Anthony Kam

Localization of Insulinomas to Regions of the Pancreas by Intraarterial Calcium Stimulation: The NIH Experience

CONTEXT Selective intraarterial calcium injection of the major pancreatic arteries with hepatic venous sampling [calcium arterial stimulation (CaStim)] has been used as a localizing tool for insulinomas at the National Institutes of Health (NIH) since 1989. The accuracy of this technique for localizing insulinomas was reported for all cases until 1996. OBJECTIVES The aim of the study was to assess the accuracy and track record of the CaStim over time and in the context of evolving technology and to review issues related to result interpretation and procedure complications. CaStim was the only invasive preoperative localization modality used at our center. Endoscopic ultrasound (US) was not studied. DESIGN AND SETTING We conducted a retrospective case review at a referral center. PATIENTS Twenty-nine women and 16 men (mean age, 47 yr; range, 13-78) were diagnosed with an insulinoma from 1996-2008. INTERVENTION A supervised fast was conducted to confirm the diagnosis of insulinoma. US, computed tomography (CT), magnetic resonance imaging (MRI), and CaStim were used as preoperative localization studies. Localization predicted by each preoperative test was compared to surgical localization for accuracy. MAIN OUTCOME We measured the accuracy of US, CT, MRI, and CaStim for localization of insulinomas preoperatively. RESULTS All 45 patients had surgically proven insulinomas. Thirty-eight of 45 (84%) localized to the correct anatomical region by CaStim. In five of 45 (11%) patients, the CaStim was falsely negative. Two of 45 (4%) had false-positive localizations. CONCLUSION The CaStim has remained vastly superior to abdominal US, CT, or MRI over time as a preoperative localizing tool for insulinomas. The utility of the CaStim for this purpose and in this setting is thus validated.

Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies

PURPOSE We conducted a phase I study of a 30-minute hepatic artery infusion of melphalan via a percutaneously placed catheter and hepatic venous hemofiltration using a double balloon catheter positioned in the retrohepatic inferior vena cava to shunt hepatic venous effluent through an activated charcoal filter and then to the systemic circulation. The purpose of the study was to demonstrate feasibility in an initial cohort and subsequently determine the maximum tolerated dose and dose-limiting toxicity of melphalan. PATIENTS AND METHODS The initial cohort (n = 12) was treated with 2.0 mg/kg of melphalan before dose escalation to 3.5 mg/kg (n = 16). Total hepatic drug delivery, systemic levels, and percent filter efficiency were determined. Patients were assessed for hepatic and systemic toxicity and response. RESULTS A total of 74 treatments were administered to 28 patients. Twelve patients with primary and metastatic hepatic tumors received 30 treatments (mean, 2.5 per patient) at an initial melphalan dose of 2.0 mg/kg. At 3.5 mg/kg, a dose-limiting toxicity (neutropenia and/or thrombocytopenia) was observed in two of six patients. Transient grade 3/4 hepatic and systemic toxicity was seen after 19% and 66% of treatments, respectively. An overall radiographic response rate of 30% was observed in treated patients. In the 10 patients with ocular melanoma, a 50% overall response rate was observed, including two complete responses. CONCLUSION Delivery of melphalan via this system is feasible, with limited, manageable toxicity and evidence of substantial antitumor activity; 3 mg/kg is the maximum safe tolerated dose of melphalan administered via this technique.

Radiofrequency Ablation of Cancer

Radiofrequency ablation (RFA) has been used for over 18 years for treatment of nerve-related chronic pain and cardiac arrhythmias. In the last 10 years, technical developments have increased ablation volumes in a controllable, versatile, and relatively inexpensive manner. The host of clinical applications for RFA have similarly expanded. Current RFA equipment, techniques, applications, results, complications, and research avenues for local tumor ablation are summarized.

Thermal Protection during Percutaneous Thermal Ablation of Renal Cell Carcinoma

Thermal injury to collateral structures is a known complication of thermal ablation of tumors. The authors present the use of CO(2) dissection and inserted balloons to protect the bowel during percutaneous radiofrequency (RF) ablation and cryotherapy of primary and locally recurrent renal cell carcinoma. These techniques offer the potential to increase the number of tumors that can be treated with RF ablation or cryotherapy from a percutaneous approach.

Thermal protection with 5% dextrose solution blanket during radiofrequency ablation.

A serious complication for any thermal radiofrequency ablation is thermal injury to adjacent structures, particularly the bowel, which can result in additional major surgery or death. Several methods using air, gas, fluid, or thermometry to protect adjacent structures from thermal injury have been reported. In the cases presented in this report, 5% dextrose water (D5W) was instilled to prevent injury to the bowel and diaphragm during radiofrequency ablation. Creating an Insulating envelope or moving organs with D5W might reduce risk for complications such as bowel perforation.

CT and Ultrasound Guided Stereotactic High Intensity Focused Ultrasound (HIFU)

To demonstrate the feasibility of CT and B‐mode Ultrasound (US) targeted HIFU, a prototype coaxial focused ultrasound transducer was registered and integrated to a CT scanner. CT and diagnostic ultrasound were used for HIFU targeting and monitoring, with the goals of both thermal ablation and non‐thermal enhanced drug delivery. A 1 megahertz coaxial ultrasound transducer was custom fabricated and attached to a passive position‐sensing arm and an active six degree‐of‐freedom robotic arm via a CT stereotactic frame. The outer therapeutic transducer with a 10 cm fixed focal zone was coaxially mounted to an inner diagnostic US transducer (2–4 megahertz, Philips Medical Systems). This coaxial US transducer was connected to a modified commercial focused ultrasound generator (Focus Surgery, Indianapolis, IN) with a maximum total acoustic power of 100 watts. This pre‐clinical paradigm was tested for ability to heat tissue in phantoms with monitoring and navigation from CT and live US. The feasibility of navigatio...

Intermittent hepatic vein balloon occlusion during radiofrequency ablation in the liver.

The purpose of the study was to assess the feasibility of intermittent hepatic vein balloon occlusion during percutaneous radiofrequency (RF) ablation. Eight non-anticoagulated patients who had primary (n = 2) and metastatic (n = 6) liver tumors with a mean diameter of 4.2 cm (range 2.4–6.5 cm) were treated, resulting in a mean ablation diameter of 6.3 cm (range 4.3–9.3 cm). Six of 9 (67%) of the balloon-occluded hepatic veins were patent. No clinical sequelae of thrombosis were noted. Mean length of follow-up with CT and/or MRI was 12 months. Local tumor control was achieved in 5 of 8 patients. Intermittent hepatic vein balloon occlusion could potentially be a low-risk adjunctive maneuver for thermal ablation therapy in the treatment of large tumors and tumors adjacent to large vessels.

New Technologies in Tumor Ablation

The technology and engineering of tumor ablation are evolving more rapidly than the clinical validation. Technical descriptions risk being obsolete by publication time. General principles and developing technical paradigms provide a simplified framework to practice and study radiofrequency ablation (RFA).This chapter reviews the general limitations of tissue ablation methods, the optimization of ablation in the radiofrequency range, and several emerging technologies and paradigms feasible in the laboratory and possibly translatable to clinical practice.

Characterization of Pulsed High Intensity Focused Ultrasound for Enhanced Drug and Gene Delivery

Within a certain range of parameters, pulsed high intensity focused ultrasound (HIFU) has been shown to increase the delivery of systemically administered drugs and plasmid DNA in tumors in mice. The sonicated tissue is not damaged by light microscopy. The mechanism for the enhanced delivery has not been shown conclusively and can include thermal, cavitational, and non‐cavitation mechanical effects. In order to assess the effects of pulsed HIFU in a manner that allows for clinical translation, pulsed HIFU is performed within a magnetic resonance (MR) scanner. In this work, the thermal effect is evaluated with phase‐shift MR thermometry in ex vivo chicken muscle. The thermal effect is small at the most common exposure parameters. In the future, non‐thermal effects like permeability, diffusion, and elasticity changes will be evaluated with dynamic contrast enhanced MRI, diffusion‐weighted MRI, and MR elastography. If changes in permeability, diffusion, and shear modulus are associated with pulsed HIFU enhan...

3D ultrasound guidance system for needle placement procedures

This paper presents an ultrasound guidance system for needle placement procedures. The system integrates a real-time 3D ultrasound transducer with a 3D localizer and a tracked needle to enable real-time visualization of the needle in ultrasound. The system uses data streaming to transfer real-time ultrasound volumetric images to a separate workstation for visualization. Multi-planar reconstructions of the ultrasound volume are computed at the workstation using the tracking information, allowing for real-time visualization of the needle in ultrasound without aligning the needle with the transducer. The system may simplify the needle placement procedure and potentially reduce the levels of skill and training needed to perform accurate needle placements. The physician can therefore focus on the needle placement procedure without paying extra attention to perfect mid-plane alignment of the needle with the ultrasound image plane. In addition, the physician has real-time visual feedback of the needle and the target, even before the needle enters the patients skin, allowing the procedure to be easily, safely and accurately planned. The superimposed needle can also greatly improve the sometimes poor visualization of the needle in an ultrasound image (e.g. in between ribs). Since the free-hand needle is not inserted through any fixed needle channel, the physician can enjoy full freedom to select the needles orientation or position. No cumbersome accessories are attached to the ultrasound transducer, allowing the physician to use his or her previous experience with regular ultrasound transducers. 3D Display of the target in relation to the treatment volume can help verify adequacy of tumor ablation as well.