RESUMO
Transmembrane integrin receptors mediate cell-extracellular matrix as well as cell-cell adhesion. As placental trophoblast cells undergo differentiation they display changes in integrin expression or switching, but the mechanism(s) of integrin activation that supports this differentiation is still unknown. The Fermitin family of adapter proteins (FERMT 1-3) are integrin activators that mediate integrin-mediated signaling. In this study, we examined the spatiotemporal pattern of expression of FERMT1 in human chorionic villi throughout gestation and its role in HTR8-SVneo substrate adhesion and invasion. Placental villous tissue was obtained from patients undergoing elective terminations at weeks 8-14, as well as from term deliveries at weeks 37-40 and analyzed by immunofluorescence. Additionally, HTR8-SVneo trophoblast cells were transfected with FERMT1-specific siRNA or non-targeting siRNA (control) and used in cell-substrate adhesion as well as invasion assays. FERMT1 was primarily localized to membrane-associated regions at the base or around the periphery of the villous cytotrophoblast and proximal as well as distal cell column trophoblast. FERMT1 was also localized to endothelial cells of blood vessels in chorionic villi. siRNA-mediated depletion of FERMT1 in HTR8-SVneo cells did not markedly alter HTR8-SVneo cell-substrate adhesion but did significantly decrease invasion (P < 0.05) compared to control cells. These novel findings identify the presence of the integrin activator FERMT1 in trophoblast cells and that FERMT1 can regulate HTR8-SVneo cell invasion. FERMT1 may directly influence integrin activation and the subsequent integrin-mediated signaling and differentiation that underlies the acquisition of the invasive trophoblast phenotype in vivo.
Assuntos
Vilosidades Coriônicas/metabolismo , Proteínas de Membrana/biossíntese , Proteínas de Neoplasias/biossíntese , Placenta/metabolismo , Adesão Celular , Células Cultivadas , Feminino , Imunofluorescência , Humanos , Proteínas de Membrana/análise , Proteínas de Neoplasias/análise , Placenta/citologia , GravidezRESUMO
Chronic GVHD (cGVHD) after allogeneic hematopoietic SCT (HSCT) is characterized by an infiltration of T cells into target organs including the oral mucosa and salivary glands. This study was designed to clarify the molecular mechanism of the local accumulation of pathogenic T cells in cGVHD. The expression of cytokines, chemokines and chemokine receptors in the buccal mucosa (BM), labial salivary glands (LSG) and PBMC from 16 patients with cGVHD after allogeneic HSCT was examined. The mRNA expression of T helper 1 (Th1) and Th2 cytokines, and several chemokines and chemokine receptors was significantly increased in the BM and LSG from cGVHD patients, in comparison with both those in the BM and LSG from controls, respectively, and also with those in the PBMC from cGVHD patients. Furthermore, the mRNA expression of Th2 cytokines, macrophage-derived chemokine and CC chemokine receptor 4 was closely associated with a strong T-cell infiltration in the BM and LSG from cGVHD patients. These results suggest that cGVHD might be initiated and/or maintained by Th1/Th0 cells and thereafter progresses in association with Th2 cell accumulation via the interaction of particular chemokine and chemokine receptors.
Assuntos
Quimiocinas/metabolismo , Citocinas/metabolismo , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/fisiopatologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Receptores de Quimiocinas/metabolismo , Subpopulações de Linfócitos T/metabolismo , Adulto , Quimiocinas/genética , Citocinas/genética , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Doença Enxerto-Hospedeiro/imunologia , Humanos , Lábio , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , RNA Mensageiro/metabolismo , Receptores de Quimiocinas/genética , Glândulas Salivares Menores/imunologia , Glândulas Salivares Menores/metabolismo , Subpopulações de Linfócitos T/imunologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Transplante Homólogo , Regulação para Cima , Adulto JovemRESUMO
In low-pressure capacitive radio frequency discharges, two mechanisms of electron heating are dominant: (i) Ohmic heating due to collisions of electrons with neutrals of the background gas and (ii) stochastic heating due to momentum transfer from the oscillating boundary sheath. In this work we show by means of a nonlinear global model that the self-excitation of the plasma series resonance which arises in asymmetric capacitive discharges due to nonlinear interaction of plasma bulk and sheath significantly affects both Ohmic heating and stochastic heating. We observe that the series resonance effect increases the dissipation by factors of 2-5. We conclude that the nonlinear plasma dynamics should be taken into account in order to describe quantitatively correct electron heating in asymmetric capacitive radio frequency discharges.
RESUMO
BACKGROUND: RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is known to induce apoptosis in its receptor-positive cells. The authors investigated RCAS1 expression in oral squamous cell carcinoma (SCC) and its association with the apoptosis of tumor-infiltrating lymphocytes (TILs). METHODS: In 130 patients with oral SCC, the expression of RCAS1 in tumor cells was immunohistochemically examined and the apoptosis of TILs was examined by Terminal Deoxynucleotidyltransferase-mediated dUTP Nick End Labeling (TUNEL) staining. RESULTS: RCAS1 was detected both on the cytoplasm and the membrane of tumor cells in 41 of 130 cases (31.5%). Focusing on the expression at the invasive front interacting with host immune cells, RCAS1 was detected in 22 of 130 cases (16.9%). The percentage of TUNEL-positive TILs in cases with RCAS1-positive SCCs was significantly higher than in cases with RCAS1-negative SCCs (P < 0.0001). CONCLUSIONS: RCAS1 can be expressed on oral SCC cells and may be involved in the tumor escape from the host immune system by inducing the apoptosis of TILs.
Assuntos
Antígenos de Neoplasias/biossíntese , Antígenos de Neoplasias/fisiologia , Carcinoma de Células Escamosas/imunologia , Neoplasias Bucais/imunologia , Evasão Tumoral/imunologia , Idoso , Apoptose , Distribuição de Qui-Quadrado , Feminino , Humanos , Técnicas Imunoenzimáticas , Vigilância Imunológica , Marcação In Situ das Extremidades Cortadas , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estatísticas não ParamétricasRESUMO
For electronegative plasmas with low gas pressure and high ion densities, we expect Coulomb collisions between positive and negative ions to dominate over collisions between ions and neutrals. We incorporated Nanbu's cumulative small-angle collision method [K. Nanbu, Phys. Rev. E, 55, 4642 (1997)] into our one-dimensional three-velocity-component particle-in-cell code PDP1 in order to study the effect of Coulomb collisions on low pressure high density electronegative discharges. Nanbu's method treats a succession of small-angle binary collisions as a single binary collision with a large scattering angle, which is far faster than treating each individual small-angle collision. We find that Coulomb collisions between positive and negative ions in low-pressure high-density electronegative discharges significantly modify the negative ion flux, density, and kinetic energy profiles.
RESUMO
BACKGROUND: Identification of a disease-specific and possibly pathogenic T-cell receptor (TCR) in oral lichen planus (OLP) is one of the most important steps to reveal the pathogenic antigen recognized by the T cells and thereby elucidate the pathogenesis and etiology of OLP. METHODS: In buccal mucosa biopsy specimens and peripheral blood mononuclear cells (PBMC) from seven patients with OLP, the TCR V beta gene usage was examined by polymerase chain reaction-based and single-strand conformation polymorphism analyses. RESULTS: The V beta families expressed in the biopsy specimens were markedly heterogeneous, but they were restricted in comparison to those observed in the PBMC. The V beta families predominantly expressed in the biopsy specimens in comparison with the PBMC were still heterogeneous in individual patients and differed from patient to patient; however, V beta 2, V beta 6, and V beta 19 were commonly predominant in the biopsy specimens from more than half of the patients. Among the V beta families predominantly expressed in the biopsy specimens, the accumulation of T-cell clonotypes was observed in the majority of the V beta families including V beta 6 and V beta 19; however, it was not observed in the minority of the V beta families including V beta 2. CONCLUSIONS: These results suggest that unique T-cell populations bearing V beta 2, V beta 6, or V beta 19 gene products tend to expand in OLP lesions as a consequence of in situ stimulation with a restricted epitope of either a nominal antigen on the MHC molecule for the majority of the V beta families, even if only in minor populations, or of a common superantigen for the minority of the V beta families.
Assuntos
Genes Codificadores da Cadeia beta de Receptores de Linfócitos T/genética , Líquen Plano Bucal/patologia , Linfócitos T/fisiologia , Idoso , Células Clonais/fisiologia , Etnicidade/genética , Feminino , Humanos , Líquen Plano Bucal/etnologia , Líquen Plano Bucal/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Especificidade do Receptor de Antígeno de Linfócitos T/genéticaRESUMO
The effect of fluorinated pyrimidine co-administered with docetaxel on transplantable human breast cancer strains MX-1 and R-27 was investigated using an in vitro succinic dehydrogenase inhibition (SDI) method and an in vivo nude mouse transplant method. The in vivo results showed that the combined use of 5-fluorouracil and docetaxel enhanced antitumor activity. No antitumor activity on MX-1 was observed in vivo in either the UFT alone or docetaxel alone group, whereas co-administration of the two drugs resulted in a tumor inhibition rate of 85.1% above the effective line. These results suggest the usefulness of 5-fluorouracil in combination with docetaxel in the treatment of solid tumors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Taxoides , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Docetaxel , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/análogos & derivados , Paclitaxel/farmacologia , Succinato Desidrogenase/antagonistas & inibidores , Tegafur/administração & dosagem , Tegafur/farmacologia , Transplante Heterólogo , Uracila/administração & dosagem , Uracila/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Background: A hepatic artery-portal vein reciprocal response and hepatic hemodynamics have well been investigated under normal condition, but not under pathologic condition with decreased vascular bed. This study was designed to determine the hemodynamic changes in the hepatic blood flow, tissue perfusion and interrelationship between portal venous flow (PVF) and hepatic arterial flow (HAF) after inflow interruption in the various size of hepatic vascular bed. Methods: Anesthetized dogs were used to measure PVF and HAF using a transit time flow meter and hepatic tissue flow (HTF) using a laser Doppler flow meter before and after portal venous (PVO) or hepatic arterial occlusion (HAO) under various range of portal triad occlusion (PTO). Results: The ratio of HAF/TLF (total liver flow) was 38+/-14% under the basal condition. This ratio did not change under the 30% PTO where there was a similar decrease in PVF and HAF, but reduced to 25+/-12% under the 70% PTO where there was more selective reduction in HAF than PVF. Although a reciprocal HAF increase was observed under any conditions after PVO, the TLF and HTF decreases after PVO were largest under the 70% PTO with the highest PVF/TLF ratio. On the other hand, there was no reciprocal PVF increase in any conditions after HAO, and the TLF and HTF decreases after HAO were minimal under the 70% PTO with the lowest HAF/TLF ratio. Conclusions: With decreasing hepatic vascular bed, dependency of the remnant hepatic hemodynamics and tissue perfusion on the portal blood flow increased. These findings suggest that an integrity of portal venous flow becomes crucial in the remnant hepatic tissue perfusion after extensive hepatic resection.
RESUMO
BACKGROUND: The liver and portal circulation contribute to production and clearance of endothelin-1 (ET-1). This study was undertaken to investigate what variables relate to the dynamics of ET-1 in hepatic resection and its clinical implication. PATIENTS AND METHODS: On 20 patients with (n = 8) or without (n = 12) chronic liver disease who underwent hepatic resection, peripheral arterial and portal venous ET-1 were serially measured to determine a correlation with pre-, intra-, and postoperative variables. RESULTS: The preoperative factors with which the portal ET-1 showed a positive correlation were the indocyanine green retention rate at 15 min (ICG R15) and portal venous pressure. The ET-1 clearance, as calculated from the difference between the portal and the peripheral ET-1 concentrations, was also correlated with the ICG R15. The peripheral ET-1 elevated significantly in the patients with increasing intraoperative blood loss or hepatic inflow occlusion. An increase in the portal ET-1 was correlated with an elevation of portal venous pressure after hepatectomy. Postoperative increase in serum bilirubin was closely correlated with the peripheral ET-1 at closure. CONCLUSION: The peripheral and portal ET-1 are correlated with not only preoperative hepatic reserve and portal venous pressure but also invasiveness of hepatectomy and postoperative course.
Assuntos
Endotelina-1/sangue , Hepatectomia , Veia Porta/metabolismo , Perda Sanguínea Cirúrgica , Feminino , Humanos , Período Intraoperatório , Fígado/irrigação sanguínea , Fígado/metabolismo , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta/fisiologia , Período Pós-Operatório , Fatores de TempoRESUMO
The antitumor effect of paclitaxel, epirubicin, and both in combination was tested using R-27, an estrogen receptor-positive human breast carcinoma. In an in vivo study using nude mice both drugs showed an additive effect, whereas they showed a supraadditive pattern in in vitro MTT assay. The combination of paclitaxel and epirubicin may enhance the antitumor effect on breast carcinoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Epirubicina/uso terapêutico , Paclitaxel/uso terapêutico , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Quimioterapia Combinada , Epirubicina/administração & dosagem , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Paclitaxel/administração & dosagem , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Transplantability of human tumors into nude mice might represent higher grade of malignancy. In our institution, surgically resected tumors have been subjected to transplantation into nude mice since 1975. We retrospectively investigated clinical outcomes of donor patients with gastric and colorectal cancer who underwent operation and analyzed the relationship between the transplantability and clinical characteristics of the patients. Thirty five out of 119 gastric tumors were successfully transplanted into nude mice with a 29.4% take rate. Results of transplantation among 92 patients' tumor in stage 2, 3 and 4 revealed 35 takes and 57 non-takes. There were only 3 ten-year survivors in the 'take' group while there were 17 ten-year survivors in the 'non-take' group. Patients with tumors which are transplantable into nude mice appeared to have poor prognosis (p < 0.05). The take rate with fifty colorectal tumors was 50%. Among 46 patient's tumors in stage 2, 3 and 4, there were 25 takes and 21 non-takes. Ten-year survivors included 11 'take' donors and 7 'non-take' donors. As opposed to gastric cancers, no statistically significant difference in survival was observed between the two groups.
Assuntos
Neoplasias Colorretais/patologia , Camundongos Nus , Transplante de Neoplasias , Neoplasias Gástricas/patologia , Transplante Heterólogo , Animais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The present study was designed to investigate if TAK-044, a novel endothelin (ET) ETA/ETB receptor antagonist, inhibits ischemia-reperfusion liver injury. The initial study showed the presence of both ETA and ETB receptors in canine hepatic membrane fractions using the specific binding assay of labeled ET-1 with ET isomers and TAK-044. The nonselective ETA/ETB receptor antagonist TAK-044 inhibited the specific binding of ET-1 to the receptors in a concentration-dependent manner. In subsequent studies using a canine 70% partial liver ischemic model (60 minutes), we found that an intravenous injection of TAK-044 (3 mg/kg) before ischemia significantly inhibited the release of serum liver enzymes (aspartate transaminase, alanine transaminase, mitochondrial glutamic oxaloacetic transaminase, and an increase of indocyanine green retention rate after reperfusion, compared with the control group. Elevation of the portal venous pressure was also suppressed significantly during the portal triad occlusion, and a rapid restoration of oxygen pressure in the liver tissue after reperfusion was observed in the TAK-044-treated group. Morphometric analysis revealed that the hepatocyte swelling and sinusoidal contraction 1 hour after reperfusion were significantly less severe in the treated group than in the control group. The sludging of erythrocytes in the sinusoidal lumens was also minimal in the treated group. In conclusion, the significant suppression of hepatic microcirculatory disturbance and tissue injury after ischemia-reperfusion were shown in the TAK-044-treated group. This finding indicates that the pretreatment of TAK-044 is useful as a hepatoprotective agent against ischemia-reperfusion injury, which is otherwise produced by a pathway involving ET-1.
Assuntos
Antagonistas dos Receptores de Endotelina , Fígado/efeitos dos fármacos , Fígado/lesões , Peptídeos Cíclicos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Cães , Endotelina-1/fisiologia , Fígado/fisiopatologia , Circulação Hepática/efeitos dos fármacos , Masculino , Receptores de Endotelina/metabolismo , Traumatismo por Reperfusão/fisiopatologiaRESUMO
The histoculture drug-response assay (HDRA) was recently evaluated in a retrospective clinical trial and was found to correlate to drug sensitivity, resistance, and patient survival. To further investigate the potential of HDRA to contribute to patient survival, 215 patients with gastric cancer from 45 medical centers were tested with the HDRA in a blinded study after resection of the primary lesion. One hundred sixty-eight patients received at least 20 mg/m2 of mitomycin C and a minimum of 30 g UFT, a mixture of tegafur and uracil at a molar ratio of 1:4, thereby making them eligible for the study. Of these cases 128 were evaluable by the HDRA. The evaluable patient tumors were tested by the HDRA with the [3H]thymidine incorporation end point measured by microautoradiography to be drug "sensitive" or "resistant." The in vitro conditions for distinguishing sensitivity and resistance that matched the response rates for historical controls for gastric carcinoma were 90% inhibition rate and 0.12 microgram/ml for mitomycin C and 70% inhibition rate and 1 microgram/ml for 5-fluorouracil, respectively. Most importantly in the blinded study, the overall and disease-free survival rates of the HDRA-sensitive group were found to be significantly higher than those of the HDRA-resistant group tested under the above conditions. The data further indicate the importance of three-dimensional tumor culture for obtaining accurate clinical information. The results demonstrate that the HDRA response correlates to patient survival, which suggests the potential of the HDRA to contribute to patient survival in gastric cancer when used prospectively.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Ensaio Tumoral de Célula-Tronco/métodos , Adulto , Idoso , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Análise Multivariada , Estudos Prospectivos , Taxa de Sobrevida , Tegafur/administração & dosagem , Uracila/administração & dosagemRESUMO
The present study reports on the usefulness of laparoscopic microwave coagulonecrotic therapy as a new option in the treatment of hepatocellular carcinoma. Five patients with liver tumors associated with cirrhosis were treated from July 1993 to March 1994 with a microwave electrode (output 100 W, 3 to 4 cm long) devised for laparoscopic use. The tumors, all with diameters less than 3 cm and superficially located, were coagulated for a total radiation period of 20 to 30 min under laparoscopic, intraoperative ultrasonographic control. Postoperative complications were negligible, and laboratory values (glutamate-pyruvate transaminase, bilirubin, prothrombin time, platelet count) returned to preoperative levels within 7 days. Complete necrosis, including the surrounding liver tissue, was confirmed by a follow-up dynamic computed tomography scan during the follow-up period of 6 to 17 months (mean, 13 months). Laparoscopic microwave coagulonecrotic therapy can exert an effect on tumor equivalent to that obtained from a wedge resection but is noninvasive and may represent a new option for unresectable liver cancers.
Assuntos
Carcinoma Hepatocelular/terapia , Diatermia/métodos , Laparoscopia , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Idoso , Alanina Transaminase/sangue , Bilirrubina/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Diatermia/efeitos adversos , Feminino , Seguimentos , Humanos , Cuidados Intraoperatórios , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Micro-Ondas/efeitos adversos , Pessoa de Meia-Idade , Necrose , Contagem de Plaquetas , Tempo de Protrombina , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ultrassonografia de IntervençãoRESUMO
The in vitro chemosensitivity test has been appreciated as an useful laboratory method for selecting the optimal anticancer drug for solid carcinomas. Using human tumor xenografts, the correlation of in vitro and in vivo tests was studied. The sensitivity results were identical between the two methods for 75% of samples tested. In the other study, five surgically resected specimens were subjected to the in vitro test and were transplanted into nude mice. The in vitro tests were repeated on the xenografts, demonstrating satisfactory reproducibility of the sensitivity results.
Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/patologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias Gástricas/patologia , Animais , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Fluoruracila/farmacologia , Humanos , Camundongos , Camundongos Nus , Mitomicina/farmacologia , Transplante de Neoplasias , Sensibilidade e Especificidade , Transplante HeterólogoRESUMO
This study was designed to investigate the changes in plasma and tissue endothelin-1/endothelin-2 (ET) after liver ischemia and to assess the protective effect of anti-ET 1/ET 2 monoclonal antibody (ET antibody) against ischemia-reperfusion injury. The ET levels in the liver tissue, hepatic venous blood of the ischemic and non-ischemic sides, and in the portal venous blood were measured before and after partial liver ischemia for 1 hour in the adult dog. The ET levels in the liver tissue and hepatic venous blood on the ischemic side increased slightly during ischemia and markedly after reperfusion, whereas those on the nonischemic side showed no significant increases. The ET levels in the portal venous blood peaked at 1 to 3 hours after ischemia, which was significantly higher than the levels in the hepatic venous blood on the ischemic side and which correlated with the portal venous pressure elevated because of the partial liver clamping. The administration of antibody (2 mg/kg, intravenous) before reperfusion resulted in a significant inhibition of the postreperfusion elevations of serum-glutamic-oxaloacetic transaminase (GOT), S-glutamic pyruvic transaminase (GPT), and the indocyanine green (ICG) dye retention rate. In conclusion, ET was produced both in the liver tissue exposed to ischemia and in the vascular endothelium of the portal bed exposed to portal congestion. The ET released from the vascular endothelium, including the liver and the portal bed, was found to be a possible factor of ischemia-reperfusion injury.
Assuntos
Endotelinas/metabolismo , Isquemia/metabolismo , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/etiologia , Animais , Cães , Fígado/metabolismo , Veia Porta/fisiologia , Pressão VenosaRESUMO
Hepatectomy was performed under in situ right lobar hypothermic perfusion combined with hepatoprotective agents in six patients who had hepatocellular carcinoma and coexisting liver disease. Following occlusion of the right hepatic vein and the right portal pedicle, in situ cold perfusion was initiated using chilled Ringer's lactate infused through a cannula placed in the right main portal vein. The right superior segments were resected in a bloodless field. The liver was cooled to 22-26 degrees C for 40 to 80 minutes with no significant changes in systemic hemodynamics or body temperature. Postoperative liver functions showed no marked derangement; the mean peak GPT was 221 U and the mean peak total bilirubin 2.3 mg d/l. Local cooling minimizes the risk of ischemia/reperfusion injury in this very vulnerable population, yet gives the surgeon adequate time to perform a challenging resection in a bloodless field.
Assuntos
Alprostadil/administração & dosagem , Carcinoma Hepatocelular/cirurgia , Glicoproteínas/administração & dosagem , Hepatectomia/métodos , Hipotermia Induzida/métodos , Neoplasias Hepáticas/cirurgia , Inibidores da Tripsina/administração & dosagem , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Carcinoma Hepatocelular/complicações , Doença Crônica , Hepatite/complicações , Humanos , Infusões Intravenosas , Soluções Isotônicas , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Perfusão , Traumatismo por Reperfusão/prevenção & controle , Lactato de RingerRESUMO
OBJECTIVE: This study reports further refinement of a prediction scoring system, which was established in 1980 as a guide to determine a safe limit for hepatectomy, based on 10 years of use. SUMMARY BACKGROUND DATA: In the past, whether major resection was safe was judged empirically from the net resection volume or the residual hepatic volume combined with the patient's liver function. However, such judgment was not based on objectively defined criteria. METHODS: Patients with hepatocellular carcinoma (HCC; n = 376) and metastatic cancer (n = 58) who had hepatectomy at some time from 1981 through 1990 were entered into this study. A prediction score (PS) was computed using a multiple regression equation that consists of computed tomographic scan-estimated resection rate, indocyanine green retention rate, and the patient's age. A PS greater than 55 was classified as a risky zone, a PS of 45 to 55 was considered borderline and a PS less than 45 was a safe zone. RESULTS: With HCC and chronic liver disease, all patients in the risky zone died, whereas 33% in the borderline zone died and 7.3% died who were in the safe zone. With metastatic cancer with normal liver, all patients in the risky zone died, whereas no patient in either the borderline or safe zones died. The major cause of death in the risky zone was liver failure due to excessive resection. In the borderline and safe zones, liver failure developed primarily after abdominal sepsis or pulmonary infection, particularly for those with adverse prognostic factors such as disturbed glucose tolerance, lower platelet count, and higher indocyanine green retention rate. CONCLUSION: Prediction scores can eliminate deaths related to excessive resection for patients with normal or injured livers. When patients have adverse prognostic factors, careful surgery and postoperative management is mandatory to avoid liver failure triggered by intra- or extra-abdominal sepsis, even if the score remains in a borderline or safe zone.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
A rare case of a successful Kasai operation for biliary atresia in a 9 month old is described. For infants over 6 months of age, there had been no reports of long-term survival after this procedure.
Assuntos
Atresia Biliar/cirurgia , Portoenterostomia Hepática , Atresia Biliar/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Prognóstico , Fatores de TempoRESUMO
A pharmacokinetic comparison was made between nude mice and human gastric cancer patients. This comparison is important in order to optimize the human tumor xenograft-nude mouse system as a screening panel for potential antitumor agents. In this report, mitomycin C (MMC), doxorubicin (DXR), 5-fluorouracil (5-FU) and cisplatin (DDP) were administered to nude mice bearing human tumor subcutaneous xenografts in maximum tolerated doses and to patients with gastric cancer at conventional doses. The concentrations of antitumor agents in serum and tumor were detected by bioassay for MMC and 5-FU, by high performance liquid chromatography for DXR, and by atomic absorption method for DDP. Peak drug concentrations in the serum (Cmax) the mice and humans correlated well with statistical significance (R = 0.999, P < 0.0001). When Cmax and drug concentrations in the tumor (T) the mice and human were compared with each other to evaluate the uptake of drugs into the tumor from the serum and calculated as T/Cmax, similar results were observed for the same agent with statistical significance (r = 0.990, p < 0.02). These results indicate that the human tumor xenograft-nude mouse system and humans are essentially similar pharmacodynamically, which further validates the uses of this system to evaluate potential antitumor agents.