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1.
Am J Surg ; 222(1): 133-138, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33390246

RESUMO

BACKGROUND: Postoperative pancreatic fistulae (POPF) are a major contributing factor to pancreatoduodenectomy-associated morbidity. Established risk calculators mostly rely on subjective or intraoperative assessments. We hypothesized that various objective preoperatively determined computed tomography (CT) measurements could predict POPF as well as validated models and allow for more informed operative consent in high-risk patients. METHODS: Patients undergoing elective pancreatoduodenectomies between January 2013 and April 2018 were identified in a prospective database. Comparative statistical analyses and multivariable logistic regression models were generated to predict POPF development. Model performance was tested with receiver operating characteristics (ROC) curves. Pancreatic neck attenuation (Hounsfield units) was measured in triplicate by pancreatic protocol CT (venous phase, coronal plane) anterior to the portal vein. A pancreatic density index (PDI) was created to adjust for differences in contrast timing by dividing the mean of these measurements by the portal vein attenuation. Total areas of subcutaneous fat and skeletal muscle were calculated at the L3 vertebral level on axial CT. Pancreatic duct (PD) diameter was determined by CT. RESULTS: In the study period 220 patients had elective pancreatoduodenectomies with 35 (16%) developing a POPF of any grade. Multivariable regression analysis revealed that demographics (age, sex, and race) were not associated with POPF, yet patients resected for pancreatic adenocarcinoma or chronic pancreatitis were less likely to develop a POPF (10 vs. 24%; p = 0.004). ROC curves were created using various combinations of gland texture, body mass index, skeletal muscle index, sarcopenia, PDI, PD diameter, and subcutaneous fat area indexed for height (SFI). A model replacing gland texture with SFI and PDI (AUC 0.844) had similar predictive performance as the established model (p = 0.169). CONCLUSION: A combination of preoperative objective CT measurements can adequately predict POPF and is comparable to established models relying on subjective intraoperative variables. Validation in a larger dataset would allow for better preoperative stratification of high-risk patients and improve informed consent among this patient population.


Assuntos
Procedimentos Cirúrgicos Eletivos/efeitos adversos , Fístula Pancreática/epidemiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Antropometria/métodos , Procedimentos Cirúrgicos Eletivos/métodos , Estudos de Viabilidade , Feminino , Humanos , Consentimento Livre e Esclarecido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Ductos Pancreáticos/diagnóstico por imagem , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/cirurgia , Pancreatite Crônica/cirurgia , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Gordura Subcutânea/diagnóstico por imagem , Adulto Jovem
2.
Chem Commun (Camb) ; 53(53): 7234-7237, 2017 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-28352901

RESUMO

Chemical genetics has arisen as a powerful approach for identifying novel anti-cancer agents. However, a major bottleneck of this approach is identifying the targets of lead compounds that arise from screens. Here, we coupled the synthesis and screening of fragment-based cysteine-reactive covalent ligands with activity-based protein profiling (ABPP) chemoproteomic approaches to identify compounds that impair colorectal cancer pathogenicity and map the druggable hotspots targeted by these hits. Through this coupled approach, we discovered a cysteine-reactive acrylamide DKM 3-30 that significantly impaired colorectal cancer cell pathogenicity through targeting C1101 on reticulon 4 (RTN4). While little is known about the role of RTN4 in colorectal cancer, this protein has been established as a critical mediator of endoplasmic reticulum tubular network formation. We show here that covalent modification of C1101 on RTN4 by DKM 3-30 or genetic knockdown of RTN4 impairs endoplasmic reticulum and nuclear envelope morphology as well as colorectal cancer pathogenicity. We thus put forth RTN4 as a potential novel colorectal cancer therapeutic target and reveal a unique druggable hotspot within RTN4 that can be targeted by covalent ligands to impair colorectal cancer pathogenicity. Our results underscore the utility of coupling the screening of fragment-based covalent ligands with isoTOP-ABPP platforms for mining the proteome for novel druggable nodes that can be targeted for cancer therapy.


Assuntos
Acrilamida/farmacologia , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Cisteína/química , Retículo Endoplasmático/efeitos dos fármacos , Proteínas Nogo/antagonistas & inibidores , Proteômica , Acrilamida/química , Antineoplásicos/química , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Retículo Endoplasmático/metabolismo , Humanos , Ligantes , Proteínas Nogo/genética , Proteínas Nogo/metabolismo , Membrana Nuclear/efeitos dos fármacos , Membrana Nuclear/metabolismo
3.
Oncogene ; 35(7): 833-45, 2016 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-25961927

RESUMO

The primary aim of this study was to evaluate the antitumor efficacy of the bromodomain inhibitor JQ1 in pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (tumorgraft) models. A secondary aim of the study was to evaluate whether JQ1 decreases expression of the oncogene c-Myc in PDAC tumors, as has been reported for other tumor types. We used five PDAC tumorgraft models that retain specific characteristics of tumors of origin to evaluate the antitumor efficacy of JQ1. Tumor-bearing mice were treated with JQ1 (50 mg/kg daily for 21 or 28 days). Expression analyses were performed with tumors harvested from host mice after treatment with JQ1 or vehicle control. An nCounter PanCancer Pathways Panel (NanoString Technologies) of 230 cancer-related genes was used to identify gene products affected by JQ1. Quantitative RT-PCR, immunohistochemistry and immunoblots were carried out to confirm that changes in RNA expression reflected changes in protein expression. JQ1 inhibited the growth of all five tumorgraft models (P<0.05), each of which harbors a KRAS mutation; but induced no consistent change in expression of c-Myc protein. Expression profiling identified CDC25B, a regulator of cell cycle progression, as one of the three RNA species (TIMP3, LMO2 and CDC25B) downregulated by JQ1 (P<0.05). Inhibition of tumor progression was more closely related to decreased expression of nuclear CDC25B than to changes in c-Myc expression. JQ1 and other agents that inhibit the function of proteins with bromodomains merit further investigation for treating PDAC tumors. Work is ongoing in our laboratory to identify effective drug combinations that include JQ1.


Assuntos
Antineoplásicos/farmacologia , Azepinas/farmacologia , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Triazóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Genes myc , Humanos , Immunoblotting , Imuno-Histoquímica , Camundongos , Camundongos SCID , Proteínas do Tecido Nervoso/antagonistas & inibidores , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Receptores de Superfície Celular/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Br J Cancer ; 105(4): 523-33, 2011 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-21792199

RESUMO

BACKGROUND: We sought to investigate the role of ErbB3-mediated signalling on the interaction between pancreatic cancer-associated fibroblasts (CAF) and carcinoma cells in an effort to disrupt tumourigenic pancreatic ductal adenocarcinoma (PDAC) stromal-epithelial cross-communication. METHODS: Primary CAF cultures were established from human PDAC surgical specimens. AsPC-1 pancreatic cancer cell murine subcutaneous xenografts were developed in the presence and absence of CAF and were subsequently treated with epidermal growth factor receptor (EGFR) inhibitors (erlotinib) and ErbB3 inhibitors (MM-121, monoclonal ErbB3 antibody). RESULTS: Cancer-associated fibroblasts were found to secrete neuregulin-1 (NRG-1), which promoted proliferation via phosphorylation of ErbB3 and AKT in AsPC-1 PDAC cells. This signalling cascade was effectively inhibited both in vitro and in vivo by specific ErbB3 blockade with MM-121, with greater degree of tumourigenesis inhibition when combined with erlotinib. The CAF-AsPC-1 pancreatic cancer xenografts reached significantly greater tumour volume than those xenografts lacking CAF and were resistant to the anti-tumour effects of EGFR inhibition with erlotinib. CONCLUSION: Cancer-associated fibroblasts-derived NRG-1 promote PDAC tumourigenesis via ErbB3-AKT signalling and overcomes single-agent EGFR inhibition. Disruption of this stromally mediated tumourigenic mechanism is best obtained through combined EGFR-ErbB3 inhibition with both erlotinib and MM-121. We have identified the NRG-1/ErbB3 axis as an attractive molecular target for the interruption of tumourigenic stromal-epithelial interactions within the PDAC microenvironment.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Ductal Pancreático/metabolismo , Receptores ErbB/antagonistas & inibidores , Fibroblastos/metabolismo , Neuregulina-1/metabolismo , Neoplasias Pancreáticas/metabolismo , Quinazolinas/farmacologia , Receptor ErbB-3/antagonistas & inibidores , Receptor ErbB-3/metabolismo , Animais , Western Blotting , Carcinoma Ductal Pancreático/tratamento farmacológico , Comunicação Celular , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Cloridrato de Erlotinib , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos SCID , Neoplasias Pancreáticas/tratamento farmacológico , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transplante Heterólogo
5.
Am Surg ; 69(12): 1067-71, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14700292

RESUMO

Current surgical treatments for hepatocellular carcinoma (HCC) include radio-frequency ablation (RFA), resection, and orthotropic liver transplant (OLT). RFA is particularly attractive in these high-risk patients because surgery is associated with high mortality and there is a relative scarcity of organs available for those in need of transplants. This study was performed to evaluate the management of cirrhotic patients with HCC undergoing RFA at a single Western institution. A retrospective study from March 1999 to June 2002 was performed to evaluate the clinicopathologic and treatment-related variables in cirrhotic patients with HCC. Forty-nine lesions in 26 patients with HCC and cirrhosis underwent RFA. Data was analyzed for safety and overall survival as the main endpoints. The mean age was 60.4 +/- 11 years, 19 patients were male, 5 had hepatitis B virus, and 19 had hepatitis C virus. The Child classification was 26 per cent, 39 per cent, and 35 per cent for A, B, and C; the number of lesions was 1 in 62 per cent, 2 in 23 per cent, and more than 2 in 15 per cent. The approach was laparoscopic in 58 per cent, percutaneous in 15 per cent, and open in 27 per cent. There were no mortalities and only 1 complication. Average hospital stay was 2.7 +/- 2 days. Subsequent to RFA, 9 patients underwent an OLT within a median of 4.1 months. The median follow-up of the whole group was 13 months and the disease-free survival 9.3 months. Tumor recurrence was identified in 3 previously ablated lesions, nonablated liver in 11, and as pulmonary metastases in 3. Overall survival (P = 0.03) was prolonged for those treated with RFA + OLT over RFA alone. We conclude that RFA is a safe ablative technique in high-risk cirrhotic patients with HCC. This technique may provide a bridge to OLT; however, it remains to be proven whether it prolongs survival in those who do not undergo OLT.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade
6.
Ann Surg Oncol ; 8(9): 716-9, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11597012

RESUMO

BACKGROUND: Selective sentinel lymphadenectomy has gained widespread acceptance for staging of melanomas arising in the trunk and extremities, but the complex lymphatic drainage of the head and neck area has limited its application in this area. METHODS: We performed a retrospective analysis of patients who underwent selective sentinel lymphadenectomy for cutaneous melanoma of the head and neck at the University of Alabama at Birmingham from 1997 through 2000, by using a standard technique of preoperative lymphoscintigram and biopsy guided with blue dye injection and a handheld gamma probe. Complete lymph node dissection was recommended only for tumor-positive sentinel lymph nodes (SLNs). Survival curves were constructed with the Kaplan-Meier method. Fisher's exact test was used for comparisons. Significance was defined as P < .05. RESULTS: Thirty-eight patients underwent selective sentinel lymphadenectomy with the standard technique during the study period. A majority (82%) of patients were men with a median age of 55 years. The most common site of the primary tumor was the face (44%), followed by the scalp (24%). Mean tumor thickness was 2.5 mm. The sentinel node was identified during surgery in 35 patients (92%). Before the use of the handheld gamma probe, the identification rate of the SLN was only 56%. A single SLN was identified in 53% of cases. The incidence of metastases in SLN was 11.4%. With a mean follow-up of 17 months, the actuarial 3-year overall survival was 92%. The accuracy of the selective sentinel lymphadenectomy in this series was 80%. CONCLUSIONS: Selective sentinel lymphadenectomy in the head and neck region is a technically demanding procedure, but the combined use of blue dye and gamma-probe radiolocalization can be a reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Masculino , Melanoma/diagnóstico por imagem , Melanoma/secundário , Azul de Metileno , Pessoa de Meia-Idade , Cintilografia , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Análise de Sobrevida
7.
Ann Surg ; 233(6): 786-92, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11371737

RESUMO

OBJECTIVE: To measure coexpression of matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9 genes by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in benign and malignant phases of colorectal carcinogenesis. SUMMARY BACKGROUND DATA: Matrix metalloproteinases degrade and remodel the extracellular matrix and have been implicated in facilitating carcinoma cells to invade and metastasize. MMP-2, MMP-7, and MMP-9 have been shown to be overexpressed in various carcinomas; however, simultaneous examination of these enzymes in human normal mucosa, adenoma, and carcinoma has not been performed to date. METHODS: Between January 1, 1998, and June 15, 2000, 40 patients underwent colectomy and harvest and snap-freezing of normal mucosa, adenoma, and carcinoma. Five patients had adenoma and carcinoma in the same specimen; 35 had either adenoma (n = 6) or carcinoma (n = 29). Taqman qRT-PCR methodology was used to measure MMP gene copy number and normalized to beta-actin RNA expression. RESULTS: The mean age was 62 +/- 4 years, with 22 men and 18 women. One fifth of the adenomas exhibited severe dysplasia. MMP-7 gene expression was significantly increased in adenomas (43 times normal mucosa) but did not increase further in carcinomas (50 times normal mucosa). MMP-2 and MMP-9 were not different in adenomas (1.8 and 1.4 times normal mucosa, respectively) but were elevated in carcinomas (2.2 and 1.8 times normal mucosa, respectively). There was no correlation between size or dysplasia in adenomas or AJCC stage in carcinomas and MMP gene expression. CONCLUSIONS: Overexpression of MMP-7 is an early event in the adenoma-to-carcinoma pathway, and expression does not appear to increase further in carcinomas. MMP-2 and MMP-9 appear to be primarily overexpressed in carcinomas. This may be one mechanism by which adenoma cells gain the ability to invade and carcinoma cells to metastasize.


Assuntos
Adenoma/etiologia , Carcinoma/etiologia , Neoplasias Colorretais/etiologia , Metaloproteinases da Matriz/genética , Adenoma/patologia , Carcinoma/patologia , Neoplasias Colorretais/patologia , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Masculino , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 7 da Matriz/biossíntese , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Metaloproteinases da Matriz/biossíntese , Pessoa de Meia-Idade
8.
Ann Surg Oncol ; 8(3): 204-8, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11314935

RESUMO

BACKGROUND: Merkel cell carcinoma (MCC) is an unusual and potentially aggressive cancer of the skin. There is no consensus regarding the optimal therapeutic approach, and the relative roles of surgery, radiotherapy, and chemotherapy still are controversial The aim of this study is to analyze the roles of these therapeutic options. METHODS: The medical records of 16 patients with a diagnosis of localized, primary MCC treated at the University of Alabama at Birmingham were reviewed. An extensive review of the English-language literature also was performed. The Kaplan-Meier method was used to develop the survival curves. Comparisons were made using Fisher's exact test. Significance was defined as P < .05. RESULTS: MCC presented primarily in Caucasians (98.3%) with a median age of 69 years. Immunosuppressive therapy appeared to play a role in the development of this cancer. In the UAB experience, 3-year actuarial survival was 31%. The only factor significantly associated with overall survival was the stage of disease at presentation: median survivals were 97 vs. 15 months for stages I and II, respectively (log-rank, P = .02). From the literature review, adjuvant radiotherapy was associated with a reduced risk of local recurrence (P < .00001). CONCLUSIONS: MCC is an aggressive cancer, with a high tendency for local recurrence and distant spread. Surgery and adjuvant radiotherapy appear to provide optimal local control. The role of chemotherapy remains to be defined.


Assuntos
Carcinoma de Célula de Merkel/radioterapia , Carcinoma de Célula de Merkel/cirurgia , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alabama/epidemiologia , Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Célula de Merkel/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida
9.
Arch Surg ; 136(3): 318-23, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11231853

RESUMO

BACKGROUND: Treatment of metastatic colorectal cancer to the liver is not uniform. We describe the management of metastatic colorectal cancer of the liver at a single institution during a 10-year period. METHODS: From January 1, 1990, through December 31, 1999, 174 patients were identified from the tumor registry at the University of Alabama at Birmingham with a diagnosis of metastatic colorectal cancer to the liver. Patient, tumor, laboratory, operative, and adjuvant therapy factors were analyzed, with overall survival as the endpoint. Log-rank tests were used for univariate analysis, Cox-proportional hazards model for multivariate analysis, and Kaplan-Meier curves were used for graphical representation of survival. Significance was defined as P<.05. RESULTS: Median age was 60 years (age range, 18-92 years). Seventy-nine percent of patients had synchronous liver metastases at the time of diagnosis of the primary colorectal tumor. The primary tumor was in the colon and rectum 75% and 25% of the time, respectively. Of the 89 patients who underwent operation, 73 received definitive surgical treatment for their liver metastases. Fifty-two patients underwent lobectomy or wedge resection, 5 underwent cryotherapy, and 16 had a hepatic artery infusion pump (HAIP) inserted. Median follow-up duration of surgically treated patients was 26 months. Operative mortality was 1.3%. The 3-year actuarial survivals for patients who underwent resection, HAIP, or those with unresectable disease were 70 months, 32 months, and 3 months, respectively (P<.001). By multivariate analysis, surgical intervention, a carcinoembryonic antigen level less than 200 microg/L, or a low T stage of the primary tumor were associated with prolongation of survival. CONCLUSIONS: Surgical resection should be attempted for hepatic colorectal metastases, as this is associated with prolonged overall survival. Hepatic artery infusion pump insertion seems to prolong overall survival for those with unresectable hepatic metastases, but it is not equal to resection. Aggressive surgical management of patients with hepatic colorectal metastases is safe, may prolong overall survival, and therefore should be considered in all patients with metastases confined to the liver.


Assuntos
Neoplasias Colorretais/cirurgia , Criocirurgia , Hepatectomia , Bombas de Infusão Implantáveis , Neoplasias Hepáticas/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Terapia Combinada , Feminino , Seguimentos , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Resultado do Tratamento
10.
Cancer ; 91(2): 324-32, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11180078

RESUMO

BACKGROUND: The objective of this study was to determine whether the use of ultrasound and percutaneous breast biopsies in patients with screen-detected nonpalpable abnormalities can reduce benign open surgical biopsies of the breast without increasing cost or sacrificing detection of potentially curable breast carcinomas. METHOD: Using a computerized mammography database and consecutive logs of needle localization procedures and fine- and large core needle biopsies of a single university-based breast imaging practice, the authors determined the breast carcinoma yield and cost of diagnosis over a 14-year period and the changes that occurred over time with the sequential introduction of ultrasound, ultrasound-guided biopsies, and stereotactic biopsies. RESULTS: The overall breast carcinoma yield for needle localization biopsies of nonpalpable lesions increased from 21% in 1984 to 68% in 1998 (P < 0.0001). The yield for nonpalpable masses increased from 21% to 87% (P < 0.0001) over the same period. The selective use of ultrasound alone and percutaneous fine- and large core needle biopsy resulted in a substantial reduction in benign open surgical biopsies. A cost analysis showed a 50% reduction in the average expense of discovering breast carcinoma. The breast carcinomas detected after introduction of these methods were prognostically favorable with 88% measuring 1.5 cm or less in size and 66% measuring less than 1 cm. CONCLUSIONS: Selective use of ultrasound and imaging-guided percutaneous biopsies can significantly reduce the number of benign open surgical biopsies generated by mammographic screening. This can result in substantial cost savings without decreasing the sensitivity for detecting small potentially curable lesions.


Assuntos
Biópsia por Agulha/economia , Neoplasias da Mama/economia , Ultrassonografia Mamária/economia , Biópsia por Agulha/métodos , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Custos e Análise de Custo , Feminino , Humanos , Mamografia/economia , Ultrassonografia de Intervenção/economia
11.
J Gastrointest Surg ; 5(6): 638-45, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12086903

RESUMO

There are few Western studies evaluating prognostic factors for survival in patients with hepatocellular carcinoma (HCC) and the influence on survival of various therapeutic options including orthotopic liver transplantation (OLT). A retrospective analysis was performed of 122 patients with HCC treated at the University of Alabama at Birmingham from January 1990 through December 1999. Clinicopathologic and treatment factors were analyzed with overall survival as the main outcome variable. Median age was 62 years. Most patients were male (74%) and white (79%). Eighty patients (66%) had associated cirrhosis. Sixty-three percent of patients presented with American Joint Committee on Cancer (AJCC) stage III or IV tumors. The median follow-up for survivors was 22 months. The 1-, 3-, and 5-year actuarial survival rates for the entire cohort were 46%, 24%, and 17%, respectively. On multivariate analysis, ablative surgery (P = 0.003), AJCC stages I and II (P = 0.0012), and absence of vascular invasion (P = 0.0001) were found to be independent favorable characteristics. Forty-four patients underwent surgical resection (including OLT, n = 20) or a surgical ablative procedure. All but two nonsurgical patients died of disease. The actuarial 1-, 3-, and 5-year survival rates for this group were 80%, 71%, and 61%, respectively. On multivariate analysis of the surgical group, only vascular invasion was associated with poor prognosis (P = 0.001). OLT was associated with a favorable prognosis on univariate analysis (P = 0.02). Forty percent of patients who received transplants underwent local/regional treatment before transplantation and the outcome in these patients was no different from that in other transplant patients. Surgical treatment is the only potential curative option for HCC, and qualifying for liver transplantation may be a favorable prognostic factor in surgical patients. Local/regional therapy prior to transplantation may provide a bridge to OLT without an increase in tumor-related mortality.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alabama , Análise de Variância , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Criança , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Probabilidade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
12.
J Gastrointest Surg ; 5(6): 658-60, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-12086905

RESUMO

Sclerosing mesenteritis is an uncommon benign condition that should be included in the differential diagnosis of abdominal masses. We present the first reported case of this condition in association with idiopathic bile duct fibrosis simulating Klatskin's tumor. A review of the literature regarding both clinical entities is presented.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Paniculite Peritoneal/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Extra-Hepáticos/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Diagnóstico Diferencial , Fibrose , Seguimentos , Humanos , Laparotomia , Masculino , Pessoa de Meia-Idade , Paniculite Peritoneal/complicações , Paniculite Peritoneal/cirurgia , Esclerose , Tomografia Computadorizada por Raios X
14.
Ann Surg Oncol ; 7(7): 515-9, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10947020

RESUMO

BACKGROUND: Gastric cancer is one of the most common gastrointestinal malignancies world-wide. Some studies have suggested that it has a worse prognosis in young than in elderly patients. METHODS: All young and elderly patients treated for gastric adenocarcinoma during the period 1988 to 1994 in a tertiary referral center in Mexico City were included. Demographic, clinical, and pathologic features of young patients (less than 40 years of age) with gastric cancer were compared with those of elderly patients (70 years of age or older) with the same diagnosis. Overall survival was the main outcome measure. RESULTS: There were 38 patients in each group. The mean age of the young and elderly groups was 33 and 77 years, respectively. Family history of gastric cancer was reported by 6 patients of the younger group and by 1 patient in the older group (P < .05). Most patients in both groups were symptomatic and had an advanced stage of the disease. With a mean follow-up of 17 months, the overall median survival for all patients was 12 months. By group, the median survival was 13 and 12 months for the young and elderly patients, respectively (P = .38). Variables with significant impact on survival were the stage of the disease, possibility of surgical resection, location of the tumor, and a family history of gastric cancer. CONCLUSIONS: Young patients represent a significant proportion of patients with gastric cancer in Hispanic populations. There were no significant differences in clinicopathological characteristics and outcome of gastric adenocarcinoma between young and elderly patients. Survival was determined by the stage of the tumor and the possibility of complete surgical resection.


Assuntos
Adenocarcinoma/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Prognóstico , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
16.
Anal Biochem ; 278(2): 175-84, 2000 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-10660460

RESUMO

Several recent studies have reported a correlation between intratumor dihydropyrimidine dehydrogenase (DPD) messenger RNA (mRNA) levels and sensitivity to 5-fluorouracil (5-FU). However, significant tissue requirements and labor-intensive methodology have limited the large-scale studies necessary for statistical validation. In addition, the semiquantitative results obtained by these methods further limit their application. We have developed a real-time reverse transcription-PCR (RT-PCR) assay, based on TaqMan fluorescence methodology, capable of rapid and accurate quantitation of DPD mRNA levels in biopsy-sized tissue samples. Results obtained with this approach indicate a linear dynamic range of 10(8)-10(3) DPD mRNA copies, with an intra-assay variation of <5%. We evaluated the data using three different methods (absolute standard curve, relative standard curve, and comparative C(T)) and show them to be equivalent. This RT-PCR assay was validated by quantitative comparison to Northern blot analysis in five tissues. In addition, analysis of 18 colorectal tumor and liver tissue specimens demonstrated a significant correlation (r(2) = 0.90) between DPD enzyme activity and mRNA levels. This method provides the first high-throughput, reproducible, and sensitive technique capable of determining DPD mRNA expression levels in nanogram amounts of total RNA.


Assuntos
Oxirredutases/análise , Reação em Cadeia da Polimerase/métodos , Di-Hidrouracila Desidrogenase (NADP) , Humanos , Sondas de Oligonucleotídeos , Oxirredutases/biossíntese , Oxirredutases/genética , Fatores de Tempo
17.
Am Surg ; 66(12): 1171-5, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11149593

RESUMO

Gastrointestinal (GI) sarcomas are uncommon tumors with the majority of previous studies performed over long time intervals. The purpose of this review is to analyze our single-institution experience with primary GI sarcomas. Between January 1990 and June 1998, 27 adult patients with primary GI sarcomas were identified in the tumor registry at the University Hospital, School of Medicine of University of Alabama at Birmingham and retrospectively reviewed. Patient, tumor, and treatment factors as well as expression of p53 and Ki-67 were analyzed with overall survival as the main outcome variable. Statistical analysis was performed by log rank test and Cox regression. Significance was defined as P < 0.05. Median age was 55 years (range 36-80 years). The stomach was the most common site of presentation (59%) followed by small bowel (29%). The average tumor size was 15 cm (range 2-46 cm). A complete resection was performed in 22 patients (81.5%). Fifteen tumors were classified as low grade (55.5%). Actuarial 3-year survival was 43 per cent with a median follow-up of 16 months. Overexpression of p53 and Ki-67 correlated with a trend to decreased survival but it did not reach statistical significance. Multivariate analysis found incomplete resection (P = 0.00001) and high grade (P = 0.003) to be significant negative prognostic factors. We conclude that GI sarcomas tend to be large tumors with most arising in the stomach and proximal GI tract. Complete surgical resection is associated with prolonged survival and despite the large size of these tumors should be attempted whenever possible.


Assuntos
Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/cirurgia , Sarcoma/diagnóstico , Sarcoma/cirurgia , Análise Atuarial , Adulto , Idoso , Idoso de 80 Anos ou mais , Alabama/epidemiologia , Feminino , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/mortalidade , Hospitais Universitários , Humanos , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Sarcoma/imunologia , Sarcoma/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Proteína Supressora de Tumor p53/análise
18.
World J Surg ; 24(12): 1477-85, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11193711

RESUMO

The role of perioperative nutritional support in the management of cancer patients remains controversial. The benefit of supplemental calories is not the only current issue: in fact, the route of delivery, composition of basic nutrients (carbohydrate, protein, fat), and the role of supplemental additives (arginine, glutamine, omega-3 fatty acids, nucleotides) in improving immune status and ultimate outcome have been the focus of much discussion. Emerging data suggest that the use of supplemental agents is associated with improvement in immune status in these patients, although there is little clear evidence that this improves outcome. Ongoing studies are aimed at defining the group of patients who would most benefit from nutritional interventions during the perioperative period.


Assuntos
Neoplasias/cirurgia , Apoio Nutricional/métodos , Suplementos Nutricionais , Humanos , Neoplasias/imunologia , Neoplasias/metabolismo , Assistência Perioperatória
19.
Am Surg ; 65(12): 1108-11; discussion 1111-2, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10597055

RESUMO

Chronic pancreatitis remains a debilitating disease with few definitive options for treatment. The purpose of this study was to evaluate the benefit of pancreaticoduodenectomy in the treatment of chronic pancreatitis. The results were evaluated by standard descriptive statistics. In a retrospective study, we reviewed the patients at a single institution undergoing pancreaticoduodenectomy between 1994 and 1997 for complications of chronic pancreatitis. Patients were evaluated for preoperative indication for surgery and perioperative morbidity and mortality, as well as long-term results. Thirty-two patients underwent pancreaticoduodenectomy for chronic pancreatitis; 56 per cent (18) underwent pylorus-preserving and 44 per cent (14) underwent classic pancreaticoduodenectomy. The mean age of these patients was 56+/-14.7 years (range, 23-79). All patients underwent preoperative CT scan and endoscopic retrograde cholangiopancreatography. The preoperative indication for surgery in 81 per cent (26) of these patients was intractable pain in the setting of a nondilated pancreatic duct. The other 19 per cent were treated for biliary/pancreatic duct stricture and pancreatic head fibrosis (mass suspicious of malignancy). Fifty-three per cent of the patients had a history of previous abdominal surgery. There were no perioperative deaths. The mean postoperative stay was 12.2+/-7.4 days. The postoperative morbidity rate was 31 per cent (10), consisting of 25 per cent with delayed gastric emptying, 3 per cent with pneumonia, and 3 per cent with wound infections. There was no occurrence of pancreatic fistulas. With a mean follow-up of 40 months (range, 10-52 months), 85 per cent reported a significant improvement in pain with 71 per cent being pain free and not requiring narcotics. Twenty per cent developed new-onset diabetes. The overall event survival rate at 5 years was 97 per cent. Thus, in a selected group of patients with severe chronic pancreatitis, resection of the head of the pancreas achieved relief of symptoms and was a safe and effective treatment for chronic pancreatitis.


Assuntos
Pancreaticoduodenectomia , Pancreatite/cirurgia , Adulto , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Doença Crônica , Constrição Patológica/fisiopatologia , Diabetes Mellitus/etiologia , Feminino , Fibrose , Seguimentos , Esvaziamento Gástrico , Humanos , Tempo de Internação , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dor Intratável/fisiopatologia , Pâncreas/patologia , Ductos Pancreáticos/patologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/classificação , Pancreatite/fisiopatologia , Pneumonia/etiologia , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/etiologia , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Ann Surg Oncol ; 6(6): 542-5, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10493621

RESUMO

BACKGROUND: Data that document academic status after surgical oncology fellowship are sparse. This study was done to report the academic status and clinical practice of graduates of a major surgical oncology program. METHODS: During the 10 years that ended in 1994, 68 fellows graduated. Each was surveyed about current academic status, number of jobs, job satisfaction, hours worked per week, and clinical practice. During 1995 and 1996, 11 fellows graduated. From this group, data were available on clinical practice while in fellowship (n = 6) and from the most recent year (ending July 1997) in a new position (n = 8). RESULTS: Sixty-seven of the 68 (99%) who were fellows from 1985 to 1994 returned surveys. Most (69%) are in "academic full-time" positions. Of those who listed an academic rank, 51% and 27% are assistant or associate professors, respectively. Job satisfaction was reported at a mean of 4.2, median of 5, on a scale from 1 to 5, with 5 being the best. Seventy-one percent remain at their first job, whereas 26% have had one previous position. The median number of hours worked per week was 70 (range, 45-100). Time allocation was patient care--60%; research--20%; education--10%; and administration--10%. CONCLUSIONS: Surgical oncology fellowship results in the majority placed in academic surgery, satisfied with their positions. Graduates are prepared for current practice patterns, and surgical oncology fellowship training should be suggested to residents interested in academic medicine.


Assuntos
Centros Médicos Acadêmicos/estatística & dados numéricos , Educação de Pós-Graduação em Medicina , Cirurgia Geral/educação , Internato e Residência/estatística & dados numéricos , Oncologia/educação , Bolsas de Estudo , Humanos , Satisfação no Emprego , Inquéritos e Questionários , Estados Unidos , Carga de Trabalho
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