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1.
Surg Innov ; 29(3): 378-384, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34637364

RESUMO

BACKGROUND: During cancer operations, the cancer itself is often hard to delineate-buried beneath healthy tissue and lacking discernable differences from the surrounding healthy organ. Long-wave infrared, or thermal, imaging poses a unique solution to this problem, allowing for the real-time label-free visualization of temperature deviations within the depth of tissues. The current study evaluated this technology for intraoperative cancer detection. METHODS: In this diagnostic study, patients with gastrointestinal, hepatobiliary, and renal cancers underwent long-wave infrared imaging of the malignancy during routine operations. RESULTS: It was found that 74% were clearly identifiable as hypothermic anomalies. The average temperature difference was 2.4°C (range 0.7 to 5.0) relative to the surrounding tissue. Cancers as deep as 3.3 cm from the surgical surface were visualized. Yet, 79% of the images had clinically relevant false positive signals [median 3 per image (range 0 to 10)] establishing an accuracy of 47%. Analysis suggests that the degree of temperature difference was primarily determined by features within the cancer and not peritumoral changes in the surrounding tissue. CONCLUSION: These findings provide important information on the unexpected hypothermal properties of intra-abdominal cancers, directions for future use of intraoperative long-wave infrared imaging, and new knowledge about the in vivo thermal energy expenditure of cancers and peritumoral tissue.


Assuntos
Neoplasias , Humanos , Temperatura
2.
Cancer Discov ; 6(7): 727-39, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27231123

RESUMO

UNLABELLED: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy exhibiting frequent isocitrate dehydrogenase (IDH1/IDH2) mutations. Through a high-throughput drug screen of a large panel of cancer cell lines, including 17 biliary tract cancers, we found that IDH mutant (IDHm) ICC cells demonstrate a striking response to the multikinase inhibitor dasatinib, with the highest sensitivity among 682 solid tumor cell lines. Using unbiased proteomics to capture the activated kinome and CRISPR/Cas9-based genome editing to introduce dasatinib-resistant "gatekeeper" mutant kinases, we identified SRC as a critical dasatinib target in IDHm ICC. Importantly, dasatinib-treated IDHm xenografts exhibited pronounced apoptosis and tumor regression. Our results show that IDHm ICC cells have a unique dependency on SRC and suggest that dasatinib may have therapeutic benefit against IDHm ICC. Moreover, these proteomic and genome-editing strategies provide a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. SIGNIFICANCE: IDH mutations define a distinct subtype of ICC, a malignancy that is largely refractory to current therapies. Our work demonstrates that IDHm ICC cells are hypersensitive to dasatinib and critically dependent on SRC activity for survival and proliferation, pointing to new therapeutic strategies against these cancers. Cancer Discov; 6(7); 727-39. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 681.


Assuntos
Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Dasatinibe/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Isocitrato Desidrogenase/genética , Mutação , Quinases da Família src/metabolismo , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Análise por Conglomerados , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Surg Endosc ; 30(4): 1656-61, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26194251

RESUMO

BACKGROUND: Selection of cancer treatment fundamentally relies on staging of the underlying malignancy. The aim of this study was to evaluate the feasibility and effectiveness of laparoscopic narrow band imaging (NBI) for operative staging and detection of occult peritoneal cancer metastases. METHODS: A randomized, controlled feasibility trial with crossover design evaluating adult patients with gastrointestinal or gynecologic malignancies who have a clinical indication for diagnostic laparoscopy was conducted. Twenty-three patients were randomized to white-light followed by NBI laparoscopy (n = 11) or NBI followed by white-light laparoscopy (n = 12) using the Olympus Evis Exera II system. Three patients were excluded from analysis. RESULTS: In all 20 study patients, the abdominal cavity was sufficiently illuminated. An enhanced contrast of microvasculature and organ surface pattern was appreciated. Eight of the 20 patients (40%) were found to have metastases of the peritoneal surface. While NBI did not show any additional peritoneal lesions, 2 of the 63 suspicious-appearing nodules seen on white-light imaging were not visible on NBI (p = 0.50). The median diameter of all the nodules identified was 2 mm (range 1-50 mm) and was identical with each method. CONCLUSIONS: The information from this feasibility study demonstrated that NBI provides adequate illumination of the abdominal cavity and a unique contrast that enhances microvasculature and architectural surface pattern. The results suggest that NBI laparoscopy is not superior in detecting peritoneal metastases compared to standard white-light laparoscopy, but might provide a technology that could be applied for other abdominal pathologies.


Assuntos
Laparoscopia/métodos , Imagem de Banda Estreita/métodos , Segunda Neoplasia Primária/diagnóstico , Neoplasias Peritoneais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
4.
Surg Innov ; 22(2): 194-200, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24786338

RESUMO

BACKGROUND: Correct recognition of the extrahepatic bile ducts is thought to be crucial to reduce the risk of bile duct injuries during various laparoscopic procedures. Image-enhanced laparoscopy techniques, utilizing various optical modalities other than white light, may help in detecting structures "hidden" underneath connective tissue. METHODS: A systematic literature search was conducted of studies describing image-enhanced laparoscopy techniques for visualization of the extrahepatic bile ducts. RESULTS: In all, 29 articles met inclusion criteria. They describe various techniques in the animal or human setting, including autofluorescence imaging, drug-enhanced fluorescence imaging, infrared thermography, and spectral imaging. This review describes these various techniques and their results. CONCLUSION: Image-enhanced laparoscopy techniques for real-time visualization of extrahepatic bile ducts are still in its infancy. Out of the techniques currently described, indocyanine green-enhanced near-infrared fluorescence laparoscopy has the most mature results, but other techniques also appear promising. It can be expected that in the future, image-enhanced laparoscopy might become a routine adjunct to any white-light laparoscopic operation near the hepatic hilum.


Assuntos
Ductos Biliares Extra-Hepáticos/cirurgia , Processamento de Imagem Assistida por Computador/métodos , Laparoscopia/métodos , Cirurgia Assistida por Computador/métodos , Animais , Engenharia Biomédica , Medicina Baseada em Evidências , Humanos , Imagem Óptica/métodos , Termografia/métodos
5.
Eur J Appl Physiol ; 115(2): 257-68, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25272970

RESUMO

PURPOSE: Harmful effects of inhaled particulates have been established in epidemiologic studies of ambient air pollution. In particular, heart rate variability responses to high levels of environmental tobacco smoke (ETS), similar to responses observed during direct smoking, have been reported. We sought to determine whether such responses could be observed at lower particulate concentrations. METHODS: We monitored cardiovascular responses of non-smoking 21 women and 19 men to work-place-relevant levels of: ETS, cooking oil fumes (Coil), wood smoke (WS), and water vapor as sham control. Responses, tested on three consecutive days (random order of aerosol presentation), were averaged for each subject. RESULTS: Low frequency spectral powers of heart rate and blood pressure rose during recovery from exposure to particulate, but not to sham exposures. At breathing frequencies, spectral power of men's systolic pressure doubled, and baroreflex effectiveness increased, following ETS exposure. An index of sympathetic control of heart rate was more pronounced in men than women, in response to ETS and Coil, compared to WS and sham. CONCLUSIONS: When measured under controlled conditions, autonomic activities in non-smoking men and women exposed to low level, short term, particulate concentrations were similar to those observed during longer term, higher level exposures to ETS and to direct smoking. These increased indexes of sympathetic control of heart rate and peripheral vasomotion followed introduction of particulates by about 15 min. Finally, coupling of heart rate and systolic pressure indicated an increase in baroreflex activity in the response to breathing ETS that was less effective in men than women.


Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Fumaça/efeitos adversos , Adulto , Sistema Nervoso Autônomo/fisiologia , Barorreflexo , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Masculino
6.
J Am Coll Surg ; 218(6): 1201-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24698487

RESUMO

BACKGROUND: The role of staging laparoscopy in pancreatic cancer in the age of high-resolution CT scans is under debate. This study's aim is to evaluate the efficacy of staging laparoscopy in this disease. STUDY DESIGN: A retrospective cohort study was conducted evaluating patients who underwent operative treatment for radiographic stage I to III pancreatic cancer between July 2003 and October 2012. Radiographic follow-up was 94% at 6 months. RESULTS: Of 274 patients who met inclusion criteria, 136 underwent staging laparoscopy, which identified radiographic occult distant metastases in 2% (3 of 136). However, subsequent laparotomy identified an additional 9% (12 of 136) harboring distant metastases in regions not visualized on standard staging laparoscopy; specifically, the posterior liver surface, paraduodenal retroperitoneum, proximal jejunal mesentery, and lesser sac. The remaining 138 patients underwent initial staging laparotomy, which showed similar results identifying radiographic occult distant disease in 11% (15 of 138). Within 6 months after the operation, peritoneal or subcapsular liver metastases developed in an additional 6% (15 of 257)-disease that potentially could have been diagnosed at the time of operation-providing a false-negative rate of 88% for staging laparoscopy compared with 36% for staging laparotomy. CONCLUSIONS: Despite the availability of high-resolution CT scans, occult distant metastases can still be found in 11% of patients during the operation. In the absence of reliable risk factors to predict distant metastases, staging laparoscopy should be offered to all patients with radiographic localized disease. However, the results favor extended laparoscopic staging with evaluation of the posterior liver surface, mobilization of the duodenum, evaluation of the proximal jejunal mesentery, and visualization of the lesser sac.


Assuntos
Laparoscopia/métodos , Laparotomia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Custos e Análise de Custo , Feminino , Humanos , Laparoscopia/economia , Laparotomia/economia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/economia , Estudos Retrospectivos
7.
Proc Natl Acad Sci U S A ; 110(33): 13528-33, 2013 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-23898174

RESUMO

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.


Assuntos
Eicosanoides/farmacologia , Células Endoteliais/metabolismo , Compostos de Epóxi/farmacologia , Neovascularização Fisiológica/fisiologia , Regeneração/fisiologia , Animais , Cromatografia Líquida , Eicosanoides/metabolismo , Epóxido Hidrolases/antagonistas & inibidores , Compostos de Epóxi/metabolismo , Olho/irrigação sanguínea , Imuno-Histoquímica , Rim/fisiologia , Fígado/fisiologia , Pulmão/fisiologia , Camundongos , Camundongos Transgênicos , Neovascularização Fisiológica/efeitos dos fármacos , Receptor TIE-2/genética , Regeneração/efeitos dos fármacos , Espectrometria de Massas em Tandem
8.
Clin Transplant ; 26(3): 470-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21980936

RESUMO

Controversy exists regarding the best method for venous outflow reconstruction after live donor liver transplantation using right lobe grafts. Some authors advocate routine inclusion of the middle hepatic vein with the graft, whereas others favor a more selective approach. In this report, we examine the evolution of our decision making and technique of selective anterior venous segment reconstruction during live donor adult liver transplantation performed in 226 recipients. We have developed a simplified back-bench procedure using sequential-composite anastomosis using various vascular conduits with syndactylization to the right hepatic vein creating a single large-outflow anastomosis in the recipient. Conduits used include iliac artery or vein allograft, recanalized umbilical vein, cryopreserved iliac artery allograft, and 6-mm synthetic expanded polytetrafluoroethylene vascular graft. This technique can be performed quickly, safely, and under cold storage conditions and results in excellent outcome while minimizing donor risk.


Assuntos
Veias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Doadores Vivos , Procedimentos de Cirurgia Plástica/mortalidade , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Vasculares/mortalidade , Adulto , Anastomose Cirúrgica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Transplante Homólogo
9.
Pediatr Transplant ; 15(7): E142-4, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20412506

RESUMO

We report a case of a pediatric en bloc liver-double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11-month-old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver-kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver-double kidney transplant from a size matched donor. In order to provide adequate venous outflow from the kidneys in the absence of a recipient infrarenal IVC, the donor liver and kidneys were procured en bloc with a common arterial inflow via the infrarenal aorta and common outflow via the suprahepatic IVC. Kidney transplantation in the absence of adequate recipient venous drainage may require unusual vascular reconstruction techniques. This case demonstrates a novel approach in patients who may require combined liver-kidney transplantation.


Assuntos
Transplante de Rim/métodos , Transplante de Fígado/métodos , Trombose/patologia , Veia Cava Inferior/fisiopatologia , Aorta/patologia , Ductos Biliares/cirurgia , Biópsia/métodos , Feminino , Hepatoblastoma/patologia , Hepatoblastoma/cirurgia , Humanos , Lactente , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Modelos Anatômicos , Veia Porta/cirurgia , Tomografia Computadorizada por Raios X/métodos
10.
Liver Transpl ; 15(12): 1861-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19938113

RESUMO

In regions with a limited deceased donor pool, living donor adult liver transplantation (LDALT) has become an important treatment modality for patients with hepatocellular carcinoma (HCC) and cirrhosis. Studies have shown higher recurrence rates of HCC after LDALT in comparison with deceased donor liver transplantation (DDLT). The aim of our study was to examine the outcome results and recurrence rates for patients with HCC who underwent LDALT at our center. During an 8-year period, 139 patients underwent LDALT, of whom 28 (20.1%) had HCC in their explanted livers. The median follow-up was 40.8 months. The mean explant tumor size was 3.3 +/- 1.2, and the mean number of tumors was 1.5 +/- 0.8. Twenty-one patients (75%) had tumors within the Milan criteria, 5 patients had tumors outside the Milan criteria but within the University of California San Francisco (UCSF) criteria, and 2 patients were beyond the UCSF criteria. The overall 1- and 5-year patient and graft survival rates were 96% and 81%, respectively. Survival following LDALT was significantly better than survival following DDLT for HCC during the same time period (P = 0.02). Eight patients (28.6%) developed tumor recurrence. Poor differentiation of tumor cells was the most significant determinant of recurrence. Despite high recurrence rates of HCC following LDALT, overall 5-year survival appears to be excellent.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Sobrevivência de Enxerto , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Doadores Vivos , Idoso , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Pathol Int ; 59(5): 312-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19432673

RESUMO

Cholestatic allograft dysfunction following liver transplantation (LT) can result from many different underlying pathogenetic mechanisms and is a major cause of morbidity and graft loss. Although recurrence of primary sclerosing cholangitis (PSC) is a described entity following LT, the diagnosis is difficult and requires exclusion of common risk factors for stricture formation. There are no reports in the literature of de novo PSC arising in a patient who did not have that disease prior to transplantation. Reported herein is the case of a patient who underwent transplantation for end-stage cryptogenic cirrhosis and who had no underlying risk factors, but who developed late post-LT cholestatic disorder with non-anastomotic biliary strictures. The combined clinical, radiological, and pathological findings resembled those of PSC. Admittedly, it is a challenging proposition but the possibility of a de novo PSC-like syndrome in this patient is raised. A recurrence in a patient who may have had a burnt-out, PSC-like syndrome presenting as cryptogenic cirrhosis, however, cannot be entirely excluded.


Assuntos
Ductos Biliares Intra-Hepáticos/patologia , Colangite Esclerosante/patologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/patologia , Idoso , Anti-Inflamatórios/uso terapêutico , Colagogos e Coleréticos/uso terapêutico , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/etiologia , Humanos , Cirrose Hepática/cirurgia , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Prednisona/uso terapêutico , Ácido Ursodesoxicólico/uso terapêutico
12.
Surg Clin North Am ; 88(6): 1409-28, x-xi, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18992602

RESUMO

Hilar cholangiocarcinoma is a rare malignancy that occurs at the bifurcation of the bile ducts. Complete surgical excision with negative histologic margins remains the only hope for cure or long-term survival. Because of its location and proximity to the vascular inflow of the liver, surgical resection is technically difficult and may require advanced vascular reconstructions to achieve complete excision. Patients who are not candidates for resection should undergo palliative biliary drainage. The role of neoadjuvant therapy and liver transplantation in the management of hilar cholangiocarcinoma remains to be defined in light of the recent promising results.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/terapia , Terapia Combinada , Técnicas de Diagnóstico do Sistema Digestório , Saúde Global , Humanos , Incidência , Prognóstico
13.
J Pediatr Surg ; 43(6): 1148-52, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18558198

RESUMO

BACKGROUND: Despite aggressive chemotherapy, recurrence of disease remains the leading cause of death after liver transplantation (LTx) for hepatoblastoma (HB). Unfortunately, little is known about the effects of immunosuppression on recurrence and posttransplant outcomes. We hypothesized that minimal immunosuppression can be safely used in these recipients. METHODS: In 2004, we adopted a minimal immunosuppression regimen using daclizumab induction and tacrolimus monotherapy. Kaplan-Meier survival curves were generated. RESULTS: From 2004 to 2006, 6 children underwent primary LTx for HB with neoadjuvant and adjuvant chemotherapy. Patient survival was 100% at 12 months and at 24 months, without graft loss. One patient died 28 months after transplantation. Recurrence-free survival was 83% at 12 months and at 24 months. Despite minimal immunosuppression (IS), 4 of 6 HB recipients remained rejection-free. When compared to other LTx recipients receiving minimal IS, HB recipients trended to have better rejection-free survival (HB, 83% at 12 months and 62.5% at 24 months vs all others, 36% and 36%, respectively; P = .19). CONCLUSION: Our short-term patient and graft survival rates are comparable to those reported for all HB recipients in the United Network for Organ Sharing database. Although not statistically significant, our rejection-free survival data suggest that HB recipients may be less likely to reject than other recipients.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Hepatoblastoma/cirurgia , Imunoglobulina G/administração & dosagem , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/imunologia , Transplante de Fígado/mortalidade , Tacrolimo/administração & dosagem , Adolescente , Anticorpos Monoclonais Humanizados , Criança , Pré-Escolar , Daclizumabe , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Hepatoblastoma/diagnóstico , Hepatoblastoma/mortalidade , Humanos , Terapia de Imunossupressão/métodos , Lactente , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Probabilidade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
15.
Hum Pathol ; 38(3): 443-52, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17188331

RESUMO

Clinicopathologic trends of recurrent hepatitis C after liver transplantation (LT) in hepatitis C (HCV) patients seem to have changed in recent years. Our aims were to define the current post-LT patterns of HCV recurrence and identify features of diagnostic and/or prognostic significance. Detailed analysis was performed on 92 HCV patients who underwent LT from June 1999 to December 2003 and survived early post-LT period. The study patients were grouped, as follows: no histologic recurrence (n = 31), "typical" recurrent HCV (n = 52), and post-LT autoimmune-like hepatitis ("AIH-like") (n = 9). The typical and AIH-like groups had mostly common features with post-LT progressive fibrosis (stage > or =2) more frequent in the latter. Based on post-LT progressive fibrosis (stage > or =2), the 2 post-LT hepatitis categories were regrouped as progressive (n = 24) and nonprogressive (n = 37). High viral counts, HCV genotype 1, and native liver inflammation grade 2 or higher with plasmacytic periseptitis were more frequent in progressive cases than nonprogressive or nonrecurrent cases. Sex mismatch of male recipient and female donor was more common in nonrecurrent group. Overall, death rate was comparable in all groups; however, post-LT HCV-related deaths were more common in progressive cases. In conclusion (1) two thirds (66.2%) of HCV patients developed histologic hepatitis after LT with either typical or AIH-like features; (2) progressive fibrosis was seen in 39.3% of patients with post-LT hepatitis and 26% of the entire study group and was more frequent in AIH-like cases; (3) inflammation grade 2 or higher with plasmacytic periseptitis in native livers may be a predictor of post-LT progressive fibrosis; and (4) male recipient/female donor combination was more common in nonrecurrent cases.


Assuntos
Hepatite C/cirurgia , Transplante de Fígado , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , Feminino , Hepatite C/patologia , Hepatite Autoimune/patologia , Humanos , Imunossupressores/uso terapêutico , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Recidiva
16.
J Anal Toxicol ; 30(3): 178-86, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16803652

RESUMO

A new analytical procedure was developed for the quantitation of nonsmoker salivary cotinine. Small volumes of saliva were diluted with water, fortified with cotinine-d3 (internal standard), then passed through small extraction columns. The analyte and internal standard were eluted with 0.1% (v/v) acetic acid/acetonitrile. Aliquots of each extract were analyzed directly, without chromatographic separation, using chip-based (NanoMate) nanospray tandem mass spectrometry. The calculated detection limit was 0.49 ng cotinine/mL saliva. This method was used to quantify salivary cotinine collected from nonsmoking human subjects living in one of three environmental tobacco smoke (ETS) exposure categories or "cells": 1. smoking home/smoking workplace; 2. smoking home/nonsmoking workplace; and 3. nonsmoking home/smoking workplace. Samples were collected during five sequential days, including Saturday, as part of a larger study to evaluate potential variability in exposure to ETS. Salivary cotinine measurements were made for the purpose of excluding misclassified smokers and for comparison with known levels of exposure to airborne nicotine in each exposure category. The concentrations observed were consistent with those reported from other large studies reported elsewhere. A non-parametric statistical test was applied to the data within each cell. No statistically significant differences were found between the mean cotinine concentrations collected on a weekday as compared to those collected on a weekend day. When the non-parametric test was applied to the three cells, a statistically significant difference was observed between cell 1 compared to cells 2 and 3. The salivary cotinine concentrations were thus statistically invariant over a five-day exposure period, and they were greatest under the conditions of smoking home and smoking workplace.


Assuntos
Cotinina/análise , Saliva/química , Poluição por Fumaça de Tabaco , Monitoramento Ambiental , Habitação , Humanos , Fumar , Espectrometria de Massas por Ionização por Electrospray , Local de Trabalho
17.
Arch Surg ; 141(4): 385-8; discussion 388, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16618897

RESUMO

HYPOTHESIS: Distal splenorenal shunt (DSRS) is a safe and effective treatment for patients with Child-Pugh class A and B cirrhosis with recurrent variceal hemorrhage after failed transjugular intrahepatic portosystemic shunt. DESIGN: Retrospective case review. SETTING: Hepatobiliary surgery and liver transplantation department in a tertiary referral medical center. PATIENTS: Between August 1, 1985, and May 1, 2005, 119 patients with Child-Pugh class A and B cirrhosis underwent DSRS for recurrent variceal hemorrhage. Of these, 17 (14.3%) had thrombosed or failing transjugular intrahepatic portosystemic shunt prior to DSRS. INTERVENTION: Distal splenorenal shunt for recurrent variceal hemorrhage after failure of conservative management. MAIN OUTCOME MEASURES: Morbidity, mortality, and subsequent liver transplantation rate. RESULTS: The overall perioperative morbidity rate was 31.5%. Thirteen patients (11.7%) developed encephalopathy and 6 (5.4%) had recurrent variceal hemorrhage. Other complications included portal vein thrombosis, pancreatitis, pancreatic pseudocyst, pneumonia, and wound infection. The 30-day operative mortality rate was 6.4% (n = 7). The 1-year survival rate was 85.9%. The incidence of DSRS for failed transjugular intrahepatic portosystemic shunt during the first 12 years of the study (1985-1997) was 11.1% (9/81). This proportion increased to 26.7% (8/30) during the second half of the study (1997-2005). During the 20-year period, 15 patients (13.5%) underwent liver transplantation a mean of 5.1 years after DSRS without an increase in morbidity or mortality after transplantation. CONCLUSIONS: Distal splenorenal shunt may be the preferred treatment for recurrent variceal hemorrhage in the patient with well-compensated cirrhosis. In addition, DSRS does not cause increased morbidity or mortality in subsequent liver transplantation.


Assuntos
Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/cirurgia , Cirrose Hepática/cirurgia , Derivação Esplenorrenal Cirúrgica , Adulto , Idoso , Idoso de 80 Anos ou mais , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Cirrose Hepática/complicações , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Recidiva , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
Liver Transpl ; 12(6): 958-65, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16598742

RESUMO

The Model for End-Stage Liver Disease (MELD) scoring system, a validated objective liver disease severity scale, was adopted in February 2002 to allocate cadaveric organs for liver transplantation (LT). To improve transplantability before succumbing to advanced disease, patients with low-stage hepatocellular carcinoma (HCC) are given extra points in this system commensurate with their predicted mortality. Our aims were to determine 1) any change in the pathological findings at LT following the implementation of this system and 2) the impact of scoring advantage given to early-stage HCC. Clinicopathologic findings were compared before (pre-MELD, n = 87) and after (MELD, n = 58) the introduction of the MELD system. The findings in the pre-MELD vs. MELD groups were as follows: HCC, 27.5% vs. 48.3% (P = 0.001); portal vein thrombosis (PVT), 13.7% vs. 25.9% (P = 0.08); cholestasis, 16.1% vs. 32.7% (P = 0.026); inflammation grade of 2 or more, 43.7% vs. 48.3% (P = not significant); hepatitis C (HCV), 45.9% vs. 51.7% (P = not significant); HCV with lymphoid aggregates, 25% vs. 60% (P = 0.003); HCV with hyperplastic hilar nodes, 15.0% vs. 36.6% (P = 0.001); and post-LT HCC recurrence, 4.1% vs. 3.4% (P = not significant). Non-HCC-related findings were further compared in the 2 subgroups of pre-MELD (n = 57) and MELD (n = 31) after exclusion of HCC and fulminant hepatic failure (FHF) cases, and only cholestasis was significantly increased in the subgroup MELD. In conclusion, increased incidence of native liver cholestasis in the MELD era may be the histologic correlate of clinically severe liver disease. The scoring advantage given to low-stage HCC did result in a significantly increased incidence of HCC in the MELD group, but it did not adversely affect the post-LT recurrence rate.


Assuntos
Hepatopatias/patologia , Transplante de Fígado , Modelos Biológicos , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias
19.
Liver Transpl ; 11(11): 1389-94, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16237690

RESUMO

Extrahepatic portal vein thrombosis (EHPVT) may occur in children or adults and usually comes to clinical attention due to complications of portal hypertension such as variceal hemorrhage. A variety of standard surgical techniques exist to manage these patients, but when these fail surgical options are limited. We describe two novel portosystemic shunts that utilize the gonadal vein as an autologous conduit. Four patients were evaluated for EHPVT with variceal bleeding. None of the patients were candidates for a standard splenorenal shunt due to prior surgical procedures. The first patient underwent a left mesogonadal shunt and the remaining 3 patients underwent a right mesogonadal shunt. Postoperative ultrasound or computed tomography (CT) scan confirmed early patency of the shunt in each patient. There have been no further episodes of variceal hemorrhage with follow-up of 3.5 years in the child who underwent the left mesogonadal shunt, and 17, 19, and 20 months in the patients who underwent the right mesogonadal shunt. Three of the 4 shunts remain patent. One shunt thrombosis occurred in a patient homozygous for the Factor V Leiden mutation despite anticoagulation with coumadin. This is the first report of the successful use of the gonadal vein as an in situ conduit for constructing a portosystemic shunt. In conclusion, the right and left mesogonadal shunts may be useful as salvage operations for patients with EHPVT who have failed standard surgical shunt procedures.


Assuntos
Ductos Biliares Extra-Hepáticos/patologia , Varizes Esofágicas e Gástricas/cirurgia , Veia Porta , Derivação Portossistêmica Cirúrgica/métodos , Trombose Venosa/diagnóstico , Trombose Venosa/cirurgia , Adolescente , Angiografia , Criança , Pré-Escolar , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico , Masculino , Pessoa de Meia-Idade , Medição de Risco , Estudos de Amostragem , Derivação Esplenorrenal Cirúrgica/métodos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia Doppler
20.
Am J Transplant ; 5(11): 2770-7, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16212639

RESUMO

We report the results of a prospective, longitudinal quality of life survey on our adult right lobe (RL) liver donors. A total of 47 donors were enrolled; a standard SF-36 form and 43 questions developed by our team were completed before donation, at 1 week, and 1, 3, 6 and 12 months after donation. There were no donor deaths. Twenty-nine complications occurred in 16 patients. Major complication rate was 12.8%. Employment status and personal finances were identified as major stressors. All donors who wished to return to work did so by 1 year (mean 3.4 months). Individuals reported between 0 dollars and 25,000 dollars in losses (wages, travel, lodging, etc.). Relationships with recipients and other family members were not altered significantly. Anticipated pain (predonation) was greater than actual pain reported. Donors indicated satisfaction with the donation process regardless of recipient outcome. Physical complaints were significant at 1 week and 1 month, but returned to baseline. Donor mental health remained stable. In conclusion, RL donors found the experience to be a positive one throughout the first postdonation year. The study identified areas (finances, employment and expected recipient outcomes) to be stressed as future donors are evaluated.


Assuntos
Hepatectomia/psicologia , Doadores Vivos/psicologia , Qualidade de Vida , Adulto , Custos e Análise de Custo , Depressão/epidemiologia , Escolaridade , Emprego , Família , Feminino , Hepatectomia/economia , Humanos , Estudos Longitudinais , Masculino , Dor Pós-Operatória , Complicações Pós-Operatórias/epidemiologia , Inquéritos e Questionários , Coleta de Tecidos e Órgãos/economia , Coleta de Tecidos e Órgãos/psicologia
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