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Background and Objective: Morton’s syndrome (MS) is a common cause of neuropathic chronic forefoot pain, characterised by the development of a swelling of the common digital plantar nerve, whose aetiology is not fully known. There is currently no gold standard of treatment, nonoperative management commonly involves manual therapies, orthoses therapy and infiltrative techniques, while surgery is indicated after failure of conservative measures. The present preliminary study prospectively evaluates patients affected by MS treated by Fascial Manipulation technique (FM), a noninvasive manual therapy, focused on the release of the deep fascia, reducing its stiffness. Materials and Methods: Patients with clinical and sonographic diagnosis of MS with at least a 4-month history of neuropathic symptoms underwent a cycle of three weekly FM sessions. Clinical follow-up, including VAS and AOFAS scores, was performed 21 days (T1) and 3 months (T2) after treatment. Results: Nine patients, among 28 recruited initially, completed the manual therapy sessions and relative follow-up points. This noninvasive pain treatment led to significant improvement of VAS (p = 0.0034) and AOFAS scores (p = 0.0240) at the first follow-up (T1). At 3-month follow-up (T2), both scores decreased slightly, remaining however superior to the pre-treatment values. Only VAS was still significant (p = 0.0184). Conclusions: Despite the small size of the case series, this pilot study is unique in supporting Fascial Manipulation in the nonoperative treatment of MS. Further studies are needed with a large cohort of gender balanced patients to confirm the encouraging results obtained.

The results achieved in 157 patients with non-metastatic Ewing's sarcoma of the bone treated at a single institution between 1991 and 1997 according to a new protocol (REN-3) are reported. Induction chemotherapy consisted of two cycles of ‘VAC’: vincristine (V), doxorubicin (A), cyclophosphamide (C) alternated with one cycle of ‘VIAc’: V, ifosfamide (I), actinomycin (Ac). After local treatment, patients received three more cycles of VAC, two of VIAc, three cycles of I plus etoposide (E) and two cycles with V, C and Ac. Local treatment was surgery in 53% of patients, surgery+radiotherapy in 25% and radiotherapy only in 22%. With a follow-up ranging between 4 and 10 years (mean: 7 years), 110 patients (70%) remained continuously event-free, 2 patients died of toxicity and 45 patients relapsed: 33 due to metastases and 12 due to local recurrence always associated with metastases. The 5-year event-free survival (EFS) and overall survival (OS) were 71.0 and 76.5% respectively. These results are significantly better that the ones achieved in our previous three studies in which a three-drug VAC regimen (REA-1), and 4-drug VACAc regimen (REA-2 and REN-1) was used, and in our most recent study (REN-2) which was based on a six-drug regimen as in the present study, but where I and Ac were used only after the local treatment. However, since REN-3 surgery was used in a significantly larger number of patients, we cannot say whether the better outcome of this study was due to the use of a six-drug regimen with an early delivery of ifosfamide and actinomycin, or to the wider use of surgery as local treatment or both.

Twenty-seven patients who had resection of the proximal femur for bone tumors and reconstruction with an allograft prosthesis composite are reported. In most of the patients, the prosthesis was a long-stem revision type, cemented in the allograft and uncemented in the femoral shaft. The abductor muscles and iliopsoas were sutured to the corresponding tendons on the allograft. Implant-related complications and functional results were evaluated and are reported. Twenty-two patients achieved a minimum followup of 36 months (range, 36-126 months; average, 58 months). The implant was removed in two patients (one for infection, one for intraoperative fracture of the allograft). One patient experienced nonunion, whereas in the remaining 24 patients, the allograft eventually united to the host bone. A frequent late complication (17 patients) was fracture of the greater trochanter of the allograft. In the whole series, only four new operations were done for implant-related complications. In 22 patients who could be evaluated, the functional evaluation according to the Musculoskeletal Tumor Society System was excellent in 16 (73%) patients, good in four (18%), and fair in two (9%). These results compare favorably with those of megaprostheses for tumor resection of the proximal femur, where a Trendelenburg gait almost always is present.

Although more and more patients with Ewing's sarcoma of bone (ESB) are being treated by surgery, the relative role of surgery and radiotherapy in the local treatment of this tumor has yet to be determined. Because the outcome of ESB may differ according to the anatomical site of the tumor, results reported in the literature, which generally refer to series with tumors located in all sites, may be selection biased. Therefore, we have retrospectively evaluated patients with ESB exclusively in the extremity and locally treated by surgery or radiotherapy. Two hundred and sixty-eight patients treated at Rizzoli 1979-1996 for non-metastatic ES of the extremities were assessed. Chemotherapy was administered according to four sequentially activated protocols. One hundred and thirty-six patients were treated by surgery, 70 by surgery and radiotherapy, and 60 patients by radiotherapy. Two patients underwent only chemotherapy. The follow-up range was 5-23 years (mean 13 years). One hundred and fifty-two patients remained continuously free of disease, 108 relapsed, 2 died of chemotherapy toxicity and 6 developed a second malignancy. The 5-year event-free survival (EFS) and overall survival (OS) were respectively 62 and 69%. Although patients of all groups were matched for possible risk factors, the rates of 5-year EFS and local control were significantly lower in patients treated with radiotherapy compared to patients treated by surgery or surgery and radiotherapy (48% vs 66%, p=0.002; 80% vs 94%, p=0.0001). Furthermore, in group 3 there were 6 secondary malignancies. Our results indicate that surgery should always be considered in the local treatment of ES of the extremities. Postoperative radiation therapy must be added in case of inadequate surgical margins.

Aims . To describe the outcomes of a large number of patients with pelvic osteosarcoma, and to define the guidelines for appropriate treatment. Methods . We reviewed 60 consecutive patients with primary pelvic high-grade osteosarcoma. The tumour involved the whole hemipelvis in 15 cases, while the most common location was the iliac wing in 29 cases (48.3%): 25 of these adjacent to or passing the sacroiliac joint. Results . Thirty patients underwent surgery; there were 16 hindquarter amputations and 14 internal hemipelvectomies. All the patients who presented with metastasis died of their disease. In 18 cases wide margins were achieved, however, eight patients experienced local recurrence. Of the series, only eight patients are still alive. Conclusion . The use of intense chemotherapy and surgical wide margin, hardly seems to achieve local control, however, tumour necrosis was correlated with positive prognosis. When internal hemipelvectomy it is not safe enough, amputation must be considered, particularly for cases with sacrifice of the sciatic nerve roots or for older patients where a shorter surgical procedure can be less risky.

To investigate somatostatin receptors (SSTRs) in primary or metastatic high-grade osteosarcoma, 18 patients (12 without metastases, 4 with synchronous lung, and 2 with metachronous bone metastases) underwent SSTR scintigraphy. After intravenous (i.v.) injection of 200-250 MPq of 111In-pentreotide, images were recorded at 4 and 24 hours. All patients underwent 99mTc-methylene diphosphonate (MDP) bone scan (BS). Scans were interpreted both with qualitative evaluation and with semiquantitative image processing, by means of tumor-to-background ratio modification over time. Primary tumor: SSTR scintigraphy was positive in 12 (75%) patients: 10 (83%) of the 12 nonmetastatic patients, and 2 (50%) of those with synchronous metastases. Metastases: SSTR scintigraphy was positive only in one (17%) of the six patients with metastatic disease. No relation was found between SSTR scintigraphy results and gender, histologic subtype, site, and size of the tumor. After primary chemotherapy, 15 patients underwent surgery of primary tumor; a good histologic response was found in 7 (64%) of the 11 patients with positive SSTR scintigraphy versus 1 (25%) of the 4 patients with negative SSTR scintigraphy. High-grade osteosarcoma exhibits somatostatin receptors, usually detectable in the primary tumor, but not in the metastatic lesions. The different expression of somatostatin receptors observed in primary and metastatic lesions, and in patients with tumors having different chemosensitivity, could indicate a possible relation between somatostatin receptors and biological behavior of the tumor.

Background: Effective adjuvant or neoadjuvant regimens of chemotherapy have dramatically improved the prognosis of patients with high-grade osteosarcoma of the extremity, localized at diagnosis. Currently, little is known about patients with metastatic disease at presentation. Patients and methods: From May 1995 to May 2000, 57 patients with osteosarcoma of the extremity, metastatic at presentation, were treated according to the following scheme: primary chemotherapy, restaging, simultaneous resection of primary tumor and metastatic lesions, and maintenance chemotherapy. Results: Thirty-five patients achieved remission. At a follow-up ranging from 2 to 7 years, seven remained continuously free of disease, one died of chemotherapy-related toxicity and 27 patients relapsed. Twenty-one of the 22 patients who never achieved remission died as a result of the tumor, as well as 20 of the 27 who achieved remission but then relapsed. Of the remaining seven relapsing patients, six are alive with uncontrolled disease, while one is alive and free of disease 24 months after the last post-relapse treatment. Two-year event-free survival (EFS) and overall survival (OS) were 21% and 55%, respectively. These results are significantly poorer than those achieved in 128 contemporary patients with non-metastatic disease at presentation, treated with the same chemotherapy protocol (2-year EFS and OS of 75% and 94%, respectively). Conclusions: The results of our study confirm that the prognosis of patients with osteosarcoma of the extremity, metastatic at presentation, remains poor, despite the use of aggressive treatments.

We describe a case of osteoid osteoma in the tibia of a 3-year-old patient who presented with a clinical and radiographic picture that suggested an exostosis. The formation of osteoid osteoma with a radiographic picture similar to that of osteophytes or exostosis has been previously documented only rarely. The authors hypothesize that the exostosis-like formation observed was actually the calcification of soft tissues that formed after the intense periosteal inflammatory reaction caused by the osteoid osteoma. As a result of its peculiar clinical and radiographic presentation, diagnosis of this lesion was delayed. Being located close to the medial growth plate of the tibia, it caused lengthening of the limb with a pronounced valgus deviation of the knee. An excisional biopsy provided histological evidence, clinical resolution and immediate pain relief, but incomplete resolution of the valgus deformity of the knee.

The purpose of this study was to evaluate the outcome of patients with Ewing sarcoma (ES) of the pelvis, attempting to identify prognostic factors to select patients for more aggressive treatment. Seventy-seven patients with nonmetastatic ES of the pelvis were treated at Rizzoli Institute between 1979 and 1996. Four different protocols of chemotherapy were used successively. Two protocols consisted of VACAc, and two of VACAc plus ifosfamide and etoposide. Local treatment consisted of surgery in 5 patients, radiotherapy in 60, and surgery followed by radiotherapy in 12. Mean follow-up was 11 years (range 5-25 years). Thirty-three patients remained continuously free of disease; 43 relapsed (24 due to metastases and 19 to local recurrence and metastases); 1 died of treatment-related complications. The 5- and 10-year event-free survival rates were 45% and 44%, respectively, and the 5- and 10-year overall survival rates were 48 and 44. These results are significantly worse than the ones achieved in 329 contemporary patients with extrapelvic lesions treated with the same protocols of chemotherapy (5- and 10-year event-free survival = 46% vs. 64% and 44% vs. 69%). Thus, despite associated chemotherapy, the outcome of ES localized in the pelvis remains poor, and new innovative methods for the treatment of this tumor are needed.

To determine whether a pathologic fracture in osteosarcoma of long bones has prognostic importance, and limb salvage can be safely performed in such cases, we reviewed the surgical treatment and oncologic results in 46 patients with nonmetastatic osteosarcoma of the extremity and pathologic fracture at presentation who had been treated in our Institution with neoadjuvant chemotherapy, between 1983 and 1999. Neoadjuvant chemotherapy was given according to 6 consecutive protocols. Surgery consisted of limb salvage (34 patients), amputation (11 patients) and rotationplasty (1 patient). The average follow-up was 11 (3-20) years. 28 patients remained continuously disease-free, 17 patients relapsed and 1 died of chemotherapy-related toxicity. Despite the high rate of limb salvage, only 2 local failures occurred, 1 after amputation and 1 after limb salvage. The 5-year disease-free survival and overall survival rates were 59% and 65%, respectively, with no differences between amputated and resected patients. These results are similar to those obtained in 689 contemporary patients having an osteosarcoma without a pathologic fracture treated in our Institution, and using the same protocols for chemotherapy. We conclude that with neoadjuvant chemotherapy, osteosarcoma patients presenting with a pathologic fracture can be surgically treated like those with no fracture, and that limb salvage procedures do not increase the risk of local recurrence or death of these patients.

Primary sarcomas of the sternum are infrequent; the most common histological types are chondrosarcoma, plasmacytoma, Ewing's sarcoma and Hodgkin's tumors. Since osteosarcoma of the sternum is a very rare entity, we have thought to explain the principal characteristics and the clinical and therapeutic approach based on our experience of two cases.

SummaryBackground: To identify predictive factors of disease-free sur-vival (DFS) in patients with non-metastatic osteosarcoma ofthe extremity, treated with primary chemotherapy and delayedsurgery.Patients and methods: The relationship between patient-related and treatment-related factors and prognosis was eval-uated in 300 patients treated from 1986 to 1992 according tochemotherapy protocols based on high-dose methotrexate,cisplatin and doxorubicin, wit h the addition of ifosfamide inthe post-operative phase. Univariate and multivariate analysesof prognostic factors for disease-free survival were performed.Results: With a median follow-up of 9.2 (4.4-12) years,eight-year DFS was 59% (95% confidence interval (95% CI):54-64.9). Univariate analyses showed that tumor volume^ 150 ml (P = 0.002), histologic subtype (P = 0.028), age > 12years (P = 0.044), high serum lactate dehydrogenase (P =0.044) and alkaline phosphatase (P — 0.064) levels adverselyaffected DFS. Gender of patients and site of tumor did notinfluenc DFS. No differences in DFS were found among thethree chemotherapy protocols, whereas the use of limb-sparingsurgery vs. amputation or rotation plasty (P = 0.006) and agood histologic response to primary chemotherapy (P = 0.014)positively correlated with DFS. After multivariate analyses,tumor volume Ss 150 ml (P = 0.028), age >I2 years (P =0.051), and histologic subtype (P = 0.052) retained prognosticsignificance.Conclusions: In patients wit non-metastatic osteosarcomaof the extremity treated with neoadjuvant chemotherapy, thedisease-free survival is significantly influenced by tumor volume,age, and histologic subtype.Key words: neoadjuvant chemotherapy, osteosarcoma. prog-nostic factors

One hundred and forty-four patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognosis. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cisplatin i.a., and doxorubicin i.v. After surgery "good responder" patients (90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same drugs, while "poor responder" patients (less than 90% tumor necrosis) received a 40 weeks treatment with ifosfamide and etoposide added to the three drugs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46%) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensity between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 patients (67%) remained continuously free of disease, 45 relapsed, and two died of doxorubicin-induced cardiopathy. The continuous disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histologic response to chemotherapy. According to the RDI, CDFS resulted significantly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dose-intensity (76.5% v.s. 57.3%; p

In 965 patients with high-grade osteosarcoma of the extremities, we investigated the correlation between diagnostic delay and the stage of the tumor at presentation. The mean interval between the onset of first symptoms and the final diagnosis was significantly shorter in patients with metastatic disease than in patients with localized disease at the time of the diagnosis. The difference was due to a late presentation of patients with localized disease to the physician and not to delays in performing radiologic examinations or in referring patients to a specialized hospital for biopsy and treatment. We conclude that in high-grade osteosarcoma of the extremity the shorter interval between onset of symptoms and diagnosis observed in patients with disseminated disease at the time of the diagnosis reflects a more aggressive behavior of tumors that are metastatic at presentation.

The current study consists of an outcome review of a consecutive series of 92 patients with knee arthrodesis using an allograft, done for malignant or aggressive tumors in two centers on different continents during a period of 18 years (mean followup, 5 +/- 4 years). The data were compiled by creating a computerized file using the information provided by both centers. Seventy-five of the patients (81%) had high-grade nonmetastatic tumors (Stage II), mostly osteosarcoma. In addition seven (8%) had metastases at outset (Stage III) and the remaining 10 (11%) had benign disease, mostly giant cell tumor or revision procedures for failed allograft or total joint replacement. Seventy-two patients (78%) had distal femoral lesions (78%) whereas the proximal tibia was the site of the tumor in 20 patients (22%). The average age of the patients was 23 +/- 16 years; 51 were males and 41 were females. Tumor complications were a major problem for patients in the series. Thirty-four percent of the patients died, 47% had metastases develop, and 9% had a local recurrence. Allograft complications included an infection rate of 20%, a fracture rate of 25%, and a nonunion rate of 44%. Repeat surgery was required for more than 50% of the patients with 26 requiring one additional operation, 11 requiring two, and 10 requiring three or more operations. Nineteen of the patients required an amputation (20%), only four of which were for recurrent tumor. When these data were compared with data for a control series of 880 patients with allografts other than allograft arthrodeses, the complications were greater and the outcome less successful, suggesting that other approaches should be considered unless there are special indications for this procedure.

The conceptual design of a biomass integrated gasification fuel cell system for small scale applications (40 kg h−1 woody biomass input with 50% mass fraction water content) is discussed in this work. Two different biomass gasifiers (circulating fluidized bed and downdraft), two different reformers, a solid oxide fuel cell, a gas turbine and a heat recovery steam cycle were investigated. A two-step optimization procedure was used to perform thermo-economic design optimizations of nine system configurations generated by combining different technologies. At the master level an evolutionary algorithm is used to optimize the system intensive parameters following the minimization of the system costs and the maximization of the net power production simultaneously (two-objective). At the inner level, system mass flow rates are optimized by linear programming subject to the thermal balance and to the heat transfer feasibility constraints which were formulated by means of Pinch Analysis techniques. The degree of system internal heat recovery was studied by including the minimum temperature difference between hot and cold streams as a decision variable at the master optimization level. Optimization results are shown by means of an optimal Pareto front for each configuration. The degree of system internal heat recovery of some specific solutions is discussed by means of Pinch Analysis composite curves. The study shows that very high system efficiencies can be obtained but only at the expense of really high system costs mainly because of the high costs of the fuel cell and of the gasifier especially at the small scale level considered here. Minimum specific plant costs of the most cost-effective configuration, based on a hybrid cycle, greater than 7000 $ kW−1 (2010 dollars) are found. The indirect circulating fluidized bed gasifier appears the most promising choice both in terms of cost and of system performance since it allows for better thermal integration at high temperatures and greater hydrogen yields. Auto-thermal reforming is a cheaper solution compared to steam reforming but does not benefit of the system internal heat recovery thus leading to comparably lower system efficiency. Steam reforming is particularly convenient when the system is pressurized and extra power can be recovered by gas expansion since a great amount of steam can be injected prior the reformer and vaporized by recovering the heat from exhaust gases.