Sentinel node biopsy in cutaneous melanoma: correlations between melanoma prognostic factors and sentinel node status.

This study aims to correlate the most important prognostic factors of primary melanoma with sentinel node (SN) positive for metastases. We have enrolled 84 patients subjected to sentinel node biopsies for cutaneous melanomas of Breslow's thickness > or = 0.75 mm by using an intra-operative gamma probe after lymphoscintigraphy, without blue dye support. SN metastases were reported in 27% of cases (14% by histology and 13% by immunohistochemistry). By chi-square test Breslow's thickness > 2mm (p= 0.004), IV and V Clark's level (p= 0.02), ulceration (p= 0.05) and high mitotic rate (p= 0.05) were statistically significant (p < 0.05) with reference to SN positive for metastases, unlike the site of cutaneous melanoma, vertical growth phase, tumour infiltrating lymphocytes, regression and vascular invasion. Breslow's thickness remains the first prognostic factor to be considered for sentinel node biopsy in cutaneous melanoma, but other markers must be carefully estimated.

TNFa-based isolated hyperthermic limb perfusion (HILP) in the treatment of limb recurrent melanoma: update 16 years after its first clinical application.

Hyperthermic Limb Perfusion (HILP) with Tumor Necrosis Factor alpha (TNFalpha) and interferon gamma (IFNgamma) was pioneered by Liénard and Lejeune in 1988. TNFalpha was empirically employed at a dosage of 3-4 mg that is ten times the systemic maximum tolerated dose (MTD). Sixteen years after its first clinical application more than 300 patients have been treated and some clarifications can be made regarding three major questions: the real role of IFNgamma, the TNFalpha dose and eligibility criteria for patient selection. A randomized phase II study has demonstrated that IFNgamma does not increase significantly the efficacy but does increase side-effects. Experimental and clinical results seem to indicate that patients with bulky melanoma disease can really benefit from TNFalpha HILP carried out with only 1 mg.

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.

[Thyroid carcinoma: evaluation of prognostic factors]. / Carcinoma della tiroide: valutazione dei fattori prognostici.

Between 1990 and 1997, 36 thyroid cancer patients were observed at the III Department of Surgical Oncology, Regina Elena Cancer Institute in Rome. There were 31 (86.1%) women and 5 (13.9%) men, with a mean age of 47.7 years (range 17-72). Diagnostic data consisted of: papillary carcinoma in 25 patients, follicular carcinoma in 9 and Hürthle cell carcinoma in 1. Twenty patients were less than 45 years old (15 papillary and 5 follicular carcinoma) and 16 were more than 45 years old (10 papillary and 4 follicular carcinoma, 1 Hürthle cell carcinoma and 1 with undifferentiated cancer). We performed total thyroidectomy in 32 cases and isthmectomy in 3 (2 papillary carcinoma, T1, < 45 years, 1 follicular carcinoma with minimal invasion). At the time of diagnosis, 6 patients with papillary carcinoma showed signs of local metastasis. No patients exhibited distant diffusion. A follow-up was performed at mean 41 months (2-84 months). Two patients with follicular carcinomas had been treated with radioiodine and showed disease progression with distant metastasis. Our results coincide with the literature on this topic. Total thyroidectomy is preferred, in low-risk patients as well, because subsequent radioiodine treatment and disease relapse monitoring are facilitated. Lateral cervical lymphadenectomy was performed only in cases when there was clinical evidence of metastasis and recurrent disease at this level has never been observed.

Role of surgery in the treatment of recurrent esophageal cancer.

Neoplastic recurrence is the most common cause of death after surgery for esophageal cancer. The Authors review the therapeutic options evaluating in terms of palliation of dysphagia and complication and mortality rates. Prognostic factors and mechanisms determining the recurrence are also reviewed. A strategy for a rational approach in the management of recurrent esophageal cancer emerges from both the literature and their own experience. Notwithstanding the small life span of these patients, the treatment of esophageal obstruction is mandatory. The therapeutic options that be considered are: palliative resection, surgical bypass, laser therapy, intubation, radiotherapy. The site of obstruction, the presence of metastasis, the general status can lead to the optimal choice. In terms of palliation of dysphagia the surgical approach seems to obtain the best results, even if high complication and mortality rates have been reported. Bypass is the second surgical choice when applicable. The other non-surgical modalities have been administered in large series of patients with good results. Combination therapies can obtain better results.

Accelerated chemotherapy with high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF in locally advanced and metastatic breast cancer.

BACKGROUND: This study evaluated the toxicity of high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF (G-CSF) given every 2 weeks and compared the dose-intensity achieved with this schedule with that obtained in a previous study we conducted in which the same regimen was given every 3 weeks without G-SCF (EC 21). The secondary objective was to explore the activity of this regimen. PATIENTS AND METHODS: Between December 1991 and March 1994, 41 patients (pts), 19 with locally advanced breast cancer (LABC) and 22 with metastatic breast cancer (MBC), were given high-dose epirubicin (Hd-Epi) (120 mg/m2) and cyclophosphamide (CTX) (600 mg/m2) on day 1 every 14 days (EC 14) plus granulocyte colony-stimulating factor (G-CSF) (5 mcg/kg/d s.c. on days 2-12). A total of 8 cycles in LABC pts (4 pre- and post-surgery), and 6-8 cycles in MCB pts were administered. The results were compared with those obtained in the previous study. RESULTS: The incidence of WHO grade 3-4 neutropenia was significantly reduced in the EC 14 + G-CSF regimen (25.2% vs. 46.8% in 214 and 250 evaluable cycles, respectively, p<0.0001), as well as the incidence of neutropenic fever (7% vs. 3%, p=0.05). Grade 3-4 anemia (36.6% vs. 8% pts, p=0.001) and grade 3-4 thrombocytopenia (17.1% vs. 0 pts, p=0.002), were significantly more frequent in EC 14 + G-CSF. No significant differences in the other side effects were found. A total of 17 of 207 of the cycles (8.2%) were delayed in the EC 14 + G-CSF vs. 58/271 (21.4%) in the EC 21 (p<0.0001). The main reasons for these treatment delays were neutropenia (1% vs. 15%), anemia (3% vs. 0) and thrombocytopenia (1% vs. 0). As a result of treatment acceleration and differences in dose delays, the patients on EC 14 + G-CSF received a higher dose-intensity (Epi 58.51 mg/m2/wk vs. 36.8 mg/m2/wk; CTX 292.52 mg/m2/wk vs. 182.9 mg/m2/wk). A complete response at surgery was obtained in 9/19 (47.4%) LABC pts. An objective CR was obtained in 11/22 MBC pts (50%) and a partial response in 8/22 (36.4%), yielding an overall response rate of 86.4%. CONCLUSIONS: Hd-Epi + CTX is very active against both LABC and MBC. The administration of G-CSF allows dose intensification of both drugs (a 59.5% increase of the actual dose intensity) with acceptable clinical tolerance (a lower incidence of neutropenia but a higher incidence of anemia and thrombocytopenia). Only a specifically designed phase III trial will lead to definitive conclusions regarding the greater antitumor activity of accelerated CSF-including regimens as compared to standard chemotherapy for advanced breast cancer.

Role of hyperthermic perfusion in the treatment of limb osteogenic sarcoma.

The role of hyperthermic perfusion (HP) for the treatment of limb osteogenic sarcoma was evaluated in 76 patients. Twelve patients were treated with HP alone, and a 5- and 10-year survival rate of 25.5% was obtained. When amputation was systematically associated to HP (12 patients), a 5- and 10-year survival rate of 50.9% was achieved. Twenty-seven patients were treated with hyperthermic antiblastic perfusion (HAP) followed by amputation 4 weeks later. With this treatment, the 5- and 10-year actuarial rates rose to 71.4 and 65%, respectively, with a 5-year disease-free survival rate of 67.4%. Fifteen patients were treated with HAP followed by an 'en bloc' resection and bone reconstruction. The 5- and 10-year actuarial survival rate obtained was 63.5% with a 5-year disease-free survival rate of 53.6%. These results seem to indicate that HAP permits carrying out conservative rather than ablative surgery for the treatment of limb osteogenic sarcoma.

Lonidamine and hyperthermia: clinical experience in melanoma. Preliminary results.

Lonidamine alone or in combination with hyperthermic perfusion, with or without melphalan, was investigated in 12 patients with stage II, III, and IV malignant melanoma. The authors evaluated the most effective methods and sequence of Lonidamine administration. Preliminary results suggest that the highest effectiveness is obtained with the simultaneous administration of Lonidamine and hyperthermia.