Splanchnic blood flow is greater in septic shock treated with norepinephrine than in severe sepsis

Objective To assess global and splanchnic blood flow and oxygen transport in patients with sepsis with and without norepinephrine treatment.Design Prospective, clinical study.Setting University hospital intensive care unit.Patients A convenience sample of 15 septic shock patients treated with norepinephrine and 13 patients with severe sepsis who did not receive norepinephrine.Measurements and main results There were no differences between the two groups in global haemodynamics and oxygen transport. Splanchnic blood flow and oxygen delivery (splanchnic DO₂ 303±43 ml/min per m²) and consumption (splanchnic VO₂ 100±13 ml/min per m²) were much higher in the septic shock group compared with the severe sepsis group (splanchnic DO₂ 175±19 ml/min per m², splanchnic VO₂ 61±6 ml/min per m²). Gastric mucosal pH was subnormal in both groups (septic shock 7.29±0.02, severe sepsis 7.25±0.02) with no significant difference. No significant differences between groups were detected in lactate values.Conclusion These data confirm a redistribution of blood flow to the splanchnic region in sepsis that is even more pronounced in patients with septic shock requiring norepinephrine. However, subnormal gastric mucosal pH suggested inadequate oxygenation in part of the splanchnic region due to factors other than splanchnic hypoperfusion. Progress in this area will depend on techniques that address not only total splanchnic blood flow, but also inter-organ flow distribution, intra-organ distribution, and other microcirculatory or metabolic malfunctions.     

The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock

Objective: To assess the effects of low-dose dopamine on splanchnic blood flow and splanchnic oxygen uptake in patients with septic shock. Design: Prospective, controlled trial. Setting: University hospital intensive care unit Patients: 11 patients with septic shock, diagnosed according the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference, who required treatment with norepinephrine. Measurements and main results: Systemic and splanchnic hemodynamics and oxygen transport were measured before and during addition of low-dose dopamine (3 μg/kg per min). Low-dose dopamine had a marked effect on total body hemodynamics and oxygen transport. The fractional splanchnic flow at baseline ranged from 0.15 to 0.57. In 7 patients with a fractional splanchnic flow less than 0.30, low-dose dopamine increased splanchnic flow and splanchnic oxygen delivery and oxygen consumption. In 4 patients with a fractional splanchnic flow above 0.30, low-dose dopamine did not appear to change splanchnic blood flow. Conclusion: Low-dose dopamine has a potential beneficial effect on splanchnic blood flow and oxygen consumption in patients with septic shock, provided the fractional splanchnic flow is not already high before treatment. Received: 19 September 1995 Accepted: 21 September 1996     

Splanchnic oxygen transport after cardiac surgery: evidence for inadequate tissue perfusion after stabilization of hemodynamics

Objective To evaluate the adequacy of visceral oxygen transport and gastric pH_i after open heart surgery in patients with stable hemodynamics.Design Nonrandomized control trial.Setting A general intensive care unit in a tertiary care center.Patients Sixteen postoperative cardiac surgery patients were studied after stabilization of systemic hemodynamics.Interventions The effect of dobutamine infusion (6 g kg^–1 min^–1) on systemic and regional oxygen transport was studied in ten patients, with six patients serving as controls. Systemic oxygen consumption was measured by indirect calorimetry and splanchnic and femoral blood flow, by continuous infusion of indocyanine green using regional catheters and gastric mucosal pH_i by gastric tonometer.Measurements and results Gastric mucosal acidosis was observed in half of the patients. Dobutamine increased cardiac output (3.2±0.6 vs 4.4±0.7l· min^–1·m^–2;P<0.05), splanchnic blood flow (0.68±0.28 vs 0.91±0.281· min^–1·m^–2;p<0.05) and femoral blood flow (0.25±0.08 vs 0.32±0.11l·min^–1·m^–2;p<0.05). Changes in splanchnic oxygen delivery and consumption were parallel in the two study groups. In response to dobutamine, gastric pH_i did not change (7.30±0.08 vs 7.31±0.06; NS), while in the control group, gastric pH_i tended to decrease (7.32±0.04 vs 7.28±0.06; NS). Systemic oxygen consumption increased in response to dobutamine (141±11 vs 149±11 ml· min^–1·m^–2;P<0.05) but did not change in the control group.Conclusions We conclude that a mismatch between splanchnic oxygen delivery and demand may be present despite stabilization of systemic hemodynamics after cardiac surgery. This is suggested by the parallel changes in splanchnic oxygen delivery and consumption. Dobutamine is likely to improve splanchnic tissue perfusion at this phase.This study was supported in part by the senior researcher's grant no. 1945/3015/92 to Dr. Takala from the Academy of Finland     

肝转移癌超声造影临床应用研究

目的探讨肝转移癌超声造影检出能力、造影增强时相特点并定量分析。方法35例肝转移癌患者为研究对象,行超声造影检查。动态观察动脉相(8~30s)、门脉相(31~120s)及实质相(121~360s)灌注和回声变化规律。记录病灶大小、位置、数目、各增强时相的表现。用QontraXt定量分析软件行量化分析。结果①35例肝转移癌常规超声共检出病灶182个,超声造影共检出386个,超声造影检出明显增加(P<0.05)。②动脉相重点观察的76个肝转移癌病灶表现四种灌注特征Ⅰ型(26.3%),周边环状增强,中心不增强或有少量点状、短线状血管向中心伸延。Ⅱ型(46.1%),周边环状增强,内部少量均匀增强。Ⅲ型(11.8%),周边环状增强,内部少量增强,可见细长分枝状血管。Ⅳ型(15.8%),快速整体团状增强,内部团状或网状走行血管。③对四种增强类型行定量分析,峰值强度Ⅰ型低于其他三型,Ⅳ型高于其他三型(P<0.05);达峰时间Ⅳ型短于其他三型(P<0.05),曲线下面积Ⅳ型高于其他三型(P<0.05)。④35例中重点观察的76个病灶门脉相和实质相均呈现不同程度低回声,其中实质相共有22例54个病灶与相邻肝组织对比非常明显呈“黑洞”现象。结论超声造影增加了肝转移癌病灶的检出数目;肝转移癌增强模式及造影表现有利于其定性诊断;定量分析有利于解释各增强类型的形成基础。     

SATB1促进肝癌增殖与转移能力的初步研究

目的本研究拟观察SATB1在肝癌中表达情况,并在此基础上利用RNA干扰技术对SATB1进行封闭,观察肝癌生长和转移情况。方法运用实时定量PCR方法检测正常肝组织、肝硬化、良性肝肿瘤及原发性肝癌组织中SATB1的表达情况,并通过实时定量PCR及Western blot检测高转移肝癌细胞株HC-CLM3、低转移肝癌细胞株MHCC-97L及正常肝脏细胞株HL-7702中SATB1的表达。运用RNA干扰技术对高转移肝癌细胞株HCCLM3中的SATB1进行干扰并验证干扰效果,干扰前后的细胞株进行MTT、划痕实验及裸鼠体内移植瘤实验,观察SATB1对高转移肝癌细胞株HCCLM3增殖及转移能力的影响。结果原发性肝癌组织中的SATB1的mRNA水平明显高于正常肝组织、肝硬化组织及良性肝肿瘤组织,且高转移肝癌细胞株HCCLM3中的SATB1表达水平显著高于正常肝脏细胞株HL-7702及低转移肝癌细胞株MHCC-97L;在HCCLM3细胞株中成功干扰SATB1,干扰后细胞株的增殖及迁移能力均明显降低,裸鼠体内肿瘤增殖能力明显减弱。结论 SATB1在肝癌中显著表达,并有促进肝癌细胞株的增殖和转移的作用。     

Ultrasonographic follow-up of liver cirrhosis

Ultrasonography and upper gastrointestinal endoscopy were prospectively used to study 100 consecutive patients with liver cirrhosis. After a period of 20 months to 55 months, 21 patients had died, 23 were lost at follow-up, and 56 patients were reevaluated. In the patients who died during follow-up, the entry liver volume, measured by means of the hepatic volumetric index, was lower as compared to the 56 cirrhotics who survived. During the study period, liver volume significantly decreased to values similar to those observed, at entry, in patients who died. Moreover, esophageal varices increased in size, and the splanchnic veins enlarged. Abdominal ultrasonography provides data regarding the natural history of liver cirrhosis, which might be used, in addition to tests of liver function and endoscopy, as prognostic factors in cirrhotic patients.     

肝癌组织中环氧化酶-2表达与微小转移的关系研究

目的 探讨肝癌组织中环氧化酶-2(Cyclooxygenase-2,Cox-2)的表达与肝癌微小转移之间的关系.方法 应用免疫组织化学生物素化过氧化物酶复合物(SABC)法,检测44例原发性肝癌手术切除肝癌组织中Cox-2表达;应用逆转录聚合酶链反应(RT-PCR)检测原发性肝癌患者外周血中AFP-mRNA.结果 肝癌组织中Cox-2表达阳性率为41.6%(18/44),外周血甲胎蛋白信使核糖核酸(AFP-mRNA)阳性率25%(11/44),其中Cox-2表达阳性者中,AFP-mRNA阳性者为9例,占50%(9/18),而Cox-2表达阴性者中,AFP-mRNA阳性者为2例,占7.7%(2/26),两者有显著性差异.结论 肝癌组织中Cox-2表达与肝癌微小转移有相关性.     

The effect of dobutamine infusion on splanchnic blood flow and oxygen transport in patients with acute pancreatitis

Objectives: To measure the blood flow distribution and oxygen transport in pancreatitis and to evaluate the regional effects of increased systemic blood flow. Design: Nonrandomized controlled trial. Setting: A general intensive care unit in a tertiary care center. Patients: 10 patients with pancreatitis requiring mechanical ventilation were studied after fluid resuscitation, and for the response to dobutamine, the patients served as their own controls. For the baseline, 11 patients scheduled for elective abdominal surgery served as a control group. Interventions: Systemic and regional hemodynamics were measured after fluid resuscitation to predefined hemodynamic endpoints. In patients with pancreatitis, the measurement was repeated after cardiac output had been increased by at least 25 % by dobutamine. Measurements and results: Hepatosplanchnic blood flow was estimated using regional catheterization and the dye dilution method. In patients with pancreatitis, the cardiac index did not differ from that of the control group (3.9 ± 0.8 vs 4.1 ± 0.7 l · min^–1· m^–2;NS). Accordingly, there was no difference in the splanchnic blood flow (1.1 ± 0.4 vs 1.2 ± 0.5 l · min^–1· m^–2;NS). Systemic and splanchnic oxygen consumption was increased in patients with pancreatitis (179 ± 25 vs 147 ± 27 ml · min^–1· m^–2, p < 0.05 and 68 ± 15 vs 49 ± 19 ml · min^–1· m^–2, p < 0.05), and systemic and splanchnic oxygen extraction was higher (0.34 ± 0.08 vs23 ± 0.05, p < 0.01 and 0.46 ± 0.18 vs 0.28 ± 0.08, p < 0.05, respectively). Dobutamine had inconsistent effects on splanchnic blood flow: in individual patients, splanchnic blood flow even decreased substantially. Conclusions: In severe pancreatitis, oxygen consumption is increased in the splanchnic region; increased splanchnic oxygen demand is not always met by adequately increased blood flow. Increasing the systemic blood flow with dobutamine does not improve perfusion in the splanchnic bed. Received: 24 September 1996 Accepted: 5 May 1997     

Splanchnic metabolism in acute liver failure and sepsis

PURPOSE OF REVIEW: A number of papers have suggested that the splanchnic circulation and oxidative metabolism are compromised in critical illness. This review discusses this hypothesis and outlines the recent advances in the understanding of splanchnic metabolism with special focus on acute liver failure and hyperdynamic sepsis. RECENT FINDINGS: Splanchnic blood flow, oxygen delivery, and consumption are increased in both acute liver failure and sepsis. The capability of the liver to extract oxygen, even under extreme conditions, renders the liver less prone to hypoxia. A common feature of acute liver failure and sepsis is a hypermetabolic state with enhanced glycolysis and production of lactate and pyruvate. Human studies on other features of intermediary metabolism are sparse, but there are indications that several intermediary processes are severely compromised in patients with acute liver failure, whereas these processes are maintained in sepsis. SUMMARY: There is increasing evidence that both acute liver failure and sepsis are accompanied by a hypermetabolic state in the hepatosplanchnic area, characterized by enhanced glycolysis and hyperlactatemia. This should not be rigorously interpreted as an indication of hypoxia. In fact, clinically important splanchnic hypoxia may be a relatively uncommon phenomenon in such patients.     

18例不明原发病灶的转移性肝癌的手术治疗

目的探讨不明原发灶的转移性肝癌的诊断、治疗及预后。方法对 18例经手术治疗及随访资料进行回顾性分析。结果均未发现转移性肝癌原发灶的部位 ,经手术和灌注治疗和中药治疗后平均生存 18.5月 ,最长生存 4年余。结论原发灶不明的转移性肝癌 ,其治疗方法与原发性肝癌相似 ,手术治疗应首选。     

Delivery dependent oxygen consumption in patients with septic shock: Daily variations,relationship with outcome and the sick-euthyroid syndrome

Delivery dependent oxygen consumption (DDOC) is observed in patients with sepsis and vital organ dysfunction, and has been related to outcome. Similarly the sick-euthyroid syndrome is associated with a high mortality. We examined the daily variations of DDOC and its relation to hormonal changes, particularly those of the thyroid. In 22 patients, 14 with septic shock and 8 post-operative controls, oxygen delivery was increased by increasing cardiac output with vasodilation by phentolamine, during a total of 207 days. DDOC varied markedly between consecutive days in individual patients with sepsis, in both survivors and non-survivors. DDOC was related to severity of illness, assessed by APACHE II score (r=0.50,p=0.017), and plasma levels of triiodothyronine (T₃),r=–0.49,p=0.011, and thyroxine (T₄),r=–0.53,p=0.012. No correlation was observed between DDOC and outcome, nor blood levels of lactate, epinephrine, norepinephrine, dopamine or cortisol. In conclusion, we observed a marked disturbance of systemic oxygen uptake autoregulation in patients with septic shock which varied during the clinical course and was related to the sick-euthyroid syndrome.With the technical assistance of J. Lopez     

Effects of fenoldopam on systemic and splanchnic haemodynamics and oxygen delivery/consumption relationship during hyperdynamic ovine endotoxaemia

Objective: To evaluate the use of a selective dopamine-1 agonist (fenoldopam) to provide selective splanchnic vasodilatation during sustained hypotensive endotoxaemia in sheep. Design: Randomised, controlled, experimental study. Setting: Animal research laboratory. Subjects: 12 adult instrumented, midazolam-sedated sheep. Interventions: The animals were randomised to receive a 20-min continuous infusion of dopamine (10 μg · kg^{− 1}· min^{− 1}), fenoldopam (10 μg · kg⁻¹· min^{− 1}) and noradrenaline (1 μg · kg^{− 1}· min^{− 1}) under control conditions and 12 h after endotoxaemia was induced by a continuous infusion of Escherichia coli endotoxin producing a stable hyperdynamic state simulating human septic shock. This drug dosage was selected to produce a 25–30 % increase in cardiac output by all three drugs during control conditions. Measurements and results: Systemic and splanchnic haemodynamic data were continuously obtained and systemic and splanchnic oxygen delivery (DO₂) and consumption (VO₂) were calculated. Hyperdynamic hypotensive endotoxaemia did not modify the splanchnic and renal reduction in DO₂ and the vasoconstrictive reactivity to noradrenaline observed during control conditions. In contrast, endotoxaemia abolished the fenoldopam and dopamine-induced increase in splanchnic DO₂ (especially in the coeliac trunk) observed during control conditions. Conclusions: During sustained hyperdynamic endotoxaemia, the dopaminergic-induced selective increase in coeliac trunk blood flow is abolished, most probably because of an already maximally vasodilated splanchnic circulation which prevented dopamine or fenoldopam to vasodilate this area further. Contrary to common belief, selective dopamine-1 agonist administration under these conditions may therefore not be beneficial to the splanchnic organs, though it improves whole body DO₂ and VO₂. Received: 22 May 1997 Accepted: 13 January 1998     

Alterations in T-lymphocyte subpopulations in patients with complicated liver cirrhosis

Aim

To investigate possible alterations of T-lymphocyte subpopulations in patients with cirrhosis complicated with infection and variceal bleeding, and to evaluate the relationship between T-lymphocyte subpopulations and outcome.

Patients and Methods

This was a prospective study on 99 patients with liver cirrhosis, who were admitted to a university hospital over a period of 18 months. Twenty-six patients (37.6%, group A) were admitted for reasons other than infection or bleeding, 24 (34.7%, group B) presented with sepsis, and 19 (27.5%, group C) were admitted with variceal bleeding. A group of 30 healthy individuals admitted to the hospital without cirrhosis and served as the control group. We evaluated T-cell subsets CD3, CD4, CD5, CD8, CD56, and CD20 as well as CD14 and CD64 subsets of monocytes and neutrophils by using flow cytometry. Measurements for group A were taken only on admission, while for patients of group B and C measurements were repeated on the third and the last hospital day.

Results

T-cell subsets (CD3, CD4, CD5, CD8, CD56, and CD20 as well as CD14 and CD64 subsets of monocytes and neutrophils) were reduced in septic cirrhotics, but this reduction was not statistically significant compared to the other groups. A significant decrease was observed in T helper cells between cirrhotic patients with and without variceal bleeding (day 3: CD4: 293 ± 214 versus 442 ± 277 [P < 0.049]; discharge day: CD4:178 ± 113 versus 442 ± 277 [P < 0.003]). Concerning phagocytic potential as detected by CD14 and/or CD64 expression on monocytes and neutrophils, a significant decrease was noted in septic versus nonseptic cirrhotics (day 1: 61.66 ± 40.16 versus 252 ± 73 [P < 0.039]; day 3: 66.99 ± 34.64 versus 252 ± 73 [P < 0.042]).

Conclusions

Our study showed that the T helper cells and phagocytic potential of monocytes and neutrophils are decreased in patients with liver cirrhosis complicated by sepsis and variceal bleeding. Particularly, these abnormalities seem to be more pronounced in cirrhosis with variceal bleeding. To our knowledge, this is the first study to show these T-cell abnormalities in patients with cirrhosis. Further studies are needed to confirm these findings.     

冠状动脉旁路移植术后氧代谢监测的初步探讨

目的:探讨冠状动脉旁路移植(CABG)术后氧代谢的变化及临床意义.方法:回顾性分析45例CABG患者,监测术后1、4、12、24、48 h氧供(DO2)、氧耗(VO2)、氧摄取值(ERO2).结果:CABG术后1 h DO2最低,为362.7 mL/(min·m2),术后4、12 h分别为395.8 mL/(min·m2)、433.3 mL/(min·m2),低于术后24 h的467.3mL/(min·m2),术后24 h后基本稳定.术后12 h VO2最高,为144.3 mL/(min·m2).术后1 h ERO2最高,为35.1%,术后12 h ERO2为33.3%,略低于术后1 h时,术后24 h降低为31.4%.结论:CABG术后1～4 h时组织处于缺氧状态,应加强氧供.术后存在病理性氧供依赖现象,氧供临界值为362.7～395.8 mL/(min·m2).CABG术后早期机体处于相对缺氧状态,此时应采用综合措施保证供氧和降低氧耗.     

肝癌转移和预后相关的miRNA

microRNA(miRNA)是近年来发现的一类长度约为20～25个核苷酸的具有转录后调节功能的非编码单链的小分子RNA.研究发现miR-21、miR-34a、miR-9、miR-151与肝癌转移密切相关,而miR-122、miR-221和miR-125等影响肝癌预后.     

Splanchnic Secretion Rates of Plasma Triglycerides and Total and Splanchnic Turnover of Plasma Free Fatty Acids in Men with Normo- and Hypertriglyceridaemia

Abstract. Plasma triglyceride (TG) “turnover rates” were estimated in the fasting state in three different ways: splanchnic chemical TG secretion, splanchnic isotope TG secretion and plasma TG clearance. Forty-two men with a wide range of fasting plasma TG concentrations, from 0.53 to 16.50 mmol/l were investigated. A constant intravenous infusion of albumin-bound ³H-labelled palmitate was given and blood was simultaneously sampled from the hepatic vein and an artery for determination of hepatic venous-arterial differences of labelled and unlabelled plasma TG. In addition total and splanchnic turnovers of plasma FFA were measured. Similar values were obtained for plasma TG “turnover rate” by the splanchnic chemical TG secretion and the plasma TG clearance method. The values for these two methods varied between 3 and 74 μmol/min. and m² body surface area, except for two cases who had considerably higher values. The splanchnic isotope TG secretion method gave lower values varying from 1 to 34 μmol/min. and m² body surface area. This method probably measures only that fraction of the splanchnic TG secretion which is derived from plasma FFA. No correlations were found among normotriglyceridaemic subjects between plasma total TG or VLDL-TG concentrations and plasma TG “turnover rates” measured by any of the three methods. For patients with hypertriglyceridaemia significant positive correlations were found between plasma VLDL-TG concentrations and plasma “turnover rates”. The “fractional turnover rate” decreased with increasing TG levels in an apparently hyperbolic fashion. The results suggest an impaired plasma TG removal capacity in patients with hypertriglyceridaemia. In 7 out of 14 patients the plasma TG “turnover rates” were in the upper part of the normal range and seemed to have contributed to the hypertriglyceridaemia in these patients. Plasma FFA turnover rate ranged between 102 and 439 μmol/min. and m² body surface area. On the average splanchnic FFA mobilization and uptake were about 30 and 60 per cent respectively of total FFA turnover rate. Significant positive correlations were found for the interrelationships between the three plasma FFA total and splanchnic transport parameters. Significant positive correlations were found between the three plasma TG “turnover rates” and total and splanchnic turnover of plasma FFA in subjects with normal plasma TG concentrations. Some patients with hypertriglyceridaemia fell outside the intervals of 99 per cent confidence of the regression analyses for the normo-triglyceridaemic subjects. This group had higher TG “turnover rates” than “expected” from plasma FFA turnover rates and may represent a distinctive group of hypertriglyceridaemia from the point of view of pathogenesis. It was concluded that all patients with hypertriglyceridaemia who were investigated had decreased “fractional turnover rates” of plasma TG indicating a decreased removal capacity which might be a primary cause of the hypertriglyceridaemia although inflow of plasma TG seemed to be an essential contributing factor in half the number of patients.     

转移性小肝癌超声造影表现特征

目的探讨转移性小肝癌的超声造影表现特征。 方法回顾性分析复旦大学附属中山医院94个转移性小肝癌病灶及150个小肝细胞癌（HCC）病灶的超声造影图像,对比2组病灶超声造影的增强方式和时相变化（增强时间、达峰时间、等回声时间、低回声时间）。 结果94个转移性小肝癌病灶中,66.0%（62/94）表现为整体增强,34.0%（32/94）表现为环状增强;150个小HCC病灶中,98.7%（148/150）表现为整体增强,1.3%（2/150）表现为环状增强,转移性小肝癌动脉期环状增强的比例显著高于小HCC（P<0.01）。转移性小肝癌的超声造影等回声时间、低回声时间、从等回声至低回声所经历的时间分别为（28.7±6.3）s、（39.1±16.2）s、（8.2±8.5）s;小HCC的超声造影等回声时间、低回声时间、从等回声至低回声所经历的时间分别为（35.8±12.5）s、（86.8±45.5）s、（52.5±44.2）s,转移性小肝癌的超声造影等回声时间、低回声时间及从等回声至低回声所经历的时间均短于小HCC（t=-8.722、-12.636、-10.571,P值均<0.01）。 结论整体增强和环状增强均为转移性小肝癌的常见表现,增强方式和减退时间有助于转移性小肝癌和小HCC的鉴别,超声造影有助于转移性小肝癌的诊断。     

Feasibility of CT scan-guided Tru-Cut serial liver biopsies to evaluate pharmacodynamic endpoints in patients with liver metastasis treated with experimental drugs

We assessed the feasibility of using computed tomographically guided, Tru-Cut serial liver biopsies to perform pharmacodynamic studies in patients with liver metastasis who had been treated with experimental drugs. Twenty-three patients with liver metastasis were enrolled in two protocols for evaluation of the response to two new biologic drugs: a farnesyltransferase inhibitor and a tyrosine kinase inhibitor of the epidermal growth factor receptor. Computed tomographically guided Tru-Cut biopsies with an 18-gauge needle were performed. The procedure was performed at baseline and 2, 6, and 24 h after starting the administration of the drug. The procedures were scheduled on an outpatient basis. We obtained 271 samples (168 from metastatic lesions and 103 from surrounding normal liver tissue) from 23 patients. Biochemical determination of farnesyltransferase activity and different immunohistochemistry stainings (pEGRF, pMAPK, p27, Ki67, and apoptosis) of the signal transduction pathway were determined in each tissue sample, and all scheduled tissue assays were performed with the tissues obtained. Complete serial biopsies were performed in 20 patients. Three patients were excluded due to minor complications after the first biopsy. The morbidity rate in relation to the number of procedures was 1.1% (three of 271 samples). We found serial liver biopsies using Tru-Cut to be a safe and easy procedure. In our series, we could evaluate samples for molecular changes that influence the optimal dose, sequence, and schedule of the new antineoplastic agents.     

Feasibility of CT scan-guided Tru-Cut serial liver biopsies to evaluate pharmacodynamic endpoints in patients with liver metastasis treated with experimental drugs

We assessed the feasibility of using computed tomographically guided, Tru-Cut serial liver biopsies to perform pharmacodynamic studies in patients with liver metastasis who had been treated with experimental drugs. Twenty-three patients with liver metastasis were enrolled in two protocols for evaluation of the response to two new biologic drugs: a farnesyltransferase inhibitor and a tyrosine kinase inhibitor of the epidermal growth factor receptor. Computed tomographically guided Tru-Cut biopsies with an 18-gauge needle were performed. The procedure was performed at baseline and 2, 6, and 24 h after starting the administration of the drug. The procedures were scheduled on an outpatient basis. We obtained 271 samples (168 from metastatic lesions and 103 from surrounding normal liver tissue) from 23 patients. Biochemical determination of farnesyltransferase activity and different immunohistochemistry stainings (pEGRF, pMAPK, p27, Ki67, and apoptosis) of the signal transduction pathway were determined in each tissue sample, and all scheduled tissue assays were performed with the tissues obtained. Complete serial biopsies were performed in 20 patients. Three patients were excluded due to minor complications after the first biopsy. The morbidity rate in relation to the number of procedures was 1.1% (three of 271 samples). We found serial liver biopsies using Tru-Cut to be a safe and easy procedure. In our series, we could evaluate samples for molecular changes that influence the optimal dose, sequence, and schedule of the new antineoplastic agents.