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1.
J Lipid Res ; 56(3): 722-736, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25598080

RESUMO

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.


Assuntos
Lipídeos/sangue , Lipídeos/urina , Hepatopatia Gordurosa não Alcoólica , Polimorfismo de Nucleotídeo Único , Adulto , Biomarcadores/metabolismo , Biomarcadores/urina , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/urina
2.
J Surg Res ; 180(2): 252-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22763216

RESUMO

BACKGROUND: Pro-inflammatory processes associated with the early postoperative state are known to contribute to peritoneal metastases in patients with advanced diseases. This study aimed to determine whether the wound healing response after an abdominal incision leads to increased matrix metalloproteinase (MMP)-9 activity locally, contributing to peritoneal metastasis. MATERIALS AND METHODS: Metastatic tumors were initiated in C57bl/6J male mice (8wk of age) using a peritoneal injection model with syngeneic MC38 murine colon cancer cells; appropriate control mice also were studied. Injections were performed into the peritoneum in the right lower quadrant. We then observed the occurrence and rate of peritoneal metastasis for each group. RESULTS: By making an incision into the abdominal wall of mice, an inflammatory response was induced at the wound site. The inflammatory response initiated by the wound, in turn, increased the proliferation of mesothelial cells and increased inflammatory cell numbers locally, which contributed to an increase in parietal peritoneal metastases. In addition, the wound healing process increased the expression of pro-inflammatory cytokines and the number of inflammatory cells in the peritoneum. Moreover, MMP-9 in the modeled postoperative injury setting increased the number and severity of peritoneal metastases. CONCLUSIONS: Thus, we conclude that wound-associated inflammation enhances pro-MMP-9 expression, which plays a key role in the growth and progression of cancer cells associated with peritoneal metastases.


Assuntos
Neoplasias Colorretais/patologia , Inflamação/etiologia , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Peritoneais/secundário , Animais , Modelos Animais de Doenças , Ativação Enzimática , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cicatrização
3.
Gastroenterology ; 138(3): 969-80.e1-3, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19909744

RESUMO

BACKGROUND & AIMS: Transforming growth factor (TGF)-beta signaling occurs through Smads 2/3/4, which translocate to the nucleus to regulate transcription; TGF-beta has tumor-suppressive effects in some tumor models and pro-metastatic effects in others. In patients with colorectal cancer (CRC), mutations or reduced levels of Smad4 have been correlated with reduced survival. However, the function of Smad signaling and the effects of TGF-beta-receptor kinase inhibitors have not been analyzed during CRC metastasis. We investigated the role of TGF-beta/Smad signaling in CRC progression. METHODS: We evaluated the role of TGF-beta/Smad signaling on cell proliferation, migration, invasion, tumorigenicity, and metastasis in Smad4-null colon carcinoma cell lines (MC38 and SW620) and in those that transgenically express Smad4. We also determined the effects of a TGF-beta-receptor kinase inhibitor (LY2109761) in CRC tumor progression and metastasis in mice. RESULTS: TGF-beta induced migration/invasion, tumorigenicity, and metastasis of Smad4-null MC38 and SW620 cells; incubation with LY2109761 reversed these effects. In mice, LY2109761 blocked metastasis of CRC cells to liver, inducing cancer cell expression of E-cadherin and reducing the expression of the tumorigenic proteins matrix metalloproteinase-9, nm23, urokinase plasminogen activator, and cyclooxygenase-2. Transgenic expression of Smad4 significantly reduced the oncogenic potential of MC38 and SW620 cells; in these transgenic cells, TGF-beta had tumor suppressor, rather than tumorigenic, effects. CONCLUSIONS: TGF-beta/Smad signaling suppresses progression and metastasis of CRC cells and tumors in mice. Loss of Smad4 might underlie the functional shift of TGF-beta from a tumor suppressor to a tumor promoter; inhibitors of TGF-beta signaling might be developed as CRC therapeutics.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Hepáticas/metabolismo , Transdução de Sinais , Proteína Smad4/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/prevenção & controle , Adenocarcinoma/secundário , Animais , Antineoplásicos/farmacologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/secundário , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Invasividade Neoplásica , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirróis/farmacologia , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad4/genética , Fatores de Tempo , Transfecção , Fator de Crescimento Transformador beta1/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
5.
Am Surg ; 76(9): 969-73, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20836345

RESUMO

Postoperative hemorrhage after orthotopic liver transplantation (OLT) may require early reoperative intervention. Previous studies have shown intraoperative transfusion requirement as a main determinant of reoperative intervention after OLT. The goal of this study was to develop an intraoperative hemorrhage model predicting need for reoperation after OLT. A single institution, retrospective review of adult primary OLT patients from January 2002 to 2008 was conducted. Multivariate logistical regression analysis was performed to identify predictors of reoperation due to postoperative hemorrhage. Secondary analysis was conducted on patients in the reoperation group managed with temporary open abdomen techniques. Four hundred and ten primary transplantations were performed with 59 patients (14.4%) requiring reoperation. The adjusted odds of reoperation when intraoperative blood loss (IBL) increases from 1.5 L to 10.0 L is 2.48 [95% confidence interval: (1.18, 5.31)]. IBL of 10.0 L predicts a 19.4 per cent probability of reoperation. Patients managed with open abdomen (n = 8) exhibited a significant IBL difference (16.0 L vs. 6.0 L, P < 0.001) when compared with the closed abdomen cohort. Our results indicate that intraoperative blood loss is the primary predictor of reoperation after OLT and provide a hemorrhage threshold to guide postoperative management of complicated OLT patients.


Assuntos
Perda Sanguínea Cirúrgica , Complicações Intraoperatórias/epidemiologia , Transplante de Fígado , Hemorragia Pós-Operatória/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prognóstico , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Transplante Homólogo
6.
Am Surg ; 76(5): 486-91, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20506877

RESUMO

The purpose of this study is to evaluate the safety and effectiveness of laparoscopic surgery by comparing laparoscopic and conventional surgery of right colonic diverticulitis (RCD). Among 124 patients who were treated for RCD from January 1997 to July 2007, we enrolled 54 patients who received resection therapy of RCD. Patients were divided into two groups: laparoscopic (LAP; n=19) and conventional (CON; n=35) surgery groups according to the respective surgical modality. The diverticulectomy (DIV; n=46) and right colectomy (COL; n=8) groups were also compared according to operative methods. There were significant differences between preoperative diagnosis and selection of the operative method and between RCD type and selection of operative method. However, there were no significant differences between preoperative diagnosis and selection of laparoscopic surgery and between RCD type and selection of laparoscopic surgery. The Kaplan-Meier estimated recurrence risk for all patients also showed no significant differences between LAP and CON and DIV and COL (P = 0.413). The Kaplan-Meier-estimated RCD-free period after surgery was 92.7 months (limited to 100 months). Laparoscopic surgery of RCD is an effective and safety method as a result of no differences in clinical data between conventional and laparoscopic surgery.


Assuntos
Colectomia , Doença Diverticular do Colo/diagnóstico , Doença Diverticular do Colo/cirurgia , Laparoscopia , Adolescente , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Doença Diverticular do Colo/etiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Ann Surg Oncol ; 16(4): 861-70, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19189191

RESUMO

BACKGROUND: Early diagnosis and management of peritoneal metastases from colorectal cancer patients are difficult clinical challenges. The aims of this study were to evaluate the clinical significance of tumor markers and cytology in peritoneal effusions (PE) and peritoneal irrigation fluid (PI) and to determine their value as prognostic indicators in this disease. METHODS: Two hundred thirty-four consecutive patients who underwent abdominal surgery for colorectal cancer from January 2006 to December 2007 were included, and tumor markers and cytology in PE and PI were analyzed prospectively. RESULTS: The incidence of free cancer cells retrieved from peritoneal samples was 7.9%. Cytology was positive in 40.0% by Papanicolaou and Giemsa staining, 73.3% by hematoxylin and eosin staining of cell blocks, and 66.7% by carcinoembryonic antigen (CEA) and calretinin immunohistochemistry. Multivariate analysis revealed that peritoneal CEA and cancer antigen (CA) 19-9 in PI were correlated with peritoneal metastasis and cytology. Level of peritoneal fluid CEA was statistically significantly correlated with recurrence and peritoneal metastatic recurrence in patients with negative peritoneal cytology. Cytology, peritoneal CEA, and peritoneal CA 19-9 showed correlations with cancer-free survival and overall survival. CONCLUSIONS: These correlations demonstrate the importance of continuous follow-up of peritoneal metastasis if there is positive cytology or an increase in CEA and CA 19-9 in peritoneal fluid.


Assuntos
Líquido Ascítico/química , Biomarcadores Tumorais/análise , Antígeno CA-19-9/análise , Antígeno Carcinoembrionário/análise , Neoplasias Colorretais/patologia , Neoplasias Peritoneais/diagnóstico , Idoso , Líquido Ascítico/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lavagem Peritoneal , Neoplasias Peritoneais/química , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Prognóstico
8.
Surg Endosc ; 23(1): 97-102, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18443863

RESUMO

BACKGROUND: Serious complications of adrenalectomy are rare but the incidence may be underestimated if they occur outside major referral centers. We report five cases of high-grade complications after adrenalectomy that have not been previously described. METHODS: The records of five cases of adrenalectomy performed at outside hospitals were reviewed. Four cases were referred for management of complications and one for medical-legal review. The nature of the adrenal lesion, operative approach, complication(s), and subsequent clinical course and complication management were assessed. Both open adrenalectomy (OA) and laparoscopic adrenalectomy (LA) cases were included. RESULTS: Operative indications were pheochromocytoma (N = 3), aldosteronoma (N = 1), and a nonfunctioning 6-cm hypervascular mass (N = 1). Complications of adrenalectomy included: case 1--complete transection of the porta hepatitis during right LA resulting in hepatic failure requiring emergent liver transplantation; case 2--ligation of the hepatic artery during right OA resulting in recurrent cholangitis and bile duct sclerosis requiring liver transplantation; case 3--ligation of the left ureter during LA resulting in postoperative hydronephrosis and loss of renal function; case 4--loss of left kidney function after OA, likely secondary to renal artery ligation ultimately requiring laparoscopic nephrectomy; case 5--LA of a normal adrenal gland for a 6-cm hypervascular mass thought to be arising from the adrenal gland. Three-month postoperative imaging demonstrated a persistent mass and the patient underwent hand-assisted laparoscopic nephrectomy for a left upper pole renal cell carcinoma that was missed at the time of LA. CONCLUSION: Despite the generally low morbidity of adrenalectomy, serious and potentially life-threatening complications can occur. Surgeon inexperience may be a factor in the occurrence of some of these complications which have not been previously described.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/efeitos adversos , Erros de Diagnóstico/efeitos adversos , Laparoscopia/efeitos adversos , Feocromocitoma/cirurgia , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/complicações , Feocromocitoma/patologia
9.
Am Surg ; 75(3): 227-31, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19350858

RESUMO

Small bowel obstruction after intra-abdominal surgery is a common cause of morbidity necessitating reoperation. The aim of this study was to determine the feasibility of and indications for laparoscopic surgery for acute adhesive small bowel obstruction (AASBO). We conducted a retrospective review of all patients with AASBO who underwent laparoscopic adhesiolysis at a major university medical center. Laparoscopic treatment was performed successfully in 16 patients, and conventional treatment was performed in 13 patients. The rate of conversion from laparoscopic to open was 16.7 per cent. In 15 of 16 total patients who underwent laparoscopic surgery, laparoscopic bandlysis was performed and one patient underwent laparoscopic adhesiolysis. Laparoscopic surgery was performed successfully in nine who had a single adhesive band demonstrated on an abdominal CT, and conventional surgery was performed in all 10 patients without a single adhesive band identified radiographically. Abdominal CT scans facilitate the selection of operative approach for AASBO based on preoperative identification of the obstruction site. Laparoscopic adhesiolysis is a safe and effective treatment modality for patients with AASBO with a single band or single transition zone identified by preoperative imaging.


Assuntos
Obstrução Intestinal/cirurgia , Intestino Delgado , Laparoscopia/métodos , Complicações Pós-Operatórias/cirurgia , Radiografia Intervencionista , Aderências Teciduais/cirurgia , Tomografia Computadorizada por Raios X , Distribuição de Qui-Quadrado , Feminino , Humanos , Obstrução Intestinal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Retrospectivos , Aderências Teciduais/diagnóstico por imagem , Resultado do Tratamento
10.
Cancer Res ; 67(6): 2720-8, 2007 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-17363593

RESUMO

Surgical resection remains the best treatment for colorectal metastases isolated to the liver; however, 5-year survival rates following liver resection are only 40% to 50%, with liver recurrence being a significant reason for treatment failure. The ischemia-reperfusion (I/R) injury incurred during liver surgery can lead to cellular dysfunction and elevations in proinflammatory cytokines and matrix metalloproteinases (MMP). In rodents, I/R injury to the liver has been shown to accelerate the outgrowth of implanted tumors. The mechanism for increased tumor growth in the setting of liver I/R injury is unknown. To investigate the effect of I/R on tumor growth, an experimental model was used whereby small hepatic metastases form after 28 days. Mice subjected to 30 min of 70% liver ischemia at the time of tumor inoculation had significantly larger tumor number and volume, and had elevated MMP9 serum and liver tissue MMP9 as evidenced by zymography and quantitative real-time PCR. Mice treated with doxycycline, a broad-spectrum MMP inhibitor, had reduced MMP9 levels and significantly smaller tumor number and volume in the liver. MMP9-null mice were used to determine if the effects of doxycycline were due to the absence of stromal-derived MMP9. The MMP9-null mice, with or without doxycycline treatment, had reduced tumor number and volume that was equivalent to wild-type mice treated with doxycycline. These findings indicate that hepatic I/R-induced elevations in MMP9 contribute to the growth of metastatic colorectal carcinoma in the liver and that postresection MMP9 inhibition may be clinically beneficial in preventing recurrence following hepatic surgery.


Assuntos
Adenocarcinoma/secundário , Neoplasias Colorretais/patologia , Isquemia/enzimologia , Neoplasias Hepáticas Experimentais/secundário , Fígado/irrigação sanguínea , Metaloproteinase 9 da Matriz/biossíntese , Traumatismo por Reperfusão/enzimologia , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/enzimologia , Doxiciclina/farmacologia , Indução Enzimática , Feminino , Isquemia/patologia , Fígado/enzimologia , Neoplasias Hepáticas Experimentais/enzimologia , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas Experimentais/cirurgia , Masculino , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/genética , Inibidores de Metaloproteinases de Matriz , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reperfusão/efeitos adversos , Reperfusão/métodos , Traumatismo por Reperfusão/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
11.
Magn Reson Med ; 60(3): 718-26, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18727087

RESUMO

Dark lumen MRI colonography detects colonic polyps by minimization of the intestinal lumen signal intensity. Here we validate the use of perfluorinated oil as an intestinal-filling agent for dark lumen MRI studies in mice, enabling the physiological characterization of colonic polyps by dynamic contrast-enhanced MRI. In control and Min (multiple intestinal neoplasia) mice with and without pretreatment with oral dextran sodium sulfate (DSS), polyps as small as 0.94 mm diameter were consistently identified using standard 2D gradient echo imaging (voxel size, 0.23 x 0.16 x 0.5 mm). In serial studies, polyp growth rates were heterogeneous with an average approximately 5% increase in polyp volume per day. In DSS-treated control mice the colon wall contrast agent extravasation rate constant, K(trans), and extravascular extracellular space volume fraction, v(e), values were measured for the first time and found to be 0.10 +/- 0.03 min(-1) and 0.23 +/- 0.09, respectively. In DSS-treated Min mice, polyp K(trans) values (0.09 +/- 0.04 min(-1)) were similar to those in the colon wall but the v(e) values were substantially lower (0.16 +/- 0.03), suggesting increased cellular density. The functional dark-lumen colonography approach described herein provides new opportunities for the noninvasive assessment of gastrointestinal disease pathology and treatment response in mouse models.


Assuntos
Colonoscopia/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Pólipos do Colo/patologia , Meios de Contraste/análise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
12.
Cancer Res ; 66(1): 259-66, 2006 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16397239

RESUMO

The role of specific stromal-derived matrix metalloproteinases (MMPs) was analyzed in experimental metastasis assays in wild-type and either MMP-9, MMP-7, or MMP-2 null mice. MMP-9 null mice showed an 81% reduction in Lewis lung carcinoma tumor number, whereas MMP-7 null mice showed a 42% increase in tumor number, and there was no difference in tumor number in MMP-2 null mice compared with wild-type controls. Similarly, in an orthotopic model of lung cancer, 50% fewer MMP-9 null mice were able to establish tumors in the lung compared with control mice, although the size of the tumors was not different. The effect of MMP-9 on lung tumor colonization was dependent on the expression of MMP-9 from bone marrow-derived cells and is most likely contributed by neutrophils. To examine temporal effects of stromal MMP-9, bioluminescence imaging from luciferase-expressing human lung cancer-derived A549 cells revealed that there were fewer tumor cells in the lungs of MMP-9 null mice as early as 19 hours after injection compared with control mice, with no difference in subsequent growth rates. Six hours after injection of tumor cells, MMP-9 null mice showed a 4-fold increase in the percent of tumor cells undergoing apoptosis compared with control mice. We conclude that MMP-9 from the bone marrow contributes to the early survival and establishment of tumors in the lung and has no effect on subsequent growth. These results provide insights into the failure of MMP inhibitors in clinical trials in patients with late-stage lung cancer.


Assuntos
Células da Medula Óssea/enzimologia , Carcinoma Pulmonar de Lewis/enzimologia , Neoplasias Pulmonares/enzimologia , Metaloproteinase 9 da Matriz/fisiologia , Animais , Transplante de Medula Óssea , Carcinoma Pulmonar de Lewis/patologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/patologia , Metaloproteinase 9 da Matriz/deficiência , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
13.
Transplantation ; 81(1): 21-5, 2006 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-16421472

RESUMO

BACKGROUND: Graft-versus-host disease (GVHD) is a rare complication following liver transplantation and carries a poor prognosis with mortality approaching 90-95%. Diagnosis of GVHD is often delayed due to early symptoms mimicking more common, entities such as drug reactions and viral syndromes. To date, definitive diagnosis has been difficult and has relied on a constellation of clinical and histopathologic variables. We present the use of short tandem repeat DNA "fingerprinting" technology as a method of early, definitive diagnosis of GVHD in patients after liver transplantation. METHODS: A patient status-postorthotopic cadaveric-liver transplant, with an uncomplicated immediate posttransplant course, presented 4 weeks after transplant with fever, diarrhea, and maculopapular rash on her palms, soles, and back. The patient's condition worsened despite empiric treatment for an infectious etiology. Skin and rectal biopsies were suspicious for GVHD. RESULTS: DNA was isolated from the skin and rectal biopsies as well as from a donor lymph node. PCR amplification was done for nine highly polymorphic short tandem repeats for each specimen and a unique DNA "fingerprint" was obtained from each. DNA from skin and rectum demonstrated mixed chimerism with both donor and recipient alleles detected. Thorough analysis confirmed GVHD. CONCLUSION: Short tandem repeats for DNA fingerprinting represents an efficient and reproducible method for the definitive diagnosis of GVHD after liver transplantation. Rapid detection of GVHD using this technology, coupled with early initiation of therapy, may lead to improved survival for patients with GVHD after solid organ transplant.


Assuntos
Impressões Digitais de DNA/métodos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/genética , Transplante de Fígado , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Fatores de Tempo
14.
Arch Surg ; 140(3): 273-7, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15781792

RESUMO

HYPOTHESIS: Donor, technical, and recipient risk factors cumulatively impact survival and health-related quality of life after liver transplantation. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: A total of 483 adults undergoing primary orthotopic liver transplantation between January 1, 1991, and July 31, 2003. MAIN OUTCOME MEASURES: Graft and patient survival, Karnofsky functional performance scores, Medical Outcomes Study Short Form 36 Health Survey scores, and Psychosocial Adjustment to Illness Scale scores as influenced by potential risk factors including donor age, weight, warm ischemia time, cold ischemia time (CIT), sex, United Network for Organ Sharing (UNOS) status (1 or 2A vs 2B or 3), recipient age and disease, bilirubin level, and creatinine level. RESULTS: Five-year graft survival was 72% for recipients of donors younger than 60 years and 35% for recipients of donors 60 years and older (P<.001). A CIT of 12 hours or more was associated with shorter 5-year graft survival (71% vs 58%; P = .004). Five-year graft survival for UNOS status 2B or 3 was 71% vs 60% for status 1 or 2A (P = .02). A comparable pattern was seen for patient survival in relation to donor age (P = .003), CIT (P = .005), and urgency status (P = .03). Urgent UNOS status, advanced donor age, and prolonged CIT were independently associated with shorter graft and patient survival (P<.05). Functional performance and health-related quality of life were not affected by donor, recipient, or technical characteristics. CONCLUSIONS: Combining advanced donor age, urgent status, and prolonged CIT adversely affects graft and patient survival, and the cumulative effects of these risk factors can be modeled to predict posttransplant survival.


Assuntos
Transplante de Fígado , Qualidade de Vida , Doadores de Tecidos , Adulto , Fatores Etários , Cadáver , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
15.
Arch Surg ; 140(5): 465-70; discussion 470-1, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15897442

RESUMO

HYPOTHESIS: Living donor liver transplantation (LDLT) results in improved survival compared with deceased whole and split organ transplantation in children. OBJECTIVE: To evaluate the effect of LDLT on graft and patient survival in pediatric liver transplantation. DESIGN: Retrospective cohort. METHODS: Data included all pediatric recipients (aged <18 years) registered in the UNOS (United Network for Organ Sharing) database from October 1, 1987, to May 24, 2004. Covariates predictive of survival by univariate analyses were included in the Cox proportional hazards regression models in a blockwise fashion to determine predictors of survival. RESULTS: Kaplan-Meier graft and patient survival rates were improved in LDLT recipients compared with recipients of deceased whole and split organ transplantations (P<.01). In the initial model (model P<.001), prognostic factors for graft and patient survival included recipient age, race, origin of liver disease, certain pretransplantation laboratory data, medical condition, multiorgan transplantation, retransplantation, recipient-donor ABO blood compatibility, and cold and warm ischemia times. The addition of graft type to the initial covariate set did not significantly change the model (P = .21, covariate P = .09). However, most of the positive prognostic factors identified in the model were inherent characteristics of LDLT recipients and the LDLT procedure. CONCLUSIONS: Graft and patient survival in the pediatric population is better with LDLT than deceased organ transplantation. Factors that contribute to this difference include recipients who are less ill, who have shorter cold and warm ischemia times, and those with a decreased need for retransplantation but not the type of graft per se.


Assuntos
Transplante de Fígado/mortalidade , Doadores Vivos , Pré-Escolar , Estudos de Coortes , Feminino , Sobrevivência de Enxerto , Humanos , Hepatopatias/mortalidade , Hepatopatias/cirurgia , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida
16.
Arch Surg ; 139(5): 476-81; discussion 481-2, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15136346

RESUMO

HYPOTHESIS: Long-term quality of life (QOL) in patients undergoing laparoscopic cholecystectomy (LC) incurring bile duct injury (BDI) and repair is comparable to that of patients undergoing uncomplicated LC. DESIGN: Case comparison study. SETTING: Secondary and tertiary care centers. PATIENTS: Eighty-six patients incurring BDI during LC between January 1, 1991, and July 31, 2003, were surveyed. Comparison subjects underwent uncomplicated LC during the same period. MAIN OUTCOME MEASURES: Health-related QOL as assessed by the Karnofsky Performance Scale, Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and Psychosocial Adjustment to Illness Scale. RESULTS: Fifty patients with BDI (39 [78%] female; mean +/- SEM age, 55 +/- 2 years) and 74 patients with uncomplicated LC (51 [69%] female, mean +/- SEM age, 52 +/- 2 years) responded. Of the 50 BDI patients, 48 (96%) had no stricture and normal liver function at QOL assessment. The mean +/- SEM follow-up period to QOL assessment for the BDI and uncomplicated LC groups was 62 +/- 6 and 47 +/- 3 months, respectively. The mean +/- SD Karnofsky Performance Scale scores were 77 +/- 9 vs 93 +/- 8 for the 2 groups, respectively (P <.001). The mean +/- SD SF-36 physical component scale scores after BDI vs uncomplicated LC were 36 +/- 11 vs 47 +/- 12, respectively (P <.001), compared with 50 +/- 10 for the normal population (P <.001). The mean +/- SD SF-36 mental component scale scores were 43 +/- 14 vs 49 +/- 11 for the 2 groups, respectively (P =.02), compared with 50 +/- 10 for the normal population (P =.01). Patients with BDI scored poorer on the Psychosocial Adjustment to Illness Scale health care orientation and domestic environment scales (P=.01). CONCLUSION: After BDI and repair, there are long-term detrimental effects of BDI on health-related QOL.


Assuntos
Ductos Biliares Extra-Hepáticos/lesões , Colecistectomia Laparoscópica/efeitos adversos , Qualidade de Vida , Ductos Biliares Extra-Hepáticos/cirurgia , Estudos de Casos e Controles , Feminino , Indicadores Básicos de Saúde , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Ajustamento Social , Resultado do Tratamento
17.
Am J Surg ; 188(5): 571-4, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15546572

RESUMO

BACKGROUND: We sought to determine if disparities in survival and health-related quality of life (HRQOL) occurred after solid organ transplantation at our institution. METHODS: Data were extracted from a database including information regarding transplants that took place from 1990 to 2002. The HRQOL was assessed in patients by using the Karnofsky functional performance (FP) index and the Medical Outcomes Study Short Form 36 (SF-36) questionnaire. RESULTS: Data were collected on recipients of liver (n = 413), heart (n = 299), kidney (n = 892), and lung (n = 156). Blacks represented a minority of recipients: liver 7%, heart 8%, kidney 23%, and lung 6%. There were no statistically significant differences in patient survival between blacks and whites. Graft survival differed in kidney only with a 5-year survival: 72% for blacks versus 79% for whites (P <0.001). The FP and HRQOL improved (P <0.05) after transplantation in both groups. There were no differences on measures of the FP or HRQOL. CONCLUSIONS: Blacks had comparable survival and improvement in FP and HRQOL in comparison with whites.


Assuntos
População Negra/estatística & dados numéricos , Rejeição de Enxerto/etnologia , Transplante de Órgãos/etnologia , Qualidade de Vida , População Branca/estatística & dados numéricos , Adulto , Feminino , Sobrevivência de Enxerto , Transplante de Coração/etnologia , Transplante de Coração/mortalidade , Transplante de Coração/normas , Humanos , Transplante de Rim/etnologia , Transplante de Rim/mortalidade , Transplante de Rim/normas , Transplante de Fígado/etnologia , Transplante de Fígado/mortalidade , Transplante de Fígado/normas , Transplante de Pulmão/etnologia , Transplante de Pulmão/mortalidade , Transplante de Pulmão/normas , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/mortalidade , Transplante de Órgãos/normas , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
18.
Am J Surg ; 186(5): 476-80, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14599610

RESUMO

BACKGROUND: Some previous studies suggested that transplantation performed in Department of Veterans Affairs (VA) patients was associated with a higher rate of complications and poorer outcomes. We examined more than a decade of experience with solid organ transplantation at a single center and compared VA patients with nonveteran patients to assess long-term patient and graft survival and health-related quality of life (HRQOL). METHODS: Demographic, clinical, and survival data were extracted from a database that included all transplants from January 1990 through December 2002 at Vanderbilt University Medical Center (non-VA) and the Nashville VA Medical Center (VA). The HRQOL was assessed in a subset of patients using the Karnofsky functional performance (FP) index and the Short-Form-36 self-report questionnaire. Data were analyzed by Kaplan-Meier survival and analysis of variance methods. RESULTS: One thousand eight hundred nine adult patients receiving solid organ transplants (1,896 grafts) between 1990 and 2002 were reviewed: 380 VA patients (141 liver, 54 heart, 183 kidney, 2 lung) and 1429 non-VA patients (280 liver, 246 heart, 749 kidney, 154 lung). Mean follow-up time was 46 +/- 1 months. Five-year graft survival for VA and non-VA patients, respectively, was liver 65% +/- 5% versus 69% +/- 3% (P = 0.97); heart 73% +/- 8% versus 73% +/- 3% (P = 0.67); and kidney 76% +/- 5% versus 77% +/- 2% (P = 0.84). Five-year patient survival was liver 75% +/- 5% versus 78% +/- 3% (P = 0.94); heart 73% +/- 8% versus 74% +/- 3% (P = 0.75); and kidney 84% +/- 4% versus 87% +/- 2% (P = 0.21) for VA and non-VA, respectively. In the first 3 years after transplant, the FP scores for VA versus non-VA patients were 85 +/- 2 versus 87 +/- 1 (P = 0.50). The SF-36 mental component scales were 47 +/- 3 versus 49 +/- 1 (P = 0.39); and the SF-36 physical component scales were 37 +/- 2 versus 38 +/- 1 (P = 0.59), respectively. Longer-term (through year 7) HRQOL scores for VA versus non-VA patients were FP 85 +/- 1 versus 88 +/- 1 (P = 0.17); mental component scales 47 +/- 2 versus 49 +/- 1 (P = 0.29); and physical component scales 35 +/- 2 versus 39 +/- 1 (P = 0.05), respectively. CONCLUSIONS: The veteran patients have similar graft and patient survival as the nonveteran patients. Overall quality of life is similar between veterans and nonveterans during the first three years after transplantation. A trend toward a later decline in the veterans' perception of their physical functioning may stem from the increased prevalence of hepatitis C virus among VA liver transplant recipients, a known factor reducing late HRQOL.


Assuntos
Transplante de Órgãos/mortalidade , Qualidade de Vida , Adulto , Estudos de Casos e Controles , Estudos Transversais , Bases de Dados Factuais , Feminino , Seguimentos , Sobrevivência de Enxerto , Hospitais de Veteranos/estatística & dados numéricos , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/psicologia , Inquéritos e Questionários , Análise de Sobrevida , Tennessee , Fatores de Tempo , Estados Unidos , United States Department of Veterans Affairs , Veteranos/psicologia , Veteranos/estatística & dados numéricos
19.
Am Surg ; 70(7): 609-12, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15279184

RESUMO

Portal vein embolization is evolving as an important adjunctive tool in hepatic surgery. In select patients, preoperative hypertrophy of the future remnant liver via contralateral portal vein embolization decreases postoperative liver dysfunction. Hepatic steatosis is the most common liver parenchymal disorder in Western populations. Moderate and severe degrees of hepatic steatosis convey an increased risk of postoperative liver dysfunction following major hepatic resections, but no studies exist examining the role of preoperative portal vein embolization in patients with hepatic steatosis. In this manuscript, we review the indications for portal vein embolization currently supported by the literature and present a patient with moderate to severe steatosis who successfully underwent portal vein embolization and a subsequent major liver resection.


Assuntos
Embolização Terapêutica , Fígado Gorduroso/complicações , Hepatectomia/efeitos adversos , Falência Hepática/prevenção & controle , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/secundário , Veia Porta , Fígado Gorduroso/fisiopatologia , Fígado Gorduroso/cirurgia , Feminino , Humanos , Falência Hepática/etiologia , Falência Hepática/fisiopatologia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos
20.
J Gastrointest Cancer ; 43(4): 521-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22544493

RESUMO

BACKGROUND: Epithelioid hemangioendothelioma is a very rare, low-grade vascular tumor known to arise in soft tissues and visceral organs. Clinical diagnosis of hepatic epithelioid hemangioendothelioma remains a challenge, and although it is frequently managed with a liver transplant due to its multifocal nature, recurrence is a common complication. METHODS: We review recent advances in the diagnosis of hepatic epithelioid hemangioendothelioma, including major genetic breakthroughs, and discuss efforts to reduce post-liver transplant recurrence of hepatic epithelioid hemangioendothelioma.


Assuntos
Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Hemangioendotelioma Epitelioide/genética , Humanos , Neoplasias Hepáticas/genética , Transplante de Fígado , Recidiva Local de Neoplasia/prevenção & controle
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