Biomedical subjects
Publications and source records attributed to G Ravasi.
In esophageal resections, esophagogastric anastomosis can be performed either at cervical or intrathoracic level. A recent paper showed a greater incidence of postoperative leakages in cervical vs. intrathoracic anastomosis (26% vs. 4%). In the present paper we describe 55 cases of esophagectomy with a modified technique of cervical stapled anastomosis, where the incidence of fistula was 5%.
In order to study the possible relationship between antigenic phenotype and tumor progression, 63 small cell lung carcinomas (SCLC) biopsies derived from primary or metastatic tumors were tested by immunofluorescence and immunoperoxidase techniques with an anti-carcinoma monoclonal antibody designated MBr1. Primary tumors were found to be less reactive with MBr1 than the local and distant metastatic lesions (57% versus 75% and 89% positivity respectively). A life table analysis on the tested cases indicated an inverse association between the expression of the marker recognized by the MBr1 MAb (CaMBr1) and overall survival (p less than 0.01): patients with MBr1-positive tumors showed a shorter survival time in comparison to patients whose tumors did not express the marker. The same correlation between survival and CaMBr1 expression was found even when only the 31 cases of early stage disease patients were considered (p less than 0.05). Different tumor aggressiveness or resistance to therapy of MBr1-positive tumors could be responsible for the shorter survival time of the patients.
From 1981 to 1986, 17 patients with resected small cell lung carcinoma (SCLC) staged as I or II according to the new TNM classification were recruited for a prospective study to evaluate the effectiveness of surgery and postoperative chemotherapy (plus locoregional radiotherapy only when a nonradical resection was accomplished) in the treatment of early stages of the disease. Six patients received full protocol chemotherapy (6 courses) and 8 a mean of 79.1% of the planned courses. Three patients received non adjuvant treatment. Locoregional radiotherapy for residual disease was administered in 2 cases. One patient died for myelosuppression due to chemotherapy and 10 for recurrences of cancer, all within the 20th postoperative month. Metastases accounted 80% of overall recurrences. Six patients were alive and tumor-free at 18, 22, 39, 44, 47 and 51 months from resection. Actuarial observed 3-year survival was 32%.
Out of 52 consecutive patients resected for small cell lung carcinoma (SCLC) from 1976 to 1986, 19 were selected because they underwent nonradical surgery, 10 of them for locoregional spread and 9 for distant metastases. Of the former subset all received postoperative radiotherapy and 8 chemotherapy also. Three patients are alive and disease-free 37, 56 and 91 months after resection. Four patients had a distant recurrence, and 3 a locoregional failure. Patients of the latter subgroup received chemotherapy in 7 instances. None survived more than 16 months, distant metastases being the cause of death. In these patients N0 status was associated with 13.3 months of mean survival, N1 with 8.5 months, and N2 with 6.7 months. Surgery and adjuvant treatments seem effective in achieving local control of SCLC despite nonradical resections. Tumor burden at locoregional sites does not preclude the possibility of long term survival.
The results of surgical management of 63 cases of pulmonary metastases from bone and soft tissue sarcomas, admitted at the Istituto Nazionale Tumori of Milan, between 1970 and 1987, are reviewed in this paper. To estimate the relative impact of metastasectomy on the overall performance of treatment, survival curves were calculated from the time of first thoracotomy, as well as from the initial treatment of primary sarcoma. In the present series, total actuarial survival at 10 years was 37% for osteosarcoma, 27% for soft tissue sarcomas, and 24% for the other bone sarcomas, with a median survival of 48, 56, and 36 months, respectively. Five-year survival from the first pulmonary resection was influenced by the number of metastases and the length of the first disease-free interval only in osteosarcoma, while in soft tissue sarcomas a major untoward factor was represented by local recurrence at the site of the primary tumor. These data support the concept of pulmonary metastasectomy as effective salvage therapy for radically treated sarcomas; this management can rescue a significant proportion of all relapsed patients.
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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.
Between October 1979 and February 1987, 30 consecutive patients with cancer of the lower stomach underwent B1-Schoemacher resection with a tubular gastric pouch. Operative mortality was 0% and operative morbidity 10% (leak 3%, anastomotic stricture 3% and abscess 3%). After a mean follow-up of 30 months, the expected 5-year survival was 32%. The causes of death were: 7 distant relapses, 2 noncancer diseases and 1 new primary cancer. The overall incidence of postgastrectomy symptoms was 23% for the whole series and 35% for the patients harboring small tumors. Mild dyspepsia occurred in 71%. The declining concept of total gastrectomy as an essential requirement for curative resection and the recent evidence that B2 for gastric lesions is a carcinogenic operation necessitate alternative procedures. The data show that modified Schoemacher resection can be consider a valid challenge to B2.
From January 1971 to June 1983, 35 lobectomies with bronchoplastic procedures for invasive non-small-cell lung carcinoma were performed. Sleeve lobectomy was carried out in 21 cases, wedge lobectomy in 11, and upper sleeve bilobectomy in 3. There were 23 stage I, 10 stage II, and 2 stage IIIa tumors. Completion pneumonectomy was required in 1 case for anastomotic fistula and in 2 for atelectasis of residual lung. One of these patients died later due to empyema. The 5-year probability of death with recurrence was 31.98%. The 5-year disease-free survival was 58.57%. Metastatic relapse was observed in 8 cases and loco-regional recurrence in 5. A new primary lung tumor occurred in 2 patients.
On the basis of epidemiologic and experimental evidence of an anticancer activity of vitamin A, a randomized clinical trial was activated in Milan with the aim of evaluating if retinol palmitate administration (per os, 300,000 I.U. daily) after complete resection of stage Ia non small-cell lung cancer could reduce the occurrence of cancer relapses (within 3 years) and/or the occurrence of new primary tumors (beyond 3 years). By September 1987, 181 patients had entered the trial: 87 in the treatment arm and 94 in the control arm. After a median follow-up of 14 months, the interim analysis was focused on the evaluation of toxicity, compliance, and early recurrences. Although the large majority of patients were affected by skin and mucous membrane desquamation and dryness during treatment, these symptoms were generally mild and well tolerated, and never induced the patient to stop the treatment. Other side effects like headache, hair loss, itching, or dyspepsia were detected at a much lower frequency. Only in 3 patients the treatment was interrupted, because of signs or symptoms potentially related to vitamin A administration. At the time of the analysis, a total of 42 (23%) patients had relapsed; 16 (18%) in the treated arm, and 26 (28%) in the control arm. The largest difference between treated patients and controls was observed for bone metastases (2 vs. 7) and brain metastases (3 vs. 6), and for squamous histology (6 vs. 11). Only 2 cases of new primary cancer were detected, both in the control arm. These results are promising both in terms of tolerance and efficacy of treatment, but given the short median follow-up they must be very cautiously interpreted. A longer follow-up is necessary to establish whether a significant proportion of early recurrences could be prevented, or only delayed, by vitamin A administration.
Three hundred and thirty consecutive cases of resected Stage Ia (TNM UICC classification) lung carcinomas were retrospectively reviewed with the aim of evaluating actuarial probabilities of recurrence within the 5th year from operation, according to the extent of resection, the cell type, and the T number. The probabilities of recurrence according to the pattern of failure were also assessed. Five-year overall probability of recurrence was 46.3%. Pneumonectomies showed a lower rate of relapse (37.4%) than lobectomies (49.2%), even though non significant. However, patients submitted to a lobectomy had a higher rate of 5-year survivors. Cell type had no significant impact on the probability of recurrence. 35.5% of patients with T1 carcinomas had evidence of relapse compared with 51.1% of patients with T2 tumors. This datum is explained by the presence in T1 group of a high share of squamous cell cases. Patients with T1 squamous cell carcinomas had, in fact, the best prognosis (26.5% recurred) among the subgroups obtained by stratification of T number and cell type together; loco-regional failure as exclusive modality of relapse had a 5-year rate of 19.7% and metastatic failure of 30.0%. Adenocarcinomas had a significantly higher impact on the occurrence of brain metastases.
This paper represents a historical analysis of the results achieved by esophageal cancer surgery over the last three decades, as they appear in the literature of the years 1954-1985, and in our own experience between 1965 and 1985, with the aim of assessing the evolution of operative mortality and long-term survival. In a review of 4930 resections reported in western literature, mean values of perioperative mortality went down from 30% to 9%, while the five-year survival increased from 8% to 19%. Similar changes were evident in Japanese and Chinese literature where the survival rose from 9% to 23% in unscreened populations and up to 90% in early cancers. In our experience, dividing the series in two decades (1965-74 and 1975-85), the overall perioperative mortality changed from 28% to 13%. The actuarial survival for the two periods was 8% vs 18% at 5 years, with a median survival of 9 and 18 months. A greater difference was evident for N0 patients where the survival rose from 15% to 35% at 5 years, with a median survival of 15 vs 38 months.
The presence of cellular retinoic acid binding protein (cRABP) was analyzed in 13 consecutive patients with large bowel cancer (one right colon and 12 rectum-sigmoid, classified as three Duke B, eight C, and two D). Specimens of neoplastic tissue and of adjacent mucosa were obtained at surgery, and cRABP was determined by an assay based on incubation of partially purified cytosol with labeled retinoic acid and ultracentrifugation in sucrose density gradients. Sixty-one percent of tumors contained detectable levels of cRABP, whereas 58.3% of normal mucosal specimens were positive for cRABP. Among the positive tumors 62.5% contained cRABP also in the corresponding mucosa; in the group of cRABP-negative tumors, 40% showed cRABP in the adjacent mucosa. No correlation could be established with the grading or the stage of the tumors; however, interestingly, 100% (three cases) of gelatinous carcinomas were cRABP positive. Since cRABP seems to be a character of neoplastic cells contrary to normal ones, it would be interesting to investigate the conditions that influence the presence of this protein in normal appearing mucosa adjacent to carcinoma.
A review of the clinical records from 1947 to 1984 of the Istituto Nazionale Tumori of Milan provided 20 cases (14 males and 6 females) of esophageal leiomyoma. Eighteen of the tumors were in the thoracic esophagus and 2 were at the cardiac level. The most frequent symptoms were dysphagia, slight epigastralgia and odynophagia. Differential diagnosis should be made with mediastinic neoplasms and esophageal cancer. Barium swallow and esophagoscopy are the most sensitive procedures for a correct preoperative diagnosis. Surgery is mandatory because of the tendency to a continuous endoluminal growth (in 97% of the cases) and a possible malignant transformation. However, surgery is conservative: extramucosal enucleation of the leiomyoma is the procedure of choice. The long-term results are excellent, and morbidity is acceptable.
Even the most sophisticated examinations, such as computerized tomography and percutaneous fine needle biopsy, often do not allow a certain preoperative diagnosis of benign lung cancer. The clinical history may also be deceiving: a smoker over 35 years of age need not necessarily have a primary lung cancer, but this event is frequent enough to justify a diagnostic thoracotomy. In our series, chest tomography proved to be useful and sometimes revealed unsuspected lesions. In contrast, bronchoscopy is useful only for centrally located lesions, and the same is true for bronchial washing and brushing. Finally, thoracotomy, possibly an axillary one with enucleation or possibly transegmentary resection, is the most frequent operation in benign lung tumors, because of the unfailing diagnosis and for the minimal functional damage to the patient. A diagnostic thoracotomy may also avoid the psychologic stress suffered by a patient with a simple but undiagnosed benign lung tumor.
Based on the experience of blood-related immunosuppression in kidney transplants, some retrospective studies have reported an adverse relationship between blood transfusion and survival after curative resection for cancer. In order to confirm these findings, we have retrospectively evaluated our population of resected stage Ia non-small cell lung cancers (years 1974-79). Two hundred and eighty-three patients were included in this analysis: 65 underwent pneumonectomy (23%), 205 lobectomy (72%) and 13 sublobar resections (5%). Patients submitted to perioperative blood transfusions were 157 (55%), without major differences according to surgery or tumour extent. The cumulative survival at 8 yr was 40% for transfused patients and 41% for nontransfused, relapse-free survival was respectively 36% and 34%; no differences were detectable stratifying for the amount of blood transfused or the extent of operation. Our experience does not support the hypothesis of an adverse prognosis related to perioperative blood transfusion.
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The relationship between growth rate, expressed as doubling time (DT), of 110 lung cancers from randomly collected patients and patient age, sex, histological type, symptoms, smoking habits, size and lymph node involvement was studied. Median DT values of epidermoid carcinomas and adenocarcinomas were superimposable (98 and 99 days, respectively), but 15% of adenocarcinomas had a DT of more than one year. Significant correlations were found with sex (slower growth rate in females) and symptoms (faster growth in symptomatic patients), but only for adenocarcinomas. The number of cigarettes smoked did not seem to affect the growth rate of lung cancers. There was no correlation between growth rate and tumor size or lymph node involvement.