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Objective:To investigate the feasibility of positron apoptosis radioactive tracer 18F-labeled 5-fluoropentyl-2-methyl-malonic acid ( 18F-ML-10) in the detection of cisplatin inducing apoptosis of lung adenocarcinoma A549 cells. Methods:Lung adenocarcinoma A549 cells were divided into the control group, cisplatin time groups and cisplatin dose groups. Cisplatin was not added to the control group. Cisplatin time groups with added 50 μg/ml cisplatin were used for 12, 18, 24, 30, 36, 42 and 48 h, respectively, and the cells of the control group were cultured for 48 h; cisplatin dose groups were treated with 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100 μg/ml cisplatin, respectively for 30 h. The apoptosis was detected by using flow cytometry, and the 18F-ML-10 uptake rate of apoptotic cells in each group was calculated. Results:With the prolongation of the action time of 50 μg/ml cisplatin, the apoptosis rate of A549 cells was increased gradually ( F = 66.87, P < 0.01), and the standavd uptate value of 18F-ML-10 was also increased gradually ( F = 86.47, P < 0.01). When cisplatin was treated for 48 h, the apoptosis rate [(63.10±14.00)%] and 18F-ML-10 standard uptake value (4.97±1.03) reached the highest (all P < 0.01). After cisplatin treatment for 30 h, with the increase of cisplatin dose, the apoptosis rate and 18F-ML-10 standavd uptate value were gradually increased (all P < 0.01), and the apoptosis rate of cisplatin 100 μg/ml group was the highest [(37.31±2.48)%], and the 18F-ML-10 standavd uptate value was the highest (3.08±0.20). Conclusions:18F-ML-10 is feasible in the detection of cisplatin inducing the apoptosis of A549 cells.
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Objective To investigate the expressions and clinical significances of MUC1-mRNA and CK20-mRNA in peripheral blood of esophageal cancer patients.Methods MUC1-mRNA and CK20-mRNA were detected in 53 patients with esophageal cancer,10 patients with esophageal benign tumor and 20 healthy volunteers by RT-PCR technique.Results The expressions of MUC1-mRNA,CK20-mRNA and combining group were 35.85 % (19/53),49.06 % (26/53) and 62.26 % (36/53) in peripheral blood of 53 esophageal cancer patients.In control group,there was no expression of MUC1-mRNA and CK20-mRNA in peripheral blood of 10 patients with benign esophageal disease and 20 healthy volunteers.The positive rate increased by combining test(x2 =11.0228,P ＜0.05).Conclusion MUC1-mRNA and CK20-mRNA might be specific and sensitive markers to detect circulating tumor cells in peripheral blood and their expressions are closely related to TNM stages of the esophageal cancer patients.The combining test might be of high value of the diagnosis of micrometastasis.
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Objective To establish reverse transcriptase-polymerase chain reaction(RT-PCR) with primers specific for CEA gene and CK20 gene to detect circulating tumor cells in peripheral blood of esophageal cancer pa-tients,and try to find the relationship between the mRNA expression and micrometastasis. Methods The expressions of CEA,CK20 were analyzed by RT-PCR in 53 cases of esophageal tumor tissue and in peripheral blood,compared with 10 patients with benign esophageal disease and 20 healthy volunteers. Results The expressions of CEA-mRNA, CK20-mRNA were 96.23% (51/53), 100% ( 53/53 ) in 53 esophageal tumor tissue and were 52.83% (28/53), 49.06% (26/53) in peripheral blood of 53 esophageal cancer patients. In control group,there was only one expression of CEA-mRNA in peripheral blood of 10 patients with benign esophageal disease,as well as in 20 healthy volunteers. There was no expression of CK20-mRNA in peripheral blood of 10 patients with benign esophageal disease and 20 healthy volunteers. Conclusion CEA-mRNA, CK20-mRNA might be specific and sensitive markers to detect circu-lating tumor cells in peripheral blood and their expression was closely related to TNM stages of the esophageal cancer patients.
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<p><b>BACKGROUND</b>According to the international standard in TNM staging of pulmonary carcinoma, pulmonary carcinoma complicated with diffuse pleural metastasis and malignant pleural effusion belongs to IIIB stage. In the past, non-operative therapy was employed, but both the therapeutic efficacy and the quality of life of patients were poor. The purpose of this study is to find out a complex treatment for this disease.</p><p><b>METHODS</b>Total pleuro-pneumonectomy was performed in 55 cases of patients with pulmonary carcinoma complicated with diffuse pleural metastasis and malignant pleural effusion from December 1978 to February 2003. The patients were followed up postoperatively, and the quality of life and survival period of them were observed.</p><p><b>RESULTS</b>In all the cases, only 2 patients died of operation. Satisfactory recovery and remarkable relief of symptoms such as short breath, dyspnea and chest pain were found in all the other patients. After a follow-up period of 1-25 years, local recurrence was found in 6 cases (11.3%), and distant metastasis in 42 cases (79.2%). A total of 48 patients died of tumor, with survival period ranging from 5-40 months (average survival period: 15 months; median survival period: 14 months), and 5 patients were still alive in good health.</p><p><b>CONCLUSIONS</b>(1) Patients appropriated for operation should be carefully selected in case that postoperative complications influence their smooth recovery; (2) Tumor tissues should be removed as clear as possible; (3) During the operation, close attention should be paid to the protection of incisions; (4) Removal of the tumor tissues can reduce the tumor load, effectively clean the immunosuppressive factors in malignant pleural effusion, and break the immunity block status, which provides basis for the following comprehensive therapy; (5) The quality of life of the patients can be improved and the median survival period can be prolonged by the operation; (6) The long-term survival rate of patients is still unsatisfactory.</p>
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Objective To investigate the surgical treatment and prognosis of bronchial mucoepidermoid cancer. Methods During a 17-year-period, 19 consecutive patients underwent surgery for bronchial mucoepidermoid cancer, and the surgical treatment and prognosis were analyzed retrospectively. Results Among them, 13 cases were treated by lobectomy, 5 by pneumonectomy, and 1 by exploratory thoracotomy. Four cases were proved pathologically to be high malignancy and 15 low malignancy. All patients were followed up postoperatively for about 68.26 months on average. The 1, 3, and 5-year survival rates were 94.44%, 80.00%, and 70.00% respectively. In the low malignancy group, the 1, 3, 5-year survival rates were 100%; in the high malignancy group, the 1-year survival rate was 33.33%, and 3-year survival rate was 0. Conclusion Patients with low malignant grade of cancers can be cured after complete resection, and those with high malignant grade predispose to metastasis and hence result in a poor prognosis.
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<p><b>OBJECTIVE</b>To study the diagnosis and treatment of thymoma and to assess its prognostic factors.</p><p><b>METHODS</b>The clinical data of 116 patients with thymoma were collected. A retrospective analysis was performed, by comparing the survival rate calculated by the Kaplan-Meier method with the rate of recurrence or metastasis.</p><p><b>RESULTS</b>The standard posteroanterior and lateral chest radiographs were reliable means of detection of most thymomas. Myasthenia gravis was the most commonly paraneoplastic disease (25.0%, 29/116). The extensive radical resection was beneficial for reducing the rate of recurrence of stage I or stage II thymomas (chi(2) = 4.941, P = 0.0219). The survival time could be prolonged by postoperative radiotherapy and chemotherapy. There was a strong correlation between the clinical stage and the histological classification (according to MH classification), through which the invasive behavior of thymoma could be predicted (chi(2) = 19.76, P = 0.007, RR = 1.47). The 3- 5- and 10-year survival rates were 81.2%, 67.9%, and 40.5%, respectively. Statistical analysis showed a significant negative correlation between the stage and the survival rate (chi(2) = 29.73, P = 0.0000, RR = 0.15).</p><p><b>CONCLUSION</b>The prognosis of thymoma depends mainly on the histological classification, clinical stage and multimodality treatment rather than on the paraneoplastic diseases.</p>
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Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Myasthenia Gravis , Prognosis , Retrospective Studies , Thymoma , Diagnosis , Mortality , Therapeutics , Thymus Neoplasms , Diagnosis , Mortality , TherapeuticsABSTRACT
<p><b>OBJECTIVE</b>To assess the relationship between histological type and fluorine-18 fluorodeoxyglucose(FDG) uptake in patients with primary lung cancer and the factors affecting FDG uptake.</p><p><b>METHODS</b>From October 1998 to April 2001, 82 patients with lung cancer were imaged with FDG-PET (Positron emission tomography) before surgery or biopsy. Their maximum and mean standard uptake value(SUVmax and SUVmean) of tumor and SUV of normal lung (SUVlung) were measured.</p><p><b>RESULTS</b>All tumors were detected by FDG-PET(r)FDG uptake of tumor was higher than that of normal lung (P < 0.01). FDG uptake was lower in adenocarcinoma(AC) than in squamous cell carcinoma (SQC), and that of bronchial aveolar carcinomas(BAC) was the lowest [SUVmax was 8.42 +/- 4.05,5.91 +/- 3.91 and 2.97 +/- 1.10, respectively; SUVmean was 6.12 +/- 2.90,4.35+/- 3.10 and 2.25 +/- 0.99, respectively (P < 0.01)]. Correlations were found between FDG uptake and tumor size (P < 0.01)(r)Glucose level and SUV of normal lung could affect SUV of lung cancer (P < 0.05).</p><p><b>CONCLUSIONS</b>SUV is higher in cancer tissue than in normal lung tissue. FDG uptake is different among SQC,AC and BAC. FDG uptake and tumor size appear to be correlated with each other.SQC, AC and BAC have their own features respectively. The effects of glucose and SUV lung should be considered in the diagnosis of lung cancer with PET.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Blood Glucose , Fluorodeoxyglucose F18 , Pharmacokinetics , Lung Neoplasms , Diagnostic Imaging , Metabolism , Radiopharmaceuticals , Pharmacokinetics , Tomography, Emission-ComputedABSTRACT
Objective Foregut cyst of the mediastinum is an uncommon but important mediastinal disease,representing 40% to 50% of all the mediastinal cysts.The purpose of present study was to summarize the clinical feature and surgical treatment of mediastinal foregut cysts in patients admitted to the authors' hospital,and to emphasize the important role of video-assisted thoracic surgery(VATS)played in the treatment of mediastinal foregut cysts.Methods Data of 51 cases of mediastinal foregut cysts confirmed by pathological examination from 1993 to 2006 were retrospectively reviewed.Results 29 male and 22 female patients were involved in the present study.Among all the cases,24(47%)manifested no conspicuous symptom,and the remainders showed various symptoms such as chest pain,dyspnea,cough etc.The findings of magnetic resonance imaging(MRI)were more helpful than that of CT in diagnosis.In the present series,5 cysts were located in the antero-superior mediastinum,18 in the middle mediastinum and 28 in the posterior mediastinum.All patients underwent operation,including 15 minimal invasive surgeries such as VATS.35 cysts were excised completely and 16 cysts were resected partially.Pathological examination confirmed that,there were 42 bronchogenic cysts,7 esophageal cysts and 2 gastro-enterogenous cysts.There was no postoperative death or major complications,but minor complications occurred in 3 patients.During an average of 26 months of follow-up(ranged 2 to 56 months),no recurrence or malignant degeneration was found.Conclusion Mediastinal foregut cysts are rarely diagnosed definitely before operation,and it should be surgically treated because its pathology can only be established after surgical extirpation.Video-assisted thoracoscopic surgery is the first choice for the treatment of mediastinal foregut situated,especially for those situated in the middle and posterior mediastinum.
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Objective To investigate the effectiveness of radio gu ided surgery (RGS) in lung carcinoma by using ~18F-FDG. Methods Forty mice bearing lung adenocarcinoma were divided randomly into two gro ups according to presence or absence of the lung metastasis. A dose of 200?l (1 00?Ci) of ~18F-FDG was injected via the tail vein. The external radioimmu nography was performed after injection. All viscerae and tumor were detected i n vivo by means of a hand-held gammaray-detecting probe (GDP), and the radio active distribution was analyzed with the well-gammaray detector. Resul ts The tumor images in mice were clear, and the images were best at two hours after injection. The values of %ID/g of tumor and heart obtained by well -gammaray detector were higher than those of other organs. Ratios of tumor/norm al tissue (T/NT) except cardiac muscle being detected by GDP ranged from 3.71 t o 13.57. There was a significant difference between the radioactivity of lung t issues in lung metastasis group and that of control group (P
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Objective To investigate a novel therapeutic strategy in the treatment of lung cancer with diffuse pleural metastasis accompanied by malignant pleural effusion. Methods From December 1978 to February 2003, 55 patients of carcinoma of lung with pleural metastasis underwent the comprehensive therapy characterized by pleuropneumonectomy. A follow-up of all the patients after hospital discharge was conducted. Results Death due to complications was found in 2 out of the 55 patients, but remission and significant improvement of symptoms were found in the rest. A follow-up period ranging from 1 to 25 years revealed that 48 patients survived for 5-40 months (median survival time: 14 months), and 5 patients were still living and well. Conclusion Strict control of the surgical indications and radical removal of the malignant tumor can improve the quality of life and prolong the survival time of patients, even there is already metastasis to the pleura.
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Objective To evaluate the value of intraoperative ultrasonography (IUS) in detecting the lymph nodes in mediastinum and hilum during lung cancer surgery. Methods Lymph nodes were detected in every part of the mediastinum and hilum by IUS in 33 cases with lung cancer during surgery. The number, size and location of lymph nodes were recorded, and the metastasis to lymph nodes was predicted by the sonographic features and geometric measurement respectively. Mediastinum was explored and lymph nodes resection was performed in each case, and each resected lymph node was sent for pathological examination. Results The sensitivity of IUS in detecting lymph nodes in mediastinum and hilum was 83.6% (163/195) and the positive predictive value was 97.0%(165/168). The result of detecting lymph nodes with IUS was influenced by their location and size. The sensitivity, specificity and accuracy of IUS in diagnosing lymphatic metastasis with respect to geometric measurement were 70.3%, 71.7%, 71.2%, respectively, and were 85.7%, 75.0%, 83.3%, respectively, with respect to sonographic features. Conclusions IUS was an effective method for lung cancer surgery in detecting mediastinum lymph nodes.
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Objective With the development in optics and video systems, video assisted thoracoscopic surgery (VATS) in the diagnosis and treatment of esophageal lesions has come to clinical use. The experience with the method in 12 patients admitted to the surgical department of the General Hospital of PLA from Oct.1993 to Sept.2001 was summarized. Methods Of the 12 patients (male 10, female 2) with the age ranging from 34 to 63, 10 were suffering from malignant tumors (9 squamous carcinoma, 1 adenoid cysticcarcinoma) with 5 in TNM stage 1, and 5 in stage 2, and 2 were having benign tumors (1 esophageal leiomyoma, 1 esophageal cyst). In 7 patients with malignant tumors, esophagectomy was performed through the right thorasic cavity followed by asophagogastrostomy in the neck, and in 3 patients the anastomosis was done in the right thoracic cavity. A left thoracoscopic extirpation of esophageal leiomyoma and esophageal cyst was performed in patients with benign tumors. Thoracotomy was necessary in 3 patients. All patients were ventilated with a double lumen endotracheal tube, so that only the ipsilateral lung collapsed. Results There was no operative mortality in the group. Mean time for freeing the esophagus through thoracoscope was 70 minutes, and mean overall operation time was 252 minutes. 7 enlarged mediastinal lympha nodes were excised. The mean postoperative drainage volume was 180ml/24h and the mean duration of drainage tube was 2 days. The patients were discharged from the hospitals 9～13 days after the operation. Two postoperative complications occurred, one presented as left recurrent laryngeal nerve injury and the other as incision infection. Conservative therapy was given and recovery was uneventful. Conclusions As a minimally invasive surgical technique, VATS was a feasible and effective option in the treatment of esophageal lesions. Complications of VATS were similar to that of conventional open chest surgery. There is still controversy with regard to esophageal resection with VATS for malignant tumors, therefore further investigation is necessary.
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To investigate the relationship between partial esophagectomy with staple anastomosis for carcinoma and gastroesophageal reflux (GER). The pressure in the esophagus and intrathoracic stomach was measured with SG-Ⅱ computer manometer in 45 patients. Twenty-four-hour esophageal pH monitoring, endoscopy and pathological examination were performed in 20 patients. Resting pressure above the esophago-gastric anastomosis was higher than that under the esophago-gastric anastomosis. Twenty-four-hour pH monitoring revealed that GER occurred. Abnormal findings were observed in 80% of patients by endoscopic and pathological examinations. The results showed that GER existed in the patients after esophagectomy and esophagogastrostomy for esophageal cancer. The occurrence of GER with stapling anastomosis were similar to that with manual anastomosis. The occurrence of GER was not related with the length of postoperative period. Sleeping in semirecumbent position was an effective method to prevent GER for postoperative patients. Twenty-four-hour pH monitoring was a reliable method for detecting GER.
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Thoracoscopic esophagectomy is an alternative to open thoracotomy in treatment of esophageal carcinoma, but its role in esophageal surgery is still controversial. Between May 2000 and May 2002, 9 patients affected by esophageal carcinoma underwent esophagectomy with thoracoscopic dissection of the esophagus. Seven patients were male, 2 were female,and the mean age was 51 (range, 42～56) years.One patient had the carcinoma at cervical segment, 2 at upper third thoracic segment, 5 at middle third, and 1 at lower third.All tumors were squamous cell type and were below stage II.Thoracoscopy and cervical esophagogastrostomy were successfully performed in 8 patients except in one case, in whom conversion to thoracotomy was necessary because of extensive tumor invasion.Thoracoscopic dissection took an average of 70 (range,40～120) minutes and the mean operative time was 252(range,230～270) minutes. the mean operative blood loss was 250ml (range,150～400ml) and the mean number of thoracic lymph nodes harvested was 7(range,5～12).One patient experienced a cervical infection,which healed with conservative treatment.One patient had a temporary left recurrent nerve palsy that disappeared during the following 6 months.These initial data indicate that thoracoscopic esophagectomy is safe and feasible. The short term result of thoracoscopy is comparable with that of open thoracotomy, and the long term result and its role in esophageal surgery deserve further investigation.
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In this paper the authors submitted their experience in application of video assisted thoracic surgery (VATS) in 204 cases at the surgical clinic of the General Hospital of PLA (Oct.1992 Jun.2002). A retrospective analytic study was carried out to assess the value of VATS in terms of the diseases and the surgical anesthesia, operation modes, complications and result. A satisfying result in the group was obtained in each of the cases. There was no operative mortality or morbidity. The mean operation time was 110 minutes, the overall median duration of chest tube drainage was 2 days, and the mean hospitalization time was 9 days. The postoperative recovery was uneventful. As a minimally invasive surgical technique with very low morbidity, VATS is worth considering and has been established as a procedure of choice with exceptional results in various chest diseases. Our experience confirms the safety of VATS in both diagnostic and therapeutic procedures. Due to progress over the past several years, VATS is by now a standard surgical procedure in thoracic surgery, and has become an inseparable part of thoracic surgery. There are differences of opinion with regard to major pulmonary and esophageal resections for cancer, thus further clinical investigation deserves to be carried out.
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Of the 49 patients(male 43, female 6) collected from October 1983 to April 2000, 46 were malignancy with 29 in TNM stage I, 15 in stage II, and 2 in stage Ⅲa. Age ranged from 10～68. Upper lobectomy with sleeve resection was performed in 43 cases(14 in left lung, 29 in right lung) and right upper lobectomy with wedge bronchoplasty in 2 cases, left upper lobectomy with bronchoplasty and angioplasty in 2 cases , left lower lobectomy with sleeve resection in 2 cases. There was no mortality in our group and all patients recovered well. No such major complications as bronchial anastomotic fistula or stenosis occurred. The 1,5 and 10 year survival rates of malignant cases were 93.0%, 48.1% and 8.3% respectively. The results suggested that the operation plan for malignant lung diseases should be made individually. However, instead of a total pneumonectomy, a sleeve lobectomy is sometimes preferabe for the sake of the safety in those with poor cardiopulmonary function to save the lung capacity as much as possible.
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Objective To investigate the biodistribution and positron emission tomography (PET) imaging of 3′-deoxy-3′-~ 18 F-fluorothymidine (~ 18 F-FLT) in a murine model of pulmonary carcinoma, and to evaluate the use of ~ 18 F-FLT as a new PET tracer for diagnosis of pulmonary malignant tumor. Methods 40 T739 mice bearing the pulmonary adenocarcinoma were randomly divided into five groups according to different tracers and time after their injection (n=8/group). The biodistribution of mice for ~ 18 F-FLT was measured with well-gamma detector at 30min, 60min, 90min, 120min after injection via the tail veins. The biodistribution of mice for ~ 18 F-FDG was examined at 60min after injection as controls. In addition, the PET imaging of mice was performed using two tracers. Results In the biodistribution study of ~ 18 F-FLT, considerable radioactive uptake in tumor was observed, and high radioactivity was showed in the kidney and spleen. The T/NT ratios of tumor/blood, tumor/muscle and tumor/lung was all above 2.0. The tumor PET images with ~ 18 F-FLT were clear, as well. Conclusions The uptake of ~ 18 F-FLT in pulmonary adenocarcinoma is higher than that in normal tissues, thus the pulmonary neoplasm could be identified accurately with PET imaging. Our preliminary study of ~ 18 F-FLT in lung carcinoma xenografts is satisfactory, and it provides a basis for further clinical study.
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Objective To explore the organic micro environmental effect of skeletal muscles on the proliferation of thoracic malignant cells, its significance in the rarity of metastases in skeletal muscles and the prospect for its clinical applications.Methods Primary culture of new born Wistar rat skeletal muscle cells was established.The murine skeletal muscle conditioned medium(MMCM)was prepared to test its effect on thoracic malignant cell lines of A549、Anip-973,PLA-801C,NCI-H466,Eca109 and benign cell line of BHK-21 by MTT assay.Results Proliferations of thoracic malignant cell lines of A549,Anip-973,PLA-801C,NCI-H466,and Eca109 were significantly restrained when cultured with MMCM,while the proliferation of benign renal cell line(BHK-21)was not affected.Conclusions The conditioned medium of new born Wistar rat skeletal muscle cells could selectively inhibit the proliferation of thoracic malignant cells in vitro.Moreover,it affects tumor cells only and has no apparent effect on normal cells,which differs from most of the chemotherapeutic agents.These findings suggest a sound mechanism in the rarity of metastases in skeletal muscles.A therapeutic agent could be generated from MMCM to complement surgery and/or chemotherapy.
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Objective To study the killing effect of hypocrellins B-photodynamic therapy (HB-PDT) for lung cancer cell line A549, to compare with that of hematoporphyrin derivative-photodynamic therapy (HpD -PDT), in order to define the superiority of HB-PDT in the therapy of lung cancer. Methods Lung cancer cell line A549 was used in the study. The cells were incubated in vitro with HB or HpD dissolved in DMEM in different concentrations, and then irradiated by copper vapor laser with mixed wavelength light under saturated light dose. Cell survival rate was respectively measured by MTT assay after 24 hours' incubation. According to cell survival curves after being cultured with different photosensitizers in different concentrations, the equation of each cell survival curve was plotted. Finally IC 50 (50% inhibition concentration) of each photosensitizer was derived. Results The results showed that HB-PDT had a strong killing effect on lung cancer cell. The IC 50 of HB was 33.82ng/ml for lung cancer cell, while the IC 50 of HpD was 1 316.88ng/ml, which was 38.94 fold of that of HB. Conclusions HB was a more effective photosensitizer than the photosensitizer HpD. HB-PDT had strong photodynamic killing effect on lung cancer cell line.
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Objective To evaluate the accuracy of intraoperative ultrasonography (IUS) in judging the relationship between central bronchogenic carcinoma and pulmonary vessels and in predicting the resectability of the tumor. Methods Intraoperative ultrasonograpy(IUS) and preoperative CT scanning were performed in 30 patients of central bronchogenic carcinoma. The relationship between vessel and tumor as assessed by IUS and preoperative CT were quantified and scored with a ranging from 0-4 respectively, and then the resectability of the tumor and optimal surgical method were predicted according to the scores. Results The accuracy of CT and IUS to determine tumor-vessel relationship was 72.3%(141/195) and 81.0%(171/211), respectively (P=0.037). The sensitivity of CT and IUS in predicting the resectability of tumor was 91.3%(21/23) and 95.6%(22/23), respectively, the specificity was 28.6%(2/7) and 57.1%(4/7), respectively, and the accuracy was 76.7%(23/30) and 86.7%(26/30), respectively. The accuracy of CT and IUS in predicting surgical strategy was 53.3%(16/30) and 63.3%(19/30), respectively(P=0.432). Conclusion IUS is a useful method in predicting the resectability of centrally located bronchogenic carcinoma.