The authors would like to thank Fred Lee, Jr., for his leadership with the clinical tumor ablation program; and Lisa Sampson, Jan Ketzler and Marci Center for their assistance with the research and clinical programs at the University of Wisconsin Madison.

1. Introduction/Case Presentation:
Example case: 50 yr old female with retroperitoneal leiomyosarcoma s/p primary resection. Had evidence of metastatic disease in the liver and lung that responded to chemotherapy. Had a single chemo-refractory hepatic lesion. Multidisciplinary discussion led to ablation as a possible treatment option, given the patient's young age, lack of comorbidities and paucity of alternative chemotherapeutic treatment options. The lesion was biopsied prior to treatment to confirm metastatic disease. Planning ultrasound demonstrated the lesion in the inferior and posterior aspect of the left hepatic lobe. Given its proximity to pancreas and bowel, the need for hydrodissection was reviewed with the patient at the time of consultation.
2. Patient selection
<ol>
	<li>One of the most important aspects of the procedure is to ensure that the patient is an appropriate candidate. This involves a multi-factorial assessment of both tumor and patient related factors including:
	<ol>
		<li>Tumor type, size, location and focality (Figure 1).</li>
		<li>Patient co-morbidities and overall health.</li>
	</ol>
	</li>
	<li>Patients should be discussed at a multi-disciplinary tumor board to determine the available treatment alternatives and choose the most efficacious and appropriate option.</li>
	<li>The most appropriate ablation modality is variable and dependent on many different factors as well, such as: location of the tumor within the organ, proximity of adjacent structures and the associated need for precision, experience of the operator, presence of underlying liver disease or bleeding diatheses. All of these factors and more must be considered to determine and choose the most appropriate ablation modality.</li>
	<li>Patient must be well informed regarding the procedure, expected risks, possibility of a complete treatment, and likely benefits. Therefore, we consult with every patient prior to the procedure, usually at the time of planning ultrasound as below.</li>
	<li>An overall assessment of the patient and procedure will determine the degree of sedation/anesthesia that is both safe and efficacious for the case.</li>
</ol>
3. Pre-treatment planning
<ol>
	<li>We perform a pre-ablation planning ultrasound to determine optimal patient positioning and approach.This also helps us determine whether or not other imaging modalities will be required for guidance and more notably, monitoring. It is often helpful to have CT available at the time of the ablation procedure for an overview evaluation of the target tumor, ablation zone, and adjacent structures.</li>
	<li>We also assess the need for adjuvant techniques at this time with an emphasis on safety and efficacy (Figure 2).</li>
	<li>During this time we determine the number of applicators likely to be needed to complete the treatment as well as their optimal placement.</li>
</ol>
4. Ablation procedure
<ol>
	<li>Patient preparation 
	<ol>
		<li>Factors to be considered/evaluated include: bowel preparation, pre/periprocedural antibiotics, renal/liver function, IV access, need for an arterial line for blood pressure monitoring, etc. These determinations are made on a case-by-case basis, but there are some general principles that can be followed and these will be discussed.</li>
		<li>General anesthesia is common, but ablation can often be performed with deep sedation, or even conscious sedation in some scenarios. Should be optimized to the individual patient.</li>
	</ol>
	</li>
	<li>Equipment setup (note that many aspects of the setup are vendor dependent)
	<ol>
		<li>Will show an example of RF, cryoablation, and MW ablation equipment and setup including ground pad placement, connections and testing. For this case, radiofrequency ablation will be utilized.</li>
	</ol>
	</li>
	<li>The ablation session
	<ol>
		<li>Guidance
		<ol>
			<li>Accurate and appropriate image-guided applicator placement is critical. Since this often includes multiple applicator placements, particularly for larger tumors, there are many factors to be considered and there are several 'tricks' that can be employed (Figure 3).</li>
		</ol>
		</li>
		<li>Adjuvant techniques
		<ol>
			<li>When performing percutaneous ablation, there are often adjacent structures that may be vulnerable to thermal damage. This has led to the development of hydrodissection and other displacement techniques, which allow physical, thermal, and electrical protection when applied appropriately. We will review the use of these techniques.</li>
			<li>We will also discuss other treatments/techniques that have been shown to, or theoretically can increase efficacy and safety of the treatment.</li>
		</ol>
		</li>
		<li>Monitoring
		<ol>
			<li>US, CT, and MRI all have specific strengths and weaknesses regarding their ability to effectively and precisely monitor the growing ablation zone. Because of this, we often utilize a multi-modality approach with both US and CT. This allows us to perform the procedure safely and effectively.</li>
			<li>Post-ablation assessment
			<ol>
				<li>The post-ablation assessment allows the determination of the efficacy of the therapy. When and how it is performed is variable and will depend on availability of resources, practicality of administering US or CT contrast, and uncertainty regarding the technical success of the treatment (Figure 4). At our institution, we perform a contrast-enhanced CT on suitable patients immediately after the ablation session has been concluded. This allows us assess for complete treatment (with immediate re-treatment while the patient is still under anesthesia if necessary), establish a post procedure baseline and identify any early complications. However, many institutions perform the initial assessment a month or more after the ablation session.</li>
			</ol>
			</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Follow-up
	<ol>
		<li>The interval and optimal modality for follow up evaluation varies depending on tumor type and patient factors. We will discuss various factors that influence this decision and describe an accepted protocol (Figure 5).</li>
	</ol>
	</li>
</ol>
5. Outcome:
The procedure was successfully carried out using a combination of ultrasound guidance with CT and ultrasound monitoring. A direct injection of 5% dextrose in water (D5W) was used for hydrodissection (Fig. 2). Ultrasound was utilized for guidance since the tumor was easily visualized by ultrasound imaging but not with non-contrast CT (as is often the case with liver lesions). In our experience, placing applicators with ultrasound guidance is faster than with CT. Ultrasound does not use ionizing radiation and is therefore safe for both the patient and personnel, and gives real-time feedback of the tumor and applicator location allowing accurate and consistent placement. Since accurate targeting is so critical to the success of the procedure, applicator guidance often determines whether or not the procedure will result in a complete treatment.
A combination of ultrasound and CT monitoring was utilized. Ultrasound allows real-time evaluation of the developing ablation while CT gives a global overview of applicator placement and proximity to adjacent structures, allowing superior assessment of the safety of the applicator placement and the likelihood of collateral damage to nearby structures. Thus, the combination of ultrasound and CT imaging results in a safer treatment.
D5W was utilized for hydrodissection for two main reasons: it acts as both a physical and electrical barrier to heating and, therefore, prevents damage to adjacent structures (i.e. pancreas and bowel), and intraperitoneal D5W has been shown to decrease post-procedural pain in patients undergoing liver tumor RF ablation. Thus, this intervention makes the procedure both safer and more comfortable for the patient. Follow up imaging shows that the procedure resulted in a complete treatment of the tumor with no associated complications and there was only minimal patient discomfort.
Liver tumor ablation is applied most commonly to hepatocellular carcinoma in cirrhotic patients, and in limited hepatic metastatic disease in patients with colon, breast or neuroendocrine tumors. Patients with other tumor types who have hepatic metastatic disease often have systemic disease and may not benefit from ablation; these patients are considered on a case-by-case basis. There is a relative paucity of long-term data in patients with metastatic sarcoma. The decision to proceed with ablation in this case was made given that all the other sites of disease in this young patient responded to chemotherapy with a single refractory hepatic lesion. Although this may control her disease in the short term and give her a reprieve from chemotherapy, with a tumor of this type, cure is unlikely. The patient later developed an additional liver lesion and two pulmonary nodules. All were treated with ablation. The patient is currently under continued surveillance.
6. Representative Results:
<img src="/files/ftp_upload/2596/2596fig1.jpg" alt="Figure 1" /> 
Figure 1. Pre-procedure CT demonstrating a low attenuation lesion in the left hepatic lobe (arrow) abutting the pancreas (P) with duodenum located just inferior and stomach just lateral.
<img src="/files/ftp_upload/2596/2596fig2.jpg" alt="Figure 2" /> 
Figure 2. Planning ultrasound with the patient in the supine position demonstrates a hypoechoic lesion (arrow) closely abutting the adjacent stomach (star) and pancreas (not visible). Therefore, a decision was made to place an NG tube for decompression during the procedure and use hydrodissection to protect the posterior structures.
<img src="/files/ftp_upload/2596/2596fig3.jpg" alt="Figure 3" /> 
Figure 3. Ultrasound image (left) demonstrates hydrodissection needle (arrow) extending through the left hepatic lobe in to the space between the liver and the pancreas with infusion of fluid. Abdominal CT (right) shows the needle in place (arrow) with accumulation of fluid between the liver and pancreas (P) with posterior displacement of the stomach (star).
<img src="/files/ftp_upload/2596/2596fig4.jpg" alt="Figure 4" /> 
Figure 4. Ultrasound image obtained during ablation demonstrates the gas cloud in the lateral left lobe (arrow). A thin layer of fluid can be observed between the liver and the pancreas (P).
<img src="/files/ftp_upload/2596/2596fig5.jpg" alt="Figure 5" /> 
Figure 5. Immediate post-procedure CT (left) demonstrates the ablation zone (arrow). The ablation zone has contracted on the one-month follow-up CT (right, arrow).

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J., Brace, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microwaves+create+larger+ablations+than+radiofrequency+when+controlled+for+power+in+ex+vivo+tissue.">Microwaves create larger ablations than radiofrequency when controlled for power in ex vivo tissue.</a> Med Phys. 37, 2967-2973 (2010).</li><li>Simon, C. J., Dupuy, D. E., Mayo-Smith, W. 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CLB: Shareholder and consultant for NeuWave Medical, Inc, which develops ablation technologies. Consultant for Triagenics, LLC.

Thermal tumor ablation is a safe and effective treatment for many abdominal tumors that are refractory to surgery, or have failed treatment with radiotherapy/chemotherapy. In addition, it is fast becoming an accepted first-line therapy for some patients. The benefits include: an exceptional safety profile, a more rapid convalescence than traditional surgical therapies, decreased costs, and excellent local control rates in appropriately triaged patients. Percutaneous procedures are generally feasible, especially when using techniques such as hydrodissection to improve safety and targeting of the tumor, thus limiting the morbidity even further. This technique has been utilized in practice for several decades now and many of the questions regarding long-term outcomes and oncological efficacy are being answered with encouraging results. Thermal ablation will certainly play an important and growing role in the management of oncology patients over the coming years.

Cool-Tip RF Ablation System from Covidien/Valleylab in Boulder, CO.

thermal ablation for the treatment of abdominal tumors

Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ablation procedure, a thin applicator is guided into the target tumor under imaging guidance. Energy is then applied to the tissue until temperatures rise to cytotoxic levels (50-60 &deg;C). Various energy sources are available to heat biological tissues, including radiofrequency (RF) electrical current, microwaves, laser light and ultrasonic waves. Of these, RF and microwave ablation are most commonly used worldwide.
During RF ablation, alternating electrical current (~500 kHz) produces resistive heating around the interstitial electrode. Skin surface electrodes (ground pads) are used to complete the electrical circuit. RF ablation has been in use for nearly 20 years, with good results for local tumor control, extended survival and low complication rates1,2. Recent studies suggest RF ablation may be a first-line treatment option for small hepatocellular carcinoma and renal-cell carcinoma3-5. However, RF heating is hampered by local blood flow and high electrical impedance tissues (eg, lung, bone, desiccated or charred tissue)6,7. Microwaves may alleviate some of these problems by producing faster, volumetric heating8-10. To create larger or conformal ablations, multiple microwave antennas can be used simultaneously while RF electrodes require sequential operation, which limits their efficiency. Early experiences with microwave systems suggest efficacy and safety similar to, or better than RF devices11-13.
Alternatively, cryoablation freezes the target tissues to lethal levels (-20 to -40 &deg;C). Percutaneous cryoablation has been shown to be effective against RCC and many metastatic tumors, particularly colorectal cancer, in the liver14-16. Cryoablation may also be associated with less post-procedure pain and faster recovery for some indications17. Cryoablation is often contraindicated for primary liver cancer due to underlying coagulopathy and associated bleeding risks frequently seen in cirrhotic patients. In addition, sudden release of tumor cellular contents when the frozen tissue thaws can lead to a potentially serious condition known as cryoshock 16.
Thermal tumor ablation can be performed at open surgery, laparoscopy or using a percutaneous approach. When performed percutaneously, the ablation procedure relies on imaging for diagnosis, planning, applicator guidance, treatment monitoring and follow-up. Ultrasound is the most popular modality for guidance and treatment monitoring worldwide, but computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used as well. Contrast-enhanced CT or MRI are typically employed for diagnosis and follow-up imaging.

Watch this Scientific Journal Video about Thermal Ablation for the Treatment of Abdominal Tumors at JoVE.com

Thermal Ablation for the Treatment of Abdominal Tumors

A thermal tumor ablation procedure is described. The entire procedure is detailed, including pretreatment planning and imaging studies, anesthesia, adjuvant techniques to facilitate a percutaneous approach, imaging guidance of the ablation device to the tumor, thermal treatment, post-treatment care and follow-up.

Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ...

thermal-ablation-for-the-treatment-of-abdominal-tumors

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34.2K Views.  University of Wisconsin-Madison. Тепловые процедуры аблации опухоли описаны. Вся процедура подробно, включая планирование предварительной обработки и визуализации исследований, анестезия, адъювантной методы для облегчения подхода чрескожная, работы с изображениями руководством абляции у...

Video: Thermal Ablation for the Treatment of Abdominal Tumors

The C-seal: A Biofragmentable Drain Protecting the Stapled Colorectal Anastomosis from Leakage

Colorectal anastomotic leakage (AL) is a serious complication in colorectal surgery leading to high morbidity and mortality rates1. The incidence of AL varies between 2.5 and 20% 2-5. Over the years, many strategies aimed at lowering the incidence of anastomotic leakage have been examined6, 7. 
The cause of AL is probably multifactorial. Etiological factors include insufficient arterial blood supply, tension on the anastomosis, hematoma and/or infection at the anastomotic site, and co-morbid factors of the patient as diabetes and atherosclerosis8. Furthermore, some anastomoses may be insufficient from the start due to technical failure.
Currently a new device is developed in our institute aimed at protecting the colorectal anastomosis and lowering the incidence of AL. This so called C-seal is a biofragmentable drain, which is stapled to the anastomosis with the circular stapler. It covers the luminal side of the colorectal anastomosis thereby preventing leakage.
The C-seal is a thin-walled tube-like drain, with an approximate diameter of 4 cm and an approximate length of 25 cm (figure 1). It is a tubular device composed of biodegradable polyurethane. Two flaps with adhesive tape are found at one end of the tube. These flaps are used to attach the C-seal to the anvil of the circular stapler, so that after the anastomosis is made the C-seal can be pulled through the anus. The C-seal remains in situ for at least 10 days. Thereafter it will lose strength and will degrade to be secreted from the body together with the gastrointestinal natural contents.
The C-seal does not prevent the formation of dehiscences. However, it prevents extravasation of faeces into the peritoneal cavity. This means that a gap at the anastomotic site does not lead to leakage.
Currently, a phase II study testing the C-seal in 35 patients undergoing (colo-)rectal resection with stapled anastomosis is recruiting. The C-seal can be used in both open procedures as well as laparoscopic procedures. The C-seal is only applied in stapled anastomoses within 15cm from the anal verge. In the video, application of the C-seal is shown in an open extended sigmoid resection in a patient suffering from diverticular disease with a stenotic colon.

The C-seal is a biofragmentable drain protecting the stapled colorectal anastomosis. In this video, details of the manufacturing, deployment and use are shown.

Colorectal anastomotic leakage (AL) is a serious complication in colorectal surgery leading to high morbidity and mortality rates1. The incidence of AL ...

Establishment and Propagation of Human Retinoblastoma Tumors in Immune Deficient Mice

Culturing retinoblastoma tumor cells in defined stem cell media gives rise to primary tumorspheres that can be grown and maintained for only a limited time. These cultured tumorspheres may exhibit markedly different cellular phenotypes when compared to the original tumors. Demonstration that cultured cells have the capability of forming new tumors is important to ensure that cultured cells model the biology of the original tumor. 
Here we present a protocol for propagating human retinoblastoma tumors in vivo using Rag2-/- immune deficient mice. Cultured human retinoblastoma tumorspheres of low passage or cells obtained from freshly harvested human retinoblastoma tumors injected directly into the vitreous cavity of murine eyes form tumors within 2-4 weeks. These tumors can be harvested and either further passaged into murine eyes in vivo or grown as tumorspheres in vitro. Propagation has been successfully carried out for at least three passages thus establishing a continuing source of human retinoblastoma tissue for further experimentation. 
Wesley S. Bond and Lalita Wadhwa are co-first authors.

A method is described to propagate human retinoblastoma tumors in mice. Tumor cells are directly injected into the eyes of immune deficient mice. Secondary tumors have been successfully established using both cells directly harvested from human tumors and cultured tumorspheres.

Culturing retinoblastoma tumor cells in defined stem cell media gives rise to primary tumorspheres that can be grown and maintained for only a limited ...

Quantitative Visualization and Detection of Skin Cancer Using Dynamic Thermal Imaging

In 2010 approximately 68,720 melanomas will be diagnosed in the US alone, with around 8,650 resulting in death 1. To date, the only effective treatment for melanoma remains surgical excision, therefore, the key to extended survival is early detection 2,3. Considering the large numbers of patients diagnosed every year and the limitations in accessing specialized care quickly, the development of objective in vivo diagnostic instruments to aid the diagnosis is essential. New techniques to detect skin cancer, especially non-invasive diagnostic tools, are being explored in numerous laboratories. Along with the surgical methods, techniques such as digital photography, dermoscopy, multispectral imaging systems (MelaFind), laser-based systems (confocal scanning laser microscopy, laser doppler perfusion imaging, optical coherence tomography), ultrasound, magnetic resonance imaging, are being tested. Each technique offers unique advantages and disadvantages, many of which pose a compromise between effectiveness and accuracy versus ease of use and cost considerations. Details about these techniques and comparisons are available in the literature 4.
Infrared (IR) imaging was shown to be a useful method to diagnose the signs of certain diseases by measuring the local skin temperature. There is a large body of evidence showing that disease or deviation from normal functioning are accompanied by changes of the temperature of the body, which again affect the temperature of the skin 5,6. Accurate data about the temperature of the human body and skin can provide a wealth of information on the processes responsible for heat generation and thermoregulation, in particular the deviation from normal conditions, often caused by disease. However, IR imaging has not been widely recognized in medicine due to the premature use of the technology 7,8 several decades ago, when temperature measurement accuracy and the spatial resolution were inadequate and sophisticated image processing tools were unavailable. This situation changed dramatically in the late 1990s-2000s. Advances in IR instrumentation, implementation of digital image processing algorithms and dynamic IR imaging, which enables scientists to analyze not only the spatial, but also the temporal thermal behavior of the skin 9, allowed breakthroughs in the field.
In our research, we explore the feasibility of IR imaging, combined with theoretical and experimental studies, as a cost effective, non-invasive, in vivo optical measurement technique for tumor detection, with emphasis on the screening and early detection of melanoma 10-13. In this study, we show data obtained in a patient study in which patients that possess a pigmented lesion with a clinical indication for biopsy are selected for imaging. We compared the difference in thermal responses between healthy and malignant tissue and compared our data with biopsy results. We concluded that the increased metabolic activity of the melanoma lesion can be detected by dynamic infrared imaging.

We demonstrated that malignant pigmented lesions with increased metabolic activity generate quantifiable amounts of heat and the measurement of the transient thermal response of the skin to a cooling excitation allows quantitative identification of melanoma and other skin cancers (vs. non-proliferative nevi) at an early stage of the disease.

In 2010 approximately 68,720 melanomas will be diagnosed in the US alone, with around 8,650 resulting in death 1. To date, the only effective treatment ...

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6.
Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8.
The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16.
Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformit&eacute; Europ&eacute;enne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19.
Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems.
The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Catheter ablation is combined with placement of the WATCHMAN Left Atrial Appendage Closure Device to prevent ischemic stroke in a patient with non-valvular atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and ...

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy.

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

Established cancer cell lines and xenografts have been the mainstay of cancer research for the past several decades. However, recent evidence suggests that therapeutic response is greatly influenced by the tumor cell microenvironment. Therefore, we have developed an ex vivo analysis of primary tumor specimens for drug development purposes.

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both ...

Creation of Abdominal Adhesions in Mice

Abdominal adhesions consist of fibrotic tissue that forms in the peritoneal space in response to an inflammatory insult, typically surgery or intraabdominal infection. The precise mechanisms underlying adhesion formation are poorly understood. Many compounds and physical barriers have been tested for their ability to prevent adhesions after surgery with varying levels of success. The mouse and rat are important models for the study of abdominal adhesions. Several different techniques for the creation of adhesions in the mouse and rat exist in the literature. Here we describe a protocol utilizing abrasion of the cecum with sandpaper and sutures placed in the right abdominal sidewall. The mouse is anesthetized and the abdomen is prepped. A midline laparotomy is created and the cecum is identified. Sandpaper is used to gently abrade the surface of the cecum. Next, several figure-of-eight sutures are placed into the peritoneum of the right abdominal sidewall. The abdominal cavity is irrigated, a small amount of starch is applied, and the incision is closed. We have found that this technique produces the most consistent adhesions with the lowest mortality rate.

Abdominal adhesions that form after surgery are a major cause of pain, infertility, and hospitalization and reoperation for small bowel obstruction. Our surgical procedure for creating abdominal adhesions in mice is a reliable tool to study the mechanisms underlying the formation of adhesions.

Abdominal adhesions consist of fibrotic tissue that forms in the peritoneal space in response to an inflammatory insult, typically surgery or ...

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area.

This protocol describes a procedure to track the evolution of mesial network measures in temporal lobe epilepsy (TLE) patients. It is based on the combination of intracranial recordings with a novel numerical technique for data analysis. Specifically, we present a protocol for network analyses of foramen ovale recordings.

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

Porcine Model of Infrarenal Abdominal Aortic Aneurysm

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called &#946;-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease.
Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone.
Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% &#177; 47.4% at day 7, 105.4% &#177; 58.1% at day 14, and 113.5% &#177; 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p &#60; 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease.
Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.&#160;

This novel model creates robust infrarenal abdominal aortic aneurysms in swine using a combination of balloon angioplasty, elastase/collagenase perfusion, topical elastase application, and oral compound &#946;-aminopropionitrile administration, which interferes with collagen cross-linking.

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal ...

Multicolor 3D Printing of Complex Intracranial Tumors in Neurosurgery

Three-dimensional (3D) printing technologies offer the possibility of visualizing patient-specific pathologies in a physical model of correct dimensions. The model can be used for planning and simulating critical steps of a surgical approach. Therefore, it is important that anatomical structures such as blood vessels inside a tumor can be printed to be colored not only on their surface, but throughout their whole volume. During simulation this allows for the removal of certain parts (e.g., with a high-speed drill) and revealing internally located structures of a different color. Thus, diagnostic information from various imaging modalities (e.g., CT, MRI) can be combined in a single compact and tangible object.
However, preparation and printing of such a fully colored anatomical model remains a difficult task. Therefore, a step-by-step guide is provided, demonstrating the fusion of different cross-sectional imaging data sets, segmentation of anatomical structures, and creation of a virtual model. In a second step the virtual model is printed with volumetrically colored anatomical structures using a plaster-based color 3D binder jetting technique. This method allows highly accurate reproduction of patient-specific anatomy as shown in a series of 3D-printed petrous apex chondrosarcomas. Furthermore, the models created can be cut and drilled, revealing internal structures that allow for simulation of surgical procedures.

The protocol describes the fabrication of fully colored three-dimensional prints of patient-specific, anatomical skull models to be used for surgical simulation. The crucial steps of combining different imaging modalities, image segmentation, three-dimensional model extraction, and production of the prints are explained.

Three-dimensional (3D) printing technologies offer the possibility of visualizing patient-specific pathologies in a physical model of correct dimensions. ...

Cooling or Warming the Esophagus to Reduce Esophageal Injury During Left Atrial Ablation in the Treatment of Atrial Fibrillation

Ablation of the left atrium using either radiofrequency (RF) or cryothermal energy is an effective treatment for atrial fibrillation (AF) and is the most frequent type of cardiac ablation procedure performed. Although generally safe, collateral injury to surrounding structures, particularly the esophagus, remains a concern. Cooling or warming the esophagus to counteract the heat from RF ablation, or the cold from cryoablation, is a method that is used to reduce thermal esophageal injury, and there are increasing data to support this approach. This protocol describes the use of a commercially available esophageal temperature management device to cool or warm the esophagus to reduce esophageal injury during left atrial ablation. The temperature management device is powered by standard water-blanket heat exchangers, and is shaped like a standard orogastric tube placed for gastric suctioning and decompression. Water circulates through the device in a closed-loop circuit, transferring heat across the silicone walls of the device, through the esophageal wall. Placement of the device is analogous to the placement of a typical orogastric tube, and temperature is adjusted via the external heat-exchanger console.

The goal of this protocol is to describe the use of esophageal temperature modulation to counteract esophageal thermal injury from left atrial ablation for the treatment of atrial fibrillation.

Ablation of the left atrium using either radiofrequency (RF) or cryothermal energy is an effective treatment for atrial fibrillation (AF) and is the most ...