Primary Lung Cancer Patients Research Articles

Postoperative interstitial pneumonia in primary lung cancer patients — Its causes and management: Miyamoto Y, Tsubota N, Yoshimura M, Murotani A, Matoba Y. Department of Thoracic Surgery, Hyogo Medical Center for Adults, Kobe. J Jpn Assoc Thorac Surg 1995;43:452–457

Eight patients who developed interstitial pneumonia after surgery for primary lung cancer were reviewed to investigate its causes and the key points in treatment. These patients accounted for 1.8% of 633 operated lung cancer patients at our institution over the last 9 years. Risk factors such as bilateral recurrent laryngeal nerve palsy, preoperative chemoradiotherapy, and extensive mediastinal involvement were present in all of them. Pneumonia developed on the nonoperated side in all patients between the 2nd and 45th postoperative day (mean: 18 days). In most of the patients, faint reticular shadows initially appeared in the lower lobe of the nonoperated lung, rapidly spread to the upper lobe, and finally affected the whole lung. Among these eight patients, the initial five patients died because steroids were only administered after the pneumonia had become widespread, whereas the last three patients received early steroid therapy and were saved. The findings that 1) this pneumonia originated from the lower lobe of the nonoperated lung where blood flow is highest postoperatively, 2) the eosinophil count increased just before the onset of pneumonia, and 3) early steroid therapy and immunosuppressive therapy were effective suggest that an allergic or autoimmune mechanism may play some role in its development. When characteristic reticular shadows appear in the lower lobe on the nonoperated side in a lung cancer patient, even if not associated with any symptoms, an early diagnosis of interstitial pneumonia and initiation of steroid therapy is mandatory to ensure survival.

Microvessel count predicts metastatic disease and survival in non-small cell lung cancer.

The growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early-stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non-small lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti-Factor VIII monoclonal antibody (Mab) in methacarn-fixed tumour samples. In univariat analysis, MC (P< 0.000001), sex (P=0.0036), histotype (P < 0.014), tumour status (P <0.007), and vessel invasion (P < 0.019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P<0.000003) retained the most important influence on nodal metastasis. The overall survival analysis calculated by the Kaplan-Meier method revealed that tumours with high MC ( > 25 vessels/field) were significantly associated with increased death risk (log-rank test P = 0.00067; Cox's test P = 0.00046; Gehan's Wilcoxon test P = 0.00108). In 94 patients, the development of metastatic disease during follow-up was significantly related to MC. Indeed, patients who developed metastasis during follow-up showed a higher MC, either as a dichotomous (P = 0.01) or as a continuous (P = 0.003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of gene-specific damage with cisplatin between human adenocarcinoma cells and peripheral blood mononuclear cells analyzed by polymerase chain reaction-stop assay.

We investigated gene‐specific damage in adenocarcinoma cells, obtained from pleural effusions of 9 primary lung cancer patients, induced by incubation with cisplation for 3 h in vitro. The 2.7 kb fragment of the hypoxanthine phosphoribosyltransferase (HPRT) gene was amplified by the polymerase chain reaction (PCR) to quantify the DNA damage. A 7‐fold difference in the extent of gene‐specific damage among the patients was observed. Mononuclear cells (MNC) were obtained from freshly isolated blood from the same patients before they received chemotherapy. These cells were also incubated with cisplatin in vitro, and PCR amplification of the HPRT gene was carried out. A 4‐fold variation of DNA damage among the patients was observed. Moreover, there was a linear correlation between the extents of the DNA damage in the tumor cells and MNCs (R2=0.676, P=0.0016). These results suggest that the PCR‐stop assay could be used to detect interindividual variations in the extent of gene‐specific damage in both tumor cells and MNC from the same patients induced by cisplatin treatment. In conclusion, MNC could be used to analyze cisplatin‐induced gene‐specific damage in cancer patients whose tumor cells are inaccessible.

Development of multifield three‐dimensional conformal radiotherapy of lung cancer using a total lung dose/volume histogram

AbstractA measurable improvement in the efficacy of the three‐dimensional radiotherapy (RT) of primary lung cancer patients with unresectable disease will require the development of a technique that increases the therapeutic ratio of dose delivered to the tumor volume relative to functional lung. A full course of definitive RT dose was delivered to six consecutive primary lung cancer patients using multiple fields with treatment portals tightly conformed to the tumor shape in beams‐eye‐view, using multileaf collimation. For each patient, a treatment planning dose/volume histogram (DVH) was constructed considering the most anatomically normal tissues in both the ipsilateral and contralateral lungs. When compared to a standard anteroposterior‐posteroanterior (AP‐PA) treatment plan followed by parallel‐opposed oblique fields with conventional blocks, the five‐field conformal technique yielded a significantly lower integral lung dose as determined by cumulative DVH data. We compared the data for total lung capacity in cubic centimeters from the treatment planning DVH with that obtained by pulmonary function tests and found good concordance. The present RT technique and patient evaluation program should provide a valuable approach toward improving the quality of life in irradiated lung cancer patients, and may also guide efforts by which to escalate the dose to a tumor volume in the chest. © 1995 Wiley‐Liss, Inc.

Diagnostic Value of Serum CYFRA 21-1 in Lung Cancer

Background: Cytokeratin 19 is 40KD acidic molecule whose distribution is restricted to simple or pseudo-stratified epithelia, such as the epithelial layer of the bronchial tree. Immunohistochemical study have shown that cytokeratin 19 is overexpressed in lung carcinoma tissue. An immunoradiometric assay, CYFRA 21-1 has been developed using two monoclonal antibody, BM 19-21 and KS 19-1, reactive to different epitopes on cytokeratin 19. We studied the diagnostic value of CYFRA 21-1 in lung cancer. Method: The serum CYFRA 21-1 level using immunoradiometric kit(ELSA-CYFRA 21-1) was measured in 54 patients who admit to Yeungnam University Hospital from April, 1993 to August, 1994. Lung cancer group was 39 primary lung cancer patients(19 patients with squamous cell carcinoma, 11 patients with adenocarcinoma and 9 patients with small cell carcinoma). Control group was 15 patients with non malignant lung diseases(8 patients with pulmonary tuberculosis, 3 patients with chronic obstructive pulmonary disease, 2 patients with pneumonia and 2 patients with chronic obstructive pulmonary disease combined with pulmonary tuberculosis). Results: The mean serum value of CYFRA 21-1 was in squamous cell carcinoma, in adenocarcinoma and in non-small cell lung cancer. The serum value of CYFRA 21-1 in control group was . All of the serum values of 3 histologic types were significantly higher than that of control group(p and not significantly different compared with control group. Using cut off value of 3.3ng/ml, sensitivity and specificity was 11.1%, 65.2% in small cell lung cancer, 70.0%, 62.5% in non-small cell lung cancer, 73.7%, 75% in squamous cell carcinoma and 63.6%, 78.9% in adenocarcinoma, respectively. Conclusion: The serum levels of CYFRA 21-1 may be useful in diagnosis of non-small cell lung carcinoma, especially in squamous cell carcinoma with its high specificity.

Multicentricity in resected occult bronchogenic squamous cell carcinoma

The frequency and the treatment of multicentricity in 127 patients with resected roentgenographically occult bronchogenic squamous cell carcinoma were studied. The cumulative rate and the incidence of postoperative metachronous multiple primary lung cancer were 0.11 at 5 years after initial operation and 0.022 per patient-year, respectively. The cumulative rate and the incidence of second primary lung cancer, which includes synchronous and subsequent metachronous cancer in patients with initial lung cancer, were 0.17 at 5 years after the initial operation and 0.041 per patient-year, respectively. The cumulative rate and the incidence of third primary lung cancer in patients with second primary lung cancer were 0.47 at 5 years, which was significantly higher (p = 0.05) than that of second primary lung cancer, and 0.11 per patient-year, respectively. In all 12 patients with synchronous multiple primary lung cancer, no recurrence was observed after treatment, but 3 had subsequent multiple primary lung cancer. Among the 13 patients with postoperative metachronous multiple primary lung cancer, recurrence was observed in 1 of the 6 patients who underwent resection and in 2 of the 4 patients treated with laser or radiation therapy or both. The overall survival rate at 5 years after initial operation in patients with solitary and those with multicentric occult bronchogenic squamous cell carcinomas was 0.90 and 0.59, respectively.

Use of carcinoembryonic antigen ratio in pleural washings from primary lung cancer patients as a parameter for pleural invasion

Use of carcinoembryonic antigen ratio in pleural washings from primary lung cancer patients as a parameter for pleural invasion

Cytological examination of intraoperative pleural lavage in primary lung cancer patients

Cytological examination of intraoperative pleural lavage in primary lung cancer patients

Randomized controlled study with Interleukin 2 and Lymphokine activated killer (LAK) cells against postoperative primary lung cancer patients : Hideki Kimura 1 and Yutaka Yamaguchi 2 Division of Chest diseases, Chiba Cancer Center 1, Japan Department of Surgery, Institute of Pulmonary Cancer Research, School of Medicine Chiba University 2, Japan

Randomized controlled study with Interleukin 2 and Lymphokine activated killer (LAK) cells against postoperative primary lung cancer patients : Hideki Kimura 1 and Yutaka Yamaguchi 2 Division of Chest diseases, Chiba Cancer Center 1, Japan Department of Surgery, Institute of Pulmonary Cancer Research, School of Medicine Chiba University 2, Japan

Tumor doubling time and prognostic assessment of primary lung cancer patients

Tumor doubling time and prognostic assessment of primary lung cancer patients

Multicentricity in resected occult bronchogenic squamous cell carcinoma

The frequency and the treatment of multicentricity in 127 patients with resected roentgenographically occult branchogenic squamous cell carcinoma were studied. The cumulative rate and the incidence of postoperative metachronous multiple primary lung cancer were 0.11 at 5 years after initial operation and 0.022 per patient-year, respectively. The cumulative rate and the incidence of second primary lung cancer, which includes synchronous and subsequent metachronous cancer in patients with initial lung cancer, were 0.17 at 5 years after the initial operation and 0.041 per patient-year, respectively. The cumulative rate and the incidence of third primary lung cancer in patients with second primary lung cancer were 0.47 at 5 years, which was significantly higher ( p = 0.05) than that of second primary lung cancer, and 0.11 per patient-year, respectively. In all 12 patients with synchronous multiple primary lung cancer, no recurrence was observed after treatment, but 3 had subsequent multiple primary lung cancer. Among the 13 patients with postoperative metachronous multiple primary lung cancer, recurrence was observed in 1 of the 6 patients who underwent resection and in 2 of the 4 patients treated with laser or radiation therapy or both. The overall survival rate at 5 yean after initial operation in patients with solitary and those with multicentric occult bronchogenic squamous cell carcinomas was 0.90 and 0.59, respectively.

Molecular deletion of 9p sequences in non‐small cell lung cancer and malignant mesothelioma

Previously we have reported non-random cytogenetic abnormalities involving the short arm of chromosome 9 (9P) in the majority of primary non-small cell lung cancer (NSCLC) patient samples, which indicated loss of DNA sequences. In another lung tumor, pleural malignant mesothelioma (MM), cytogenetic changes also include apparent deletions of 9p. To define the location and extent of deletions of 9p in NSCLC and MM, Southern blot analyses on six NSCLC and five MM cell lines using molecular probes to 9p loci (IFNA, IFNB1, D9S3, and D9S19) were performed, and DNA dosage was determined by densitometry. Our data demonstrated reduced dosage of 9p sequences in three of six NSCLC and four of five MM lines. A homozygous deletion of D9S3 was found in one NSCLC and one MM cell line. The region of common loss overlapped the D9S3 locus and was flanked by the IFNB1 and D9S19 loci. IFNB as previously been localized to 9p22, and the D9S3 and D9S19 loci have been mapped in this study by in situ hybridization to 9p21 and 9p13, respectively. We hypothesize the existence of one or more tumor suppressor genes on 9p with a role in the development or progression of NSCLC and MM.

A survival study of surgically treated lung cancer in Korea

Survival rate over a 5-year period were studied in a series of 658 proven primary lung cancer patients treated by thoracic surgeons at 8 institutes during the period from 1976 to 1987 in Korea. The study was designed as a multi-center cooperative work for the statistical analysis of the followup result. Clinical data of age, sex, morbidity, and staging of the tumor were assessed in 540 patients to evaluate their 5-year survival rates. Eventually, 405 resectable patients were analyzed by stage, cell type, surgical procedure, and TNM status. The 5-year actuarial survival rates by stage in the resectable group were: stage I 39.7%, II 30.6% III A 16.3%, III B 6.7%, and IV 0%. The 5-year survival rates by cell type were: squamous cell 31.9%, adenocarcinoma 21.2%, large cell 11%, and small cell 6%. The survival rates by surgical procedures were: lobectomy 30.7% and pneumonectomy 25.7%. The survival rates by TNM status in the operable group were: T1 34.7%, T2 26.8%, T3 7.5%, T4 5%; N1 23%, N2 10%, N3 3%; MO 21%, and M1 0%, respectively. The overall actuarial 5-year survival rate in the group of 405 resectable patients was 25.9%.

Detection of 6-thioguanine resistance in human peripheral blood lymphocytes (PBL) of industrial workers and lung cancer patients

Human peripheral blood lymphocytes (PBL) were selected for 6-thioguanine (6-TG) resistance in short-term (42-h) cultures in 110 high-cancer-risk industrial workers, 131 primary lung cancer patients and 96 low-risk controls. The lymphocytes were cultured and stimulated by phytohemagglutinin (PHA). A labeling index (LI) was scored using light microscope autoradiography, based on the lymphocyte's ability to incorporate tritiated thymidine with or without selective agent 6-TG. The number of 6-TG-resistant cells increased in the high-occupational-cancer-risk group of vinyl chloride- and mixed organic industrial dust (MOID)-exposed workers as well as in primary lung cancer patients. The results were compared with the low-occupational-cancer-risk groups and with samples taken from the 70 healthy individuals and 26 hospitalized, non-cancerous controls. In both risk-exposed groups the frequency of 6-TG-resistant lymphocytes was significantly higher ( P < 0.01) than in the controls. These results suggest that the original Strauss and Albertini (1977, 1979) method can be used to study qualitative risk assessment in carcinogen- or mutagen-exposed occupational groups.

Clinical evaluations of Serum sialyl Lewis X-i(SLX) in primary lung cancer patients : Noguchi M, Hiraiwa N, Yoshimura K et al. Department of Respiratory Disease, Toranomon Hospital, 105 Tokyo. J Tumor Marker Oncol 1988;3:21–33

Clinical evaluations of Serum sialyl Lewis X-i(SLX) in primary lung cancer patients : Noguchi M, Hiraiwa N, Yoshimura K et al. Department of Respiratory Disease, Toranomon Hospital, 105 Tokyo. J Tumor Marker Oncol 1988;3:21–33

Antitumor activity of regional lymph node lymphocytes in patients with lung cancer.

Cytotoxic activities of regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) of 49 primary lung cancer patients who were subjected to surgical resection were examined by 4 h 51Cr release assay. PBL showed significantly lower cytotoxicity against autologous tumor cells than against K562 and QG-56. On the other hand, RLNL exhibited the same level of cytotoxicity against autologous tumor cells as PBL, although the cytotoxicities against K562 and QG-56 were low. Cytotoxicity of RLNL against autologous tumor cells exhibited a significant degree of depression with the advance of stage, T and N factors. Cytotoxicity of PBL did not significantly change as the stage progressed. When both PBL and RLNL were cultured with purified interleukin-2 (p-IL2) in vitro, their cytotoxic activities were markedly augmented and the cytotoxicities could not be diminished by the treatment with anti-Leu-7 + anti-Leu-11b + C'. These facts indicate that the augmented cytotoxicity may be due to lymphokine activated killer (LAK) cells.

肺癌患者における細胞性免疫能の検討

肺癌患者における細胞性免疫能の検討

Relationship between patient characteristics and the sputum cytologic diagnosis of lung cancer

In 421 patients with a malignant lung process, from whom samples of sputum of satisfactory quality were received, patient characteristics relevant to the cytologic diagnosis of malignancy were investigated. In patients with primary lung cancer, the presence of blood in the sputum was highly significant from the point of view of its association with a correct positive cytologic diagnosis on sputum. The same relationship was noted in patients with metastatic lung cancer. In patients producing bloody sputum, the examination of at least three sputum samples gave a proportion of correct positive diagnoses of 0.88 in primary lung cancer patients and of 0.77 in patients with metastatic lung disease. Furthermore, a high sensitivity of the sputum cytology diagnosis of malignancy was found in primary lung cancer patients with low forced expiratory volume values (less than 50% of the vital capacity), with large tumors (greater than 24 mm in diameter) and with squamous-cell cancers. A central location of the tumor correlated with significantly better cytodiagnostic results in patients with both primary and metastatic cancers.

T-Lymphocyte Subsets in Primary Lung Cancer

T-cell subsets in the peripheral blood of 63 primary lung cancer patients (23 with adenocarcinoma, 23 with squamous cell carcinoma and 17 with small cell carcinoma) and 24 normal healthy controls were determined by indirect immunofluorescence, using the monoclonal antibody reagents OKT3, OKT4 and OKT8. Correlations between T-lymphocyte subset values and stages or cell types of disease were sought. Total lymphocytes in the patient group were decreased. However, no significant difference from controls was seen in the percentage of OKT3-positive cells (Pan T-cells) in the cancer patients. The percentage of OKT8-positive cells (cytotoxic/suppressor) was increased in the early stage of disease whereas the percentage of OKT4 positive cells (inducer/helper) remained at the control level throughout all stages. The ratio of OKT4-positive to OKT8-positive T-cells (OKT4/OKT8), reflecting the balance of immunoregulatory T-cells, was, therefore, significantly decreased in patients with stage I-II lung cancer (P less than 0.05), especially in squamous cell lung cancer (P less than 0.05), whereas in stages III or IV, this T4/T8 ratio returned to the control level. In small cell carcinoma, the T4/T8 ratio was significantly decreased in stage III (P less than 0.01) and returned to the control level in stage IV.

白血球減少に感染を伴う肺癌患者に対するＥｍｐｉｒｉｃ Ａｎｔｉｂｉｏｔｉｃ Ｔｈｅｒａｐｙの試み

抗癌化学療法後に1000/mm3未満の白血球減少と38℃以上の発熱をみた29例の原発性肺癌患者に対し, のべ33件のチカルシリンとアミカシンの併用を第1選択とするempiricantibiotic therapyを試み48.5%の有効率を得た. 無効例はチカルシリンとセファゾリンの併用に変更し, 全体の有効率は90.9%であった. 残り3例は, 敗血症, 真菌症, 呼吸不全で死亡した. 全例の2/3以上がシスプラチンの投与を受けていたが, アミカシン使用による副作用の相乗的な増加は認められなかった. 肺癌患者に対し, チカルシリンとアミカシンの併用によるempiric antibiotic therapyは有用と考えられた.