What are the problems associated with the surgical treatment of patients with pancreatic cancer?

Modern surgical therapy of pancreatic cancer has resulted in few long-term survivors. There are several reasons. First, most patients are not diagnosed in an early tumor stage, resulting in a minority of patients undergoing surgical resection. A breakthrough in screening methodology is required until this most major of obstacles can be overcome. Second, inaccurate clinical tumor staging is all that is available for the majority of patients, since most patients are not resected. Imaging techniques used for clinical staging require anatomic verification before clinical staging can be reliable. Then adequate comparison of treatments for patients who never receive anatomical staging can accomplished. Postoperative tumor staging using anatomical methods from intraoperative findings and examination of a surgical specimen require a staging system that is simple and directly correlates with survival. The best staging system can be developed only with international cooperation. An adequate comparison of the results of treatment will then be possible. Two broad treatment areas that are most promising are surgical (extending resections to yield negative surgical margins) and adjuvant protocols (beginning with a variety of radio sensitizing chemotherapeutic agents). Received for publication on Sept. 29, 1997; accepted on Nov. 15, 1997     

Current concepts for management of soft tissue sarcomas of the extremities

Wide resection and limb-salvage surgery remain the gold standard for the management of patients with soft tissue sarcomas of the extremities. Innovations in understanding tumor biology and limb-salvage techniques have led amputation rates to decline. Radiation therapy and novel chemotherapy agents and dosing regimens are supplementing oncology-related surgical treatment. A multidisciplinary team approach with input from oncologists, pathologists, radiation oncologists, and orthopaedic and plastic surgeons is necessary for the management of patients with soft tissue sarcomas of the extremities.     

Preoperative Isolated Limb Infusion of Doxorubicin and External Irradiation for Limb-Threatening Soft Tissue Sarcomas

Background At present, limb-sparing surgery is the most appropriate and acceptable treatment option for soft tissue sarcomas of the extremities. To increase the number of limb-sparing resections in the treatment of locally advanced soft tissue sarcomas of the extremities, preoperative radiotherapy and/or chemotherapy are often used. Isolated limb perfusion of cytostatic agents is an effective alternative option but technically complex. Isolated limb infusion, essentially a low-flow isolated limb perfusion without oxygenation via a percutaneous catheter, had been developed as a simple alternative. Objective The objective of this study was to achieve limb-sparing surgery in patients with locally advanced soft tissue sarcomas of the extremities that would otherwise have required an amputation or a functionally mutilating surgery by performing preoperative isolated limb infusion with doxorubicin and external beam irradiation to obtain local control and make limb-sparing surgery feasible. Methods A total of 40 patients with locally advanced soft tissue sarcomas of the extremities were evaluated between 2002 and 2005. Tumors were located in the lower limb in 28 patients (70%) and in the upper limb in 12 patients (30%). All of these patients were felt to be unresectable and were referred because amputation was considered the only available treatment option. They underwent preoperative isolated limb infusion with doxorubicin (0.7 and 1.4 mg/kg for the upper and lower limbs, respectively). Preoperative external beam radiotherapy started within 3–7 days after isolated limb infusion was administered. The total dose was 35 Gy in ten fractions. After 3–7 weeks, surgery was performed aiming at limb preservation. Results Tumor response was seen in 85% of patients, rendering these large sarcomas resectable in most cases. The mean values of pretreatment tumor volume and post-treatment volume were 2797 cm³ and 1781 cm³, respectively, with a significant p value of 0.0001. Histologic response was seen in 80% of patients. At a median followup of 15 months (range = 5–35), limb salvage was achieved in 82.5%. Procedure-related complications were limited and easily managed. Conclusion Isolated limb infusion with doxorubicin is a simple and safe method of regional chemotherapy. The addition of preoperative external beam irradiation helped to increase the rate of limb salvage in patients with large and/or high-grade soft tissue sarcomas of the extremities.     

Reconstructions after resections of tumors involving the proximal femur

Advances in prosthesis design, the use of allografts, and a systematic approach to the staging and surgical treatment of musculoskeletal tumors have made limb salvage possible in the proximal femoral region. With the use of effective adjuvant therapy, limb salvage is now an option for the majority of patients presenting with locally invasive neoplasms in this area. The increase in functional outcome is sufficient to warrant serious consideration of limb salvage over the corresponding amputation. Preoperative planning is discussed along with surgical techniques.     

Complex surgery for locally advanced bone and soft tissue sarcomas of the shoulder girdle

Surgical management of primary musculoskeletal tumors of the shoulder girdle is cognitively and technically demanding. Over the last decades, advances in the medical treatments, imaging and surgical techniques have fostered limb salvage surgery and reduced the need for amputation. Despite well-accepted general principles, an individualized approach is often necessary to accommodate tumor extension, anatomical challenges and patient characteristics. A combination of techniques is often required to achieve optimal oncologic and durable functional outcome. Goal of this article is to review approach and management of patients with locally advanced sarcomas of the shoulder girdle requiring major tumor surgery, to illustrate principles of surgical strategy, outcome and complications, and to provide useful guidelines for the treating physicians.     

Pelvic resections

The complexity of pelvic anatomy and the extent of tumor growth makes treatment of patients with primary bone sarcomas in the pelvis difficult in terms of local control. Before the 1970s, most tumors in the bony pelvis were surgically treated with hindquarter amputation. Currently, improved techniques for clinical staging, adjuvant treatments, evolutions in metallurgy, and development of new surgical techniques make limb-salvage surgery and reconstruction possible alternatives to hemipelvectomy and resection-arthrodesis. The advantages of amputation over resections at the pelvis are a lower incidence of complications, a limited area at risk for recurrence, and a faster recovery time compared with all but the most limited pelvic resections. The disadvantages, especially after periacetabular resections, are leg-length discrepancy and impaired hip and gait function. The indication for limb salvage is the ability to obtain wide margins without compromising survival and function. Although having to resect the sciatic nerve to obtain adequate margins does not always mean that an amputation should be performed, the combination of a major pelvic resection and the functional consequences of sciatic nerve resection results in an extremity usually not worth saving; loss of femoral nerve function does not result in a significant gait disturbance, especially if the hemipelvis is stable. Reconstruction options after major pelvic resections have also evolved, but they remain difficult, especially when the acetabulum is involved.     

INTRA-OPERATIVE IMPLANT BRACHYTHERAPY IN THE MANAGEMENT OF SOFT-TISSUE SARCOMAS

Background : The management of localized soft-tissue sarcomas remains complex. This is a retrospective review of a single institution experience with manual afterloaded brachytherapy following intra-operative implantation of the tumour bed during surgery. Methods : Twelve patients over a 3-year period had resection for localized soft-tissue sarcomas and desmoids with insertion of intra-operative brachytherapy implants combined with resection for localized soft-tissue sarcomas. Manual afterloading of the implant with iridium wires was performed postoperatively in all patients. The low dose rate brachytherapy dose varied from 13 to 20 Gy. Supplementary external beam radiation was administered pre-operatively or postoperatively to bring the total dose of adjuvant irradiation to 60–65 Gy. Results : After a median follow-up period of 29 months, the 3-year local disease-free survival rate was 63%. The 3-year actuarial survival rate was 83%. There were no failures within the high-dose region of the implant, although two patients had locoregional failures adjacent to the tumour bed at the edge of the radiation field. Three patients developed distant metastases. Side effects were noted in five patients. Wound breakdown and delayed wound healing occurred in two patients. One patient required an amputation as a result of chronic non-healing and wound pain. Pathological fractures occurred in two patients. Those patients who did not develop wound breakdown had good cosmetic and functional outcomes. Conclusion : Intra-operative implantation of the tumour bed in combination with tumour resection for soft-tissue sarcomas results in a high degree of local control with acceptable complications. This modality offers the patient a high chance of avoiding a more radical surgical procedure such as limb amputation.     

Limb salvage in musculoskeletal oncology: Recent advances

The treatment of musculoskeletal sarcomas has made vast strides in the last few decades. From an era where amputation was the only option to the current day function preserving resections and complex reconstructions has been a major advance. The objectives of extremity reconstruction after oncologic resection include providing skeletal stability where necessary, adequate wound coverage to allow early subsequent adjuvant therapy, optimising the aesthetic outcome and preservation of functional capability with early return to function. This article highlights the concepts of surgical margins in oncology, discusses the principles governing safe surgical resection in these tumors and summarises the current modalities and recent developments relevant to reconstruction after limb salvage. The rationale of choice of a particular resection modality, the unique challenges of reconstruction in skeletally immature individuals and the impact of adjuvant modalities like chemotherapy and radiotherapy on surgical outcomes are also discussed.KEY WORDS: Bone tumor, reconstruction, sarcoma     

Is Amputation Necessary for Sarcomas? A Seven-Year Experience with Limb Salvage

The rationale for amputation for local tumor control of skeletal and soft tissue sarcomas was based on results obtained from surgical therapy alone. However, our previous results from a pilot trial of multimodality therapy of preoperative chemotherapy and radiation therapy followed by surgical resection indicated that limb salvage (without amputation) could be accomplished in most patients with little morbidity and low recurrence rate. This report summarizes our experience in a prospective trial from January 1972 to December 1979. A total of 105 consecutive patients with soft tissue sarcomas (65 patients) or bone sarcomas (40 patients) were treated with preoperative intraarterial adriamycin, 3500 rads of rapid-fraction radiation and radical en bloc resection of primary tumor. Diseased bones were replaced with cadaver allografts (22 patients), metallic endoprostheses (10 patients) autologous bone (2 patients), or no replacement (ilium or fibula—4 patients). Salvage of a viable, neurologically intact, functional extremity was achieved in 98/105 patients (98%); 97% of limb salvage patients were free of local recurrence after a median follow-up period of 28 months. Major complication rate that required amputation was 3/105 patients (2%). Postoperative adjuvant chemotherapy with cyclical adriamycin and high-dose methotrexate was employed for all patients with osteosarcoma and 35 patients with grade III soft tissue sarcomas. The overall disease-free rate is 50% (18/35) for osteosarcomas and 65% (42/65) for soft tissue sarcomas. These results indicate that local tumor control can be achieved in 91% of patients without amputation. Their functional capabilities are excellent with a low complication rate. Since the advent of adriamycin and methotrexate has significantly improved the overall survival for patients with skeletal and soft tissue sarcomas, the quality of this survival has become even more important. Preoperative multimodality therapy is a major advance in this direction and since results of limb salvage procedures appear to be equal or superior to those achieved by amputation we believe these alternatives should be offered to all patients.     

Isolated Limb Perfusion With Tumor Necrosis Factor and Melphalan Prevents Amputation in Patients With Multiple Sarcomas in Arm or Leg

Background Treatment for extremity soft tissue sarcoma (STS) has shifted in recent years from amputation to local wide excision combined with irradiation. For multiple sarcomas, this limb-sparing approach is often not possible. To avoid amputations, isolated limb perfusion (ILP) with tumor necrosis factor and melphalan is an attractive treatment option for patients with multiple extremity sarcomas.Methods We investigated a prospective database at a tertiary referral institute. From July 1991 to July 2003, out of 217 ILPs, 64 ILPs were performed for either multifocal primary sarcomas or multiple sarcoma recurrences in 53 patients. All ILPs were performed under mild hyperthermic conditions by using 1 to 4 mg of tumor necrosis factor and 10 to 13 mg/L of limb volume for leg and arm perfusions, respectively.Results The overall response was 88%, with 42% complete response, 45% partial response, 11% no change, and 2% progressive disease. This response rate is significantly better than our experience in 153 locally advanced single-STS cases (88% vs. 69%). The toxicity of the procedure was mild to moderate in almost all cases; no treatment-related amputation had to be performed. The time to local recurrence was 29 months and differed significantly between multiple primary and multiple recurrent STS. The 5-year survival rate was 39%. Limb salvage was achieved in 45 (82%) of 55 treated limbs.Conclusions In a group of patients who are uniformly candidates for amputation, ILP can achieve limb salvage in approximately four out of five patients. Because this treatment option provides excellent local control, it should be considered before an amputation is planned.     

Treatment of advanced and inaccessible sarcomas with continuous intra-arterial chemotherapy prior to definitive surgery or radiotherapy--a possible alternative to amputation or disabling radical surgery

Four patients with advanced and inaccessible soft tissue sarcomas were treated with a regimen of intra-arterial chemotherapy followed by radiotherapy and/or surgical excision. Two of the patients had advanced sarcomas in the buttock and thigh regions which would otherwise have required hindquarter amputation in one case or disarticulation of the hip in the other case. These sarcomas responded significantly to intra-arterial chemotherapy to the extent that subsequent local surgery was effective in eradicating the residual tumours. No viable tumour cells were found in the resected specimens. In both patients amputation was avoided and local tumour eradication was achieved. In the other two patients, advanced and non-resectable sarcomas in the head were first treated with a similar regimen of intra-arterial chemotherapy. In both cases the tumours regressed in size prior to administration of local radiotherapy. After completion of chemotherapy and radiotherapy no viable tumour cells were detected in either lesion. In one case (originally a very extensive sarcoma of the jaw in a 5 year old child) a residual lump was resected but no viable tumour was detected in the resected specimen. These four patients represent our total experience with this plan of management. All responded well and there has been no evidence of local disease recurrence in any of the four patients. One patient (Case 2) did develop pulmonary and bone metastases from which she died 2 years later but the other three patients remain well with no evidence of residual disease, 11 years, 4 years and 20 months after presentation.     

Surgical site infection in malignant soft tissue tumors

Background  

Postoperative wound complications, including surgical site infections, which frequently occur in the course of management of musculoskeletal sarcomas, sometimes necessitate repeat surgeries, including amputation, and may result in a prolonged healing time, prolonged hospital stay, or fatal outcome. A comprehensive understanding of surgical site infections associated with specific diseases is needed to reduce the risk.     

Enhanced apoptosis of soft tissue sarcoma cells with chemotherapy: A potential new approach using TRAIL

Soft tissue sarcomas are less responsive to conventional chemotherapy when compared to bone sarcomas. We investigated the possibility of enhancing the efficacy of chemotherapy by utilising the recently identified cytokine, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) in combination with standard chemotherapeutic agents. Fresh human soft tissue sarcomas (rhabdomyosarcoma, fibrosarcoma, malignant fibrous histiocytoma) were obtained at biopsy and dispersed tumour cells were incubated in cell culture with standard cytotoxic agents, either as single agents or in combination with TRAIL. The chemotherapeutic agents were, at best, moderately effective, in terms of induction of cellular apoptosis, although the fibrosarcoma was completely unresponsive to all single agents. TRAIL alone had no effect on any sarcoma cell culture. In contrast, the addition of TRAIL and drug together produced a significant increase in sarcoma cell apoptosis, with TRAIL and doxorubicin the most effective combination.     

TREATMENT OF ADVANCED AND INACCESSIBLE SARCOMAS WITH CONTINUOUS INTRA-ARTERIAL CHEMOTHERAPY PRIOR TO DEFINITIVE SURGERY OR RADIOTHERAPY—A POSSIBLE ALTERNATIVE TO AMPUTATION OR DISABLING RADICAL SURGERY

Four patients with advanced and inaccessible soft tissue sarcomas were treated with a regimen of intra-arterial chemotherapy followed by radiotherapy and/or surgical excision. Two of the patients had advanced sarcomas in the buttock and thigh regions which would otherwise have required hindquarter amputation in one case or disarticulation of the hip in the other case. These sarcomas responded significantly to intra-arterial chemotherapy to the extent that subsequent local surgery was effective in eradicating the residual tumours. No viable tumour cells were found in the resected specimens. In both patients amputation was avoided and local tumour eradication was achieved. In the other two patients, advanced and non-resectable sarcomas in the head were first treated with a similar regimen of intra-arterial chemotherapy. In both cases the tumours regressed in size prior to administration of local radiotherapy. After completion of chemotherapy and radiotherapy no viable tumour cells were detected in either lesion. In one case (originally a very extensive sarcoma of the jaw in a 5 year old child) a residual lump was resected but no viable tumour was detected in the resected specimen. These four patients represent our total experience with this plan of management. All responded well and there has been no evidence of local disease recurrence in any of the four patients. One patient (case 2) did develop pulmonary and bone metastases from which she died 2 years later but the other three patients remain well with no evidence of residual disease, 11 years, 4 years and 20 months after presentation.     

An abbreviated history of orthopaedic oncology in North America

Orthopaedic oncology in North America has its roots in European medicine of the 1800s where sarcomas were first classified on the basis of their gross characteristics (1804) and amended on the basis of their histologic features (1867). Surgical treatment, local excision, with unacceptable mortality led to amputation in the 1870s and remained so until limb-sparing resection was cautiously embarked on in the mid-1900s. Nonsurgical adjuvant therapy was first devised in the 1880s (as Coley's toxins) but remained largely ineffective until the advent of chemotherapy in the 1970s. The combination of these techniques in the past 30 years, and the vastly improved staging and reconstructive techniques has led to the current preponderance of limb-salvaging surgery and greatly improved survival rates. The application of these treatments has been enhanced by the development of orthopaedic oncology fellowships, orthopaedic oncology societies, and federally funded regional cancer centers and multidisciplinary teams to treat patients with sarcomas.     

Osteosarcoma of the pelvis.

Over a 25-year period we have treated 36 patients with osteosarcoma of the pelvis. Of the tumours, 24 (67%) were primary osteosarcomas and 12 (33%) arose either after irradiation or in association with Paget's disease. Six patients had a hindquarter amputation and 12 were treated by a limb-salvage procedure with intrapelvic excision. The five-year survival rate of all the patients with pelvic osteosarcoma was 18%, while for 17 treated by chemotherapy and surgery it was 41%. The prognosis for patients presenting with metastases or with secondary osteosarcoma was appalling and none survived after 29 months. No patient over the age of 50 years when seen initially survived for a year. Youth and a good response to chemotherapy along with complete surgical excision offer the best chance of cure.     

Amputations of the hand and upper extremity in the management of malignant tumors

The primary goal of treatment for malignant bone and soft tissue tumors of the hand and upper extremity is an oncologic cure. The secondary goal is maintenance of function.Despite recent advances in chemotherapy and radiation techniques, amputation still provides a means for achieving surgical cure for some bone and soft tissue sarcomas. A well planned amputation with attention to level, soft tissue closure, muscle transfer as needed, and nerve handling combined with early fitting of modern prosthetic devices provides patients with a rapid return to normal activity. This article reviews the general principles and specific techniques of amputation in the patient with an upper extremity malignancy.     

Foot malignancies: a multidisciplinary approach

Malignant osseous and soft tissue tumors of the foot are rare and should be considered in patients who have foot-related symptoms. Most sarcomas affect patients who are older than 55 years; however, many young patients who are otherwise healthy, may present with malignant foot and ankle lesions. In addition to benign and malignant neoplasms, pseudotumorous conditions mimic neoplastic lesions and should be differentiated before any treatment is undertaken. Invasiveness is a characteristic of sarcomas. The foot is a terminal anatomic structure, with closed and tight compartments and well-vascularized tissues, that predispose it to hematogenous and lymphatic metastases. Patients who have a malignant foot tumor should be referred to an orthopedic oncologist for further evaluation and treatment. The goals of treatment include local tumor control, restoration of function and stability during standing and walking, long-term survival, and improved quality of life. In most cases, wide surgical margins require a ray, Syme, midtarsal, or below-the-knee amputation. Recent advances in chemotherapy and radiotherapy have allowed limb salvage procedures with wide tumor resections. Because overall survival is greatly improved in these patients, the reconstruction of skeletal defects needs to be more functional and durable. After tumor resection, reconstruction of the skeletal and soft tissue defects is possible by using bone allografts or vascularized autografts, arthrodesis, and free vascularized musculocutaneous flaps.     

Bildgebung und Interventionen bei Weichteilsarkomen der Extremitäten

Background

Soft tissue sarcomas are rare tumors comprising approximately 1% of all adult malignancies. The long-term outcome as well as the success of local and systemic therapeutic methods crucially depends on the correct local staging of the primary tumor as well as the tumor extent using whole body staging.

Principles

In addition to classical projection radiographic techniques and ultrasound, magnetic resonance imaging (MRI) plays a leading role in local staging of soft tissue sarcomas. Due to the high soft tissue contrast as well as the lack of ionizing radiation, it is the ideal method for evaluation and therapy monitoring after treatment of soft tissue sarcomas. Due to the metastatic pattern of soft tissue sarcomas, whole body staging is recommended. A sensitive method is available with computed tomography (CT). The combination with metabolic methods, such as positron emission tomography (PET) in terms of PET/CT, allows a further increase in the sensitivity for pathological findings. Interventional methods, e.g. biopsy and embolization for preoperative preparation, are also used to optimize the outcome.

Conclusion

Only through the targeted use of modern imaging techniques is it now possible to ensure correct local and systemic staging of soft tissue sarcomas to ensure adequate long-term survival. In interdisciplinary cooperation in a sarcoma center, the selection of methods and the use of interventional procedures should be decided based on the individual patient situation in order to ensure optimal treatment success up to long-term freedom from tumors.

     

Amputations in natural disasters and mass casualties: staged approach

Amputation is a commonly performed procedure during natural disasters and mass casualties related to industrial accidents and military conflicts where large civilian populations are subjected to severe musculoskeletal trauma. Crush injuries and crush syndrome, an often-overwhelming number of casualties, delayed presentations, regional cultural and other factors, all can mandate a surgical approach to amputation that is different than that typically used under non-disaster conditions. The following article will review the subject of amputation during natural disasters and mass casualties with emphasis on a staged approach to minimise post-surgical complications, especially infection.