Novel approaches

NOVEL APPROACHES TO RESTORING DEFECTS IN BONE TUMORS

Introduction

Musculoskeletal oncology is a challenging field of medicine in which only a small group of doctors in Singapore are trained. It concerns the management of tumor and tumor-like conditions of the bones, joints and soft-tissues of the extremities and spine. These are broadly classified as benign (tumors that grow and expand and cause local problems and diagnostic difficulties) and malignant (these are the cancers of the bones and soft tissues). Malignant tumors can be primary or originally derived from the bones and soft tissues (also known as sarcomas) or secondary or spread from a distant site. Malignant tumors in turn are classified by grade into low and high grade lesions. Occasionally an intermediate grade is also described for chondrosarcomas.

Sarcomas are very difficult life-threatening problems and require great expertise not just in surgery but also in organizing multidisciplinary teams to tackle individual specific problems. Some musculoskeletal oncology conditions may not be life-threatening but, nevertheless, these problems provide unique challenges for medical practitioners because they often hamper daily activities and hence need to be dealt with urgently.

Benign tumors of the bones and soft tissues

These conditions are commonly encountered and treated by general orthopedists and surgeons. Our special input in this field is in meeting two of the main challenges provided by these conditions.

Firstly, these conditions provide diagnostic problems – that is they can be mistaken for more serious conditions like cancers. Our service works closely with the Departments of Pathology and Radiology with whom we meet regularly and such cases are amply discussed before embarking on surgery. This minimizes the risk of mis-diagnoses.

Next, when such conditions compromise function and need to be operated on (eg. weakening the bone to the point that they may break) we should be able to reconstruct these conditions with minimal functional embarrassment.

Cancers of the bone

Also known as bone sarcomas, osteosarcomas and chondrosarcomas are the two most common primary variants. These affect individuals of all ages but in particular people in the second and sixth decades of life. The challenges in managing these conditions revolve around removal of these tumors in a way that they do not recur and then reconstruct the structure to replace the missing anatomical structure and restore function.

The general approaches to reconstruction can be both biological and prosthetic. In biological solutions the draw is that one is able to reconstruct the missing structure with biological materials and host bone which have a virtually life-long durability. These methods, however, do result in donor site morbidity and have a relatively high early complication rate. The prosthetic approach where joints and segments are replaced by metal implants have high patient acceptability and good function but are subject to wear. Ideally both approaches should be available and hence only the most appropriate is offered in specific cases.

Secondary cancers can also benefit from some of the procedures describe here. When cancers in other parts of the body spread to the bone and soft tissues, these structures become compromised. As a result patients develop fractures that do not heal and they become invalid. This in turn reduces their life expectancy.

Approach

There is a fine balance in selecting the most appropriate procedure for the given patient. This is based on the trifactor of aggressiveness, presence of an effective adjuvant (like chemotherapy) and age. This results in a number of combinations and treatment options accordingly (Figure 1). Hence the well controlled tumor in a child may allow for biological options stressing tissue conservation and biological solutions whereas an aggressive poorly controlled solution in an adult argues for either an ablative or non-biological ablative solution.

Figure 1. Treatment of the patient is a multi-disciplinary effort. It balances the tri-factor of aggressiveness, age and effectiveness of local control (a). In this way it may be determined if the patient will benefit from the proposed treatment option. It should be understood however that above all, the patients survival is not to be compromised. In this study conducted by the author reviewing the survival of patients with osteosarcoma over thirty years it is found that the survival of patients with osteosarcoma in the National University of Singapore was superior to the national average and that this in turn was superior to the national US average (statistically significant). Hence we may conclude that the treatment modalities offered to our patients in Singapore have not compromised their survival over the last 30 years.


What’s novel in bone sarcoma treatment

The paradigm and understanding in bone sarcoma treatment has virtually been dictated by the experience in osteosarcoma – this being the most common bone sarcoma. The developments in the field have ranged from fairly intuitive solutions to solutions that may be regarded audacious- but yet have been justified by ample literature. In general musculoskeletal oncologists are a fairly critical community and really only successful approaches have stood the test of time.

The basic schema in bone sarcoma care involves staging, a biopsy, a period of chemotherapy (neoadjuvant), surgery and consolidation (adjuvant) chemotherapy. There have been novel approaches at each stage of treatment. We will highlight the approaches developed in restoring bone defects subsequent to a resection.

Amputations

Due to the advanced stage in which sarcomas present, amputations have become the dominant mode of treatment in Asia for bone sarcomas. In general in the National University of Singapore (NUS), this has rarely been necessary except perhaps in the salvage situation for recurrent disease when limb salvage is no longer feasible. Techniques in amputations have not changed over centuries. Nevertheless with the advent and strong development of microsurgical techniques we now possess the ability to transplant composite tissues from remote areas onto remnant limbs. While the transplantation of cadaveric tissue has now become a reality, it is still somewhat experimental and not in common use due to the issues of immunosuppression in what may be considered non-lifesaving surgery. Nevertheless there are other areas of relevance. It should be understood for example, that because most tumors occur around the knee, amputations in bone sarcomas are usually above knee amputations. This is vastly different from below knee amputations, where, because the knee is present the energy requirements are considerably lower. Hence, being able to provide a knee mechanism is highly desirable. In the rotationplasty described by Van Ness, an above knee amputation is performed and the remnant tibia and ankle is transposed onto the remnant femur (Figure 2) – the reversed ankle becoming a knee mechanism. While this may sound unpalatable, the fitting of a below knee prosthesis in this situation results in a highly functional limb. The development of prostheses with space-aged materials have resulted in highly functional lightweight designs with good patient acceptance.

Figure 2. It is rarely if ever necessary to perform an amputation in this era of modern medicine for bone tumors unless the tumor has fungated through the skin. This patient who had a neglected bone tumor and had sought a second opinion from a neighboring country was offered an amputation above the knee (a).We agreed that an amputation was necessary but offered the option of replanting the amputated segment using microsurgical techniques (b). We were able to re-anastamose all his vessels and his nerves which were lost in the amputated segment (a so called amputation replantation procedure). The huge advantage of this procedure is that the ankle now functions as a knee and can take a below knee prosthesis which is many times superior to an above knee amputation prosthesis (c). The variants of this procedure and how it compares to an above knee amputation (d) illustrate how this procedure may be superior over an above knee amputation.


Bone transplants

The prospect of using bone donated from a deceased individual to reconstruct defects offers a potentially durable life-time solution. There are problems however. They fracture or do not incorporate in one in five patients and get infected in one in ten patients. Immunocompatibility is now presently not required for bone transplants. Contrary to popular belief, they do not “come alive” within the body but rather stay as intercalary replacements. Availability is an issue and often bone needs to be imported from foreign countries. NUS presently has a working relationship with the Perth Bone bank who have kindly consented to providing bone for tumor reconstructions for a modest handling fee (Figure 3).

Figure 3. This 4 year-old child had a Ewing’s sarcoma of the tibia (a). It had was about 15 mm from the growth plate (b). In view of her age, she was offered an amputation by her referring physician. Nevertheless we were able to offer her a limb salvage procedure after resecting the tumor (c). The only thing that would fit the dimensions of this toddler was the humerus of an adult (d). By doing an intercalary replacement, the author was able to save the growth plate (e). Surgery was uneventful and the epiphyseal screws were removed to allow growth (f). Six months later (g) the growth in the epiphysis was appreciable (arrowed).


Re-using resected bones

This is a remarkable approach that has been predominantly developed in the Asia Pacific Region where traditionally bone banks were scarce and implant costs prohibitive. The most important advantage of this approach is that the reused tissue is a perfect match for the defect. The worst disadvantage is that the treatments to render the tumor bearing bone sterile makes it prone to fracture and disintegration. One approach would be to resect tumors, freeze the tumor bearing bone and replant the tissue. The main advantage of this method is that the growth factors within resected bone is preserved and allows for ready incorporation of the re-implanted tissue. This has become the preferred method of re-implantation in NUS. Similarly, resected bone can be autoclaved, irradiated or pasteurized. All these methods result in degradation and often require biological supplementation with a vascularised fibular graft (Figure 4).

Figure 4. Reusing the tumor bearing bone is an excellent solution to the challenges faced by tumors around the pelvis – in particular the hip joint. This 9 year-old boy had a Ewing’s sarcoma of the acetabulum (a). Resecting tumor (b) would result in an unstable joint and some surgeons would fuse the hip resulting in problems for the child sitting and causing long term back problems.  The author elected to preserve the joint by hyper-freezing it in liquid nitrogen (c) and replanting it. This gives a perfect match for size and anatomy. Unfortunately the process of freezing, while it still preserves the growth factors kills off the cells both normal and malignant. Hence rods and cement are used to re-enforce the structure. Two years later the patient walks with a limp but is able to perform functionally well. There has been no signs of recurrence.


Joint Replacement Surgery

While perhaps the most visible of the options available, megaendoprostheses use have many attendant problems, chief amongst which are size discrepancies and poor longevity. Nevertheless, next to amputations, they allow the fastest return to chemotherapy. Their high cost is often a consideration as well. They are classically indicated in the 14 to 16 year-old osteosarcoma patient who has reached the end of their growth potential. They have been used in growing children where growing mechanisms are incorporated. This involves multiple surgeries about 3 to 4 times per year to lengthen the limb or an electromagnet to effect lengthening without further surgery. While inviting in theory, often the desired length is not achievable and most implants will fail for a number of reasons by the end of the lengthening procedure whether from failures in fixation, failures in lengthening mechanisms or infections due to multiple surgeries. Their use has essentially become confined to a few dedicated research centers around the world. They are three times as expensive as the non-lengthening megaendoprosthesis described earlier. They are not the preferred method of bone lengthening in NUS (Figure 5).

Figure 5. The author has extensive experience in using endoprosthetics in the reconstruction of bone tumors. These work very well in teens and adults. This 42 year-old male had a sarcoma of the left distal femur (a). Following the biopsy the tumor was filled with cement and metallic rods to prevent any fracture while chemotherapy was initiated. After 2 months the entire segment was resected and a megaendoprosthesis was used to reconstruct the defect. Another case shows the segments of bone which the megaendoprosthesis attempts to replicate (d). While a convenient approach, in this study by the author financed by the National University of Singapore, it was found that physical satisfaction was only superior if the patients’ own joint can be preserved (e). Hence the main thrust in surgical approach at the University has been to preserve the joint where possible unless as in this case the joint cannot be preserved without endangering local control.


Minimally invasive options 

Minimally invasive approaches to aggressive non-malignant and metastatic lesions include cryosurgical and radio-frequency ablation. NUS has invested in cryosurgical probes that allow the delivery of freezing techniques into a remote area through percutaneous technique. The big advantage of probe delivery techniques are that they are easier to control and have fewer side effects of skin burns and nitrogen gas embolisation compared to older techniques using liquid nitrogen pour techniques (Figure 6). 

Figure 6. Professor Nathan led an initiative presently into the third phase of implementing cryosurgical ablation of tumors. The first phase involved ablation using liquid nitrogen pouring techniques. The second phase involved open procedures using the cryoprobe system shown (a). Presently we are developing minimally invasive technology using CT fluoroscopy to target the tumors in situ percutaneously (b). Each probe has a known and reproducible zone of ablation (c) which freezes down to -200 degrees Celsius. The process is monitored using thermocouples. It allows the percutaneous freezing of tumors without requiring large incisions (d).


Computer assisted technologies
Under this category are a group of technologies including computer navigation and robotic technology. This is covered elsewhere on our site. The primary problem with these technologies is the cost of the machines which ultimately becomes borne by an already stressed healthcare industry. In this space 3D cutting jigs have become available. Here we make use of high resolution scanners to scan the area of interest. This is then used to print in three-dimensions not only the cutting jigs but the surgical plans as well. Our centre is a leader in this field regionally and has come to the conclusion that it is the best compromise of cost and efficacy for highly specialized resection situations (Figure 7 and 8). We present a mini-lecture  about 3D printing in orthopedic applications here.


Figure 8. This is the video of a highly specialized resection and reconstruction of a bone tumor using 3D printing technology. Further information about this is available here.


Conclusion 

Musculoskeletal oncology is a highly specialized branch of orthopedic surgery practiced by a very select few in Singapore. Some are well published in the field and have been involved in the evolution of the specialty since its inception some 30 years ago with Singapore being the host of the 6th International Symposium of Limb Salvage Surgeons in 1993. Many techniques of limb salvage have come and gone in that time but the more resilient and proven techniques have stood the test of time. The challenges at hand may now be met by individualized approaches which in the right hands can yield remarkable results.