Gianni Ravasi

Sternal resection for primary or secondary tumors

METHODS From January 1980 to December 1993, 52 patients underwent surgical-resection for tumors involving the sternum. The series included 20 primary malignant tumors, 4 desmoid tumors, 2 malignant tumors infiltrating the sternum from adjacent organs, 19 local recurrences or metastases of breast tumors, and 7 metastases of other tumors. Total sternectomy was performed in 5 patients, subtotal sternal resection in 19, and partial resection (less than 50% of the sternum) in 28. Concurrent en bloc resection included anterior ribs in 37 patients, clavicle in 11, lung in 12 patients, pericardium in 7, and diaphragm in 2. The chest was reconstructed with prosthetic material and a myocutaneous flap in 26 patients (50%), prosthetic material only in 12 patients (23%), a myocutaneous flap in 5 patients (10%), and other techniques in the remaining patients. In 47 patients (90%) the resection was radical, and in the remaining 5 patients it was palliative. RESULTS No perioperative deaths occurred. After a median follow-up of 39 months, the overall 3-year survival was 58% and the 5-year survival 46%, with a median survival of 50 months. In 24 patients with primary tumor the 5-year survival after radical resection was 63%, and in 23 patients with secondary invasion (direct extension or metastasis) the 5-year survival was 38% (median 35 months). In recurrent breast cancer the 5-year survival was 48% in patients with direct extension to the chest wall and 60% in patients with distant bone metastasis. CONCLUSIONS Our experience demonstrates that sternal resection is a safe and effective treatment, which may improve the patients quality of life and achieve a long-term survival not only in primary tumors but also in selected secondary malignant tumors of the sternum.

The contribution of salvage surgery to the management of childhood osteosarcoma.

Between January 1970 and December 1988, 174 consecutive patients under the age of 20 years with curatively resected primary osteosarcoma were treated at our institute; 72 in the years of 1970 to 1981 and 102 in the years 1982 to 1988. In the latter period, adjuvant chemotherapy was replaced by neoadjuvant programs, and new criteria were adopted for the management of lung metastases, consisting in early bilateral surgical staging and lung resection through median sternotomy for all patients with purely intrathoracic relapse. Follow-up was updated in December 1989. During the last period, the overall 5-year survival improved significantly from 35% to 58% (P less than .001). The disease-free survival rose from 38% to 45% at 5 years, with median values of 15 months versus 33 months, while the frequency of isolated lung metastases dropped from 58% to the actuarial 48%. The proportion of patients who underwent complete resections of their pulmonary metastases rose from 17% (seven of 42) to 55% (27 of 49), without operative mortality. Due to such a high proportion of patients eligible for salvage surgery, the overall survival from detection of lung metastases improved from 0% to 28% at 5 years (P less than .001). Contralateral occult metastases were resected in three of 15 subjects with monolateral clinical lesions, and five patients underwent subsequent lung resections. These data indicate that systematic bilateral pulmonary resection plays an important role in improving the final cure rate of childhood osteosarcoma, beyond the benefit resulting from neoadjuvant chemotherapy.

Molecular Alterations in Spontaneous Sputum of Cancer-Free Heavy Smokers: Results from a Large Screening Program

Purpose: The high mortality rate for lung cancer is likely to be reduced by the development of a panel of sensitive biological markers able to identify early-stage lung cancers or subjects at high risk. The aim of this study was to establish the frequency of K-ras and p53 mutations and p16INK4A, RASSF1A, and NORE1A hypermethylation in sputum of a large cohort of cancer-free heavy smokers and to assess whether these markers are suitable for a routine use in the clinical practice for the early diagnosis of pulmonary cancer. Experimental Design: Sputum samples were collected from 820 heavy smokers. Inclusion criteria consisted of radiologic and cytologic absence of pulmonary lesions, age at least 60 years, male gender, and a smoking history of at least 20 pack-years. Results: The analysis identified 56 individuals (6.9%) with one molecular alteration. p53 mutation and p16INK4A, RASSF1A, and NORE1A methylation frequencies were 1.9%, 5.1%, 0.8%, and 1.0%, respectively; no K-ras mutations were found. One patient with p53 mutations was diagnosed with an early-stage lung cancer after 3-years of follow-up. The molecular analysis of bronchoscopy samples confirmed in half of the cases alterations present in sputum without revealing additional molecular changes. Conclusions: Genetic and epigenetic abnormalities can be detected in cancer-free heavy smokers. Although the predictive value of the cancer risk is still to be established as it requires not less than 5 years of follow-up, p53 and p16INK4A are more promising candidates than K-ras, RASSF1A, and NORE1A for the pulmonary molecular screening of heavy smokers healthy individuals.

Safety of high-dose vitamin A : randomized trial on lung cancer chemoprevention

The paper reports on the efficacy and side effects of high-dose vitamin A, administered as adjuvant treatment for resected stage I lung cancer in a randomized clinical trial. After a median follow-up

Bcl-2 protein and prognosis in patients with potentially curable non-small-cell lung cancer

Abstract The bcl-2 proto-oncogene functions as a cell death suppressor, and its expression prolongs cell survival by blocking apoptosis. Data available on the clinical relevance of bcl-2 protein expression in patients with non-small-cell lung cancer (NSCLC) are controversial. We analysed the role of bcl-2 protein expression on 6-year relapse-free survival in 229 patients with stage I-IIIa NSCLC (101 squamous cell carcinomas and 128 adenocarcinomas) subjected to surgery, with curative intent. Immunohistochemical analysis was performed on archival material by using a monoclonal antibody anti-bcl-2 (clone 124). Bcl-2 protein expression, which was detected in 22% of the cases, was significantly related to stage, histology and grading, and was an indicator of clinical outcome. The probability of relapse-free survival at 6 years was longer for patients with bcl-2-positive tumours (74%) than for those with bcl-2-negative tumours (57%) (P=0.02). This finding was mainly evident for the subgroups of patients with stage IIIa tumours (P=0.05), squamous cell carcinoma (P=0.03) or moderately/poorly differentiated tumours (P=0.02). However, multivariate analysis by Weibull’s regression model indicated that bcl-2 protein expression was not an independent prognostic risk factor in patients with curable NSCLC when the information provided by stage was available.

Prolonged venous infusion of cisplatin and concurrent radiation therapy for lung carcinoma. A feasibility study

Fifty patients with non resectable and/or inoperable bronchogenic carcinoma were entered into a feasibility study of cisplatin (CDDP) given in continuous infusion with concurrent radiation therapy. The radiation therapy regimen consisted of 2 Gy given 5 days a week in the first 3 and last 2 weeks of a 7‐week split course (50 Gy of total dose). The CDDP (daily dose of 4 to 6 mg/m2) was administered to cover the days of radiation treatment by means of a central venous catheter and a portable pump. Less than 1% of predicted duration of infusion was lost due to complications related to venous access and pump. Toxicity was moderate. The overall probability of a locoregional major response (complete + partial) within 1 month after treatment completion was 86%. Twenty‐three patients underwent resection. The 1‐year actuarial probability of survival was 64%. The high response and survival rates warrant further studies on concurrent CDDP continuous infusion and radiation therapy in inoperable lung carcinoma.

Lung resection as salvage treatment for metastatic osteosarcoma.

Resection of pulmonary metastases has achieved a central role in the overall management of osteosarcoma, since a number of studies have demonstrated that salvage surgery is able to cure 20 to 40% of all relapsing patients. This paper presents the results of surgical management of 27 consecutive cases of pulmonary metastases from osteosarcoma, who underwent complete resection at the Istituto Nazionale Tumori of Milan between 1975 and 1986. In the present series, overall actuarial survival at 3 years from the first thoracotomy was 47%, with a median survival of 28 months and no operative mortality. Better results were observed in patients with single lesions (68% survival) or when the interval to lung metastases exceeded 12 months (60% survival). These data support the concept of pulmonary metastasectomy as effective salvage therapy for metastatic osteosarcomas whose distant spread is confined in the lungs.

Effect of chronic cardiopulmonary disease on survival after resection for stage Ia lung cancer.

The role of chronic cardiopulmonary disease as a risk factor for immediate and late mortality was evaluated retrospectively in a consecutive series of 116 patients who had had resections for stage Ia non-oat-cell lung cancers. The presence of chronic cardiopulmonary disease was diagnosed on the clinical history and preoperative assessment of lung and heart function by traditional means. Patients with chronic cardiopulmonary disease showed a lower five-year survival rate than controls--35% versus 53% (p less than 0.08). The difference increased and became significant if besides having cardiopulmonary disease the patient was over 60 years of age or had had a pneumonectomy--30% versus 52% (p less than 0.025). A higher operative mortality was the main reason for the lower observed survival. Nevertheless, survival of patients at risk exceeded 30% in each subgroup, being 33% for patients over 60 undergoing pneumonectomy. In our series the benefits of resection of lung cancer in patients with impaired cardiopulmonary function were greater than the risks of perioperative and later death even in the groups with a poorer prognosis.

Preoperative concomitant cisplatin/VP16 and radiotherapy in stage III non-small cell lung cancer

PURPOSE To evaluate the therapeutic effectiveness of a combined chemoradiotherapy program, followed by surgery in selected cases, in Stage III non-small cell lung cancer. METHODS AND MATERIALS Between August 1988 and February 1990, 43 patients Staged IIIa-b (UICC 1987, 58% IIIb) have been treated with concomitant chemotherapy (cisplatin 15 mg/m2 and VP16 75 mg/m2, 5 days a week on week 1 and 5) and radiotherapy (40 Gy split course, 2 Gy/day on week 1, 2, 5, and 6), followed by attempted curative thoracotomy or more cycles of full dose chemotherapy with the same two drugs. RESULTS Planned chemoradiotherapy has been given to 91% of patients; 13/43 patients have been operated, with 12 complete resections and three (7%) pathological complete responses. Toxicity was significant, with two postoperative deaths and two fatal radiation pneumonitis. Crude progression-free survival rate is 21% at 30 months, with nine patients (21%) alive and free from progression at follow-up times ranging from 31 to 49 months. Subset survival analysis showed a possibly greater therapeutic effect for non-squamous histology as compared to squamous carcinoma. CONCLUSION These results are encouraging in a cohort of patients with quite advanced disease (58% Stage IIIb).

Reverse flap of distal latissimus dorsi for diaphragm reconstruction in the adult: specification of the technical procedure and report on six cases.

autograft rather than other valve prostheses in children, some specific reasons were present in this special situation. Resection of the aneurysmal aortic root was necessary and the relatively difficult access to the aortic root made the choice of a homograft less preferable in view of the inevitable reoperation. The operation turned out to be straightforward. The anterior placement of the pulmonary trunk made its harvesting easy. Coronary artery problems were not encountered. Transposition may, however, be combined with coronary artery patterns that make harvesting of the pulmonary trunk more difficult, especially a right coronary artery crossing the right ventricular outflow tract. No important mismatch between the diameters of the pulmonary trunk and aortic anulus existed, which further encouraged us to choose the pulmonary autograft for aortic root replacement. In conclusion, the Ross procedure is technically feasible after an arterial switch operation and may be a particularly attractive alternative for this special population. This may be even more true because it is the original aortic valve that is used to replace the insufficient neoaortic valve. R E F E R E N C E S 1. Gittenberger-de Groot AC, Sauer U, Oppenheimer-Dekker A, Quaegebeur JM. Coronary arterial anatomy in transposition of the great arteries: a morphological study. Pediatr Cardiol 1983;4(suppl 1):15-24. 2. Klautz RIM, Ottenkamp J, Quaegebeur JM, Buis-Liem TN, Rohmer J. Anatomic correction for transposition of the great arteries: first follow-up (38 patients). Pediatr Cardiol 1989;10: 1-9. 3. Yamaguchi M, Hosokawa Y, Imai Y, Kurosawa H, Yasui H, Yagihari T, et al. Early and midterm results of the arterial switch operation for transposition of the great arteries in Japan. J Thorac Cardiovasc Surg 1990;100:261-9. 4. Ungerleider RM, Gaynor JW, Israel P, Kanter RJ, Armstrong BE. Report of neoaortic valve replacement in a ten-year-old girl after an arterial switch procedure for transposition. J Thorac Cardiovasc Surg 1992;104:213-5. 5. Serraf A, Roux D, Lacour-Gayet F, Touchot A, Bruniaux J, Sousa-Uva M, et al. Reoperation after arterial switch operation for transposition of the great arteries. J Thorac Cardiovasc Surg 1995;110:892-9.