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.

Hyperthermic antiblastic perfusion in the treatment of locoregional spreading limb melanoma.

On the basis of personal experience and a review of the literature, the authors have evaluated the results obtained with hyperthermic antiblastic perfusion (HAP) for the treatment of stage II, III and IIIAB limb melanoma. The evaluation showed that today HAP may be considered a safe and effective treatment, with a major complication rate ranging between 1% and 4%. In terms of tumor response, locoregional control and survival, this treatment has provided better results than other regional chemotherapeutic modalities and undoubtedly better results than those obtained with conventional, even radical, surgery. The multivariate analysis showed that, of the treatment-related prognostic factors, the minimum tumor temperature influenced the percentage of complete response (CR) to the greatest extent (P<0.03), with a positive trend also with regard to the dosage of the antiblastic drug employed (P<0.08). In turn, the complete response rate was a determinant as far as locoregional control (50%; P<0.0009) and disease-free (51.4%; P=0.0009) and overall survival (63%; P<0.009) rates were concerned. Of the tumor-related prognostic factors, the number of lesions (P<0.0014), sex (P<0.04), and the number of disease recurrences (P<0.01) appear to influence overall survival.

Peritonectomy and hyperthermic antiblastic perfusion in the treatment of peritoneal carcinomatosis.

AIMS: Some low-grade malignant tumours arising in the abdomen tend to remain loco-regionally confined to peritoneal surfaces, without systemic dissemination. In these cases complete surgical tumour cytoreduction followed by intra- or post-operative regional chemotherapy has curative potential. The aim of this study was to evaluate the outcome for patients treated in this way. METHODS: Peritonectomy was performed, involving the complete removal of all the visceral and parietal peritoneum involved by disease. After peritonectomy, hyperthermic antiblastic perfusion was carried out throughout the abdominopelvic cavity for 90 min, at a temperature of 41.5-42.5 degrees C, with mitomycin C (3.3 mg/m2/l) and cisplatin (25 mg/m2/l) (for appendicular or colorectal primaries), or cisplatin alone (for ovarian primaries). Alternatively, the immediate post-operative regional chemotherapy was performed with 5-fluorouracil (13.5 mg/kg) and Lederfolin (125 mg/m2) (for colonic or appendicular tumours) or cisplatin (25 mg/m2) (for ovarian tumours), each day for 5 days. RESULTS: Thirty-five patients affected by extensive peritoneal carcinomatosis were submitted to peritonectomy, with no residual macroscopic disease in all cases except three. Twenty-six patients were able to undergo the combined treatment involving loco-regional chemotherapy. Complications were observed in 54% of the patients and led to death in four of them. At a mean follow-up of 17 months overall 2-year survival was 55.2%, with a median survival of 26 months. CONCLUSIONS: After a learning curve of 18 months the feasibility of the integrated treatment increased to more than 90%, while mortality decreased dramatically. The curative potential of the combined therapeutic approach seems high in selected patients with peritoneal carcinomatosis not responding to systemic chemotherapy. Careful selection of patients can minimize the surgical risk, but the treatment should currently be reserved for clinical trials.

The integrated treatment of peritoneal carcinomatosis. A preliminary experience.

Some low-grade malignant tumors arising in the abdomen, lack of infiltrative attitude and "redistribute" on the peritoneum with no extraregional spreading. In this cases the complete tumor cytoreduction followed by intra- or postoperative regional chemotherapy has curative intent. Peritonectomy is the complete removal of all the parietal peritoneum and the visceral peritoneum involved by disease. After peritonectomy hyperthermic antiblastic perfusion is carried out throughout the abdomino-pelvic cavity for 60 minutes, at a temperature of 41.5 degrees C, with mitomycin C (3.3 mg/m2/Lt of perfusate) and cisplatin (25 mg/m2/Lt) (appendicular or colorectal primary), or cisplatin alone is (ovarian primary). Alternatively the immediate postoperative regional chemotherapy is performed with 5-fluorouracil (13.5 mg/Kg) and Lederfolin (125 mg/m2) (colic or appendicular tumor) or cisplatin (25 ng/m2) (ovarian tumor), each day for 5 days. Twenty patients affected by extensive peritoneal carcinomatosis (12 ovarian, 5 colonic, 1 appendicular, 1 mesothelial and 1 gastric primary) were submitted to peritonectomy with no residual macroscopic disease in all cases except three. Six patients were treated with intraoperative intra-abdominal hyperthermic antiblastic perfusion, while immediate postoperative intra-abdominal chemotherapy was given in 4 patients and systemic chemotherapy in other 5. Hospital mortality was 20%. At a mean follow-up of 11 months 14 patients are alive, 11 without disease and the median overall survival is 10.2 months. The curative potential of the combined therapeutic approach seems high in patients with peritoneal carcinomatosis from ovarian or colorectal primary not responding to systemic chemotherapy. Selection criteria of patients can strictly affect the surgical risk and the treatment has to be reserved for controlled clinical trials.

Bolus vs. continuous hepatic arterial infusion of cisplatin plus intravenous 5-fluorouracil chemotherapy for unresectable colorectal metastases.

UNLABELLED: A multicenter, randomized Phase 2 study that compared patients, affected by colorectal liver metastases, who received intrahepatic arterial infusion with two different schedules of cisplatin, bolus vs. continuous infusion, and systemic 5-fluorouracil. PURPOSE: The aim of this study was to validate results of a previous Phase 2 trial on bolus cisplatin intrahepatic arterial infusion, which reported a 47 percent response rate and a 32 percent 4-year survival rate for Gennari's Stage 2 patients, with a high rate of neurologic, gastrointestinal, and hematologic toxicity. METHODS: One hundred nine patients were randomized in a Phase 2 study to receive cisplatin intrahepatic arterial infusion (24 mg/m2/day, 1-->5, bolus vs. continuous infusion) and systemic intravenous 5-fluorouracil (250, 375, or 500 mg/m2/day, 1-->5; escalating doses, respectively, at cycles I, II, III, and VI). To avoid neurotoxicity a maximum of six cycles was administered. RESULTS: Preliminary results for the 78 evaluable patients are similar to those of the previous study: response rate 46 percent and at a median follow-up of 16.5 months, the overall survival was 16.5 months, with 45 percent of the patients who received more than 3 cycles alive at 3 years. Toxicity, evaluable in 99 patients, showed a decreased incidence of neurotoxicity and a tolerable gastrointestinal and hematologic toxicity, lower in the cisplatin continuous infusion arm. CONCLUSION: This study clearly shows that cisplatin intrahepatic arterial infusion is able to provide a good palliative effect with a tolerable toxicity.

Flow cytometric study of lymphocyte subsets in patients at different stages of colorectal carcinoma.

PURPOSE: The evaluation of lymphocyte subsets by using monoclonal antibodies in neoplastic patients has provided different results, partly in relation to the stage of the disease. Therefore, as a preliminary study of cancer patients treated with immunomodulating drugs, an analysis of lymphocyte subsets was performed in colorectal carcinoma patients. METHODS: In this study, a flow cytometric evaluation of lymphocyte subsets was performed in 33 patients affected by colorectal carcinoma, with or without metastases. RESULTS: A significant reduction of hemoglobin concentrations and hematocrit was observed in all of these subjects, associated with an evident increase of white blood cells, platelets, and HLA DR-positive T lymphocytes, whereas CD 3-CD 4-positive and CD 20-positive lymphocyte concentrations were decreased. Subjects without metastases showed an evident decrease of hemoglobin concentrations and an increase of white blood cells, platelets and CD 3-HLA DR-positive lymphocytes, while patients with disseminated disease also had reduced mean values of hematocrit, red blood cells, CD 3-CD 4-positive, and CD 20-positive lymphocytes. CONCLUSIONS: The main differences between colorectal carcinoma patients with or without metastases were represented by a decrease of red blood cells, CD 3-CD 4-positive, and CD 20-positive lymphocyte concentrations in the latter group.

[Exposure to low-frequency vibrations and spinal diseases in dock workers]. / Esposizione a vibrazioni a bassa frequenza ed affezioni del rachide nei lavoratori portuali.

The authors studied the prevalence of disorders of the spine in a group of dockers working on lifting gear. They stress the great sensitivity of clinical examination performed according to a standardized protocol for the evaluation of spine pathology.