磁共振弥散加权成像评价肝癌冷冻术后近期疗效

目的:探讨采用磁共振弥散加权成像(MRI-DWI)对鉴别肝细胞性肝癌(HCC)冷冻术后肿瘤坏死、残留的应用价值.方法:对接受冷冻治疗的27例肝癌患者共30个病灶行T1 WI、T2WI常规MRI平扫、DWI序列及动态增强扫描.观察肿瘤冷冻前、后MRI信号改变.对HCC一般特征与ADC值的相关性进行分析.比较冷冻前后正常肝脏、肿瘤组织及术后坏死、残留组织的ADC值.结果:冷冻坏死的肝肿瘤组织在T1WI图中呈稍低或稍高信号,T2WI呈低或等信号,DWI呈低信号,动态增强无强化.活性残留肿瘤14个(其中12个肿瘤直径＞5.0 cm),残留率为46.7％.b值=800 s/mm2时,ADC值由低到高依次为:术后残留肿瘤组织(0.98±0.17)×10-3 mm2/s、术前肝肿瘤组织(1.03±0.20)×10-3 mm2/s、正常肝组织(1.14 ±0.07)×10-3mm2/s、术后坏死肿瘤组织(2.07±0.23)×10-3 mm2/s.肝肿瘤组织与对照组正常肝组织ADC值相比,差异有统计学意义(P=0.016).肝肿瘤组织ADC值与肿瘤大小不相关(r=-0.10,P=0.614),与直径范围,肿瘤分期、是否远端转移无关(P＞0.05)、与分化程度有关(P＜0.05).肿瘤坏死区ADC值与术前肿瘤组织相比,差异均有显著统计学意义(P＜0.01).残留组织ADC值与坏死组织及正常肝组织相比,差异均有统计学差异(P＜0.01,P=0.03),与肿瘤组织相比无统计学差异(P=0.192).结论:MRI-DWI能有效鉴别肝癌冷冻术后的病灶坏死及残留,为进一步的临床诊治提供影像学依据.     

Complete shutdown of microvascular perfusion upon hepatic cryothermia is critically dependent on local tissue temperature

Since microvascular dysfunction with complete circulatory arrest and, thus, prolongation of tissue ischaemia is considered a potential mechanism for cell necrosis following hepatic cryosurgery, we determined the temperature necessary for induction of complete nutritive perfusion failure in cryothermia-treated rat livers. After localization of the cryoprobe with seven thermocouples and application of a single or double freeze-thaw cycle, in vivo fluorescence microscopy of the cryoinjured left lobe was performed over a 2-h period using a computer-controlled stepping motor, which guaranteed analysis of the identical liver tissue segments with exact allocation of the thermocouples and thus determination of tissue temperature. Cryothermia resulted in a central non-perfused part of injury, surrounded by a heterogeneously perfused peripheral zone. The non-perfused area after single and double freezing continuously increased over the first 90-min period due to a successive shutdown of perfusion within the peripheral border zone. Analysis of the thermocouples' temperature at the end of freezing revealed the 0 degrees C-front at 11.7 mm (single freeze-thaw cycle) and 12.1 mm (double freeze-thaw cycle) distant from the centre of the cryoprobe, which exactly corresponds with the initial (30 min) expansion of the area with nutritive perfusion failure. The increased non-perfused tissue area at 2 h conformed a critical border temperature between 8.29 +/- 1.63 degrees C and 9.07 +/- 0.24 degrees C. From these findings, we conclude that freezing of liver tissue to temperatures of at least < 0 degrees C causes complete/irreversible perfusion failure, which consequently will result in cell death and tissue necrosis, and may thus be supposed as a prerequisite for the safe and successful application of cryosurgery in hepatic tumour ablation.     

Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon carcinoma. Preliminary results

Cryosurgery, the in situ freezing of cancer, has been proposed in the past as a possible treatment for unresectable hepatic tumors. Its advantage lies in the fact that it is a very focal treatment sacrificing less normal tissue than surgical resection, allowing treatment of multiple lobes. Because cryosurgery does not affect large vessels, tumors in difficult locations, such as adjacent to the inferior vena cava (IVC), can be treated. With the use of intraoperative ultrasound to place the cryoprobes and monitor the freezing process, 18 patients with unresectable metastatic colon carcinoma confined to the liver were treated. Of the 18 patients treated, 4 (22%) are in complete remission as determined by computed tomography (CT) scans and carcinoembryonic antigen (CEA) levels, with a mean follow-up of 28.8 months. Four patients (22%) were not adequately treated at the time of cryosurgery. The number of lesions frozen in each patient ranged from 1 to 12, with a mean of 6 lesions. Fourteen patients had bilobar disease; three patients had previous right lobectomies with recurrences in their remaining left lobes prior to cryosurgery, and one patient had unilobar disease. Mean survival of the 14 cases with recurrence was 21.4 months, with 2 of the 14 still alive. Ultrasound-guided hepatic cryosurgery appears to be an effective treatment for metastatic colon carcinoma to the liver that is unresectable (including patients with bilobar and multiple lesions). These preliminary results indicate that the procedure warrants further study.     

Cryosurgery: ultrastructural changes in pancreas tissue after low temperature exposure

A number of theoretical and experimental studies, both in vitro and in vivo, have been performed to explain the action of low temperatures on tissue. It is now evident that the thermal parameters used in the past for freezing during cryosurgery were not precise; this may have resulted in the failure of treatment. For the first time, this report describes the early ultrastructural features of pancreatic parenchyma after low temperature exposure, i.e., cryosurgery, in vivo. We demonstrate the effect of freeze-thawing processes using temperatures of various intensities. The cryosurgical response of pancreas parenchyma, i.e., ultrastructural cellular changes in pancreas tissue, was investigated. The electronic microscopic analysis showed that, after local cryodestruction at temperatures of -80 degrees C and -180 degrees C, similar processes occurred within the pancreas tissue in the early postcryosurgical phase -- immediately and up to 24 hours after low temperature exposure on tissue. The exocrine pancreatic cells in the center of the cryozone changed upon thawing. Ultrastructural changes in the exocrine pancreatic cells, where the first signs of dystrophic processes had been noticed, were increased. These ultrastructural changes in the pancreatic cells provide a platform to better understand the mechanisms of damage and the pathogenesis of frostbite after cryosurgery. The properties of the pancreas parenchyma response after low temperature exposure provide important insights into the mechanisms of damage and the cryogenic lesion immediately after thawing in cryosurgery. Our new insights prove on the cell level that suddenly and progressively damaged pancreatic cells in the postcryosurgical zone lead to aseptic cryonecrosis and then to aseptic cryoapoptosis of vital normal tissue. The vascular capillary changes and circulatory stagnation demonstrate the anti-angiogenesis mechanism, which, together with cryoaponecrosis and cryoapoptosis, are some of the main mechanisms of biological tissue injury following the low temperature exposure.     

Experimental study on pulmonary cryoablation in a porcine model of normal lungs

Objective of this study is to analyze the range of necrosis after using different freezing times and freeze-thaw cycles during percutaneous cryosurgery, in order to create a suggestion for optimizing the technique for lung cryoablation. Six healthy pigs were given a CT scan and histological investigation after percutaneous cryosurgery on both lungs. Three cryoprobes were inserted into both the left and right lungs of each pig, respectively. Cryoablation was performed with two cycles of an active 10-minute freezing using argon in the left lung, each freeze followed by an active 5-minute thaw using helium. In contrast to the left lung cryoablation, the right lungs underwent 3 cycles of freeze/thaw, the first and second cycles consisted of an active 5-minute freezing followed by an active 5-minute thaw, and the third cycle of 10-minute freezing and an active 5-minute thaw. The CT imaging change of an ice ball was continuously observed. The lung tissues were taken 4 hours after cryosurgery on day 3 and on day 7, respectively, for pathological observation. One pig presented acute symptoms including bradycardia and hypothermia 30 minutes after cryosurgery, and died 4 hours after the freezing, and the other 5 pigs experienced a weak condition for 4-6 hours and then exhibited relatively normal behavior and regularly took food. The freezing area (ice ball) on CT imaging during the cryoablation grew gradually in relation to the increase over time, and along with the increase in the number of cycles. The size of the cryolesion on the lung samples became larger than the ice ball during cryosurgery, regardless of whether 2 or 3 freeze-thaw cycles were performed. The area of necrosis histologically gradually increased for the time being. Percutaneous cryosurgery on the lung can achieve complete ablation of targeted tissue. Three freeze-thaw cycles are recommended, and the range of cryoablation may not be mandatory "1 cm safe border" during cryosurgery in order to avoid harming the organ and tissue which is close to the cancer. Correct use of the technique is especially important to treat the lung neoplasms, especially the malignant tumors, which are close to the heart and large vessels.     

Progress toward optimization of cryosurgery

Cryosurgery for diverse neoplastic and non-neoplastic diseases has expanded in applicability in recent years, especially since intraoperative ultrasound became available as a method of monitoring the process of tissue freezing. However, persistence of disease after presumably adequate cryosurgical treatment has disclosed deficiencies in the technique, perhaps due to faulty application of the freeze-thaw cycles or due to shortcomings in the imaging method. Clearly cryosurgical technique is less than optimal. The optimal dosimetry for tissue freezing, the recent improvements in imaging techniques, and the need for adjunctive therapy are defined in this review, which assesses the progress toward improving the efficacy of cryosurgery.     

Cryosurgery for tumors - a clinical overview

Cryosurgery, a method of treating disease by the production of freezing temperatures in the tissue, is a useful technique for the treatment of tumors. When the modern era of cryosurgery began in the mid 1960's, the technique was used only for tumors easily accessible by direct observation or via endoscopy, such as those of the skin, oral cavity, and prostate gland. In general, the technique had limited usefulness in the next two decades. However, with the advent of intraoperative ultrasound as a method of monitoring the process of freezing and with the development of more effective cryosurgical apparatus, the cryosurgical treatment of tumors of the viscera and other deep tissues became practical in the 1990's. This review assesses the present day status of cryosurgery in the management of diverse tumors.     

Intra-luminal thermometry: Is tissue type assignment a necessity for thermal analysis?

Introduction: Tissue type assignment, i.e. differentiation tumour from normal tissue, is a normal procedure for interstitial thermometry. In our department, thermometry in patients with a tumour in the lower pelvis is usually restricted to the intra-luminal tracks. It is unknown whether discrimination between normal and tumour tissue is relevant for deep regional hyperthermia thermal dosimetry using only intra-luminal tumour contact and tumour adjacent thermometry. This study has analysed the acquired temperature data in order to answer this question.

Patients and methods: Seventy-five patients with locally advanced cervical carcinoma were selected randomly. Patients were treated with a two or three modality combination, i.e. radiotherapy?+hyperthermia or radiotherapy?+?hyperthermia?+?chemotherapy from October 1997 to September 2003. The first 100 hyperthermia treatments fulfilling the only selection criterion: no displacement of the thermometry catheter along the insertion length during the treatment, were included in the study, resulting in 43 patients with one-to-five treatments/patient (median 2). Using RHyThM (Rotterdam Hyperthermia Thermal Modulator), for each single treatment tissue type, was defined on the basis of information given by a CT scan in radiotherapy position. A step change in the slope of the profile of the first temperature map was identified to verify the insertion length of the catheter.

Results: The average T₅₀ (median temperature) in bladder tumour indicative, vagina tumour contact and rectum tumour indicative was 40.9?±?0.9°C, 39.7?±?0.9°C and 40.6?±?0.8°C, respectively. The average normal tissue T₅₀ in bladder, vagina and rectum was 40.8?±?0.9°C, 40.1?±?0.9°C and 40.7?±?0.8°C, respectively. The differences between bladder tumour indicative T₅₀ and bladder normal tissue T₅₀ and also between vagina tumour contact T₅₀ and vagina normal tissue T₅₀ were significant (?p?=?0.0001). No statistical difference was found between rectum tumour indicative T₅₀ and rectum normal tissue T₅₀.

Conclusion: At present the cause of the temperature difference is not known. However, as the difference between tumour (indicative/contact) and normal tissue is very small and considering also the inaccuracy in the tissue type assignment it can be stated that this study does not provide sufficient evidence to conclude that the statistical difference has clinical relevance. Therefore, it was concluded that at this time there is no need to differentiate between normal and tumour tissue in intra-luminal thermometry.     

Distributed network imaging and electrical impedance tomography of minimally invasive surgery

Minimally invasive surgery has become highly dependent on imaging. For instance, the effectiveness of cryosurgery in treating cancer is dependent on knowledge of freezing extent, and relies on real-time imaging techniques for monitoring. However, medical imaging is often very expensive and therefore not available to most of the world population. Here we propose the concept of distributed network imaging (DNI) which could make medical imaging and minimally invasive surgery available to all who need these advanced medical modalities. We demonstrate the concept through electrical impedance tomography (EIT) of cryosurgery. The central idea is to develop an inexpensive measurend (data collection hardware) at a remote site and then to connect the measurend apparatus to an advanced image reconstruction server, which can serve a large number of distributed measurends at remote sites, using existing communication conduits (Ethernet, telephone, satellite, etc.). These conduits transfer the raw data from the measurend to the server and the reconstructed image from the server to the measurend. Electrical impedance tomography (EIT) is an imaging modality which utilizes tissue impedance variation to construct an image. The EIT measurend which consists of electrodes, a power supply, and means to measure voltage is inexpensive, and therefore suitable for DNI. EIT is also very well-suited to imaging cryosurgery since frozen tissue impedance is much higher than that of unfrozen tissue. In this study, we first develop numerical models to illustrate the theoretical ability of EIT to image cryosurgery. We begin with a simplified two dimensional model, and then extend the study to the more appropriate three dimensional model. Our simulated finite element phantoms and pixel-based Newton-Raphson reconstruction algorithms were able to produce easily identifiable images of frozen regions within tissue. Then, we demonstrate the feasibility of the DNI concept though a case study using EIT to image an in vitro liver cryosurgery procedure through a modem. We find that the acquired raw data packets are less than 5KB per image and the images, using compression, do not exceed 50KB per image.     

Evaluation and selection of anatomic sites for magnetic resonance imaging-guided mild hyperthermia therapy: a healthy volunteer study

Purpose: Since mild hyperthermia therapy (MHT) requires maintaining the temperature within a narrow window (e.g. 40–43?°C) for an extended duration (up to 1?h), accurate and precise temperature measurements are essential for ensuring safe and effective treatment. This study evaluated the precision and accuracy of MR thermometry in healthy volunteers at different anatomical sites for long scan times.

Methods: A proton resonance frequency shift method was used for MR thermometry. Eight volunteers were subjected to a 5-min scanning protocol, targeting chest wall, bladder wall, and leg muscles. Six volunteers were subjected to a 30-min scanning protocol and three volunteers were subjected to a 60-min scanning protocol, both targeting the leg muscles. The precision and accuracy of the MR thermometry were quantified. Both the mean precision and accuracy <1?°C were used as criteria for acceptable thermometry.

Results: Drift-corrected MR thermometry measurements based on 5-min scans of the chest wall, bladder wall, and leg muscles had accuracies of 1.41?±?0.65, 1.86?±?1.20, and 0.34?±?0.44?°C, and precisions of 2.30?±?1.21, 1.64?±?0.56, and 0.48?±?0.05?°C, respectively. Measurements based on 30-min scans of the leg muscles had accuracy and precision of 0.56?±?0.05?°C and 0.42?±?0.50?°C, respectively, while the 60-min scans had accuracy and precision of 0.49?±?0.03?°C and 0.56?±?0.05?°C, respectively.

Conclusions: Respiration, cardiac, and digestive-related motion pose challenges to MR thermometry of the chest wall and bladder wall. The leg muscles had satisfactory temperature accuracy and precision per the chosen criteria. These results indicate that extremity locations may be preferable targets for MR-guided MHT using the existing MR thermometry technique.     

Effect of cryosurgery on liver blood flow.

The effect of cryosurgery on normal liver and liver tumour was investigated using 60 adult male rats. Animals were divided into four groups Group A implanted tumour/cryosurgery (n = 19), Group B normal liver/cryosurgery (n = 17), Group C normal liver/sham cryosurgery (n = 10) and Group D implanted tumour/sham cryosurgery (n = 14). At laparotomy animals were injected into the left lateral lobe of the liver with 10(5) HSN fibrosarcoma cells or vehicle. Two weeks after implantation red cell flux was recorded in all animals, the appropriate groups treated with cryosurgery and after thawing red cell flux was monitored over the tumour and at the edge of the cryolesion and over the corresponding normal area in controls. In certain animals red cell flux was measured at hourly intervals for 8 h, and in further groups at 24 h and at 2 weeks after cryosurgery. Results demonstrated that cryosurgery significantly reduced (P < 0.01) red cell flux in both normal and tumour liver, immediately after treatment. Red cell flux remained significantly reduced (P < 0.005) at 8 h after treatment but by 24 h had returned to preoperative levels which was maintained at 2 weeks. The results suggest that microcirculatory shutdown may be a contributing factor to the tumour necrosis occurring after cryosurgery.     

Microwave ablation of the liver abutting the stomach: Insulating effect of a chitosan-based thermosensitive hydrogel

Purpose: Collateral thermal injury can occur as a serious complication of microwave ablation. This study aimed to assess the insulating effect of a thermosensitive, chitosan-based hydrogel during the percutaneous microwave ablation of liver tissue abutting the stomach. Materials and methods: Thermometry needles (R1–R4) were positioned at 5-mm intervals from a thermal source to measure in vitro the temperature differences due to the hydrogel (R1 closest to the thermal source). Subsequently, two groups of eight rabbits each were injected with 10?mL of hydrogel solution or 410?±?95?mL of 5% saline between the liver and stomach wall. A control group of eight rabbits received no ablation protection measures. The livers were ablated with 40?W for 300?s in 24 ablation zones. The severity of thermal injury to the stomach wall was assessed histologically. Results: In vitro, the mean maximum temperature difference between the R1 and R2 thermometry needles was 31.3°?±?0.1?°C. When R1 was over 60?°C, the mean temperatures at R2, R3, and R4 were 29.8°?±?0.1?°C, 18.6?±?0.3?°C, and 18.1°?±?0.1?°C, respectively. After ablation for 300?s, the maximum temperature at R2 was 48.7°?±?0.2?°C. None of the rabbits injected with gel showed any injury after ablation; however, the other two groups showed varying degrees of thermal injury. Conclusion: The in situ gel protected the adjacent stomach wall from injury during percutaneous microwave ablation of liver tissue. Although the present technique appears promising, further studies are necessary prior to clinical application.     

Effect of thermal variables on human breast cancer in cryosurgery

There is a growing interest in the use of cryosurgery to treat breast cancer, following recent breakthroughs in non-invasive imaging and in cryotechnology, as well as the recent success of cryosurgery in treating various types of cancer. However, since haphazard freezing does not guarantee tissue destruction, in order to apply this technique effectively it is essential to determine the thermal parameters that produce complete destruction of malignant tissue. This study seeks to quantitatively identify the relationship between thermal variables and the degree of freezing damage to human breast cancer cells. In order to do this, human breast cancer and normal cells were frozen with controlled thermal parameters using a directional solidification apparatus. Cell viability was determined after thawing using trypan blue, and correlated to the thermal variables used during freezing. Cellular damage is observed to increase with increasing cooling rates, due to the higher probability of intracellular ice formation. A double freeze thaw cycle significantly increases the extent of cell damage, and is sufficient to ensure complete cell destruction at final freezing temperatures of –40°c for a 25°c/min cooling rate, and –20°C for a 50°C/min cooling rate. The correlations between cell death and thermal parameters are qualitatively identical for all the cell types in this study, although there is some variation from one cell type to another in the overall susceptibility to freezing damage. The correlations established in this study can be used to design systematic and optimal breast cryosurgery protocols.     

Raman spectroscopy to distinguish grey matter,necrosis, and glioblastoma multiforme in frozen tissue sections

The need exists for a highly accurate, efficient and inexpensive tool to distinguish normal brain tissue from glioblastoma multiforme (GBM) and necrosis boundaries rapidly, in real-time, in the operating room. Raman spectroscopy provides a unique biochemical signature of a tissue type, with the potential to provide intraoperative identification of tumor and necrosis boundaries. We aimed to develop a database of Raman spectra from normal brain, GBM, and necrosis, and a methodology for distinguishing these pathologies. Raman spectroscopy was used to measure 95 regions from 40 frozen tissue sections using 785 nm excitation wavelength. Review of adjacent hematoxylin and eosin sections confirmed histology of each region. Three regions each of normal grey matter, necrosis, and GBM were selected as a training set. Ten regions were selected as a validation set, with a secondary validation set of tissue regions containing freeze artifact. Grey matter contained higher lipid (1061, 1081 cm^?1) content, whereas necrosis revealed increased protein and nucleic acid content (1003, 1206, 1239, 1255–1266, 1552 cm^?1). GBM fell between these two extremes. Discriminant function analysis showed 99.6, 97.8, and 77.5 % accuracy in distinguishing tissue types in the training, validation, and validation with freeze artifact datasets, respectively. Decreased classification in the freeze artifact group was due to tissue preparation damage. This study shows the potential of Raman spectroscopy to accurately identify normal brain, necrosis, and GBM as a tool to augment pathologic diagnosis. Future work will develop mapped images of diffuse glioma and neoplastic margins toward development of an intraoperative surgical tool.     

Cryosurgery in aggressive, benign, and low-grade malignant bone tumours

Cryosurgery is a method of treatment for various tumours that induces tissue necrosis with ablative intent. It is used in benign, aggressive, and low-grade malignant bone tumours such as chondrosarcoma grade 1. We describe the history of the technique and the issues associated with cryobiology, as well as the indications, technique, complications, and results of cryosurgery. At the University Medical Centre Nijmegen, Netherlands, 302 tumours have been treated by use of cryosurgery with at least 2 years' follow-up. 96-100% of patients were cured-the response depended on tumour type. Comparison of functional results with data from studies shows that these results concur with other studies on cryosurgery, and are at least equal to results of marginal excision and mostly better than those of wide excisions of grade 1 chondrosarcomas. Thus from an oncological point of view, cryosurgery combined with intralesional excision is equal to marginal excision.     

CT fluoroscopy-guided closed-tip catheter placement before regional hyperthermia treatment of soft tissue sarcomas: 5-Year experience in 35 consecutive patients

Purpose: This study was designed to assess technical success and complications in patients with high-risk soft tissue sarcomas undergoing CT fluoroscopy-guided closed-tip catheter placement before treatment with combined chemotherapy and regional hyperthermia. Materials and methods: This retrospective study comprised all patients referred for insertion of closed-tip catheters for the introduction of thermometry probes before regional hyperthermia treatment at a single university centre from 2010 to 2015. Catheter placements were performed under local anaesthesia and intermittent CT fluoroscopy guidance. Technical success, complication rate, duration of catheter insertion and dose–length product (DLP) were analysed. Technical success was defined as intratumoural catheter placement suitable for subsequent thermometry. Results: A total of 35 procedures were performed on 35 patients (22 men, 13 women). In 34 out of 35 interventions catheters were inserted successfully; in one patient catheter placement was not feasible. No intra-interventional complications occurred. In six patients post-interventional complications were observed – two major (one abscess formation and one severe catheter dislocation) and four minor complications. Technical failure was observed in 11.4% of patients, especially catheter kinking. A total of 55 catheters were placed, with a mean number of 1.7?±?0.7 per patient. Mean total DLP was 723.2?±?355.9 mGy*cm. Conclusion: CT fluoroscopy-guided closed-tip catheter placement into high-risk soft tissue sarcomas was characterised by high technical success and relatively low complication rate. While major complications were rarely observed, catheter-kinking preventing successful thermometry represented the most frequent technical failure.     

Development of a tissue engineered human prostate tumor equivalent for use in the evaluation of cryoablative techniques

The study of the effectiveness of cryotherapy as a curative treatment for prostate cancer has often relied on the use of either in vitro cell culture monolayers or animal models. While the data gleaned from these studies have been valuable, each model has inherent limitations. In order to bridge the gap between in vitro studies and clinical applications, we developed a 3-dimensional, tissue engineered human prostate cancer model to simulate and assess the effects of cryotherapy and adjunctive treatments on cell viability and activation of cell death pathways throughout the thermally variable freeze zone. Human prostate cancer cells (PC3) were seeded into collagen based matrices and cryolesions were generated using an Oncura SeedNet Gold cryosurgical device with 17-gauge cryoprobes. Analyses revealed widespread necrosis diminishing towards the edge of the freeze zone, and a time-dependent wave of apoptosis starting as early as 1 hr post-thaw at low temperatures (< -40 degrees C) and moving toward the periphery (-20 degrees C) as recovery times reached 12 and 24 hr. Distal to the -10 degrees C isotherm, minimal cell death was apparent (< 20%) over controls. The adjunctive use of chemotherapeutic agents in conjunction with cryosurgery displayed a similar induction of cell death cascades, but with the zone of cryodestruction extending approximately 10 to 15 degrees C further into the freeze zone periphery. By providing an extracellular environment and a matrix to minimize innate variables, the tissue engineered model yielded a more in vivo-like, tumor-like environment supportive of a deeper understanding of the specific biological responses of cancer cells/tumors to cryotherapeutic intervention.     

Immunotherapeutic effect of tumor necrosis after cryosurgery, electrocoagulation, and ligation.

Tumor necrosis in situ by cryosurgery, electrocoagulation, or ligation generally induces or augments some increase in tumor-specific transplantation immunity (TSTI) as compared with excision. Excision of the tumor 24 hours after it has been rendered ischemic by either ligation or cryosurgery seems to produce TSTI that is significantly greater than that after excision of viable tumor without prior ligation or cryosurgery; the degree of this immunity is similar to that seen after the tumor is left in situ indefinitely after treatment. These data suggest that most of the immunization following tumor necrosis in situ occurs within 24 hours of treatment. The experimental findings support the clinical reports of putative immunologic potentiation after tumor necrosis in situ.     

Temperature field estimation using electrical impedance profiling methods. II. Experimental system description and phantom results

An electrical impedance tomography system has been developed and tested for the purpose of thermal imaging. Since impedance changes with temperature, images of impedance subtracted from normothermic baselines will provide a map of temperature data. A system was designed to be operational at 10–50 kHz and to utilize 16 external electrodes around the periphery of a tissue-equivalent phantom encompassing the region of interest. These electrodes serve as current sources for the 5 mA constant-current inputs and are also used for reading differential voltages. Hyperthermia treatments for cancer require that internal thermometry probes be inserted into the tumour volume. Linear arrays of electrodes with thermometry tracks for micro-dimension thermometry serve this function, as well as providing localized voltage measurements in the region of interest. The embedded temperature sensors provide a quality assurance and calibration standard for the linear arrays in reconstruction of impedance profiles. Results of transient heating experiments with conductive and ultrasound heating are shown where image reconstruction is performed using a finite element model. Temperature predictions in these studies were accurate to better than 1°C on average when using information from surface electrodes combined with internal linear arrays. Maximum temperature errors, however, was found to be > 5°C which suggests that further noise reduction during data acquisition and improvements in the reconstructions algorithms are needed.     

Improved cryosurgery by use of thermophysical and inflammatory adjuvants

In the present article, recent research efforts in our laboratory to improve cryosurgery by use of mechanistically derived adjuvants are reviewed. Our research has been focused on enhancing two freezing induced injury mechanisms - i) direct cell injury by use of thermophysical adjuvants, and ii) vascular injury by use of an inflammatory adjuvant. The thermophysical adjuvants are chemicals, usually salts, which can induce secondary crystallization, called eutectic solidification, in a cryolesion; thereby enhancing direct cell injury. The inflammatory adjuvant is a cytokine, tumor necrosis factor-alpha (TNF-alpha), which upregulates inflammation of microvasculature in tumors prior to freezing to promote vascular injury in the cryolesion. Even though the individual mechanism of injury enhancement within the cryolesion of each adjuvant requires further study, both adjuvants are envisioned to enlarge the complete killing zone so that the boundary of the cryolesion matches more closely with the edge of iceball. By bringing the edge of the cryolesion closer to the edge of iceball, the adjuvants hold promise for improvement of image guidance and outcome of cryosurgery.