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Biomedical subjects

R Capanna

Publications and source records attributed to R Capanna.

At least 19 recordsLinked to original sources

Soft tissue sarcomas of the popliteal fossa: outcome and risk factors.

BACKGROUND: Limb salvage surgery of popliteal soft tissue sarcomas may be hampered due to the incomplete anatomical containment of this region and the vicinity of neurovascular structures. The scope of this study was to determine outcome and to define risk factors. PATIENTS AND METHODS: 27 patients (53.3+/-15.8 y; 16/27 male) with popliteal soft tissue sarcomas were assessed. Mean follow-up was 40.9+/-33.8 months (48.5+/-36.7 months in surviving patients). 9/27 patients were included after prior treatment elsewhere (5 after intralesional resections and 4 local recurrences). The lesions were staged IB in 8/27 patients, IIB in 17/27 and III in 2/27. Immediate amputations were performed in 7/27 patients. 15/27 patients were subjected to radiation therapy (preoperative in 6/15 cases), 8/27 patients received chemotherapy (5/8 preoperatively). RESULTS: Overall survival and disease-free survival at 5 y was 63.0% and 59.5%. Local recurrence occurred in 2 patients. 8/27 patients developed metastatic disease after 28.9+/-9.8 months. Survival (p=0.397) and disease-free survival (p=0.113) did not differ in patients after amputations vs limb salvage. Application of radiation therapy was associated with a better survival (p=0.003). Complications related to the surgical intervention were recorded in 2/27 patients, complications related to radiation therapy occurred in 6/15 patients. DISCUSSION: Despite being extra-compartmental, popliteal sarcomas can be treated with a high rate of limb salvage while equal safety compared to amputations is maintained. Irradiation improved survival in our patient population. In cases with involvement of neurovascular structures, preoperative down-staging with radio or chemo-therapy may prevent amputation.

Adult↗

Prognostic factors in soft tissue leiomyosarcoma of the extremities: a retrospective analysis of 42 cases.

AIMS: Soft tissue leiomyosarcomas (LMS) are rare tumours which are associated with a poor prognosis. The goals of the present study were to describe the clinico-pathological and prognostic features of 42 patients affected by soft tissue LMS of the extremities. METHODS: The following clinical and pathological parameters were analysed: age, sex, site, size, depth, previous surgical procedures, stage, histological type, nuclear atypia, grade, mitotic activity, necrosis, surgical margins, therapy. Disease-free survival rates were calculated. RESULTS: The overall 2-year and 5-year disease free survival rates were 42.3% and 32.6%, respectively. By univariate analysis, tumour size (< or =10 cm vs. >10 cm; p = 0.01), average mitotic rate (< or =19/10 HPF vs. >19/10 HPF; p = 0.05), type of excision (wide vs. marginal or intralesional; p = 0.001) and adjuvant radiotherapy (none vs. brachytherapy+external beam radiotherapy vs. external beam radiotherapy; p = 0.02) were significantly correlated with disease progression. By multivariate analysis, the only factor that was found to be an independent predictor of disease relapse was type of excision (p = 0.001). CONCLUSIONS: Large tumour size and high mitotic rate resulted adverse prognostic factors. Adjuvant radiation therapy, in combination with wide surgical excision, allowed the best chance of cure.

Adult↗

Histopathological re-classification of extremity pleomorphic soft tissue sarcoma has clinical relevance.

AIMS: The aims were to describe the clinico-pathological features of 65 patients affected by soft tissue pleomorphic sarcomas of the extremities, to evaluate their clinical outcome and to explore the prognostic impact of clinical and pathologic parameters, on disease-free and overall survival. METHODS: Soft tissue pleomorphic sarcomas of the extremities were retrieved to be retrospectively re-evaluated in the current analysis. The following parameters were analysed: age, sex, site, size, stage, histotype, grade, surgical margins, therapy. Disease-free and overall survival rates were calculated according to the Kaplan-Meier method. A multivariate analysis was used to determine which variable had an independent effect on clinical outcome. RESULTS: Sixty-five patients with soft tissue pleomorphic sarcomas of the extremities were included in the study. Upon revision, there were 22 leiomyosarcomas, 13 myxofibrosarcomas, 9 liposarcomas, 10 pleomorphic MFH/undifferentiated high grade pleomorphic sarcomas, and 11 cases were other types of plemorphic sarcomas, including rhabdomyosarcoma (n=4), osteosarcoma (n=2), myofibrosarcoma (n=5). In the whole series, by multivariate analysis, stage was the only factor predictor of disease progression (p=0.001; RR 6.9; 95% CI 1.3-15.6). Considering only localized pleomorphic sarcomas the independent predictors of disease relapse were site (p=0.03; RR 3.6; 95% CI 1.0-12.4) and myogenic differentiation (p=0.04; RR 2.9; 95% CI 0.9-10.0), whereas myogenic differentiation resulted the only independent predictor of overall survival (p=0.03; RR 6.5; 95% CI 1.1-37.9). DISCUSSION: These results indicate that histopathological classification of soft tissue pleomorphic sarcomas is clinically relevant. In our experience, AJCC stage and myogenic differentiation are the factors which independently affect prognosis.

Adolescent↗

[Gait analysis after rotationplasty hip surgery for malignant tumor of the proximal femur].

Rotationplasty of the hip joint is a special surgical technique used for the treatment of malignant tumors of the proximal part of the femur. We report a clinical case and gait analysis results before and after rehabilitation training. Evaluation of joint motion, kinetic moments, and the electromyographic findings enabled us to document progressive adaptation of muscle and joint function to their new role in the motor pattern, demonstrating the exceptional strength of rotationplasty. Active control of two fulcrums in the lower limb, the pseudo hip proximally and the pseudo knee intermedially, makes this type of operation extremely advantageous compared to the alternative of hip disarticulation or hemipelvectomy. Total absence of pain together with the preservation of articular and cutaneous proprioception are important advantages. Rotationplasty is an attractive alternative for treatment of malignant tumors of the proximal part of the femur.

Child↗

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Report II.

In a limited study, comprising only ten patients, we have previously reported that allogeneic irradiated RCC-cell-line cells, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells were used to vaccinate MRCC patients in progression of disease and also receiving IL-2 immunotherapy. The cells, admixed to autologous TC, were administered subcutaneously. We now report an extended study on thirty patients and one hundred thirty-one controls. Patients received 4-20 injections (mean 10 +/- 4), containing an average of 92 x 10(6) +/- 45 x 10(6) ACHN-IL-2 transfected cells (a minimum of 25 x 10(6), and a maximum of 200 x 10(6)). Autologous TC, admixed to allogeneic, were also administered by 4-16 s.c. injections (mean 7 +/- 3), i.e. a total of 12 x 10(6)-160 x 10(6) cells. Vaccination was administered during 73-1451 (307 +/- 316) days, and the follow-up continued for 1122 +/- 1240 days (106-5137). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were noticed. One complete and four partial tumour responses were observed, as well as nine cases of stable disease. Thirteen patients died in the treated group (43%) and 63 (44%) in the control group. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. The Gehan Wilcoxon's test showed a significantly (P < 0.01) better survival in the vaccinated patients compared to that of the controls. Thus, we confirm, in an increased number of patients and an extensive follow-up, that our vaccination protocol is safe, devoid of adverse side effects, and promising.

Adult↗

Autosomal malignant osteopetrosis. From diagnosis to therapy.

Osteopetrosis is a heterogeneous family of rare human genetic disorders due to markedly decreased bone resorption. It is one among disorders causing osteosclerosis of the trabecular bone and/or hyperostosis of the cortical bone. Four types of human osteopetrosis have been clearly defined, but patients with atypical symptoms are frequent, suggesting that there are additional forms. The most severe expression of this condition in its malignant form is inherited as an autosomal recessive disorder and it is usually fatal before school age. It presents with failure to thrive, severe hepatosplenomegaly, pancytopenia and nerve compression leading to blindness and deafness during infancy. The case of a 2-month-old female child with severe hepatosplenomegaly, failure to thrive, nystagmus, pancytopenia, gengival hyperplasia, optic atrophy, absent evoked visual potential and increased bone density within the total skeleton, is reported. Diagnosis of autosomal recessive malignant osteopetrosis was established by transiliac bone biopsy. She underwent bone marrow transplantation, but died soon afterwards. This rare and mortal disorder of bone formation requires early diagnosis and immediate pharmacological treatment, consisting in administration of vitamin D, in order to enhance bone resorption and of prednisone to improve hematological indexes and, if possible, bone marrow transplantation in order to ameliorate quality of life and survival.

Anti-Infective Agents↗

Peptide receptor radiotherapy: a new option for the management of aggressive fibromatosis on behalf of the Italian Sarcoma Group.

The management of aggressive fibromatosis (AF) is problematic, and few options are available to patients unsuitable for surgery and resistant to external-beam radiation therapy (EBRT). We report on two patients with fast-growing recurrences of AF resistant to EBRT who obtained protracted clinical benefits with (90)Y-DOTATOC. (90)Y-DOTATOC should be further investigated in this setting.

Adult↗

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Preliminary report.

An allogeneic irradiated RCC cell line, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells, was used to vaccinate ten MRCC patients in progression of disease in spite of IL-2 immunotherapy. The cells were administered subcutaneously and/or intra-tumourally. Sixty-four MRCC patients in progressive disease, not treated by vaccination but receiving similar IL-2 immunotherapy, were considered as the control group. Patients received 4-16 injections (mean 9 +/- 4), containing an average of 10.6 x 10(7) +/- 7.7 x 10(7) ACHN-IL-2-transfected cells (a minimum of 4 x 10(7), and a maximum of 31 x 10(7)). Four patients also received intra-tumour injections. Vaccination was administered during 30-418 days, and the follow-up continued for 649 +/- 353 days (190-1342). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were observed. One complete and one partial tumour response were observed, as well as two stable and one no-relapse disease. All but one patient died. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. In spite of the small number of treated patients, Wilcoxon's test showed a significant (P < 0.05) improvement of the survival in the vaccinated group compared to that of the control. The described vaccination protocol seems safe, devoid of adverse side effects and promising. It warrants further investigation.

Aged↗

Immunotherapy of metastatic kidney cancer.

From April 1986 to September 2000, 122 MRCC patients were treated by monthly intralymphatic injections (containing a mean of 573 IL-2 U and 26 x 10(6) LAK cells) and i.m. administration of IFN and TF; 71 patients also received a 3-day cycle of monthly IL-2 inhalations with a mean of 998 daily U. MRCC cases not treated by immunotherapy (n = 89) represent our historical controls. Adverse clinical side effects related to treatment were negligible. CR (n = 11) and PR (n = 13) were noticed in 24/122 patients. Of 24 responding patients, 17 resumed progression, whereas 7 remain in remission 11-69 months later. The overall median survival of treated patients (28 months) was 3.5-fold higher than the median survival of historical controls (7.5 months), and a Kaplan-Meier curve showed 25% survival 11 years after the beginning of immunotherapy. Apparently, the addition of IL-2 by inhalation improved survival. The present immunotherapy protocol appears to be efficacious, safe, devoid of adverse side effects, far less costly than others and able to offer a good quality of life to MRCC patients; if confirmed in a multicenter trial, it could set the basis for developing low-dose immunomodulatory treatments.

Adolescent↗

Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli's 4th protocol.

From January 1993 to March 1995, 162 patients with osteosarcoma of extremities were treated according to the IOR/OS-4 protocol. 133 patients had localised disease, while 29 had metastases at diagnosis. These last patients were simultaneously operated upon for their primary and metastatic lesions. Chemotherapy consisted preoperatively of two cycles of high dose methotrexate (HDMTX) and one cycle each of cisplatin (CDP)-doxorubicin (ADM), CDP/ifosfamide (IFO) and IFO/ADM. After surgery, patients were treated with the aforementioned drugs used as single agents. The mean follow-up of all patients was 6.5 years (5.5-8 years). Surgery was a limb salvage in 94% of cases, and the 5-year event-free survival (EFS) and overall survival (OS) rates were 56 and 71% for patients with localised disease, and 17 and 24% for patients with metastases at diagnosis. These results did not differ from those achieved in our previous study (IOR/OS-3) in which IFO was used only postoperatively in poor responders.

Adolescent↗

Skeletal reconstruction with a free vascularized fibula graft associated to bone allograft after resection of malignant bone tumor of limbs.

Over the last twenty years, progress in diagnosis and in adjuvant therapy in the field of malignant bone tumor treatment has allowed for development of limb-saving surgical techniques after oncological excision. In this context, the use of vascularized fibula for transplantation represents an important instrument in the reconstruction of bone, either with or without allografts.Moreover, in pediatric cases, the vascularized transplant of the proximal fibula with its open physis allows for an adequate reconstruction of the bone loss and the possibility of conserving the growth potential of the segment. The purpose of this article is to illustrate the various reconstructive possibilities that the use of the combined graft technique (VFT plus allograft) offers in the treatment of large-scale bone loss. In our department from 1988 to 2000, 142 vascularized fibula transplants were performed in oncological cases. Surgical reconstruction was carried out on the tibia in 70 cases, on the femur in 40, on the humerus in 26 and on the radius in 6. Combined graft intercalary reconstructions were 92. In 22 pediatric cases the fibula was transplanted, including the proximal growing epiphysis in the graft; in two of these cases massive allograft was associated to the VFG. Because of its biological properties, the grafted vascularized fibula allowed for fast bone fusion at the level of the osteotomy. It has also demonstrated a tendency of progressive hypertrophy and osteointegration with the allograft, when used. In 22 pediatric cases, the fibula graft with the proximal epiphysis maintained its ability to grow. Unsuccessful outcomes caused by vascular, mechanical, or septic failure were equal to 8.2 %. The fibula graft in the reconstruction of bone loss secondary to oncological excision is a trustworthy and versatile technique.

Adolescent↗

Neoadjuvant chemotherapy for patients with synchronous multifocal osteosarcoma: results in eleven cases.

Between January 1995 and December 1999, 11 patients with synchronous multifocal osteosarcoma (SMO) received neoadjuvant treatment with high-dose methotrexate, cisplatinum, Adriamycin, and ifosfamide. After primary chemotherapy in 4 patients who had only two bone localizations, it was possible to treat all tumor foci locally. The remaining patients, with more than three bones involved, were treated surgically only in 3 cases at the primary site, while secondary lesions did not receive any treatment. The final results of our study were disappointing. All patients died of the tumor 6 to 24 months after the beginning of treatment (mean 11.9 months). Nevertheless, the survival time of the 4 patients with locally treated lesions was significantly longer than the one of 7 patients in whom the secondary lesions were not locally treated (18.2 vs 9.1 months; P<0.008). It should be noted that those patients simultaneously operated on two sites, the response to chemotherapy of "primary" and "secondary" lesions was always similar. This homogeneity supports the thesis that in synchronous multifocal osteosarcoma the tumors are not multicentric in origin but represent bone-to-bone metastases from a monocentric tumor.

Adolescent↗

Osteoid osteoma and osteoblastoma of the sacrum.

This retrospective study examined 10 patients with osteoid osteoma and 11 patients with osteoblastoma localized in the sacrococcyx. In the sacrum, the diagnosis was delayed compared to other sites. Curettage through a posterior approach is the treatment of choice. Radiotherapy as well as embolization of feeding arteries may be used for the most aggressive lesions. Prognosis is generally good with a low incidence of local recurrence (<10%).

Adolescent↗

Massive bone allograft reconstruction in high-grade osteosarcoma.

From 1986 to 1994, 112 bone allograft reconstructions were performed in patients with high-grade osteosarcoma in whom neoadjuvant chemotherapy was administered. The allograft reconstruction was used in arthrodesis in 44 cases (41 knees, three ankles), as an intercalary graft in 39 (28 femurs, 11 tibias), as an osteoarticular graft in 22 (three proximal and/or distal humeri, six distal femurs, 13 proximal tibias), and as an allograft and prosthesis composite in seven (two proximal humeri, one proximal femurs, four proximal tibias). In 20 patients an autologous vascularized fibula was used to augment the allograft. Functional results were excellent or good in 74% of the patients after the primary surgery, and in 83% of the patients after secondary surgery. Complications include delayed union (49%) and fracture (27%), although there were no cases of deep infection. The incidence of delayed union, but not infection or fracture, was increased by the use of chemotherapy.

Adolescent↗

Intraepiphyseal resection of the proximal tibia and its impact on lower limb growth.

From 1989 through 1996, 10 children affected by high grade bone tumors of the proximal tibia underwent an intraepiphyseal intercalary resection. The residual epiphyseal bone segment measured less than 2 cm in thickness in all cases and reconstruction always was performed using the combination of a vascularized fibular autograft and a massive bone allograft. The proximal epiphyseal osteosynthesis was fixed by small fragment screws. The aim of this study was to report the growth pattern of the residual proximal tibial epiphysis and to evaluate any possible lower limb discrepancy and/or deformity after the end of skeletal maturity. At current followup six patients were available for the final evaluation. Radiographic documentation included computed tomography scan of both knees before surgery, a panoramic radiographic view and a computed tomography scan of both lower limbs after the end of skeletal growth. The length of both femurs and tibias, the size of the tibial plateau and of the opposite distal femur, and any possible deformity of femur or tibia were measured and compared with the preoperative data. No patient had a limb length discrepancy greater than 3.5 cm. In all cases the ipsilateral femur had a valgus deformity of the hip develop. In two patients this deformity was associated with an elongation of the femur, partially compensating for the shortening of the tibia. The tibial plateau close to reconstruction grew less than the contralateral one (range 2%-8%) but maintained its normal relationship with the distal femur. None of these patients reported any restriction in recreational activities. They could walk, run, and jump. Their functional result according the International Society of Limb Salvage functional grading system was satisfactory in all cases.

Bone Neoplasms↗

Expression of transforming growth factor beta isoforms in osteosarcoma variants: association of TGF beta 1 with high-grade osteosarcomas.

Studies on osteosarcoma cell lines point to the potential importance of transforming growth factor beta (TGF beta) as an autocrine factor which controls the growth of human osteosarcomas. To define further the role of TGF beta isoforms in these neoplasms, a series of 27 osteosarcomas was studied using immunohistochemical, mRNA in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. All 14 central high-grade osteosarcomas, two telangiectatic osteosarcomas, and one high-grade surface osteosarcoma showed cytoplasmic immunoreactivity for TGF beta 1, -2, and -3. The expression of TGF beta 1 was moderate or diffuse in 14 cases (82.3 per cent), while low expression was detected in only three cases (17.7 per cent). For TGF beta 2 and -3, only moderate or diffuse staining was observed. Low-grade parosteal and periosteal osteosarcomas showed low or undetectable levels of TGF beta 1, while TGF beta 2 and -3 were moderately or diffusely expressed. Finally, three dedifferentiated parosteal osteosarcomas were diffusely positive for TGF beta 1, -2, and -3 in the high-grade component, while in the low-grade component, available for analysis in two of these cases, TGF beta 1 was demonstrated in a few neoplastic cells, and TGF beta 2 and -3 maintained a diffuse distribution. Statistical analysis of these data showed that high-grade osteosarcomas had a significantly higher expression of TGF beta 1 than low-grade osteosarcomas, while levels of TGF beta 2 and -3 were comparable in the two groups (p < 0.001; p = 0.3; p = 0.3, respectively; Fisher's exact test). Similarly, mRNA levels of TGF beta 1 detected by in situ hybridization were significantly higher (p = 0.04, Fisher's exact test) in high-grade osteosarcoma variants, while no differences were found for TGF beta 2 and -3 mRNA (p = 1.0; p = 0.2, respectively; Fisher's exact test). In addition, mRNA analysis performed by RT-PCR in seven cases (five high-grade and two low-grade osteosarcomas) confirmed the presence of high levels of TGF beta 1 in high-grade osteosarcomas, while low-grade tumours had low or absent mRNA expression. In conclusion, this positive association suggests that TGF beta 1 may be involved in determining the aggressive clinical behaviour of high-grade osteosarcomas.

Bone Neoplasms↗

Synovial chondromatosis in a lumbar apophyseal joint.

A 31-year-old woman presented with painful swelling in the right paravertebral region that had been present for 2 years. Radiography and CT revealed an area of increased density due to multiple calcifications localized at the fourth lumbar vertebra. Histological examination revealed that the lesion consisted of nodules of hyaline cartilage, with focal areas of calcification, growing within synovial tissue.

Adult↗