Interstitial fluid pressure and blood flow in canine osteosarcoma and other tumors

This study aims to characterize interstitial fluid pressure and blood flow in naturally occurring appendicular bone tumors in dogs because high pressure may influence the response of tumors to chemotherapy and radiation therapy. Eighteen client-owned dogs with naturally occurring appendicular bone tumors were included in this study. At the time of surgical biopsy, interstitial fluid pressure and blood flow were measured using wick-in-needle probes and laser Doppler flowmetry, respectively, within the soft tissue and bony components of the lesions and in normal muscle. Interstitial fluid pressure within the bony and soft tissue components of the tumors was significantly higher than interstitial fluid pressure in normal muscle. Blood flow in the bony component of the tumors was significantly lower than blood flow in normal muscle. There was no significant difference between blood flow in the soft tissue component of the tumors compared with that in normal muscle. Appendicular bone tumors in dogs have significantly higher interstitial fluid pressure and lower blood flow than do adjacent, unaffected soft tissues. The higher interstitial fluid pressure and lower blood flow may reduce tissue oxygenation and impede drug delivery. The effects of increased interstitial fluid pressure and decreased blood flow should be considered in the formulation of treatment strategies for the clinical management of appendicular bone tumors.     

Chemosensitivity testing by regrowth assay against malignant bone and soft tissue tumors

In order to improve the clinical results of chemotherapy protocols for patients with malignant bone and soft tissue tumors, an attempt was made to establish a methodological approach to chemo-sensitivity testing using a modified regrowth assay system. We have established a chemo-sensitivity testing system using methylcholanthrene-induced round cell sarcoma in BALB/c mouse. This system was applied clinically and the sensitivity to anticancer drugs was found within two weeks of cell culture. Fifteen patients with malignant tumors were treated using a chemotherapy protocol composed of drugs selected by means of our system. Eleven patients (73.3%) showed an excellent therapeutic response. Our simple assay system is available to determine sensitivity to drugs in a short time. Drugs with no sensitivity can be eliminated from the protocol so that adverse effects on normal tissue can also be reduced.     

Validation of radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas: Japanese Orthopaedic Association Committee on Musculoskeletal Tumors Cooperative Study

BACKGROUND: The radiographic evaluation of the response to preoperative chemotherapy for bone and soft tissue sarcomas is based mostly on the change in primary tumor size before and after chemotherapy, as is done for many solid cancers. Its prognostic correlation, however, has hardly been validated. METHODS: We conducted a retrospective validation study of the Japanese Orthopaedic Association (JOA) radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas as a JOA Committee on Musculoskeletal Tumors cooperative study. A total of 125 consecutive patients with high-grade bone (n = 77) and soft tissue (n = 48) sarcomas treated with neoadjuvant chemotherapy and definitive surgery in 25 tertiary referral hospitals were selected for the study. We investigated the correlation between the tumor size-based radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas provided by the JOA Committee on Musculoskeletal Tumors (hereafter called the JOA criteria) and the patients' overall survival using the Kaplan-Meier method and the log-rank test. RESULTS: The JOA criteria correlated relatively well with survival for malignant bone tumors (mostly comprising osteosarcoma and Ewing's sarcoma) but not for soft tissue sarcomas, suggesting that the tumor size-based radiographic evaluation criteria for the response to preoperative chemotherapy in patients with soft tissue sarcomas is invalid. CONCLUSIONS: The JOA criteria, based on the change in primary tumor size, is valid for malignant bone tumors but invalid for soft tissue sarcomas. Other new evaluation modalities of the response to preoperative chemotherapy using innovative functional imaging techniques are needed for soft tissue sarcomas.     

Limb salvage from a multidisciplinary treatment approach for skeletal and soft tissue sarcomas of the extremity.

Multimodality management of extremity skeletal and soft tissue sarcomas with preoperative intra-arterial Adriamycin and radiation therapy, radical surgical resection and postoperative chemotherapy or chemo-immunotherapy has resulted in preservation of a functional extremity in 13 or 14 patients. Seven of 8 patients with Stage IIIA and IIIB soft tissue sarcomas, managed with preoperative intra-arterial Adriamycin and radiation therapy, followed by en bloc soft tissue resection and 6 patients with bone sarcomas managed by preoperative treatment, followed by bone resection and replacement with cadaver bone allografts, remained free of disease from 4 to 34 months. The results of the combined modality approach were significantly better than the results obtained in patients managed by surgical resection alone, or by combination of operation with another single modality, both in terms of short term-recurrence free survival and salvage of a functional extremity.     

软组织恶性纤维组织细胞瘤的治疗(附12例报告)

发生于软组织的恶性纤维组织细胞瘤１２例，平均年龄６１．９岁，平均随访２９个月。本病与发生在骨组织的恶性纤维组织细胞瘤不同，病理学还可分为席纹样－多形性型、粘液样型、巨细胞型、黄色肉芽肿型。本病局部广泛切除可以得到较好的治疗，综合治疗特别放疗及化疗药物的应用，对减少复发，治疗转移有一定的疗效。     

脊柱结核病灶中抗痨药物浓度的测定

目的研究脊柱结核病椎各部位抗结核药物的分布特点,为脊柱结核化疗方案与手术治疗方法的改进提供理论依据。方法24例应用2SHRZ/2.5H2R2Z2(4.5个月)方案化疗结合手术治疗的脊柱结核患者,按有无病椎骨硬化分为硬化组和非硬化组。化疗第4周手术,依据手术取材时间分为术晨服药后120~130、180~190min两个时相点,取硬化组的病椎硬化壁、硬化壁外“亚正常骨”、硬化壁内结核病变组织和非硬化组的病椎结核病变组织、病变组织外“亚正常骨”以及两组患者的血浆、髂骨,采用高效液相色谱法测定上述样本的药物浓度。结果(1)吡嗪酰胺(PZA)和异烟肼(INH)各时相血药浓度与文献报道健康人单次服药的药时数据相近,利福平(RFP)则低25%,各药血药浓度高于髂骨及病椎组织中的药物浓度。(2)两组中“亚正常骨”与髂骨内的INH和RFP均达到了各自的杀菌浓度水平,PZA超过其细胞内酸性条件下MIC的5倍。三种药物各自在“亚正常骨”与自身对照的髂骨之间浓度相近。(3)硬化组中硬化壁的药物浓度仅为各药的最小抑菌浓度水平(MICs),远低于壁外围“亚正常骨”,壁内的结核病变组织中未检出上述三种药。(4)非硬化组结核坏死、干酪组织中RFP及PZA的浓度相当于各自的MICs,远低于其他组分,而INH却达到细胞内杀菌浓度。结论INH、RFP和PZA在脊柱结     

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.     

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??Interventional therapy plus sorafenib in patients with limbs alveolar soft tissue sarcoma??a report of 9 cases HE Xin-hong, LI Wen-tao, PENG Wei-jun, et al. Department of Radiology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University,Shanghai 200032, China
Corresponding author: LI Wen-tao , E-mail:wentao.li.sh@gmail.com
Abstract Objective To evaluate the efficacy and safety of interventional therapy combined with sorafenib in patients with limbs alveolar soft tissue sarcoma. Methods The clinical data of 9 cases of advanced limbs alveolar soft tissue sarcoma admitted between July 2007 and July 2010 in Fudan University Shanghai Cancer Center were analyzed retrospectively. All cases were obtained artery interventional embolism chemotherapy combined with sorafenib therapy. The efficacy, safety and prognosis survival situation were analyzed. Results After interventional embolism chemotherapy and sorafenib therapy, limbs primary lesions were not reduced significantly by MRI follow-up. But focal necrosis liquefied obviously and subjective symptoms improved including the pain relief or painkillers decrement, walking disorder or body activities obstacles eased. For the patients with lung or liver metastasis, the metastatic lesions got effective control, haemoptysis and cyanosis symptoms were alleviated obviously, and outdoor activities were increased. For the patients with multiple bone metastases, the bone pain symptoms have no obvious relief, and painkillers were still need to maintenance therapy. No serious adverse reaction related to interventional embolism chemotherapy and sorafenib therapy was observed in all patients, which needn’t adjustment of dose or interrupt treatment. Conclusion Interventional therapy combined with sorafenib therapy can relieve the tumor local symptoms and tumor related complications, improve quality of life significantly in patients with advanced limbs alveolar soft tissue sarcoma. The short-term survival benefit is good. It can be used as important supplement of the treatment for advanced limbs alveolar soft tissue sarcoma.     

Distraction osteogenesis in management of composite bone and soft tissue defects

A soft tissue defect is one of the most difficult problems that may accompany bone defects. Plastic surgery is often required. During distraction osteogenesis, not only the bone but also the soft tissues are lengthened, which may help in spontaneous closure of the soft tissue defects. This study examines 11 cases of composite bone and soft tissue defects which were managed by distraction osteogenesis. After debridement of the necrotic tissues, the soft tissue defects ranged from three by four centimetres to five by 14 centimetres and the bone defects ranged from four to 12 centimetres. All the soft tissue defects healed during the process of bone transport without the need for plastic surgery, except in one case. The complications were successfully managed during the course of treatment. Distraction osteogenesis is a good method for simultaneous treatment of composite bone and soft tissue defects.     

Osteomyelitis in the adult.

The acute form of osteomyelitis in the adult is distinctly uncommon except for that seen in the vertebrae. A significant increase in osteomyelitis due to gram-negative rods has been observed. The proper choice of antibacterial drugs is essential. Surgical treatment is still required for removal of infected and scarred tissue. Inadequate removal will lead to treatment failure. However, the defect produced in soft tissue and bone may tax the surgeon's ingenuity.     

Use of suture anchors in the reconstruction of soft tissue defects with pedicled muscle flaps

Suture anchors have been commercially developed to facilitate stable attachment of soft tissues to bone. Although their use is well characterized in orthopedic literature, suture anchors may also be of benefit in the reconstruction of large soft tissue defects by plastic surgeons. Suture anchors (Mitek Surgical Products, Inc., Westwood, MA) were used to fasten pedicled muscle flaps to exposed bone in 7 patients at Duke University undergoing reconstruction of large soft tissue defects. The suture anchor appeared to provide stability for the advancement flap, and there were no suspected postoperative muscle dehiscences or suture breakages. The suture anchor provides an easy, secure method to attach soft tissue to exposed bone, and preliminary experience appears to support their use in certain soft tissue reconstruction procedures by plastic surgeons. Suture anchors should be reserved for cases in which a large muscle flap is needed to cover exposed bone and poses a risk of shearing away from the bone, or adequate periosteum and soft tissue is not available for standard suture techniques.     

Carcinoma arising in pilonidal sinuses.

Pilonidal carcinoma is an infrequent complication of pilonidal disease. The surgeon's suspicion should be raised in cases of longstanding pilonidal inflammation. The disease occurs most frequently in men. The lesion is often a well-differentiated squamous carcinoma. Wide excisions at the initial procedure following a brief period of local wound care, is the optimum treatment and increases the chances for a five-year survival. Definitive closure of the defect is delayed and accomplished by rotational flaps or skin grafts. It palpable nodes are present in the inguinal region they should be biopsied even though this does not necessarily connote metastasis. When inguinal node metastasis is present, this is associated with a poor prognosis. The incidence of occult node metastasis is not known because no prophylactic groin dissections were performed. Staged groin dissections were not associated with any long-term survivals. The series was too small to determine its palliative potential. Radiation therapy may palliate local bone or soft tissue recurrences. Re-excisions of local soft tissue recurrences can provide, in some instances, long disease-free intervals. Both topical and systemic chemotherapy were administered in more recent cases with poor results, but this series is not large enough to form conclusions for this modality of treatment.     

Strength of cancellous bone trabecular tissue from normal, ovariectomized and drug-treated rats over the course of ageing

Hormone therapy (HT) drugs and bisphosphonates prevent osteoporosis by inhibiting osteoclastic bone resorption. However, the effects of osteoporosis and anti-resorptive drugs on the mechanical behavior of the bone tissue constituting individual trabeculae have not yet been quantified. In this study, we test the hypothesis that the mechanical properties of bone trabecular tissue will differ for normal, ovariectomized and drug-treated rat bones over the course of ageing. Microtensile testing is carried on individual trabeculae from tibial bone of ovariectomized (OVX) rats, OVX rats treated with tibolone and placebo-treated controls. The method developed minimizes errors due to misalignment and stress concentrations at the grips. The local mineralization of single trabeculae is compared using micro-CT images calibrated for bone mineral content assessment. Our results indicate that ovariectomy in rats increases the stiffness, yield strength, yield strain and ultimate stress of the mineralized tissue constituting trabecular bone relative to normal; we found significant differences (P < 0.05) at 14, 34 and 54 weeks of treatment. These increases are complemented by a significant increase in the mineral content at the tissue level, although overall bone mineral density and mass are reduced. With drug treatment, the properties remain at, or slightly below, the placebo-treated controls levels for 54 weeks. The higher bone strength in the OVX group may cause the trabecular architecture to adapt as seen during osteopenia/osteoporosis, or alternately it may compensate for loss of trabecular architecture. These findings suggest that, in addition to the effects of osteoporosis and subsequent treatment on bone architecture, there are also more subtle processes ongoing to alter bone strength at the tissue level.     

Percutaneous lovastatin accelerates bone healing but is associated with periosseous soft tissue inflammation in a canine tibial osteotomy model

Experimental studies have shown the ability of statins to stimulate bone formation when delivered locally or in large oral doses, however most have been studied in rodents. This anabolic effect is through the selective activation of BMP‐2. Our purpose was to determine the effects of local treatment with lovastatin on bone healing in mammals as a preclinical animal model. We administered lovastatin (6 mg/kg) by percutaneous injection to a canine tibial osteotomy stabilized with external fixation. We found that lovastatin improved bone healing after a single injection into the fracture site assessed by serial radiography and histology at bone union. However, lovastatin treatment resulted in adverse local soft tissue inflammation. These results suggest that percutaneous lovastatin injection may be a useful adjuvant treatment over the course of bone healing to augment fracture repair, although further investigation into the mechanism of soft tissue adverse effects is warranted. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:210–216, 2014.     

Reconstruction of Massive Midfoot Bone and Soft Tissue Loss as a Result of Blast Injury

Lower extremity blast injuries represent a unique challenge to surgeons and often involve complex, limb-threatening wounds with extensive soft tissue and bone loss. Surgical treatment of these injuries can be difficult because of limited autogenous resources for reconstruction of the defect. In this article, we describe a technique for medial column reconstruction using iliac crest bone graft and soft tissue coverage with an abductor hallucis rotational flap combined with a split-thickness skin graft. This method addresses the extensive bone and soft tissue defects that frequently characterize blast injuries to the foot, and may be applicable in other situations where trauma or infection has caused extensive destruction of the medial column.     

Primary chest wall tumors

The differential diagnosis of chest wall tumors is diverse, including both benign and malignant lesions (primary and malignant), local extension of adjacent disease, and local manifestations of infectious and inflammatory processes. Primary chest wall tumors are best classified by their primary component: soft tissue or bone. Work-up consists of a thorough history, physical examination and imaging to best assess location, size, composition, association with surrounding structures, and evidence of any soft tissue component. Biopsies are often required, especially for soft tissue masses. Treatment depends on histological subtype and location, but may include chemotherapy and radiotherapy in addition to surgical resection.     

Cost-effectiveness of pulmonary resection and systemic chemotherapy in the management of metastatic soft tissue sarcoma: a combined analysis from the University of Texas M. D. Anderson and Memorial Sloan-Kettering Cancer Centers

BACKGROUND: We sought to determine the cost-effectiveness of different treatment strategies for patients with pulmonary metastases from soft tissue sarcoma. METHODS: We constructed a decision tree to model the outcomes of 4 treatment strategies for patients with pulmonary metastases from soft tissue sarcoma: pulmonary resection, systemic chemotherapy, pulmonary resection and systemic chemotherapy, and no treatment. Data from 1124 patients with pulmonary metastases from soft tissue sarcoma were used to estimate disease-specific survival for pulmonary resection and no treatment. Outcomes of systemic chemotherapy and pulmonary resection and of systemic chemotherapy were estimated by assuming a 12-month improvement in disease-specific survival with chemotherapy; this was done on the basis of the widely held but unproven assumption that chemotherapy provides a survival benefit in patients with metastatic soft tissue sarcoma. Direct costs were examined for a series of patients who underwent protocol-based pulmonary resection or doxorubicin/ifosfamide-based chemotherapy. RESULTS: The mean cost of pulmonary resection was 20,339 dollars per patient; the mean cost of 6 cycles of chemotherapy was 99,033 dollars. Compared with no treatment and assuming a 12-month survival advantage with chemotherapy, the incremental cost-effectiveness ratio was 14,357 dollars per life-year gained for pulmonary resection, 104,210 dollars per life-year gained for systemic chemotherapy, and 51,159 dollars per life-year gained for pulmonary resection and systemic chemotherapy. Compared with pulmonary resection, the incremental cost-effectiveness ratio of pulmonary resection and systemic chemotherapy was 108,036 dollars per life-year gained. Sensitivity analyses showed that certain patient and tumor features, as well as the assumed benefit of chemotherapy, affected cost-effectiveness. CONCLUSIONS: For patients with pulmonary metastases from soft tissue sarcoma who were surgical candidates, pulmonary resection was the most cost-effective treatment strategy evaluated. Even with favorable assumptions regarding its clinical benefit, systemic chemotherapy alone, compared with no treatment, was not a cost-effective treatment strategy for these patients.     

Revision of 120 tibial infected non-unions with bone and soft tissue loss treated with epidermato-fascial osteoplasty according to Umiarov

Treatment of tibial infected non-unions with bone and soft tissue loss has to solve three problems: infection, lack of bone continuity and lack of skin coverage. The aims of treatment are infection healing, bone consolidation with preservation of limb length and soft tissue reconstruction. The most important stage in the planning is an accurate débridement. Soft tissue reconstruction can be achieved using plastic surgery, and bone reconstruction is accomplished with bone grafts or induced membrane technique, but these methods may present disadvantages and risks.     

介入栓塞化疗联合索拉非尼治疗肢体腺泡状软组织肉瘤9例分析

目的 探讨介入联合索拉非尼治疗肢体腺泡状软组织肉瘤的有效性与安全性。方法 回顾性分析2007年7月至2010年7月就诊于复旦大学附属肿瘤医院的9例晚期腺泡状软组织肉瘤病人的临床资料。9例病人予以动脉介入栓塞化疗联合索拉非尼治疗,分析其有效性与安全性,了解其预后情况。结果 经介入栓塞化疗及索拉非尼治疗后,MRI随访显示肢体原发病灶均无明显缩小,但病灶坏死液化明显,主观症状改善,表现为疼痛的缓解或止痛药的减量,行走障碍或肢体活动障碍得到缓解。肺及肝内转移病人转移病灶能得到有效控制,咯血、紫绀症状得到明显缓解,户外活动量增加。多发骨转移病人疼痛症状无明显改善,仍需止痛药维持治疗。所有病人均未出现与介入栓塞化疗及索拉非尼相关的严重不良反应,无需调整剂量或中断治疗。结论 介入联合索拉非尼治疗,可显著改善晚期腺泡状肉瘤病人肿瘤局部症状及肿瘤相关并发症,明显提高生活质量,短期生存获益好,可作为晚期腺泡状肉瘤治疗的重要补充。     

Systemische Therapie und Hyperthermie beim lokal fortgeschrittenen Weichteilsarkom

Patients with high-risk soft tissue sarcomas (FNCLCC grades 2–3, >?5 cm and deep lying) are at a high risk of local recurrence or distant metastases despite optimal surgical tumor resection. Therefore, multimodal treatment should be considered for this difficult to treat patient group. Besides surgery, radiation therapy and chemotherapy, hyperthermia has become a valid, complementary treatment option within multimodal treatment concepts. Hyperthermia in this context means the selective heating of the tumor region to temperatures of 40–43?°C for 60 min by microwave radiation in addition to simultaneous chemotherapy or radiation therapy. A randomized phase III study demonstrated that the addition of hyperthermia to neoadjuvant chemotherapy improved tumor response and was associated with a minimal risk of early disease progression as compared to chemotherapy alone. The addition of hyperthermia to a multimodal treatment regimen for high-risk soft tissue sarcoma consisting of surgery, radiation therapy and chemotherapy, either in the neoadjuvant or adjuvant setting after incomplete or marginal tumor resection, significantly improved local progression-free and disease-free survival. Based on these results and due to the generally good tolerability of hyperthermia, this treatment method in combination with chemotherapy should be considered as a standard treatment option within multimodal treatment approaches for locally advanced high-risk soft tissue sarcoma.