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Biomedical subjects

R Casadei

Publications and source records attributed to R Casadei.

At least 37 records · Page 2Linked to original sources

Functional epitope mapping of human interleukin-1 beta by surface plasmon resonance.

A panel of monoclonal antibodies to human IL-1 beta has been used to probe its conformational and functional characteristics. Real time antibody-protein interaction was assessed by surface plasmon resonance with a BIAcore apparatus, in order to determine the kinetic and thermodynamic parameters of the interaction and to map the recognition sites of the antibodies on the IL-1 beta surface. Topological analysis was thus compared to the inhibitory capacity of antibodies for IL-1 beta bioactivity and binding to the activating receptor IL-1RI. This functional mapping analysis allows the following hypothesis. At least two discrete areas of IL-1 beta, located within the sequences 133-147 and 177-186 (as defined by mAbs MhC1 and BRhD2, respectively), are apparently involved in IL-1RI-independent agonist activity, and thus possibly take part in the interaction with the receptor accessory protein IL-1RAcP. Another area in the 133-147 sequence (defined by mAb BRhC3) is involved in agonist binding to its receptor CDw121a (IL-1RI), whereas a site recognized by mAb BRhG5 within the sequence 218-243 is selectively responsible for non-agonist binding to the activating receptor. The loop between the 4th and the 5th beta-strand, at the open end of the IL-1 beta-barrel structure, may possibly take part in both non-agonist binding to IL-1RI and in the interaction with IL-1RAcP.

Amino Acid Sequence↗

Macrocystic serous cystadenoma of the pancreas. Diagnostic, therapeutic and pathological considerations of three cases.

BACKGROUND: Macrocystic serous cystadenoma (MSC) of the pancreas is a new entity that has recently been well recognised. This tumour is quite similar in aspect to the mucinous cystic tumours (MCT) but its prognosis is much better, so that a correct diagnosis before surgery is important. PATIENTS: Three patients undergoing surgery in the 1st Surgical Clinic of the University of Bologna for suspected cystic lesions were found to have macrocystic serous cystadenoma (MSC) of the pancreas. In two cases a biopsy was performed during surgery, but in only one was a correct diagnosis of MSC made; in the other the diagnosis was lymphangioma. In the remaining case a biopsy was not performed because the high 19/9 CA level in the blood suggested a diagnosis of MCT of the pancreas. In all 3 cases the tumour was successfully removed by surgery. CONCLUSIONS: Macrocystic serous cystadenoma (MSC) of the pancreas represents a variant of the serous cystic tumors, which encompass microcystic adenoma and serous cystadenocarcinoma. MSC must be distinguished from MCT because it exhibits a different biological pattern and requires a different surgical approach. Therefore, we would underline the importance of a biopsy in making the differential diagnosis.

Adult↗

Gastrointestinal autonomic nerve tumor of the jejunum. Case report and review of the literature.

Gastrointestinal autonomic nerve tumor is very rare and it is difficult to distinguish this tumor from other gastrointestinal tumors due to the absence of clinical, instrumental and macroscopic features which allow pre- or intraoperative diagnosis. Our aim was to recognize the characteristic features (preoperative, intraoperative, pathological) that would allow diagnosis of gastrointestinal autonomic nerve tumor. A case of gastrointestinal autonomic nerve tumor of the jejunum is reported. Surgical specimen was routinely processed. Immunohistochemical staining was performed according to modified immunoperoxidase Avidin-Biotin-Peroxidase Complex method. An electron microscopy study was also performed. The tumor mass showed some characteristic pathological findings: histologically, it was composed of spindle cells and epithelioid cells; immunohistochemically, a focal positivity for Neuron Specific Enolase was shown, and finally, ultrastructural examination showed neuron-like cells with long cytoplasmic processes containing microtubules and bulbouns synapse-like structures with dense core neurosecretory-type granules. Preoperatively gastrointestinal autonomic nerve tumor of the jejunum must be considered and treated as a malignant tumor. A correct diagnosis is possible only with immunohistochemical and ultrastructural studies. It is probable that this tumor is more common than previously thought.

Aged↗

Aneurysmal bone cyst and giant cell tumor of the foot.

From 1950 to 1994, 257 cases of benign bone tumors of the foot were treated at the Bone Tumor Center of the Rizzoli Institute. Aneurysmal bone cysts (ABC) and giant cell tumors (GCT) are rare and often they are misdiagnosed. To define the clinical and radiographic features useful for diagnosis, x-rays of 24 ABCs and 21 GCTs of the foot were reviewed. Adding our series to the cases reported in the literature, the only important clinical data that emerged was the average age of patients affected by ABC and GCT (15 and 27 years, respectively). ABCs localized in small tarsal bones were rare (6%), whereas 19% of GCTs were found in this site. The eccentric, round shape of a lytic lesion was more characteristic of GCT. An aggressive pattern of radiographic bone destruction was observed more frequently in GCT than in ABC (P = 0.01). Septation was seen in both tumors. Typical of ABC was a sharp and trabeculated margin, whereas GCT had an ill-defined edge with normal cancellous bone (P = 0.007). The growth of ABCs often expanded the cortex, while GCTs eroded, thinned, and broke the cortical bone (P = 0.001). A saucerized cortex was observed only in ABCs. A bony shelf was more characteristic of ABC than of GCT (P = 0.002). Pathologic fractures (67%) and joint involvement, evaluated by computed tomography and magnetic resonance imaging (83%), were more frequent in GCTs, whereas fluid levels were more frequently observed in ABCs (47%). The majority of the tumors were stage 2, but GCTs represented 70% of stage 3 aggressive lesions.

Adolescent↗

Alcoholic liver disease in alcoholic chronic pancreatitis: a prospective study.

The prevalence and characteristics of alcoholic liver disease (ALD) in patients with alcohol-induced chronic pancreatitis (AICP) are not well defined. Fifty consecutive patients undergoing surgery for AICP were investigated for evidence of ALD. In addition to preoperative functional and imaging assessment of the liver, all had liver biopsy during surgery. Hepatic biopsy results were as follows: 12 patients had normal liver and 10 minimal aspecific changes; of the remaining 28 patients, 7 had liver cirrhosis, 11 showed features of alcoholic hepatitis, 2 had moderate steatosis, 6 extrahepatic cholestasis, and the remaining 2 had a combination of alcoholic hepatitis and cholestasis. Of the 7 patients with cirrhosis, 3 had oesophageal varices and 2 of these developed ascites in the postoperative period; in the remaining patients with ALD, this disease was subclinical. Patients with ALD consumed significantly (p < 0.005) more alcohol than those without ALD. In patients with cirrhosis, the duration of alcohol consumption (mean 27.6 years, range 18-42 years) was significantly longer (p < 0.05) than in patients without ALD (mean 19.7 years, range 8-36 years). The association of ALD with AICP is much more common than previously believed. The fact that AICP occurs earlier than liver cirrhosis and the fact that many patients stop alcohol consumption after the first attacks of pancreatic pain may explain, at least in part, the apparent rarity with which this association has been indicated by previous studies.

Adolescent↗

Prognostic significance of serum lactate dehydrogenase in patients with osteosarcoma of the extremities.

Six hundred and fifty-six patients with osteosarcoma of the extremities (107 metastatic and 549 with localized disease) were followed from 2.5 to 20 years (average: 10 years) to evaluate whether their pretreatment serum lactate dehydrogenase (LDH) enzyme levels had a clinical value in predicting the course of the disease. The percentage of patients who had an elevated serum LDH at the time of diagnosis was significantly higher in those patients with metastatic disease than those who had localized disease (64% versus 33%, p < 0.0001). For those who presented with localized disease and had an increased serum LDH level, far more ultimately developed a relapse of disease (60% versus 38%, p < 0.0001) than those patients with a normal pre-treatment value. The prognostic significance of the serum LDH was more pronounced for the 247 patients treated with adjuvant chemotherapy (relapse rate of 72% versus 48%; p < 0.0002) than the 271 patients treated with neoadjuvant chemotherapy (relapse rate: 46% versus 28%, p < 0.005). Following treatment, serum LDH levels almost uniformly returned to normal and no correlation between postoperative levels and relapse of disease could be identified. We have demonstrated that in patients with osteosarcoma of the extremities, pretreatment serum LDH levels have a definite prognostic value which should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.

Adolescent↗

Ankle resection arthrodesis in patients with bone tumors.

The authors report 12 cases of bone tumors localized in the distal tibia treated by resection and reconstruction with ankle arthrodesis, using bone grafts and fixation with Kuntscher or Grosse-Kempf nail or plate. In seven cases autografts were used, and in five cases autografts combined with allografts were used. In three of these five patients, a vascularized fibula combined with a "gutter-like" allograft was used to reconstruct the bone defect. In all cases, the functional and oncologic results were good and all patients were disease free at an average follow-up of 68 months.

Adolescent↗

Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma.

PURPOSE AND METHODS: To assess patients with high-grade osteosarcoma treated at our institution for various prognostic factors for the development of local recurrence of disease. Follow-up data were available for all patients and the mean follow-up duration was 65 months in surviving patients. RESULTS: There were 28 local recurrences in this study (7%). Of these, only three patients (11%) were alive at the most recent follow-up point, 28, 53, and 54 months after local recurrence. None of 59 patients who were treated primarily with a radical amputation and none of 10 who underwent a rotationplasty developed local recurrence. Four of 48 patients (8%) who had wide amputations, one of whom had an intralesional amputation, and 23 of 237 (10%) who had limb-salvage surgery developed locally recurrent disease. Of 237 patients who underwent limb-sparing resection, three prognostic factors for local control were identified. The strongest association with local recurrence was chemotherapy response (P < .0001), followed closely by surgical margins (P = .0001). Older patients were more likely to have locally recurrent disease (P = .033), with each decade of life older than the first decade having a relative risk of 1.5 times greater per decade (SE = 0.16; 95% confidence interval, 0.034 to .0650). Factors that were not associated with local recurrence included sex, date of diagnosis, and anatomic site of disease. CONCLUSION: Chemotherapy-induced tumor necrosis and surgical margins are important prognostic factors for local control of patients with osteosarcoma.

Adolescent↗

Serum soluble interleukin-2 receptor in pancreatic cancer and chronic pancreatitis.

Activated lymphocytes can release a soluble form of interleukin-2 receptor (sIL-2R) and abnormally high serum levels of sIL-2R have been reported in patients with advanced solid tumours and in those with chronic disease. We determined serum sIL-2R concentrations in 34 patients with chronic pancreatitis (8 in painful relapse), in 40 with pancreatic tumours in various stages, and in 40 healthy subjects as controls. Patients with pancreatic cancer and those with chronic pancreatitis had significantly higher serum concentrations of sIL-2R than healthy subjects (p < 0.001). In patients with Stage II pancreatic cancer, serum levels of soluble receptors were similar to those in patients with Stage III tumours, and these concentrations were significantly higher than in patients with resectable cancer (p < 0.01 and p < 0.05, respectively). In chronic pancreatitis patients, those studied during painful relapse of the disease had higher serum concentrations of sIL-2R than those studied during clinical remission (p < 0.05). The results of our study suggest an activation of the cellular immune system in pancreatic cancer and in chronic pancreatitis.

Aged↗

Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin.

BACKGROUND: Neoadjuvant chemotherapy is the most accepted treatment for localized osteosarcoma. This has led to a great improvement in limb-sparing surgery and in disease-free survival. Patients with a good response to preoperative chemotherapy showed a higher disease-free survival rate. Current studies examine the possibility of patients whose limbs could be rescued with a poor necrosis and a reduction of the side effects related to aggressive treatments. METHODS: Between September 1986 and December 1989, 164 patients entered the second neoadjuvant study conducted at the Rizzoli Institute, Bologna, Italy, for non-metastatic osteosarcoma of the extremities. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate intravenously (i.v.) followed by cisplatin intraarterially and doxorubicin i.v. After surgery, patients classified as good responders (> 90% tumor necrosis) received three more cycles of these drugs, whereas poor responders (< 90% tumor necrosis) had more chemotherapy, which included ifosfamide and etoposide in addition to the other three drugs. RESULTS: Limb salvage was performed in 83% of cases. At an average follow-up of 54 months (36-76), 109 patients (66%) were continuously disease-free, 2 died from doxorubicin cardiotoxicity, and 52 experienced metastases and 3 had local recurrence. In two of these three patients, metastases followed local recurrence. The 5-year actuarial continuously disease-free survival rate was 63%, with no differences between good and poor responders. Excluding 20 patients who had major protocol violations, the projected continuous disease-free survival rate was 71%. CONCLUSIONS: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of nonmetastatic osteosarcoma of the extremities, avoiding amputation in most cases. Ifosfamide and etoposide seem to be effective in patients who did not respond to preoperative chemotherapy.

Adolescent↗

Prognostic significance of serum alkaline phosphatase measurements in patients with osteosarcoma treated with adjuvant or neoadjuvant chemotherapy.

BACKGROUND: It is known that many patients with osteosarcoma have high serum alkaline phosphatase (SAP) levels. The prognostic significance of this finding, however, is still controversial. METHODS: The pretreatment SAP levels of 656 patients with osteosarcoma of the extremities (107 metastatic and 549 localized at presentation) were examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. RESULTS: The percentage of patients with increased SAP levels was significantly higher in the metastatic group than in the group of patients with localized disease (91.5% versus 61.3%; P < 0.001). In the latter group, treated with adjuvant and neoadjuvant chemotherapy, the relapse rate was significantly higher in patients with elevated pretreatment SAP levels than in those with normal levels (55.1% versus 26.4%; P < 0.001). Among patients with elevated SAP levels, the percentage of relapses was higher in patients with high levels of the enzyme in comparison with patients with moderately elevated values (66.4% versus 47%; P < 0.05). After treatment, SAP levels almost always return to normal values, and a correlation between postoperative levels of the enzyme and prognosis could not be made. CONCLUSIONS: These data demonstrate that in osteosarcoma of the extremities, pretreatment SAP levels have a prognostic value and they should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.

Adult↗

Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy: results of two sequential studies.

The results of two sequential studies of neoadjuvant chemotherapy for osteosarcoma of the extremities performed at Rizzoli Institute between 1986 and 1991 in 228 patients are presented. In both studies preoperative chemotherapy consisted of two cycles of high dose methotrexate (HDMTX), cisplatinum (CDP) and adriamycin (ADM). Postoperatively the good responder patients were treated with the same drugs used before surgery while in the poor responder patients ifosfamide was added to these three drugs. The preoperative treatment was the same in both studies while after surgery in the second protocol either the cumulative dose of ADM (270 mg/m2 instead of 360 mg/m2) or the single dose per cycle of this drug (60 mg/m2 instead of 90 mg/m2) was reduced. These changes in the last protocol were done to reduce the cardiotoxicity of ADM that was high in the first study (2 deaths and 1 heart transplantation). Since in the last protocol--in comparison with the first protocol--after surgery chemotherapy was restarted earlier and ADM was administered not as a single drug but in combination with the CDP the dose intensity of ADM was unchanged while the dose intensity of MTX, CDP and ifosfamide was higher than in the first study. The preliminary results of the 84 patients treated in the second study show a 2-year disease free survival significantly lower than that achieved in the 144 patients treated in the first study (37/51--73% vs 123/144--85%: P < 0.008). In addition, even if in the last study there were no cases of clinical cardiotoxicity due to ADM, there was a significantly higher percentage of severe myelodepression that led to two deaths for infectious complications. These results suggest that in neoadjuvant treatment of osteosarcoma the total dose of ADM and/or the single dose per cycle of the same drug are an important determinant of outcome and that increasing the dose-intensity of less toxic but less active agents, MTX, CDP and ifosfamide, at the expense of the more active and more toxic agent, ADM, can lead to a poorer outcome without reducing toxicity.

Adolescent↗

No advantages in the addition of ifosfamide and VP-16 to the standard four-drug regimen in the maintenance phase of neoadjuvant chemotherapy of Ewing's sarcoma of bone: results of two sequential studies.

Between January 1988 and December 1990, 74 patients with localized Ewing's sarcoma of bone were treated with a new protocol that consisted of an initial 6-week period of chemotherapy with vincristine (VCR), adriamycin (ADM) and cyclophosphamide (EDX) followed by local therapy and additional chemotherapy with the same drugs previously indicated plus ifosfamide and VP-16. The rationale for the addition of ifosfamide and VP-16 to the four drugs of the standard chemotherapy of this tumor was that this drug combination was previously very effective in the treatment of metastases from Ewing's sarcoma even in patients who did not respond to cyclophosphamide. As local treatment all patients were offered surgery, when feasible (70 cases). Forty-three patients accepted and 27 refused. These patients, as the 4 patients in whom surgery was not considered feasible, were treated with radiation therapy alone (50-60 Gy). In the remaining patients amputation was performed in 4 cases, rotationplasty in 3 and resection in 36. Where conservative surgery was marginal or intralesional (30 cases), radiotherapy at lower doses (40-45 Gy) was also delivered. At a mean follow-up of 3.5 years (2-7), 43 patients (58%) remained continuously disease-free and 31 relapsed (29 with metastases and 2 with both metastases and local recurrences). These results do not differ from those obtained at our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol in which only VCR, ADM, EDX and dactinomycin (DAC) were used (3-year continuously disease-free survival (CDFS) respectively of 54% and 55%). Despite the fact that these results came from a nonrandomized study, the Authors conclude that the addition of ifosfamide and VP-16 to the four-drug standard regimen did not improve the outcome of the patients with Ewing's sarcoma of bone which remains a lethal disease in about 50% of the cases. These findings stress the need to find more effective chemotherapeutic regimens for the associated treatment of this tumor.

Adolescent↗