Adulto , Idoso , Sequência de Bases , Feminino , Seguimentos , Humanos , Masculino , Melanócitos/patologia , Melanoma/sangue , Melanoma/patologia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Monofenol Mono-Oxigenase/genética , Reação em Cadeia da Polimerase , RNA Neoplásico/sangue , Sensibilidade e Especificidade , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas , Microglobulina beta-2/metabolismo
12.
Cancer Epidemiol Biomarkers Prev ; 6(12): 1095-100, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9419409

RESUMO

Mutation of the K-ras oncogene occurs frequently in human malignancy. However, there are few reports concerning K-ras mutations in soft-tissue sarcoma, including leiomyosarcoma. We therefore designed a study to determine the prevalence of mutations in the first exon of K-ras in leiomyosarcoma and to evaluate its prognostic potential. Fifty-one leiomyosarcomas were reviewed, and their diagnoses were confirmed on pathological review. Tissue blocks were retrieved, and new sections were prepared for confirmation of diagnosis. Additional tissue sections were used for DNA isolation. PCR and denaturing gradient gel electrophoresis (DGGE) were used to detect K-ras mutations in the first exon of genomic DNA isolated from the specimens. Seven (14%) K-ras mutations were detected using DGGE. Subsequent sequencing of the K-ras gene from each of the mutated tumors confirmed the DGGE results in each case. The median survival for patients whose tumors did not contain mutations of K-ras was 42 months (n = 42) versus 25 months (n = 7) for those with mutations (P = 0.06). However, patients with stages I and II tumors had a median survival of 82 months (n = 28) compared to 28 months for those with stages III and IV disease (n = 20, P = 0.02). The results suggest that K-ras codon 12 mutations are uncommon in leiomyosarcoma; however, when such mutations are found, there is a trend toward worse survival. Furthermore, the data confirm that stage is a significant prognostic indicator.


Assuntos
Genes ras/genética , Leiomiossarcoma/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Marcadores Genéticos , Humanos , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Taxa de Sobrevida
13.
Surgery ; 115(5): 650-2, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8178266

RESUMO

Rosai Dorfman disease (RDD), or sinus histiocytosis with massive lymphadenopathy, is a well-described phenomenon in lymph nodes and other organs. However, it has only recently been described as a distinct entity in soft tissue. Here we present what we believe to be the first report of a case of multiply recurrent RDD occurring exclusively in the soft tissue. Recognition that RDD of soft tissues can be a pernicious locally recurrent lesion is important and suggests that an aggressive surgical approach to this lesion may be warranted.


Assuntos
Histiocitose Sinusal/cirurgia , Adulto , Feminino , Histiocitose Sinusal/patologia , Humanos , Recidiva
14.
Surgery ; 104(2): 365-9, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3400066

RESUMO

Risks of transfusion are minimized with autologous blood. However, autologous donation programs require 2 to 5 weeks to yield only 2.2 units per patient. Recombinant human erythropoietin (r-HuEPO) has been shown to increase erythropoiesis. This study evaluated the effects of r-HuEPO on an aggressive autologous donation program. Twelve adult male baboons were randomized into two groups of six. All animals were studied three times per week for 5 weeks. A unit of blood was donated when on any study day the hematocrit was greater than 30%. Animals received intravenously either 750 units/kg of r-HuEPO (n = 6) or placebo (n = 6) on each study day. Iron dextran was given intravenously to replace 150% of shed iron. The r-HuEPO group had an earlier onset of reticulocytosis (2.7 vs 5.5 days, p less than 0.01) and donated 35% more blood (13.5 vs 10.0 units, p = 0.01) than the control group. No adverse reactions to r-HuEPO were observed. The data show that an aggressive autologous donation program can yield 10 units of blood over a 5-week period. Further, r-HuEPO increases that yield by an additional 35%. This aggressive autologous donation program with r-HuEPO may significantly reduce the need for homologous transfusion and its attendant risks.


Assuntos
Transfusão de Sangue Autóloga , Eritropoetina/farmacologia , Hematopoese/efeitos dos fármacos , Animais , Hematócrito , Humanos , Complexo Ferro-Dextran/uso terapêutico , Contagem de Leucócitos , Masculino , Papio , Distribuição Aleatória , Proteínas Recombinantes/farmacologia , Reticulócitos
15.
Surgery ; 106(2): 432-7; discussion 437-8, 1989 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2763040

RESUMO

The risks of transfusion-associated infectious disease have made increased efforts to avoid homologous transfusion imperative. Little attention has been focused on efforts to accelerate erythropoiesis as a method of reducing homologous blood use. Recombinant human erythropoietin (rHuEPO) has been shown to enhance erythropoiesis. The purpose of this study was to evaluate the effects of perioperative rHuEPO administration on postoperative erythropoiesis. Fifteen baboons were divided into three groups of five each. Group I received no rHuEPO. Group II received five daily preoperative doses of rHuEPO (1000 U/kg). Group III received five daily preoperative doses and 14 daily postoperative doses of rHuEPO (1000 U/kg). All animals underwent a laparotomy followed by an exchange transfusion to a final hematocrit of 15%. The time in days required to recover to hematocrits of 20% was significantly shorter in both groups that received preoperative doses of rHuEPO when compared with that of controls (3.3 vs 5.7 days, p less than 0.01). The recovery times to hematocrits of 25%, 30%, and baseline levels were all significantly shorter in the group that received both preoperative and postoperative doses of rHuEPO. The data show that perioperative dosage of rHuEPO significantly accelerates postoperative erythropoiesis. Perioperative administration of rHuEPO may reduce the requirements for homologous transfusion.


Assuntos
Eritropoetina/uso terapêutico , Cuidados Pré-Operatórios , Animais , Análise Química do Sangue , Contagem de Células/efeitos dos fármacos , Eritropoetina/sangue , Transfusão Total , Hematócrito , Humanos , Masculino , Papio , Contagem de Plaquetas/efeitos dos fármacos , Cuidados Pós-Operatórios , Período Pós-Operatório , Proteínas Recombinantes , Reticulócitos/citologia
16.
Ann Thorac Surg ; 70(2): 660-2, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10969699

RESUMO

Esophageal sarcoma is an uncommon tumor, sporadically reported in the literature. Radiation therapy is frequently employed in the treatment of carcinoma of the esophagus, and the increased risk of development of sarcoma arising in irradiated fields is well known. However, to our knowledge, the occurrence of radiation-associated sarcoma of the esophagus after radiation therapy for carcinoma of the esophagus has not been reported. We therefore report the case of a 43-year-old female who developed a gastrointestinal stroma sarcoma 9 years following radiation therapy for esophageal squamous cell carcinoma. The patient underwent resection of her gastrointestinal stromal sarcoma by transhiatal esophagectomy with cervical anastomosis and is doing well 18 months later. The increasing use of radiation therapy for esophageal carcinoma suggests that radiation-associated sarcoma of the esophagus may be seen more frequently in the future.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Neoplasias Induzidas por Radiação/patologia , Segunda Neoplasia Primária/patologia , Sarcoma/patologia , Adulto , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Induzidas por Radiação/cirurgia , Segunda Neoplasia Primária/cirurgia , Sarcoma/cirurgia
17.
Ann Thorac Surg ; 51(5): 764-6, 1991 May.
Artigo em Inglês | MEDLINE | ID: mdl-2025080

RESUMO

Erythropoietin is the primary regulator of erythropoiesis. Erythropoietin has been shown to increase exponentially in response to linear decreases in hematocrit in normal, unstressed animals. However, the effect of operation, with its attendant stress, on erythropoietin levels is unknown. The purpose of this study is to evaluate the effect of surgical stress on erythropoietin. Twenty otherwise healthy patients scheduled for elective surgical procedures were studied. The cholecystectomy group included 10 patients who underwent cholecystectomy for documented stone disease. Ten patients who underwent coronary artery bypass procedures constituted the coronary artery bypass grafting group. Patients were studied preoperatively as well as on the first and second postoperative days. The hematocrit and erythropoietin levels were similar in both groups preoperatively. The hematocrit in the coronary artery bypass grafting group was lower than that of the cholecystectomy group on postoperative day 1 (0.31 versus 0.36; p less than 0.003) and postoperative day 2 (0.30 versus 0.36; p less than 0.001). During the first two postoperative days the erythropoietin levels were similar between groups. The data show that postoperative erythropoietin levels are similar after coronary artery bypass grafting, despite more severe anemia, when compared with cholecystectomy. This suggests that after coronary artery bypass grafting there is a relative deficiency of erythropoietin. Administration of recombinant human erythropoietin to patients undergoing surgical procedures could correct the erythropoietin deficiency and accelerate postoperative erythropoiesis.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Eritropoetina/deficiência , Adulto , Idoso , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Feminino , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estresse Fisiológico/complicações
18.
Life Sci ; 61(25): 2475-84, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9416766

RESUMO

In patients with advanced cancer, anemia is a common complication indicative of a poor prognosis. Attempts to alleviate this have met with mixed success and interventions including erythropoietin often fail to elicit an appropriate response. We have used rats implanted with the Walker 256 carcinosarcoma as a model of non-responsive anemia. This study demonstrates that the provision of recombinant erythropoietin in the presence of clenbuterol, a beta2 agonist, attenuates both the cancer induced anemia and the growth of the tumor in this model. We hypothesize that this treatment relieves the tumor induced inhibition of hematopoiesis, which allows for not only an increase in hematocrit but an increased immunosurveillance resulting in tumor suppression.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Anemia/tratamento farmacológico , Carcinoma 256 de Walker/tratamento farmacológico , Clembuterol/farmacologia , Eritropoetina/farmacologia , Anemia/etiologia , Animais , Carcinoma 256 de Walker/patologia , Divisão Celular/efeitos dos fármacos , Clembuterol/uso terapêutico , Eritropoetina/uso terapêutico , Hematócrito , Pentoxifilina/farmacologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes
19.
Am J Surg ; 180(2): 104-7, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11044522

RESUMO

BACKGROUND: The number of core biopsies done for breast abnormalities is increasing. The risk of skin seeding resulting from core biopsy is unknown. METHODS: Consecutive patients diagnosed with breast cancer were studied. The skin and subcutaneous fat surrounding the site of core needle penetration were excised and studied by routine histologic staining. Findings were correlated with other clinical variables. RESULTS: Eighty-nine consecutive patients were studied. Thirty-one had stereotactic core biopsies, 23 had vacuum-assisted biopsy, 8 had multiple-puncture biopsy, and 58 had ultrasound-guided core biopsy. Two patients who were biopsied using multiple-puncture biopsy were found to have nests of cancer cells in the dermis. One of these patients had recurrence in the skin biopsy site at 34 months. CONCLUSION: Skin seeding may be important in light of increasing use of image-directed biopsy, and particularly for cases in which the biopsy puncture site is outside the index quadrant and in which no radiation is anticipated.


Assuntos
Biópsia/efeitos adversos , Neoplasias da Mama/patologia , Inoculação de Neoplasia , Neoplasias Cutâneas/etiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Am J Surg ; 175(3): 194-7, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9560118

RESUMO

BACKGROUND: The purpose of this study is to review initial experience with a colonic stent as an alternative to colostomy in patients with colonic obstruction. METHODS: Ten patients diagnosed with acute colonic obstructions from both benign and malignant causes underwent stent placement. Self-expandable metallic stents were deployed using fluoroscopic guidance. Patients were followed up clinically until removal of the stent or death. RESULTS: Nine of the 10 patients who underwent colonic stent placement achieved clinical decompression within 6 hours. Six patients underwent standard mechanical bowel preparation and elective resection of obstructing lesions. The other 4 patients received stent placement for palliative purposes. Complications included 4 cases of migration and 1 death. Migrated stents in the rectum were easily retrieved and replaced using fluoroscopic techniques. There were no perforations. CONCLUSION: Placement of self-expandable metallic stents for acute colonic obstructions may allow patients to undergo elective surgical resection avoiding possible colostomy.


Assuntos
Doenças do Colo/terapia , Obstrução Intestinal/terapia , Stents , Doença Aguda , Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Colo/etiologia , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgia , Feminino , Humanos , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Resultado do Tratamento
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