Extremity sarcoma

Hoekstra HJ, Meller I, Nieweg OE, Kettelhack C, Ben-Ari G, Pector JC, Lejeune FJ. Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience. Ann Surg 1996 224(6) 756- 5. 

Pharmacokinetic Principles 33 Dose-Response Relationship 34 Intraperitoneal Application 34 Intra-arterial Application 34 Isolated Perfusion Techniques Application Techniques 35 Intracavitary Application 35 Intra-arterial Infusion 36 Regional Perfusion Techniques Stop-Flow Perfusions 36 Isolated Extremity Perfusion (ILP) 37 Hyperthermic Peritoneal Perfusion (HIPEC) 38 Clinical Indications 38 Pancreas Carcinoma 38 Bronchial Carcinoma 39 Extremity Sarcoma 40 Peritoneum 41 Surgical Technique 41 Rationale 42 Clinical Results 43 References 44 Further Reading 45... 

Several treatment modalities have been developed to facilitate limb-sparing in patients with advanced tumors. Neoadjuvant therapies, mainly radiation or combined chemo- and radiotherapy, have led to a significant reduction in amputation rates, although 8%-15% of patients with extremity sarcoma still undergo amputation. 

A transmissible sarcoma of the chicken has been under observation in this laboratory for the past fourteen months, and it has assumed of late a special interest because of its extreme malignancy and a tendency to widespread metastasis. In a careful study of the growth, tests have been made to determine whether it can be transmitted by a filtrate free of the tumour cells. Attempts to so transmit rat, mouse, and dog tumours have never succeeded and it was supposed that the sarcoma of the fowl would not differ from them in this regard, since it is a typical neoplasm. On the contrary, small quantities of a cell-free filtrate have sufficed to transmit the growth to susceptible fowls. 

Isocyanide-based MCR was also applied for the total synthesis studies of natural products containing piperazine substructure. For example, trabectedin (also known as ecteinascidin 743 or ET-743) is undergoing clinical trials for the treatment of breast, prostate, and pediatric sarcomas. Ecteinascidin 743 (2) is an extremely potent antitumor agent isolated from a marine tunicate, Ecteinascidia turbinate [12]. Eukuyama et al. developed the total synthesis of ecteinascidin 743 from a Ugi reaction [13]. The reaction of p-methoxyphenyl isocyanide 3 gave Ugi product 7, which was cyclized to DKP intermediate 8 (Scheme 1). 

TNF- has been extensively tested in the therapy of various malignancies, but results have been disappointing due to dose-limiting toxicities. One exception is the use of intra-arterial high-dose TNF- for malignant melanoma and soft tissue sarcoma of the extremities. In these settings, response rates greater than 80% have been noted. 

Ewing s sarcoma is the second most common malignant bone tumor in children. The majority of patients have microscopic metastases at diagnosis the lung is the most common metastatic site. This sarcoma is a relatively rare disease with limited therapeutic options. The majority of patients are initially responsive to chemotherapy with vincristine, doxorubicin (Adriamycin), and cyclophosphamide. However, relapsed disease is usually extremely difficult to treat because of its resistance to chemotherapy (Zhou et al., 2001). 

Casper ES, Gaynor JJ, Hajdu SI, Magill GB, Tan C, Friedrich C, Brennan MF. A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors. Cancer 1991 68(6) 1221-9. 

Leiomyosarcomas are most commonly found in the retroperitoneum in adults. They uncommonly occur in the deep soft tissues of the extremities but may be seen in more superficial sites, particularly in the dermis and subcutis. The differential diagnosis of LMS traditionally includes other sarcomas composed of intersecting spindle-cell fascicles, including fibrosarcoma, MPNST, synovial sarcoma, and spindle cell rhabdomyosarcoma. Additional conditions such as IMT (inflammatory pseudotumor), neurofibroma, and hemangiopericytoma (see Fig. 4.5) are also considerations. 

Monophasic spindle cell (so-called fibrous) synovial sarcomas represent one extreme of the morphologic spectrum of those neoplasms. Classic biphasic synovial... 

Epithelioid sarcoma Young adults. Deep soft tissue of extremities. Metastases to lung, lymph node, skin. Epithelioid tumor cells, granuloma-like growth pattern Keratin+, EMA+, vimentin+, CD34+, CK5/6-, p63- Nothing specific EM may be helpful... 

Recently, Coggon and Acheson summarized the Swedish studies (3 ). They concluded "Further research is urgently needed to confirm or refute these associations, to define the extent of the risk (if any) and to identify the carcinogen(s)." The Swedish studies could not be substantiated by Milham (32) Preliminary results from a case-control study in New Zealand have not indicated an excess risk of soft tissue sarcoma (38). We must kept in mind, however, that the mortality rate for soft-tissue sarcoma for U.S. males between the ages of 40 and 64 is extremely low and ranges from about 5 to 20 per million. This low incidence severely limits the power in some reported studies to detect such rare tumors. 

Taubert H, WM P, Greither T, Kappler M, Bache M, Bartel F, Kehlen A, Lautenschlaga-C, Harris LC, Kaushal D, Fiissel S, Meye A, Bohnke A, Schmidt H, Holzhausen HJ. Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients. Oncogene. 2007 26 7170-4. 

Mundt AJ, Vijayakumar S, Nemunaitis J, Sandler A, Schwartz H, Hanna N, Peabody T, Senzer N, Chu K, Rasmussen CS et al (2004) A phase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities. Clin Cancer Res 10 5747-5753... 

Malawer M et al. (1991) Impact of two cycles of preoperative chemotherapy with intraarterial cisplatin and intravenous doxorubicin on the choice of surgical procedure for high-grade bone sarcomas of the extremities. Clin Ortho 270 214-222... 

Most penile tumors are squamous cell carcinomas. Non-squamous cell primary tumors are very uncommon and include benign lesions, such as hemangiomas (Kim et al. 1991), neurilemmomas (Kousseff and Hoover 1999 Jung et al. 2006) and leiomyomas (Stehr et al. 2000 Bartoletti et al. 2002 Liu et al. 2007), and malignant lesions such as epithelioid sarcoma (Sirikci et al. 1999), Kaposi s sarcoma (Hermida Gutierrez et al. 1995), lymphoma (El-Sharkawi and Murphy 1996 Lo et al. 2003 Wei et al. 2006) and melanoma (Sanchez-Ortiz et al. 2005). Other penile tumors are extremely rare. 

FIGURE 1 Kaposi sarcoma in leflunomide treated patient, (a) Gross photograph of Kaposi sarcoma. Multiple erythematous and raised purpuric rash and nodules in both lower and upper extremities, (b) Kaposi sarcoma, stomach involvement a strawberry color (Grey in print versions) and 0.6 cm sized mass lesion discovered in stomach mid body great curvature side. From Lee S. Rheumatol Int 2012 31 1065-68. 

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