**3. Polymethyl methacrylate (PMMA) bone cement injection**

**Figure 1.** RF ablation can be applied for the pelvic bone metastasis.

**Figure 2.** Cryosurgery with probe type rod is applied for femoral neck metastasis.

**2.5. MRI-HIFU (high-intensity focused ultrasound) ablation**

ultrasound produced by a transducer on tumors.

Liquid nitrogen has been used as an intraoperative adjuvant method in the open bone tumor surgery. For the percutaneous application, technical progress was made for probe manufac‐ turing, and utilization of argon gas as a cryogen. The argon gas freezes the tumor tissues at −100°C around the active probe, forming ice balls around the probe. Temperature below −20°C leads to cellular necrosis causing protein denaturation and rupture of cell membranes.

In general, the size of the necrosis is likely to be smaller than the ice ball and its maximum is up to 3 cm in diameter. The forming ice ball can be monitored by ultrasonography or computer tomogram but cannot be detected by fluoroscopy. Processes of the cryoablation are categorized into three phases: a first freezing phase (10 minutes), a thawing phase with helium gas (5 minutes), and a second freezing phase (10 minutes). Cryoablation is commonly used to treat prostate cancer. Treating metastatic bone tumor using cryoablation, however, may not be a good choice; the method fails to cover its big sizes, takes a long time, and is unable to perform moving tip technique [1]. **Figure 2** illustrates a treatment for femoral neck metastasis by

HIFU induces coagulation necrosis of the tumors by focusing high heat transformed from

**2.4. Cryoablation**

130 Tumor Metastasis

cryoablation.

Percutaneous bone cement injection is known as a cementoplasty or an osteoplasty. The PMMA has been used in orthopedic surgery from 1945 including joint replacement surgery, spinal compression fractures, chronic osteomyelitis with antibiotics and tumors. The structure of methyl methacrylate monomer allows polymerization at room temperature to produce solid PMMA. The avidity of the polymer to dissolve in monomer aids this reaction. The composition of PMMA is shown in **Figure 3** and **Table 1**.

**Figure 3.** The PMMA bone cement is activated by mixing powder and liquid components.

Percutaneous vertebroplasty was originally developed as a treatment for angiomas, but its application to the osteoporotic spine has been shown to provide significant and prolonged relief of pain. It controls the symptoms of compression fractures by recreating mechanical stability. The technique involves the percutaneous transpedicular injection of low viscosity biomaterial into the vertebral body guided by an image intensifier.

Percutaneous bone cement injection for the metastatic bone tumor has been shown favorable outcomes in the vertebral body and the flat bones such as pelvis, scapula, and sternum. The PMMA has been one of the most useful agents in the treatment of bone tumors since it provides immediate mechanical stability and reduces bone pain. The reason for pain improvement after percutaneous cementoplasty (PC) procedure is due to tumor suppression, microfracture recovery, nerve ending sacrifice, mechanical strengthening, etc. When the heat is generated from solidification of bone cement, cytotoxic effect causes the destruction of tumor. The PMMA can also have a mass effect by interrupting circulation to the tumor. Nonetheless, the risk of pathologic fracture is still high when PC is solely performed in long tubular bones such as femur, tibia, and humerus without metal fixation [2].


**Table 1.** Bone cement composition.

#### **3.1. Percutaneous cementoplasty for pelvic bone metastasis**

The pelvic bone is a connecting area between spine and femur. The acetabulum of pelvis is a direct contact area with femoral head and important for weight bearing. When the metastatic tumor occurred at the acetabulum, the percutaneous PMMA injection will be a good option [3].

#### *3.1.1. Surgical technique*

The PC is performed under regional spinal anesthesia. A patient is positioned in lateral decubitus position. A sterile field is prepared and skin is punctured with 10 or 11 gauge osteoplasty needle at the 10 cm posterior from anterior superior iliac spine. The needle is advanced from posterior to anterior at an angle about 70° from the horizontal plane. The osteoplasty needle is usually used over two needles to reduce intraosseous pressure at the time of bone cement injection: the bone cement is injected through a single needle, until bloody fluids, and injected bone cement regurgitate through the other needles. Empty syringe will aspirate the unnecessary fluids and then bone cement is injected through all needles. Under fluoroscopic guidance, with anterior-posterior and oblique views of a pelvis, the PV needle penetrates the outer cortex and the tip is positioned in the lesion. The low-viscosity radiopaque PMMA is mixed and transferred to a 30 ml or 50 ml syringe, depending on the number of cement pack (20 g per a pack). Then, PMMA is transferred again into several 1 ml syringes. With the frequent check of oblique fluoroscopic view to avoid sciatic nerve injury by leakage, bone cement is injected as much as possible. If injection is not easily accomplished, a stylet is used to push PMMA through the lumen of needle. The bone cement injection is usually conducted within 3–4 minutes after making the cement mixture.

can also have a mass effect by interrupting circulation to the tumor. Nonetheless, the risk of pathologic fracture is still high when PC is solely performed in long tubular bones such as

femur, tibia, and humerus without metal fixation [2].

**Composition Function**

Polymer Polymethyl methacrylate

Antibiotics Antimicrobial prophylaxis Dye (e.g., chlorophyll) Distinguish cement from bone

Monomer Methyl methacrylate monomer N,N-dimethyl-p-toluidine (DMPT) Initiates cold curing of polymer

Dye (e.g., chlorophyll) Distinguish cement from bone

**3.1. Percutaneous cementoplasty for pelvic bone metastasis**

Benzoyl peroxide Reacts with DMPT to catalyze polymerization Hydroquinone Stabilizer preventing premature polymerization

The pelvic bone is a connecting area between spine and femur. The acetabulum of pelvis is a direct contact area with femoral head and important for weight bearing. When the metastatic tumor occurred at the acetabulum, the percutaneous PMMA injection will be a good option [3].

The PC is performed under regional spinal anesthesia. A patient is positioned in lateral decubitus position. A sterile field is prepared and skin is punctured with 10 or 11 gauge osteoplasty needle at the 10 cm posterior from anterior superior iliac spine. The needle is advanced from posterior to anterior at an angle about 70° from the horizontal plane. The osteoplasty needle is usually used over two needles to reduce intraosseous pressure at the time of bone cement injection: the bone cement is injected through a single needle, until bloody fluids, and injected bone cement regurgitate through the other needles. Empty syringe will aspirate the unnecessary fluids and then bone cement is injected through all needles. Under fluoroscopic guidance, with anterior-posterior and oblique views of a pelvis, the PV needle penetrates the outer cortex and the tip is positioned in the lesion. The low-viscosity radiopaque PMMA is mixed and transferred to a 30 ml or 50 ml syringe, depending on the number of cement pack (20 g per a pack). Then, PMMA is transferred again into several 1 ml syringes. With the frequent check of oblique fluoroscopic view to avoid sciatic nerve injury by leakage,

Barium sulfate or zirconium dioxide Radio-opacifiers

Copolymers (e.g., methacrylate-methyl methacrylate) Alter physical properties of the cement

Powder compositions

132 Tumor Metastasis

Liquid compositions

**Table 1.** Bone cement composition.

*3.1.1. Surgical technique*

PMMA injection has to start slowly to prevent venous leakage with careful C-arm fluoroscopy monitoring. If the bone cement flows rapidly to the regional vein on the fluoroscopy, the injection has to be delayed to achieve thicker mixed bone cement. **Figures 4** and **5** show the operative process of percutaneous cementoplasty.

**Figure 4.** A 54-year-old female has left pelvic bone metastasis of breast cancer. Bloody osteolytic lesion managed by PMMA bone cement injection.

**Figure 5.** Intraoperative photographs showing preparation of bone cement and start of injection through one needle for intraosseous pressure decompression. Multiple bone metastases are frequently involved around hip joint and these can be treated with one time surgery by minimally invasive surgery.

The anesthesiologist is asked to monitor temporary change of blood pressure, pulse rate, and respiration due to toxicity and volatility smell of PMMA. In the case of a larger lesion en‐ croaching most of the ilium, another VP needle can be employed in the same way.

#### **3.2. Evaluation of percutaneous PMMA bone cement injection**

F-18-FDG PET-CT is known for good detectability of bone metastases in several types of cancers, and became widely used for treatment response evaluation and recurrence detection. The quantitative PET-CT values, SUVmax, and SUVmean showed significant uptake decrease after PMMA injection procedure, which means less glucose uptake and reflects tumor suppression. However, most control lesions were aggravated in the same individual patient.

Previous studies report that after bone cement injection, tumor volume is reduced and histology showed tumor necrosis, which support our hypothesis. Bone scan (BS) is known for good detectability, therapy response monitoring, and long-term follow-up of bone metastases. BS is advantageous for whole skeletal metastases detection [4]. BS and F-18-FDG PET-CT have complementary value as BS can detect osteoblastic metastasis well, and both are good imaging modality to detect bone metastasis.

Interpatient study was unable to be performed due to the differences in patient status (primary tumor, treatment, etc). So we performed comparison study of PS lesion and control lesion in the same patient. In our study, as shown in **Figure 6**, BS showed improved or stable state after PMMA injection procedure, which means local tumor suppression. However, most control lesions showed aggravated state [5].

**Figure 6.** PET-CT evaluation after combined percutaneous cement injection surgery showed effective tumor suppres‐ sion in the metastatic bone tumor. Before (above) and after (below) operation.
