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Biomedical subjects

M Santinami

Publications and source records attributed to M Santinami.

At least 19 recordsLinked to original sources
PubMed2006

Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been and is still widely used as an adjuvant in clinical trials of vaccination with autologous tumor cells, peptides and/or dendritic cells in a variety of human neoplasms. This cytokine was administered either as product of gene-transduced tumor cells or as recombinant protein together with the vaccine given subcutaneously or intradermally. Results of these trials were heterogeneous in terms of induction of vaccine-specific immune response and of clinical response. Though in some of these studies GM-CSF appeared to help in generating an immune response, in others no effect or even a suppressive effect was reported. Here, we review the literature dealing with the immune adjuvant activity of GM-CSF both in animal models and clinical trials. As a consequence of such analysis, we conclude that GM-CSF may increase the vaccine-induced immune response when administered repeatedly at relatively low doses (range 40-80 microg for 1-5 days) whereas an opposite effect was often reported at dosages of 100-500 microg. The potential mechanisms of the GM-CSF-mediated immune suppression are discussed at the light of studies describing the activation and expansion of myeloid suppressor cells by endogenous tumor-derived or exogenous GM-CSF.

Adjuvants, Immunologic↗
PubMed2006

Micro-melanoma detection: a clinical study on 206 consecutive cases of pigmented skin lesions with a diameter < or = 3 mm.

BACKGROUND: Very small pigmented lesions may represent an important diagnostic challenge to the clinician. OBJECTIVES: The aim of the present study was to establish the diagnostic value, in terms of sensitivity and specificity, of both clinical and dermoscopic examinations in a population of patients with unselected consecutive pigmented lesions with a maximum clinical diameter of 3 mm. PATIENTS AND METHODS: Two hundred and four consecutive patients bearing 206 pigmented skin lesions with a maximum diameter of 3 mm were seen and operated on. Twenty-three of these lesions were melanomas. Each lesion was subjected to both clinical and dermoscopic evaluation before surgery. The results were expressed in terms of sensitivity and specificity of both kinds of evaluation. RESULTS: Clinical evaluation produced a diagnostic sensitivity of 43% and a specificity of 91%. Dermoscopy resulted in a sensitivity of 83% and in a specificity of 69%. The comparison between the sensitivity values of the two diagnostic methods showed a significant difference (P < 0.01). A high value of significance was also obtained comparing the respective specificity values (P < 0.001). CONCLUSIONS: Detection of very small melanomas is feasible by accurate visual inspection. Dermoscopy appears to be an important aid to diagnosis, provided that physicians are aware of this type of lesion and maintain the index of suspicion at a high level.

Adolescent↗
PubMed2005

Lymphoscintigraphy with intraoperative gamma probe sentinel node detection: clinical impact in patients with head and neck melanomas.

AIM: The aims of this paper were to evaluate the clinical relevance of lymphoscintigraphy with intraoperative gamma-probe detection in identifying sentinel nodes (SNs) and to study the prognostic value of SN biopsy in head and neck melanoma patients. METHODS: Sixty-one patients had lymphoscintigraphy with intradermal injections of 99mTc-Nanocoll (40 MBq), 24 h before surgery. Tumor-positive SNs patients underwent total lymph node dissection. Postoperative histological examination was performed. Patients were followed up for 1 to 5 years (median 3 years). The tumor relapses and the overall survival were evaluated by means of statistical methods. RESULTS: Lymphoscintigraphy showed lymphatic distribution to more than one basin in 45 patients (74%), in 15 patients one basin was visualized and no basin in 1 patient. In 41 patients the SN was negative for metastases, while in 20 was positive. In a high percentage of patients (30%), metastatic involvement occurred in more than one lymph node basin. During follow-up in the negative SN group, 40 patients remained disease free and 1 relapsed. In the positive SN group, 10 patients remained disease free and 10 relapsed. Recurrence time ranged from 6 to 11 months. The overall survival of the SNs negative group was significantly higher than the positive SN group. CONCLUSIONS: This approach was able to distinguish: a) patients with tumor-negative SNs with a favorable clinical course (98% did not relapse, P<0.001); b) patients with tumor-positive SNs with a high rate of tumor relapse (50%, P<0.001). Therefore SN biopsy may give information about prognosis in head and neck melanoma patients.

Adult↗
PubMed2004

Atypical pleomorphic epithelioid angiomyolipoma localized to the pelvis: a case report and review of the literature.

AIMS: Angiomyolipoma is the most common mesenchymal tumour of the kidney. It has been reported in several other sites outside the kidney, mainly in the liver. We report the first case of atypical pleomorphic angiomyolipoma in a man, arising from the pouch of Douglas and extending to the entire abdominal cavity. METHODS: A 17-year-old man underwent a complete resection of a giant abdominopelvic mass. The tissue was formalin fixed and paraffin embedded and 4 micro m thick histological sections were stained with haematoxylin-eosin. Immunohistochemical stains for HMB-45, smooth muscle actin, vimentin, calponin, S100 and desmin were performed. Sections for electron microscopy were also prepared. RESULTS: Microscopic examination revealed a neoplasm composed of pleomorphic epithelioid cells with atypical features, immunoreactive for HMB-45, MART-1, actin, vimentin and calponin, while S100 protein and desmin stains were negative. Ultrastructurally, the tumour cells showed prominent nucleoli, vacuolated cytoplasm, and some premelanosomes. A diagnosis of atypical pleomorphic epithelioid angiomyolipoma was then made. CONCLUSIONS: To date five patients with abdominal epithelioid angiomyolipoma have been described in the literature. All were women. Three of the five patients reported developed metastasis, while our patient is still free of disease at 16 months of follow-up. Clear prognostic pathological features have not been identified.

Adolescent↗
PubMed2003

Quality of surgery and outcome in extra-abdominal aggressive fibromatosis: a series of patients surgically treated at a single institution.

PURPOSE: To explore prognostic factors in surgically treated aggressive fibromatosis (extra-abdominal desmoid tumor). PATIENTS AND METHODS: A total of 203 consecutive patients treated with surgery over a 35-year period at a single referral center were retrospectively reviewed. One hundred twenty-eight were first seen at our institution with primary disease, whereas 75 had a recurrent tumor. All patients underwent macroscopically complete resection. Margins were rated as negative in 146 (97 with primary tumors, 49 with recurrences) and positive in 57 (31 in primary, 26 in recurrences) patients. Median follow-up was 135 months. RESULTS: Patients with primary disease had a better disease-free survival rate than those with recurrence (76% v 59% at 10 years). Presenting with a recurrence was also the strongest predictor of local failure in the multivariate analysis. In patients first treated for primary disease, size and site had prognostic significance, whereas microscopically positive surgical margins did not. In contrast, in patients with recurrence, there was a trend toward better prognosis if margins were negative (although this was not significant at multivariate analysis). CONCLUSION: Presence of microscopic disease does not necessarily affect long-term disease-free survival in patients with primary presentation of extra-abdominal desmoid tumors. Thus, function-sparing surgery may be a reasonable choice when feasible without leaving macroscopic residual disease. In patients with recurrences, positive margins may more clearly affect prognosis, potentially necessitating adjuvant radiation in selected cases.

Adolescent↗
PubMed2003

World Health Organization experience in the treatment of melanoma.

The method of randomized trials, as performed by the WHO Melanoma Program, has definitely been a legitimate clinical study design in patients with melanoma from about 1970 to the end of the last century. Three important results of these WHO trials have substantially influenced the approach of the clinician towards melanoma: (1) There is no role for elective regional lymph node dissection, (2) narrow local excision of the primary melanoma does not entail additional risks, and (3) adjuvant treatment with chemotherapy or immunotherapy after radical surgery for regional lymph node metastases has not, until now, shown any substantial benefit. A problem arises because randomized clinical studies require long periods of time for patients accrual and completion. Frequently their legitimacy is challenged due to the appearance of new parameters, both regarding staging (eg, the introduction of new technical method such as sentinel node biopsy) and prognosis. Therefore, it would be better to define different clinical study models to quickly test a hypothesis on a small group of selected patients in order to provide quick results. We believe that this is the future of clinical research in the new millennium, because it does not seem reasonable today to plan large clinical trials that need 10 years or more of accrual and follow-up without reaching definite conclusions.

Chemotherapy, Adjuvant↗
PubMed2003

Chordoma: natural history and results in 28 patients treated at a single institution.

BACKGROUND: The natural history of chordoma is characterized by a high failure rate and a poor functional outcome. The purpose of this study was to review the long-term outcome of our institutional experience. METHODS: The clinical features, type of treatment, pathologic assessment, and follow-up of 56 consecutive patients with chordoma were reviewed. RESULTS: Fifty sacral and six mobile spine chordomas (median size, 13 cm; range, 2-30 cm) were treated at our center between January 1933 and December 2000. Twenty-eight patients affected by sacrococcygeal chordoma and operated on after 1977 form the basis of our study. Surgical margins were rated as wide in 11 cases, marginal in 13 cases, and intralesional in 4 cases. The median follow-up was 71 months (range, 15-200 months). Seventeen patients' disease recurred. Ten patients died as a result of disease. Nine patients remained continuously free of disease. The estimated 5- and 10-year overall survival was, respectively, 87.8% and 48.9%; disease-free survival was 60.6% and 24.2%. Radiotherapy was considered for marginal and intralesional resections. CONCLUSIONS: High sacral amputation can achieve a good rate of wide-margin resections for sacrococcygeal chordomas. Adjuvant radiotherapy may offset the negative effect in the prognosis of marginal resections.

Adult↗
PubMed2003

Doxorubicin in isolation limb perfusion in the treatment of advanced limb soft tissue sarcoma.

Hyperthermic antiblastic perfusion/HAP) has been proven to be an effective neoadjuvant treatment in the treatment of advanced soft tissue limb sarcoma. As a matter of fact high percentage of limb sparing surgery, local control and functional results have been obtained wide this technique. Many antineoplastic drugs have been associated to hyperthermia by isolation limb perfusion, the aim of this paper was to describe the results obtained with doxorubicin in association to hyperthermia with or without Tumor Necrosis Factor (TNF) alpha in order to identify the most effective regimen in the multidisciplinary treatment of soft tissue limb sarcoma. A total of 106 patients have been evaluated. Three different study were performed: the first was a phase I study carried out in order to assess the maximum tolerable dose (MTD) of doxorubicin during HAP; the second was a phase II study with doxorubicin, and the third was a phase I - II study aimed at evaluating the MTD and tumor response of TNF alpha in association to doxorubicin and hyperthermia. Grade IV limb toxicity was recorded in 11 patients ( 4 in trial A, 3 in trial B, and 4 in trial C). The grade of limb reaction was strictly related to TNF dosage (> 1 mg) and temperature level (> 41.5 degrees C), therefore the best regimen is represented by temperature level not exceeding 41.5 degrees C and 1 mg of TNFalpha. The trimodality association (TNF, doxorubicin and hyperthermia) was proven to be the best regimen able to obtain a 77% of objective response (complete response, 22%) and a 77% of limb sparing in patients candidate to amputation. The results above mentioned showed the HAP with doxorubicin and TNFalpha (1 mg) is a very effective neoadjuvant treatment in the multidisciplinary treatment of advanced soft tissue limb sarcoma.

Adolescent↗
PubMed2001

Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomised trial.

BACKGROUND: Less than half of patients with melanoma that has spread to local draining regional lymph nodes (stage III melanoma) live with no disease for 5 years or longer after surgery. We aimed to see whether interferon alpha-2a increased survival prospects in these patients. METHODS: 444 patients from 23 centres in the WHO Melanoma Programme had complete lymphadenectomy for pathologically proven regional nodal spread of melanoma and were randomly assigned to receive either 3 MU subcutaneously of recombinant interferon alpha-2a three times a week for 3 years, or to observation alone after surgery. Patients were stratified by centre, nodes with macroscopic or microscopic melanoma, number of affected nodes, and nodal metastatic spread. Treatment was continued for 3 years or until first sign of relapse. FINDINGS: 424 patients entered the study. 5-year disease-free survival of those who had surgery plus interferon alpha-2a was 27.5% (95% CI 21.7-33.6); for those who received surgery alone, survival was 28.4% (22.5-34.6) (p=0.50). Neither Kaplan-Meier cumulative survival rates, nor multivariate analysis of survival, showed a difference between those who had surgery and interferon alpha-2a (35%, 95% CI 29-42) and those who had surgery alone (37%, 31-44). INTERPRETATION: Patients with melanoma that has spread to the local draining regional lymph nodes tolerate well 3 MU of interferon alpha-2a given subcutaneously three times a week for 3 years, but this treatment does not improve either disease-free or overall survival.

Adolescent↗
PubMed2001

Do patients with tumor-positive sentinel nodes constitute a homogeneous group?

From January 1993 to May 2000, 1062 patients with primary cutaneous melanoma and no evidence of clinically detectable regional node metastases underwent sentinel node (SN) dissection to microscopically define the tumor status of the regional lymph nodes. A total of 1165 biopsies were performed. The SN identification rate was 89.6%. In 62.2% of the cases, only one SN was detected; 26.4% of patients had two SNs; and 11.4% had three or more SNs. Analysis of survival indicated that the tumor status of the nodes was the most important prognostic factor. Breslow's thickness had a significant impact on survival in tumors 4 mm or thicker, and ulceration dropped to a borderline-significant P value. To assess the tumor burden in positive SNs, all slides for patients at the Istituto Nazionale Tumori and S. Pio X Hospital were reviewed. Of 658 patients in this series, 90 had positive SNs. Eighteen of these patients had evidence of metastasis in other nodes. Of the remaining 72 with a single tumor-involved SN, 62% had a single metastatic deposit. Preliminary data from this study indicate that several subgroups may be identified among patients with positive nodes, but adequate analysis of survival requires a larger number of patients and a multicenter study.

Female↗
PubMed2001

Isolated limb perfusion: the European experience.

Isolated limb perfusion (ILP) is a method of cancer treatment allowing the administration of high doses of anticancer agents in a limb surgically isolated from systemic circulation. By using continuous leakage monitoring and using the drug melphalan, a high complete remission rate is obtained in patients with melanoma. In patients with sarcomas, ILP with tumor necrosis factor and melphalan represents a neoadjuvant treatment for limb-sparing surgery. This treatment is the first demonstration of an active anti-angiogenic regimen in the clinic.

Antineoplastic Agents↗
PubMed2001

Impact of clinical trials on the treatment of melanoma.

Today the role of clinical trials is being challenged and it seems that this investigative tool does not keep in step with the rhythms imposed by the progress of scientific knowledge and the expectations of the public and media. From the 1970's to the 1990's, however, clinical trials have been the most important way for clinical researchers to find answers to therapeutic questions.

Humans↗
PubMed2000

Sentinel lymph node biopsy in cutaneous melanoma: the WHO Melanoma Program experience.

BACKGROUND: We report the experience of the World Health Organization (WHO) Melanoma Program concerning sentinel lymph node (SLN) biopsy for detecting patients with occult regional nodal metastases to submit to selective regional node dissection. METHODS: From February 1994 to August 1998, in 12 centers of the WHO Melanoma Program, 892 SLN biopsies were performed in 829 patients with clinical stage I melanoma (male: 370; female: 459; median age: 50 years old). The location of the primary melanoma was as follows: trunk 35%; lower limbs, 45%; upper limbs, 18%; and head and neck, 2%. Blue dye injection for SLN identification was performed in all cases; preoperative lymphoscintigraphy was done in 440 patients, and an intra-operative probe for a radio-guided biopsy was used in 141 cases. Overall, the SLN identification rate was 88%. In 68% of the patients, only one SLN was identified, whereas two and three or more SLN were detected in 24% and 8% of the remaining cases, respectively. RESULTS: Overall SLN positivity rate was 18%. Intra-operative frozen section examination was performed in 39% of the cases and was helpful in detecting occult localizations only in 47% of the positive SLNs. Distribution of positive cases by primary thickness was as follows: < 1mm: 2%; 1-1.99 mm: 7%; 2-2.99 mm: 13%; and > or = 3 mm: 31%. Positive nonsentinel lymph nodes were found in 22% of cases with positive SLN submitted for selective dissection. No complications due to the procedure were registered. Of 710 patients who were evaluated, 40 (6%) presented a regional nodal relapse after a negative SLN biopsy and underwent a delayed therapeutic dissection. From the 710 enrolled cases, 638 (88.5%) were alive without evidence of disease at the time of this writing. A multivariate analysis showed SLN status as one of the most significant prognostic factors (P = .000) along with thickness (P = .001) and ulceration (P = .015) of primary tumor. CONCLUSIONS: These data confirm the feasibility and safety of the SLN technique for selecting patients to submit to a radical node dissection. The data represent the basis for a future trial by the WHO Melanoma Program in this field to evaluate the most appropriate surgical approach for treating patients with occult regional nodal metastases.

Adolescent↗
PubMed1999

Hyperthermic antiblastic perfusion with alpha tumor necrosis factor and doxorubicin for the treatment of soft tissue limb sarcoma in candidates for amputation: results of a phase I study.

To improve the therapeutic effectiveness of hyperthermic antiblastic perfusion (HAP), the association of recombinant tumor necrosis factor alpha (rTNF alpha), doxorubicin, and true hyperthermia (41 degrees C) was employed for the treatment of soft tissue limb sarcoma. A dose-escalation study according to Fibonacci's modified scheme was conducted, starting with a rTNF alpha dose of 0.5-3.3 mg. The doxorubicin doses (0.7 and 1.4 mg for the upper and lower limbs, respectively) and temperature level (41 degrees C) remained unchanged. Eighteen patients have been treated thus far: 9 males and 9 females of a mean age of 33 years (range: 24-71 years). The tumor was located in the upper limb in one patient and in the lower limbs in seventeen. Only 16 patients were evaluable, as 2 refused further treatment after the perfusion. In terms of local toxicity, a grade I limb reaction was observed in 3 patients, a grade II or III in 10 patients, and a grade IV in 5 patients, showing a strict correlation between the TNF dose and the grade of limb reaction. In fact, a grade III-IV limb reaction was observed in 66.6% of the patients treated with > 1 mg of rTNF alpha. The maximum tolerable dose in association with doxorubicin and true hyperthermia (41 degrees C) was 2.4 mg. Eleven patients showed a good pathological response (> 75%) and five patients showed a partial response (> 25%-< 75%). In no case was stable or progressive disease observed. The postperfusional tumor shrinkage permitted limb-sparing surgery in 75% of the patients, all of whom were candidates for amputation before HAP. No recurrences have been observed thus far. Two patients developed regional disease: one presented with a skip femur metastasis that disappeared after radiotherapy and systemic chemotherapy; the second developed regional node involvement, requiring a radical node dissection. Another patient had pulmonary metastases, 2 months after the HAP, which were resected. At a median follow-up of 12 months, all the patients are living without disease. The results of this phase I study suggest that the association of rTNF alpha, doxorubicin, and true HAP (41 degrees C) by regional perfusion is feasible and safe at a maximum tolerable rTNF alpha dose of 2.4 mg. However, because no correlation was found between the amount of rTNF alpha and the tumor response, 1 mg is recommended as the dose able to provide a high tumor necrosis rate and low local and systemic toxicity. This association appears to play an important role in the neoadjuvant treatment of soft tissue limb sarcoma.

Adult↗
PubMed1999

Sentinel node biopsy and selective lymph node dissection in cutaneous melanoma patients.

Sentinel node biopsy allows an accurate selection of melanoma patients to be submitted to therapeutic dissection. From February 1994 to August 1998, at the National Cancer Institute, S. Pio X Hospital in Milan and Bufalini Hospital in Cesena, 580 sentinel node biopsies were performed in 540 stage I melanoma patients (242 males; 298 females; median age 47). Primary melanoma was located in the trunk in 201 patients, in lower limbs in 242 cases, in upper limbs in 80 cases and in head and neck in 17 patients. Injection of blue dye for sentinel node identification was performed in all cases; 372 patients were submitted to preoperative lymphoscintigraphy and in 272 cases an intraoperatory probe for a radioguided biopsy was utilized. Sentinel node identification rate was 91%. Sentinel node positivity rate was 15%. Frozen sections were examined in 199 cases. Distribution of positive cases according to primary thickness is the following: <1 mm: 1%; 1-1.99 mm: 5%; 2-2.99 mm: 18% and > or =3 mm: 27%. Sentinel node appeared to be the only metastatic node in 77% of patients submitted to dissection. The adoption of preoperative lymphoscintigraphy and the intraoperative use of the gamma probe contributed substantially in S.N. identification. No complications caused by the procedure were reported. Eight patients had a regional node relapse after a negative sentinel node biopsy and were submitted to therapeutic distant dissection. Currently 513 patients are alive with no evidence of disease. Present data confirm the feasibility and safety of sentinel node technique for selection of patients to be submitted to radical node dissection and to eventual adjuvant treatments.

Adolescent↗
PubMed1998

Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme.

BACKGROUND: The use of elective regional node dissection in patients with cutaneous melanoma without any clinical evidence of metastatic spread is still debated. Our aim was to evaluate the efficacy of immediate node dissection in patients with melanoma of the trunk and without clinical evidence of regional node and distant metastases. METHODS: An international multicentre randomised trial was carried out by the WHO Melanoma Programme from 1982 to 1989. The trial included only patients with a trunk melanoma 1.5 mm or more in thickness. After wide excision of primary melanoma, patients were randomised to either immediate regional node dissection or a regional node dissection delayed until appearance of regional-node metastases. FINDINGS: Of the 252 patients entered, 240 (95%) were eligible and evaluable for analysis. 122 of these were randomised to immediate node dissection. 5-year survival observed in patients who had delayed node dissection was 51.3% (95% CI 41.7-60.1) compared with 61.7% (52.0-70.1) of patients who had immediate node dissection (p=0.09). 5-year survival rate in patients with occult regional node metastases was 48.2% (28.0-65.8) and 26.6% (13.4-41.8, p=0.04) in patients in whom the regional node dissection was delayed until the time of appearance of regional node metastases. Multivariate analysis showed that routine use of immediate node dissection had no impact on survival (hazard ratio 0.72, 95% CI 0.5-1.02), whilst the status of regional nodes affected survival significantly (p=0.007). The patients with regional nodes that became clinically and histologically positive during follow-up had the poorest prognosis. INTERPRETATION: Node dissection offers increased survival in patients with node metastases only. Sentinel node biopsy may become a tool to identify patients with occult node metastases, who could then undergo node dissection.

Elective Surgical Procedures↗