Cytologic changes in small hepatocellular carcinomas after radiofrequency ablation

OBJECTIVE: To illustrate the cytologic changes in hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). STUDY DESIGN: The study included 20 patients with 23 HCC who had undergone RFA under ultrasound guidance. Baseline cytomorphology of HCC was evaluated by fine needle aspiration (FNA) in all cases. Triphasic helical computed tomography (CT) and FNA cytology were done to evaluate the efficacy of the treatment within two weeks after RFA. The cytologic specimens were stained with Riu's method (Romanowsky stain). RESULTS: A range of cytologic findings after RFA was found, including granular and amorphous debris with artefactual aggregation, degenerated cells or necrotic material, and dyshesive, degenerated cells in a necrotic background. The cytologic patterns included necrotic cells and debris in 14 tumors and fine, granular necrosis in 9. Helical CT showed no enhancement in any of the tumors after RFA. CONCLUSION: The cell patterns indicated complete necrosis in HCC after RFA.     

Intérêt de l’imagerie hybride TEMP/TDM pour la scintigraphie des récepteurs de la somatostatine dans le bilan des tumeurs endocrines gastro-entéro-pancréatiques

In this work, we have evaluated the potential of image fusion and attenuation correction (AC) of SPECT-CT imaging for the assessment of gastro-entero-pancreatic endocrine tumors by somatostatin receptor scintigraphy (SRS).MethodAfter optimisation of acquisition and reconstruction parameters, we have evaluated, in a prospective study, SRS performed over a period of one year. We have compared visual interpretations of planar and tomographic images versus SPECT/CT images to determine if anatomical localisation and diagnostic contributions are improved. In a semi-quantitative analysis of pathological foci, we have measured maximal intensity values (T_max), tumour to background ratios (T/B) and tumour contrasts (Ct) with and without AC.ResultsIn 25 SRS, visual analysis has shown anatomical localisation improvements in 60% of cases (CI95%, 39–79) and diagnostic improvements in 64% of cases (CI95%, 43–82). Doubtful foci proportion changed from 44 to 11%. In the semi-quantitative analysis of 41 pathological foci, Wilcoxon matched-pairs tests showed significantly higher T_max, T/B and Ct values after AC.ConclusionSPECT/CT imaging improves diagnostic quality of SRS thanks to a better foci localisation and a better lesional contrast in the image.     

不同声功率聚焦超声治疗不同时期胰腺癌疗效分析

目的:对不同声功率聚焦超声治疗不同时期胰腺癌疗效进行分析。方法:以胰腺癌患者为研究对象,分为低功率组和高功率组,其中低功率组治疗功率为100249 W,高功率组治疗功率为250350 W,以疼痛缓解效果、肿瘤坏死体积和体积消融率、血管内皮生长因子(vascular endothelial growth facto,VEGF)和肝细胞生长因子(hepatocyte growth factor,HGF)水平、并发症和生存时间为指标,评价治疗效果。结果:低功率疼痛缓解总有效率为97.5%,高功率组总有效率为92.5%,两组比较无显著差异(P>0.05);所有患者的胰腺癌肿瘤均呈现不同程度的坏死,且坏死区域体积在13个月内逐渐缩小,表现为增强扫描无强化,肿瘤周围存在环形强化带;高功率组IIIIV期患者的肿瘤体积消融率显著高于低功率组(P<0.05);与治疗前相比,低功率组和高功率组IIIIV分期患者的VEGF和HGF水平均显著下降,与低功率组相比,高功率组各时期VEGF和HGF水平降低更显著(P<0.05);高功率组和低功率组并发症发生率分别为12.5%和15.0%,经比较无统计学差异(P>0.05);治疗后低功率组患者中位生存期为6.37±1.13个月,高功率组患者中位生存期为6.72±1.34个月,经比较无显著差异(P>0.05)。结论:不同声功率聚焦超声消融治疗不同时期胰腺癌均有较好疗效,减轻患者疼痛,延长中位生存期,安全性较好。     

小鼠腹腔注射硫酸铍的病理形态学观察

目的研究腹腔注射硫酸铍（BeSO4.4H2O）对小鼠主要脏器的损害作用。方法将30只6周龄昆明（KM）雄性小鼠随机分为三组,分别予以不同剂量硫酸铍生理盐水溶液腹腔注射染毒,隔日一次,染毒两周。观察主要脏器的病理组织学变化并测定脏器系数。结果与对照组比较,染毒组心、脾、肾、睾丸脏器系数无显著差异,肝、肺脏器系数差异有统计学意义（P〈0.05）;对照组肺、肝病理学组织检查未见异常,低剂量组小鼠肺组织可见淤血、出血、支气管扩张出血,肺泡腔内有少量炎性渗出物、支气管周围炎、间质性肺炎、小叶性肺炎等;高剂量组小鼠肺组织可见支气管扩张出血,支气管腔内有大量炎性渗出物,支气管周围肺泡扩张,间质性肺炎、小叶性肺炎、融合性小叶性肺炎;低剂量组肝细胞水肿,可见点状坏死和小灶性坏死;高剂量组小鼠肝组织损伤严重,肝细胞排列紊乱,多数肝细胞呈细胞水肿,肝细胞胞质成空泡状,可见明显的点状坏死和小灶性坏死,并伴有炎细胞浸润,坏死区周围肝细胞细胞质呈嗜酸性变,轻度核固缩,并且肝细胞呈不同程度的胞质疏松,肝窦以及肝中央静脉扩张有广泛变性、坏死等病理改变。睾丸、心、脾、肾未见明显异常。结论小鼠腹腔注射本试验剂量的硫酸铍后主要引起肺组织和肝脏损伤,其它脏器未见明显异常。     

Mechanisms for virus-induced liver disease: tumor necrosis factor-mediated pathology independent of natural killer and T cells during murine cytomegalovirus infection.

The contribution of endogenous NK cells and cytokines to virus-induced liver pathology was evaluated during murine cytomegalovirus infections of mice. In immunocompetent C57BL/6 mice, the virus induced a self-limited liver disease characterized by hepatitis, with focal inflammation, and large grossly visible subcapsular necrotic foci. The inflammatory foci were most numerous and contained the greatest number of cells 3 days after infection; they colocalized with areas of viral antigen expression. The largest number of necrotic foci was found 2 days after infection. Overall hepatic damage, assessed as increased expression of liver enzymes in serum, accompanied the development of inflammatory and necrotic foci. Experiments with neutralizing antibodies demonstrated that although virus-induced tumor necrosis factor (TNF) can have antiviral effects, it also mediated significant liver pathology. TNF was required for development of hepatic necrotic foci and increased levels of liver enzymes in serum but not for increased numbers of inflammatory foci. The necrotic foci and liver enzyme indications of pathology occurred independently of NK and T cells, because mice rendered NK-cell deficient by treatment with antibodies, T- and B-cell-deficient Rag-/- mice, and NK- and T-cell-deficient E26 mice all manifested both parameters of disease. Development of necrotic foci and maximally increased levels of liver enzymes in serum also were TNF dependent in NK-cell-deficient mice. Moreover, in the immunodeficient E26 mice, virus-induced liver disease was progressive, with eventual death of the host, and neutralization of TNF significantly increased longevity. These results establish conditions separating hepatitis from significant liver damage and demonstrate a cytokine-mediated component to viral pathogenesis.     

Therapeutic Efficacy of Percutaneous Radiofrequency Ablation versus Microwave Ablation for Hepatocellular Carcinoma

The aim of this study was to investigate the therapeutic efficacy of percutaneous radiofrequency (RF) ablation versus microwave (MW) ablation for hepatocellular carcinoma (HCC) measuring ≤5 cm in greatest diameter. From January 2006 to December 2006, 78 patients had undergone RF ablation whereas 77 had undergone MW ablation. Complete ablation (CA), local tumour progression (LTP) and distant recurrence (DR) were compared. The overall survival curves were calculated with the Kaplan-Meier technique and compared with the log-rank test. The CA rate was 83.4% (78/93) for RF ablation and 86.7%(91/105 for MW ablation. The LTP rate was 11.8% (11/93) for RF ablation and 10.5% (11/105) for MW ablation. DR was found in 51 (65.4%) in the RF ablation and 62 (80.5%) in the MW ablation. There was no significant difference in the 1-, 3-, and 5-year overall survival rates (P = 0.780) and the 1-, 3-, and 5-year disease-free survival rates (P = 0.123) between RF and MW ablation. At subgroup analyses, for patients with tumors ≤3.0 cm, there was no significant difference in the 1-, 3-, and 5-year overall survival rates (P = 0.067) and the corresponding disease-free survival rates(P = 0.849). For patients with tumor diameters of 3.1–5.0 cm, the 1-, 3-, and 5-year overall survival rates were 87.1%, 61.3%, and 40.1% for RF ablation and 85.4%, 36.6%, and 22% for MW ablation, with no significant difference (P = 0.068). The corresponding disease-free survival rates were 74.2%, 54.8%, and 45.2% for the RF ablation group and 53.3%, 26.8%, and 17.1% for the MW ablation group. The disease-free survival curve for the RF ablation group was significantly better than that for the MW ablation group (P = 0.018). RF ablation and MW ablation are both effective methods in treating hepatocellular carcinomas, with no significant differences in CA, LTP, DR, and overall survival.     

Thermochemical Ablation Therapy of VX2 Tumor Using a Permeable Oil-Packed Liquid Alkali Metal

Objective

Alkali metal appears to be a promising tool in thermochemical ablation, but, it requires additional data on safety is required. The objective of this study was to explore the effectiveness of permeable oil-packed liquid alkali metal in the thermochemical ablation of tumors.

Methods

Permeable oil-packed sodium–potassium (NaK) was prepared using ultrasonic mixing of different ratios of metal to oil. The thermal effect of the mixture during ablation of muscle tissue ex vivo was evaluated using the Fluke Ti400 Thermal Imager. The thermochemical effect of the NaK-oil mixture on VX2 tumors was evaluated by performing perfusion CT scans both before and after treatment in 10 VX2 rabbit model tumors. VX2 tumors were harvested from two rabbits immediately after treatment to assess their viability using trypan blue and hematoxylin and eosin (H.E.) staining.

Results

The injection of the NaK–oil mixture resulted in significantly higher heat in the ablation areas. The permeable oil controlled the rate of heat released during the NaK reaction with water in the living tissue. Perfusion computed tomography and its parameter map confirmed that the NaK–oil mixture had curative effects on VX2 tumors. Both trypan blue and H.E. staining showed partial necrosis of the VX2 tumors.

Conclusions

The NaK–oil mixture may be used successfully to ablate tumor tissue in vivo. With reference to the controlled thermal and chemical lethal injury to tumors, using a liquid alkali in ablation is potentially an effective and safe method to treat malignant tumors.     

The Value of Proton Magnetic Resonance Spectroscopy in High-Intensity Focused Ultrasound Treatment of Experimental Liver Cancer

High-intensity focused ultrasound (HIFU) is a rapidly developing, non-invasive technique for local treatment of solid tumors that produce coagulative tumor necrosis. This study is aimed to investigate the feasibility of proton magnetic resonance spectroscopy (MRS) on early assessing treatment of HIFU ablation in rabbit with VX2 liver tumor. HIFU ablation was performed on normal liver and VX2 tumor in rabbit, and MRS was performed on normal liver and VX2 tumor before and 2 days after 100% HIFU ablation or 80% ablation in tumor volume. Choline (Cho) and choline/lipid (Cho/Lip) ratios between complete and partial HIFU ablation of tumor were compared. Tissues were harvested and sequentially sliced to confirm the necrosis. In normal liver, the Cho value liver was not obviously changed after HIFU (P > .05), but the Cho/Lip ratio was decreased (P < .05). Cho in liver VX2 tumor was much higher than that in normal liver (P < .001). Cho and Cho/Lip ratio were significantly decreased in tumor after complete HIFU ablation and partial HIFU ablation, and the Cho value in complete HIFU tumor ablation did not show any difference from that in normal liver after HIFU (P > .05); however, the Cho value in partial ablation was still higher than that in normal liver before or in tumor after complete HIFU treatment due to the residual part of tumors, and Cho/Lip ratio is lower than that in complete HIFU treatment (P < .001). The changes in MRS parameters were consistent with histopathologic changes of the tumor tissues after treatment. MRS could differentiate the complete tumor necrosis from residual tumor tissue, when combined with magnetic resonance imaging. We conclude that MRS may be applied as an important, non-invasive biomarker for monitoring the thoroughness of HIFU ablation.     

The role of macrophages in the early resistance to mouse hepatitus virus infection in nude mice.

Nude mice which had received intraperitoneal injection of silica simultaneously with infection of mouse hepatitis virus, NuU strain, died of severe necrotic hepatitis within 2 weeks postinfection, whereas those having received no silica survived for 3 weeks or more after challenge. Silica given day 4 postinoculation had no effect. The virus titers of the liver and spleen at day 4 as well as serum interferon levels at day 2 were much higher in silica-treated mice than those without silica treatment. At day 2 or 3 postinoculation, silica-treated mice were found to have a considerable number of necrotic foci in the liver with some neutrophil and lymphocyte infiltration, and viral antigen was present in the cytoplasm of some hepatocytes around necrotic foci. In contrast, those without silica treatment showed only some necrotic foci with some lymphocyte infiltration. Viral antigen was detected only in a few littoral cells but not in hepatocytes. The role of macrophages in the resistance at early stage of inection in nude mice is discussed.     

重症五步蛇咬伤深筋膜室网状切开的早期应用

目的探讨重症五步蛇伤患者行深筋膜室网状切开的早期应用。方法选择2007年4月～2011年12月我院收治被五步蛇咬伤后3h内就诊,且患肢组织压在25mmHg以上的患者44例,其中行深筋膜室网状切开13例作为研究组（A组）,使用传统保守非手术治疗31例作为对照组（B组）,观察两组患者72h内组织压的变化、肿胀程度的改变、创口出血及坏死情况,并进行比较。结果两组比较,A组24h后组织压基本降至正常,肿胀程度比B组轻;A组患者伤口有明显出血渗血,早期B组优于A组,但3h后两组的出血情况对比无明显差异。A组2例患者伤处有片状坏死;B组绝大部分患者72h后经切除坏死组织后肿胀明显消退,1例患者因骨筋膜室综合征导致截肢,两组对比有显著统计学差异。结论在重症五步蛇伤中,审慎深筋膜室网状切开患肢,可避免组织坏死、骨筋膜室综合征形成及大出血的发生。     

Electron microscopy description of cardiomyocytes from the left ventricle of rat heart after apoptosis induction by isoproterenol

Changes in cardiomyocytes from the left ventricle of rat heart were studied by light and electron microscopic and morphometric methods in the myocardial regions neighboring necrotic foci formed after the injection of 80 mg/kg β adrenomimetic isoproterenol. TUNEL assay was used to detect apoptotic cardiomyocytes. Three types of cardiomyocytes (A, B, and C) differing by the ultrastructure of the nucleus and the degree of mitochondrial changes were identified at all studied stages of necrotic focus development (4–48 h). B and C type cardiomyocytes could represent cells at different stages of apoptosis. The apoptotic changes in cardiomyocytes proved to prevail in early lesion foci (4–18 h), while cardiomyocytes at later stages were prone to necrosis; cardiomyocytes can exhibit signs of apoptosis and necrosis at the same time.     

A review of antenna designs for percutaneous microwave ablation

Microwave (MW) antenna is a key element in microwave ablation (MWA) treatments as the means that energy is delivered in a focused manner to the tumor and its surrounding area. The energy delivered results in a rise in temperature to a lethal level, resulting in cell death in the ablation zone. The delivery of energy and hence the success of MWA is closely dependent on the structure of the antennas. Therefore, three design criteria, such as expected ablation zone pattern, efficiency of energy delivery, and minimization of the diameter of the antennas have been the focus along the evolution of the MW antenna. To further improve the performance of MWA in the treatment of various tumors through inventing novel antennas, this article reviews the state-of-the-art and summarizes the development of MW antenna designs regarding the three design criteria.     

Histopathological study of breast cancer and normal breast tissue after magnetic resonance-guided cryotherapy ablation

BACKGROUND: Cryotherapy ablation is a minimally invasive procedure being investigated as an alternative to conventional surgery. There are few reports in breast cancer. AIM: Evaluate the histopathology of tumoral and normal breast tissue after cryotherapy. METHODS: Eleven patients with clinically <2.0cm and ultrasound visible tumors were studied. Invasive carcinoma was documented by preoperative mammography, magnetic resonance imaging and biopsies. Cryotherapy needles were inserted in the tumor under magnetic resonance guidance and deep freezed with a CRYO-HIT TM System-3. Lumpectomy was performed within 4-5 weeks following cryoablation and submitted for pathological examination including immunostaining of keratins. RESULTS: The tumoral response after cryoablation was variable. In 4 cases there was no viable invasive carcinoma left and focal DCIS only in 2. In 6 cases, residual invasive carcinoma of various size was present with DCIS inside or outside the cryozone. One case could not be evaluated because the cryozone was adjacent to the tumor due to technical problems. Histologically, the normal breast parenchyma of the cryozone showed dense fibrosis, fat necrosis, xanthogranulomatous reaction, endovascular fibrosis and haemorrhages in all cases. The positive immunostaining of keratins revealed remnants of cytoskeleton of carcinomatous cells in the necrotic areas without any viable tumoral cells on routine stains. Skin ulceration and/or necrosis were observed in five patients. CONCLUSIONS: Cryotherapy allows tumor destruction of variable extent in breast carcinomas <2.0cm in diameter. Immunostaining of keratins is useful to identify cytoskeleton remnants of tumor cells in devitalized areas.     

兔VX2肝癌模型微波消融后磁共振灌注成像的可行性与应用价值

目的通过兔VX2模型探讨肿瘤消融治疗后动态变化过程中,磁共振灌注成像动态量化研究的可行性及其价值。方法16只新西兰大白兔分为实验组12只,对照组4只。实验组在兔肝脏种植VX2肿瘤后,观察肿瘤直径超过2.0 cm时行微波消融治疗。对比术后当天7、d、14 d及28 d实验组与对照组磁共振灌注成像量化指标—最大增强斜率（MSI）的动态变化差异,并与病理结果对照分析。结果对照组兔及实验组兔术后当天肝实质灌注MSI差异无显著性;实验组兔术前肿瘤与术后当天残留肿瘤的平均MSI差异无显著性;实验组兔残留肿瘤与良性强化组织的MSI差异有显著性。残留肿瘤的时间-信号强度曲线表现为快速上升型;良性强化组织的时间-信号强度曲线表现为缓慢上升型。结论磁共振灌注成像的动态量化研究是可行的,量化指标MSI与消融治疗后各种组织的病理结果相吻合,可更为准确地量化表达病变组织的病理状态的改变。     

Inflammatory reaction to the human bot-fly,Dermatobia hominis,in infested and reinfested mice

Two groups of mice were infested with first stage larvae of the human bot-fly, Dermatobia hominis (Linnaeus Jr) (Diptera: Oestridae). In the first group, skin biopsies were carried out 1, 3, 5, 7, 10 and 18 days after infestation. The second group was also infested but had all the larvae removed 5 days after infestation. The mice in the latter group were reinfested 4 weeks later and skin biopsies were carried out 1, 3, 5, 7, 10 and 18 days after reinfestation. In the first group, an inflammatory reaction began slowly, the neutrophils being the main inflammatory cells, eosinophils being scarce. The reaction progressed with time, developing a necrotic halo around the larvae containing inflammatory cells surrounded by fibroblasts. The inflammation invaded the adjacent tissue. In the second group, the inflammatory reaction was intense on the day immediately after reinfestation, the pattern being changed by the presence of a large number of eosinophils. Activated fibroblasts surrounding the necrotic area around the larvae appeared 3 days after reinfestation in the second group and 7 days after infestation in the first group. The results demonstrated that the previous contact with the antigens elicited the early arrival of eosinophils, probably through the chemotactic factors liberated by mast cells in the anaphylactic reaction.     

Tumor regrowth after irradiation; an experimental approach.

Structural changes in irradiated tumors and their regrowth were studied in a rat hepatoma, AH109A, using histological and transparent-chamber techniques. The development of the tumour was examined by means of vascular morphometry as observed in the chamber. Schematically, the tumour tissue was divided into four isocentric layers according to vascular morphology and measurements of vessel volume, surface area, and length per mm3 of tissue. The vascularity was greatest in the outermost region, decreased towards the inner parts and reached an absence of vascularity at the central necrosis. The tumors were gamma- or X-irradiated with various doses. The inside hypoxic region was destroyed completely after 3000 rad, and regrowths started exclusively from the outermost area of the tumour where enhancement of the effect of radiation by oxygen was thought to be greatest. Possible mechanisms of tumour regrowth are discussed.     

Change in the mitotic activity of hepatocytes and resorption of necrotic areas in the formation of liver cirrhosis]

Cirrhosis of the liver was induced in rats weighing 120--140 g by CCl4 administration for a period of 2 months. Iodated oil, which caused emboly of the portal vein branches and foci of necrosis in the heptic tissue, was administered through the spleen to experimental and intact animals. The volume of necrotic foci, and also the mitotic actinity of hepatites were determined. Necrotic foci resolved more rapidly in cirrhosis of the liver. An increase of mitotic index of the second day after the administration of iodated oil was more significant in control rats.     

Radiofrequency ablation of hepatic tumors: simulation, planning, and contribution of virtual reality and haptics

For radiofrequency ablation (RFA) of liver tumors, evaluation of vascular architecture, post-RFA necrosis prediction, and the choice of a suitable needle placement strategy using conventional radiological techniques remain difficult. In an attempt to enhance the safety of RFA, a 3D simulator, treatment planning, and training tool, that simulates the insertion of the needle, the necrosis of the treated area, and proposes an optimal needle placement, has been developed. The 3D scenes are automatically reconstructed from enhanced spiral CT scans. The simulator takes into account the cooling effect of local vessels greater than 3 mm in diameter, making necrosis shapes more realistic. Optimal needle positioning can be automatically generated by the software to produce complete destruction of the tumor, with maximum respect of the healthy liver and of all major structures to avoid. We also studied how the use of virtual reality and haptic devices are valuable to make simulation and training realistic and effective.     

Computerized tomographic imaging of cryosurgical iceball formation in brain

Computerized tomography (CT) was used to monitor the exact anatomical location and dimensions of the cryosurgical iceball within the brain. The gross and microscopic appearance of the tissue iceball was examined in both acute and chronic animals. Iceball formation was monitored in the brain of four dogs under a general anesthesia. The radiographic image of the iceball was that of a well-demarcated radiolucent sphere that disappeared upon thawing. The post-thaw contrast-enhanced CT scan revealed a zone of blood-brain barrier breakdown extending no more than 1 mm beyond the maximum diameter that the iceball had attained. Histological examination demonstrated a sharp transition from frankly necrotic brain within the iceball to the normal cytoarchitecture of the surrounding neuropil. The safety and efficacy of a neurosurgical ablative procedure depends on the precision with which it can be generated. The use of CT imaging to monitor the formation of the cryosurgical iceball offers the neurosurgeon a means to precisely control the size of the ablative lesion. Small deeply situated brain tumors can be incorporated into the iceball under direct CT observation, thereby ensuring the completeness of the cryoablation while minimizing damage to the surrounding brain.     

化疗联合冷循环射频消融术治疗原发性肝癌的效果分析

目的：探讨化疗联合冷循环射频消融术治疗原发性肝癌的疗效及安全性。方法：108例原发性肝癌患者随机分为两组,均给予灌注化疗,每4周进行一次灌注化疗,对照组（n=54）进行3次,治疗组（n=54）只进行一次。治疗组给予冷循环射频消融术。评价生活质量Kamofsky评分,治疗前后检查患者的血、尿、便常规,肝肾功能（包括天冬氨酸转氨酶、丙氨酸转氨酶（AVr）、白蛋白（ALB）、总胆红素、肌酐及尿素氮等指标）,甲胎蛋白（AFP）,T细胞亚群和加强肝脏CT扫描。随访1年,经CT确定肝癌复发。结果：治疗组Kamofsky评分有效率为59．26％,对照组Kamofsky评分有效率为37．03％,两组Kamofsky评分有效率相比较,差异有统计学意义（P〈0．05）。两组治疗后症状变化相比较,除腹胀外其余各项指标差异均有统计学意义（P〈O．05）。治疗后两组相比较,ALT和AFP差异有统计学意义（P〈0．05）。治疗后两组T细胞亚群变化相比较,治疗组各项指标均变化显著（P〈0．05）。治疗后随访一年,治疗组复发率为22．22％;对照组复发率为53．70％。两组治疗一年后复发率相比较,差异有统计学意义（P〈0．05）。结论：化疗结合冷循环射频消融术治疗原发性肝癌疗效肯定,并发症及副作用小,复发率低。