The current state of the art in treating stage IIIA (N2) lung cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
N Martini
Publications and source records attributed to N Martini.
Evolution of the surgical management of pulmonary metastases.
Surgical treatment of pulmonary metastases dates back to the late 19th century. However, for the ensuing 50 years, the number of cases operated upon were few. Since the 1960s, the eligibility of patients for resection of pulmonary metastases has broadened. Neither the number of lesions nor the length of the disease-free interval excludes a patient from resection provided the primary tumor has been treated adequately and the patient can tolerate the resection. Resection of pulmonary metastases is predicated on the absence of effective treatment of nonoperative means and the ability to safely and completely resect all tumor and yet conserve sufficient lung tissue to provide a good quality of life. Major areas of controversy that remain are the number of metastases amenable to complete resection, the disease-free interval, the applicability by tumor type, and the role of chemotherapy. The data published to date suggest that pulmonary resection for metastases can improve overall survival with minimal morbidity and mortality.
Antineoplastic Agents↗
Multi-functional acetyl-CoA carboxylase from Brassica napus is encoded by a multi-gene family: indication for plastidic localization of at least one isoform.
Three genes coding for different multifunctional acetyl-CoA carboxylase (ACCase; EC 6.4.1.2) isoenzymes from Brassica napus were isolated and divided into two major classes according to structural features in their 5' regions: class I comprises two genes with an additional coding exon of approximately 300 bp at the 5' end, and class II is represented by one gene carrying an intron of 586 bp in its 5' untranslated region. Fusion of the peptide sequence encoded by the additional first exon of a class I ACCase gene to the jellyfish Aequorea victoria green fluorescent protein (GFP) and transient expression in tobacco protoplasts targeted GFP to the chloroplasts. In contrast to the deduced primary structure of the biotin carboxylase domain encoded by the class I gene, the corresponding amino acid sequence of the class II ACCase shows higher identity with that of the Arabidopsis ACCase, both lacking a transit peptide. The Arabidopsis ACCase has been proposed to be a cytosolic isoenzyme. These observations indicate that the two classes of ACCase genes encode plastidic and cytosolic isoforms of multi-functional, eukaryotic type, respectively, and that B. napus contains at least one multi-functional ACCase besides the multi-subunit, prokaryotic type located in plastids. Southern blot analysis of genomic DNA from B. napus, Brassica rapa, and Brassica oleracea, the ancestors of amphidiploid rapeseed, using a fragment of a multi-functional ACCase gene as a probe revealed that ACCase is encoded by a multi-gene family of at least five members.
Acetyl-CoA Carboxylase↗
Resection of lung cancer invading the diaphragm.
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Aged↗
Magnetic resonance imaging of the postpneumonectomy chest: normal and abnormal findings.
To determine the normal findings at magnetic resonance imaging (MRI) of the postpneumonectomy space (PPS), and to evaluate the utility of MRI in detection of recurrent tumor in the postpneumonectomy chest, 32 MRI scans were performed in 31 patients at varying time intervals after pneumonectomy. Eleven patients also had 12 computed tomography (CT) scans performed at the same time to evaluate possible tumor recurrence. Of the 32 scans, 5 demonstrated complete obliteration of the fluid containing PPS, and 4 showed gas in the PPS; the remainder (n = 23) demonstrated persistence of fluid-filled spaces of varying size. The presence of a fibrotic rim of tissue was constant. In 11 patients with clinically suspected tumor recurrences, both CT and MRI were obtained: the two modalities performed with similar accuracy in diagnosing tumor recurrence at 16 sites; CT detected opposite-lung metastatic nodules not seen on MRI in one patient, and a rib metastasis described as "indeterminate" on MRI in a second patient. MRI detected a focus of recurrence in the PPS that was indeterminate on CT. There is considerable variability in the amount of fluid seen in the PPS on MRI. CT remains the procedure of choice for routine follow-up or in suspected tumor recurrence in the postpneumonectomy patient; MRI can be helpful if the CT scan is nondiagnostic or equivocal.
Adult↗
Advanced HIV infection treated with zidovudine monotherapy: lifetime values of absolute cost-effectiveness as a pharmacoeconomic reference for future studies evaluating antiretroviral combination treatments. The Osservatorio SIFO sui Farmaci.
OBJECTIVE: This study was undertaken to evaluate the cost and the effectiveness of zidovudine monotherapy in patients with advanced HIV infection and to derive preliminary data on the cost-effectiveness of the triple treatment with saquinavir plus zalcitabine plus zidovudine compared with zidovudine alone. DESIGN: We used a combined method of survival analysis utilizing both the quality-adjusted time without symptoms or toxicity (Q-TWIST) method and the Gompertz approach. This combined method was applied to assess the absolute cost-effectiveness and cost-utility ratios of zidovudine monotherapy and to perform a preliminary incremental cost-effectiveness comparison of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone. The clinical material used in our study was derived from two reports on the treatment of advanced HIV infection. Data of lifetime costs of HIV infection were obtained from published information. RESULTS: In patients with advanced HIV infection treated with zidovudine monotherapy, lifetime survival was 252.1 discounted person-years per 100 patients. Using an average lifetime cost of $93,000 (discounted) per individual, the absolute ratio of cost-effectiveness for zidovudine monotherapy was $36,980 per life-year, while the absolute cost-utility ratio was $47,112 per quality-adjusted life-year. In the comparative analysis of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone, our calculations showed that the administration of the triple treatment can have an "average" cost-effectiveness, provided that mean lifetime survival per patient (discounted) is improved to at least 3.68 years (with an average survival gain of at least 14 mo per patient). CONCLUSIONS: The values of absolute cost-effectiveness and cost-utility ratios for zidovudine monotherapy are a useful reference point for further pharmacoeconomic studies in the area of antiretroviral drugs.
Anti-HIV Agents↗
The role of multimodality therapy in locoregional non-small cell lung cancer.
Surgical treatment is offered to all patients with stage I or II disease and to specific groups of patients with stage III or IV disease. Cisplatin based on regimens of induction chemotherapy or chemoradiotherapy have proven to be valuable in stage IIIA (N2) disease. We now recommend induction therapy on an investigational basis to most patients with stage I or II tumors and to all those with stage IIIA tumors, when the 5 year survival is anticipated to be less than 50% with conventional therapy. Many new chemotherapy agents effective in advanced stage lung cancer are currently integrated into this multimodality approach in hopes of further improvement in tumor control and survival.
Antineoplastic Agents↗
Health services: an Italian market.
One of the glories of Italy is its capacity to surprise. In out-of-the-way places extraordinary things are suddenly encountered; and this is hardly less true of science than of architecture or music or painting. Italian medicine can boast excellence in many quiet spots. Yet Italy's record in medical science and practice is perceived to be below par, and one reason may be a lack of central coordination--forgivable in a country that had fifty governments in half a century. The latest administration offers a rare chance of political stability and the prospect of reforms. In this profile of Italian medicine The Lancet's guide was Dr Giuseppe Remuzzi, whose central coordination was exemplary.
Acquired Immunodeficiency Syndrome↗
Predictors of survival in malignant tumors of the sternum.
From 1930 to 1994, 54 patients with primary malignant tumors of the sternum were seen. Fifty patients were first seen with a mass, and one half of them also had pain in the sternal region. Two patients had no symptoms at presentation. Among 39 solid tumors were 26 chondrosarcomas, 10 osteosarcomas, 1 fibrosarcoma, 1 angiosarcoma, and 1 malignant fibrous histiocytoma. Of these, 25 were low-grade and 14 were high-grade tumors. Among 15 small cell tumors were 8 plasmacytomas, 6 malignant lymphomas, and 1 Ewing's sarcoma. Partial or subtotal sternectomy was done in 37 patients and total sternectomy in 3. Of the remaining 14 patients, 3 had local excision; 10 had external radiation or chemotherapy without operation, or both; and 1 had no treatment. All but one patient treated by wide resection (N = 40) had some form of skeletal reconstruction of the chest wall defect. Thirty-one (78%) underwent repair with Marlex mesh, and in 25 this was combined with methyl methacrylate. The skin edges were closed per primum in 32 patients; 8 required muscle, omentum, or skin flaps. Resection in chondrosarcomas yielded a 5-year survival (Kaplan-Meier) of 80% (median follow-up, 17 years). The 5-year survival in osteosarcomas was 14%. Resection was curative in 64% of low-grade sarcomas but in only 7% of high-grade sarcomas. In small cell tumors, resection and radiation were helpful for local control; all failures were a result of distant metastases. We conclude that primary sarcomas of the sternum though uncommon are potentially curable by wide surgical excision. With rigid prostheses to repair the skeletal defects, the surgical complication rates are low. Overall survival after complete surgical resection is related to tumor histologic type and grade.
Bone Cements↗
Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer.
The development of cisplatin-based induction chemotherapy followed by surgical resection or radiation has improved the poor prognosis of stage III non-small cell lung cancer (NSCLC). In vitro studies indicate that p53 can modulate cisplatin-induced cytotoxicity, but the molecular genetic features determining response or resistance to cisplatin in vivo must be defined. For this reason, tumor specimens from 52 patients with stage IIIA NSCLC entered in a prospective clinical trial of cisplatin-based induction chemotherapy followed by surgical resection were examined for p53 expression by immunohistochemical staining before and after induction chemotherapy. p53 expression was correlated with clinical and pathological response using Fisher's exact test. No correlation was established between p53 expression and clinical response because 47 of the 52 patients studied had a major response. However, a significant association was observed between aberrant p53 expression and resistance to chemotherapy as assessed by pathological response. Only 3 of the 20 patients whose tumors exhibited a high level (+ + to + + + +) of p53 staining experienced a major (+ + + to + + + +) pathological response to chemotherapy. Only 7 of 52 cases examined before and after chemotherapy treatment exhibited a change in the level of p53 expression after cisplatin-based chemotherapy. These results indicate that cisplatin alters p53 expression infrequently and suggest a direct link between aberrant p53 expression and resistance to cisplatin-based chemotherapy in NSCLC.
Carcinoma, Non-Small-Cell Lung↗
Effectiveness of gabexate mesilate in acute pancreatitis. A metaanalysis.
Since the effectiveness of gabexate mesilate in patients with acute pancreatitis is controversial, a metaanalysis of the published literature was conducted to address this problem. Five randomized trials were identified by our literature search. Three end points (mortality, complications, and complications requiring surgery) were evaluated. The results of our metaanalysis indicate that the treatment with gabexate mesilate does not affect mortality at 90 days (P = 0.27), but significantly reduces the incidence of complications requiring surgery (odds ratio = 0.61, 95% CI: 0.41-0.89; P < 0.05) and of complications in general (odds ratio = 0.69, 95% CI: 0.54-0.89; P < 0.05). Because the drug proves to be beneficial only to a low proportion of the treated patients, its clinical impact seems to be small. A pharmacoeconomic evaluation shows that its use in all patients with acute pancreatitis would imply a very high cost for preventing each complication. The administration of the drug to select patients who are at higher risk of complications could have a better cost-effectiveness ratio. However, specific studies on this point are still lacking.
Acute Disease↗
Thymoma: a multivariate analysis of factors predicting survival.
BACKGROUND: Despite complete surgical excision, malignant thymomas often recur with resultant death. We reviewed our series to determine which factors independently predict survival after surgical resection. METHODS: A retrospective analysis of patients operated on for thymoma between 1949 and 1993 at Memorial Sloan-Kettering Cancer Center was performed. Clinical data were collected from chart review. Only patients with a pathology report confirming the diagnosis of thymoma were included in this analysis. Kaplan-Meier survival curves were generated and comparisons of survival analyzed by log rank test. Multivariate analysis was performed by the Cox proportional hazard model. RESULTS: One hundred eighteen patients with thymoma underwent operation. There were 86 complete resections (73%), 18 partial resections (15%), and 14 biopsies (12%). By Masaoka staging, 25 patients were stage I (21%), 41 stage II (35%), 43 stage III (36%), and 9 stage IVa (8%). Overall survival was 77% at 5 years and 55% at 10 years. Tumor recurred in 25 (29%) of 86 completely resected thymomas. Stage of disease (p = 0.03) was the only independent prognostic factor affecting recurrence. By multivariate analysis, stage (p = 0.003), tumor size (p = 0.0001), histology (p = 0.004), and extent of surgical resection (p = 0.0006) were independent predictors of long-term survival. CONCLUSIONS: Patients with stage I disease require no further therapy after complete surgical resection. Neoadjuvant therapy should be considered for patients with large tumors and invasive disease.
Combined Modality Therapy↗
Successful treatment of solitary extracranial metastases from non-small cell lung cancer.
BACKGROUND: Recurrence after resection of non-small cell lung carcinoma is generally associated with a poor outcome and is treated with either systemic agents or palliative irradiation. Recently, long-term survival has been reported after resection of isolated brain metastases from non-small cell lung carcinoma, but resection of other metastatic sites has not been explored fully. METHODS: We have identified 14 patients who had solitary extracranial metastases treated aggressively after curative treatment of their non-small cell lung carcinoma. The histology was squamous carcinoma in 5, adenocarcinoma in 8, and large cell carcinoma in 1. Initially, 3 patients had stage I, 5 stage II, and 6 stage IIIa disease. RESULTS: The sites of metastases included extrathoracic lymph nodes (six), skeletal muscle (four), bone (three), and small bowel (one). The median disease-free interval before metastases was 19.5 months (range, 5 to 71 months). Complete surgical resection of the metastatic site was the treatment in 12 of 14 patients. Two patients received only curative irradiation to the metastatic site, with complete response. The overall 10-year actuarial survival (Kaplan-Meier) was 86%. To date, 11 patients are alive and well after treatment of their metastases (17 months to 13 years), 1 has recurrent disease, 1 died of recurrent widespread metastases, and 2 died of unrelated causes. CONCLUSION: Long-term survival is possible after treatment of isolated metastases to various sites from non-small cell lung carcinoma, but patient selection is critical.
Actuarial Analysis↗
Effectiveness and toxicity of preoperative therapy in stage IIIA non-small cell lung cancer including the Memorial Sloan-Kettering experience with induction MVP in patients with bulky mediastinal lymph node metastases (Clinical N2).
The use of preoperative chemotherapy with mitomycin, vinblastine and cisplatin (MVP) has led to improved complete resection rates and survival in Stage IIIA non-small cell lung cancer with bulky, ipsilateral, mediastinal lymph node metastases (Clinical N2 disease). The addition of preoperative irradiation has also been explored with results not substantially different from preoperative cisplatin-based chemotherapy alone. While preoperative chemotherapy has been shown to be feasible, the toxicity of both the chemotherapy and the subsequent resection is of concern with an overall treatment-related mortality of nearly 8%. The careful selection of patients, swift management of neutropenia, and meticulous perioperative pulmonary care has the potential to reduce the mortality from multimodality therapy. Having shown survival benefit in multiple single-institution and randomized trials, induction chemotherapy followed by surgery or irradiation is now the treatment of choice for patients with Stage IIIA non-small cell lung cancer with mediastinal lymph node metastases.
Antineoplastic Combined Chemotherapy Protocols↗
Incidence of local recurrence and second primary tumors in resected stage I lung cancer.
From 1973 to 1985, 598 patients underwent resection for stage I non-small-cell lung cancer. There were 291 T1 lesions and 307 T2 lesions. The male/female ratio was 1.9:1. The histologic type was squamous carcinoma in 233 and nonsquamous carcinoma in 365. Lobectomy was performed in 511 patients (85%), pneumonectomy in 25 (4%), and wedge resection or segmentectomy in 62 (11%). A mediastinal lymph node dissection was carried out in 560 patients (94%) and no lymph node dissection in 38 (6%). Fourteen postoperative deaths occurred (2.3%). Ninety-nine percent of the patients were observed for a minimum of 5 years or until death with an overall median follow-up of 91 months. The overall 5- and 10-year survivals (Kaplan-Meier) were 75% and 67%, respectively. Survival in patients with T1 N0 tumors was 82% at 5 years and 74% at 10 years compared with 68% at 5 years and 60% at 10 years for patients with T2 tumors (p < 0.0004). The overall incidence of recurrence was 27% (local or regional 7%, systemic 20%) and was not influenced by histologic type. Second primary cancers developed in 206 patients (34%). Of these, 70 (34%) were second primary lung cancers. Despite complete resection, 31 of 62 patients (50%) who had wedge resection or segmentectomy had recurrence. Five- and 10-year survivals after wedge resection or segmentectomy were 59% and 35%, respectively, significantly less than survivals of those undergoing lobectomy (5 years, 77%; 10 years, 70%). The 5- and 10-year survivals in the 38 patients who had no lymph node dissection were reduced to 59% and 32%, respectively. Apart from the favorable prognosis observed in this group of patients, three facts emerge as significant: (1) Systematic lymph node dissection is necessary to ensure that the disease is accurately staged; (2) lesser resections (wedge/segment) result in high recurrence rates and reduced survival regardless of histologic type; and (3) second primary lung cancers are prevalent in long-term survivors.
Adenocarcinoma↗
Mediastinal lymph node dissection for lung cancer. The Memorial experience.
A mediastinal lymph node dissection as opposed to lymph node sampling should be an integral part of the operation in all patients with resectable lung cancers. A systematic mediastinal node dissection affords the most accurate staging and a long-term survival in some patients when the positive regional nodes are also removed. It is safe and easy to do, adds only 20 to 30 minutes to the surgical procedure, and morbidity is minimal. Our reported survival data have been based on the routine use of mediastinal lymph node dissection in conjunction with pulmonary resection. Techniques of lymph node dissection for both right- and left-sided tumors are described along with a historical background of their evolution.
Humans↗
Randomized trial comparing postoperative chemotherapy with vindesine and cisplatin plus thoracic irradiation with irradiation alone in stage III (N2) non-small cell lung cancer.
This prospective randomized trial was performed to determine whether postoperative chemotherapy with vindesine and cisplatin could lengthen time to progression and overall survival in stage III (T1-3N2M0) non-small cell lung cancer (NSCLC) patients. Seventy-two patients were entered; 36 were randomized to receive chemotherapy. Patients were stratified by extent of resection (complete vs. incomplete) and histology (squamous vs. nonsquamous). All had surgery and mediastinal irradiation 6-7 weeks post-thoracotomy. Incompletely resected patients had intraoperative 125I and/or 192Ir implantation. Vindesine (3 mg/m2) weekly x 5, then every 2 weeks x 8, and cisplatin (120 mg/m2) days 1, 29, 71, 113 were planned for those randomized to chemotherapy. No difference in time to progression (median 9.2 months for radiation + chemotherapy vs. 9.0 months for radiation, P = 0.35) or overall survival (16.3 months for radiation + chemotherapy vs. 19.1 months for radiation, P = 0.42) was found. Postoperative vindesine and cisplatin did not prolong time to progression or survival in this population of stage III NSCLC.
Adult↗
Influence of surgical resection and brachytherapy in the management of superior sulcus tumor.
We analyzed the results of surgical treatment of all patients presenting with untreated superior sulcus tumors between 1974 to 1991 inclusive at our institution. Most patients received preoperative radiotherapy. We attempted to analyze the influence of surgical resection and intraoperative brachytherapy in obtaining locoregional control and disease-free survival. One hundred twenty-four patients underwent thoracotomy and 100 patients underwent resection. The overall 5-year survival rate was 26% for all patients and 30% for resected patients. Those patients receiving a complete resection achieved a 41% 5-year survival. The best single group were those patients undergoing a lobectomy (versus wedge resection) and en-bloc chest wall resection (60% 5-year survival). We were unable to demonstrate an advantage for the use of intraoperative brachytherapy in those patients with complete resection. For those patients with incomplete resection, the use of brachytherapy combined with preoperative or postoperative external radiation therapy resulted in a 9% 5-year survival. Locoregional failure was significant both in patients with complete resection and in patients with incomplete resection. Adverse prognostic factors included Horner's syndrome, N2 and N3 disease, T4 disease, and incomplete resections. In superior sulcus tumors, every attempt to completely resect the tumor by en-bloc chest wall resection combined with lobectomy and adequate nodal staging remains the surgical treatment of choice together with either preoperative, postoperative, or "sandwich" external radiation therapy.
Adult↗