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Biomedical subjects

M Santinami

Publications and source records attributed to M Santinami.

46 records · Page 3Linked to original sources

Limb-salvage procedure in two patients with spindle cell carcinoma of the lower extremities using isolation perfusion.

Two patients with extensive squamous cell carcinoma of the lower extremities, candidate for demolitive surgery, were treated by hyperthermic antiblastic perfusion in extracorporeal circulation. The temperature reached was 41 degrees C and the drug used was methotrexate at the dosage of 500 mg. Radical excision of the ulcer was possible in the 2 patients. Both tumors underwent extensive necrosis, and histology done 1 month after perfusion on surgical specimens showed limited areas of residual malignancy. These 2 patients suggest that hyperthermic antiblastic perfusion may be a limb salvage procedure in the multimodal management of extended squamous cell carcinoma of the extremities.

Aged↗

Prognosis of skin melanoma with regional node metastases (stage II).

566 stage-II melanoma patients treated at the National Cancer Institute of Milan, Italy, were analyzed to evaluate the prognosis. Among the criteria considered, four were significantly associated with survival when considered as single factors: growth pattern, levels of invasion, the number of involved lymph nodes, and the extent of metastatic growth. As regards growth pattern, the observed 5-year survival rates were 41.9% for superficial spreading melanoma and 20.5% for nodular melanoma (P = 10(-3)). As regards levels, the 5-year survival rates were as follows: level II, 20.9%; level III, 33.1%; level IV, 43.2%; level V, 10.2% (P = 10(-3)). Patients with a partial node metastasis had 64.5% 10-year survival, while those with extension beyond the capsule had 32.6% 10-year survival (P = 10(-9). Patients with one metastatic node had 43.4% 10-year survival, and patients with three or more positive nodes had 26.0% 10-year survival (P = 10(-9)). Multifactorial analysis shows that growth pattern and extent of node metastases significantly affect survival (P = 10(-2) and P = 10(-4), respectively) while the number of involved nodes turns to borderline P-value (0.051) and the levels are no longer significant (P = 0.4).

Adolescent↗

Regional perfusion at high temperature in treatment of stage IIIA-IIIAB melanoma patients.

The results obtained with isolation perfusions in stage IIIA-IIIAB melanoma patients, performed at 42.5-43 degrees C for 2.5 h, are reported. These temperatures and perfusion times were chosen on the basis of experimental data in animal models and in vitro. The clinical results were impressive, but the high percentage of complications and the high cost from a social and human point of view make this experience negative with regard to its clinical applicability, at least with such a high temperature and long perfusion time.

Adult↗

Cardiac and pulmonary effects of alpha tumor necrosis factor administered by isolation perfusion.

AIMS: We studied cardiac and pulmonary function in 22 patients affected by in transit metastases from cutaneous melanoma and metastases from soft tissue sarcoma of the limbs and treated with isolation perfusion in extracorporeal circulation with rTNF alpha at doses ranging from 0.5 to 4 mg/m2 in mild hyperthermia. PATIENTS AND METHODS: All patients experienced a septic-like shock syndrome of variable severity: this feature lasted from 24 to 72 h and was controlled by the infusion of dopamine. Seventeen patients suffered from respiratory insufficiency, which required assisted ventilation (7 cases mechanical ventilation for 1 day, 8 cases for 2 days, and 2 cases synchronized intermittent mandatory ventilation). RESULTS: Spirometric parameters recorded 7-15 days after treatment did not change from baseline values. In contrast, lung transfer factor for carbon monoxide significantly declined in a dose dependent fashion. CONCLUSIONS: Our data confirm that rTNF alpha administered by isolation perfusion technique induces systemic cardiovascular and pulmonary side effects. Further studies are required to better define time course and reversibility of impaired pulmonary function.

Adult↗

Isolated pelvic perfusion for the treatment of unresectable primary or recurrent rectal cancer.

Between May 1990 and December 1995, 16 patients with primary or recurrent unresectable rectal cancer were treated by isolated pelvic perfusion. All patients had been previously treated and were considered unsuitable for surgery or further systemic chemotherapy or radiotherapy. The treatment was based on a perfusion lasting 90 min at 40.5 C degrees with 5-fluorouracil, mitomycin-C and mitoxantrone. Whenever technically feasible (10 cases), continuous intraarterial chemotherapy (through a Medtronic device with a catheter in the inferior mesenteric artery) was administered postoperatively. Two complete responses and 2 partial responses were observed; 8 other patients showed stable disease. One patient did not show any response. Finally, 3 patients for various reasons were not assessable. All patients experienced immediate relief of pain. No major side effects directly related to isolated pelvic perfusion were recorded; a transitory bone marrow depletion was observed in all cases. In conclusion, isolated pelvic perfusion is useful in inoperable disease of the pelvis by reliably relieving pain and thereby improving the patients quality of life.

Adult↗

Treatment of recurrent sarcoma of the extremities by isolated limb perfusion using tumor necrosis factor alpha and melphalan.

BACKGROUND: 24-60% of patients with soft tissue sarcoma shows local recurrences after treatment of the primary tumor. The event is associated with a high incidence of macroscopic or microscopic metastases and a poor survival. Our goal is to preserve a patient's functional limb by treating such cases with isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rHu TNF-alpha) and melphalan, which have demonstrated a potent antitumor activity in vivo and in vitro studies. METHODS: During the period November 1991 to November 1995, 10 patients with unresectable recurrent soft tissue sarcoma of the limb were treated by ILP at intermediate hyperthermia (40-40.5 degrees C) with rHu TNF-alpha and melphalan. Two patients also received recombinant interferon gamma (rIFN-gamma) before and during ILP. We used a range of 2-4 mg for rHu TNF-alpha and 50-100 mg of melphalan. rIFN-gamma was administered on days -2 and -1 (15 x 10(6) IU) subcutaneously and the same dose was injected in the arterial line during ILP. RESULTS: No perioperative surgical complication was observed. Local toxicity was moderate (grade I or II); general toxicity was observed in 6 patients (2 grade I and 4 grade III). Complete response was obtained in 7 cases; 2 patients had a partial response and finally 1 was a nonresponder and showed local progression, which required surgical amputation. Tumor necrosis (observed in 5 cases) was maximal in 4 patients (80-100%) and absent in the patient who had local progression. CONCLUSIONS: The results we obtained with the treatment of soft tissue sarcoma confirm the efficacy of ILP as a limb-sparing methodology for unresectable recurrences. Furthermore, rHu TNF-alpha and melphalan confirmed their antitumor activity when associated with hyperthermia. Amputation or disarticulation may be reliable as a second-choice treatment for these patients.

Adult↗

Proliferative activity (Ki-67), WT p53, Bcl-2 expression and their relationship to the tumor grade, in invasive ductal breast carcinomas.

To study the relationship between the expressions of Ki-67, WT p53, Bcl-2 proteins and tumor grade, on fine needle aspiration biopsies (FNABs), in patients with invasive ductal breast carcinomas. One hundred (100) FNABs were performed from the same number of female patients, diagnosed cytologically and confirmed histologically after oncectomy. The same cases were studied immunocytochemically using the monoclonal antibodies Ki-67, WT p53 and Bcl-2 by the alkaline phosphatase (APAAP) method and correlated to the nuclear and histological grade of the tumors. An association and a relationship was found between the grade of the tumors and the immunoexpression of Ki-67, WT p53 and Bcl-2 proteins (p < 0.005). The relationship between Ki-67, WT p53 and Bcl-2 proteins and the grade of the invasive ductal breast carcinomas seems to be a significant prognostic factor and should be kept in mind in follow-up patients after previous treatment for breast cancer.

Biomarkers, Tumor↗

[Impact of sentinel lymph node biopsy on the treatment of melanoma].

In the National Cancer Institute and S Pio X Hospital series we registered 981 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. In 62.2% of cases, only one SN was detected; 26.4% of patients had two SNs and 11.4% had three or more SNs. A positive SNB was demonstrated in 18.1%. 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 of 4 mm or thicker, and ulceration dropped to a borderline significant P-value. To assess the tumor burden in positive SNB, all slides (148 SN pos) were reviewed. Twenty per cent of these patients had evidence of metastasis in other nodes. Of the remaining 80% 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 1 positive node, but adequate analysis of survival requires a larger number of patients and a multicentric study.

Humans↗

Elective lymph node dissection for melanoma: two perspectives.

Node dissection for melanoma remains the most important therapeutic decision for the optimal management of the patient with melanoma. In Australia and in some parts of the United States, the majority of patients with intermediate thickness melanoma (1.6-4.00 mm) will undergo elective lymph node dissection. In Europe, the majority of patients with similar lesions are treated with wide local excision only. The development of an agreed policy for node dissection for melanoma awaits the results of 2 current, prospective randomized trials confirming or disproving the efficacy of elective lymph node dissection. Non-randomized studies showing a benefit or not showing a benefit are readily available but the only 2 prospective randomized studies published to date showing a benefit, have been criticized on methodologic grounds. This paper summarizes the evidence and opinions on both sides of this debate. The clinician charged with responsibility for this important decision must, as yet, make the decision to dissect lymph nodes on the basis of a perspective derived from the best available evidence.

Humans↗

HSP-70, C-myc and HLA-DR expression in patients with cutaneous malignant melanoma metastatic in lymph nodes.

HSP-70, C-myc and HLA-DR were examined in patients with cutaneous malignant melanoma metastatic to lymph nodes. Lymph-nodal fine-needle aspiration biopsies (FNABs) were analyzed and the results were correlated to other variables, such as the gender of the patients, Clark level and Breslow thickness of the primary tumor. Thirty cases of metastatic melanoma in lymph nodes from 30 patients with cutaneous malignant melanoma were studied. All patients (100%) had microscopic regional nodal metastasis and a recurrence of the lesion during the first two years. The HSP-70, C-myc and HLA-DR expressions were investigated immunocytologically, using the APAAP (alkaline phosphatase) method on the FNAB samples. The immunocytochemical expressions of HSP-70 protein, C-myc oncogene, and HLA-DR antigen were found in 18 cases (60%), in 14 cases (43.3%) and in 12 cases (40%), respectively. Clark levels were significantly associated with HSP-70 protein (< 0.01), C-myc oncogene expression (< 0.05) and HLA-DR antigen (< 0.01) expression. The HLA-DR antigen was also found to be related (< 0.05) to higher Breslow thickness (> 1.5 mm). The clinical course of malignant cutaneous melanoma is related to the expression of these indices, which seem to play a significant role in the metastasis and prognosis of this aggressive tumor. The immunocytochemical expression of HSP-70 in the malignant melanoma tumor could be of particular value in the identification of patients with poor prognosis.

Biomarkers, Tumor↗