Antitumor activity of macrophages in lung cancer patients with special reference to location of macrophages.

Antitumor activity of macrophages from the peripheral blood, pleural cavity, and alveoli of 35 patients with primary lung cancer was examined. Cytostatic activities of peripheral blood monocytes and alveolar macrophages from either tumor-bearing or non-tumor-bearing segments declined in association with metastasis to regional lymph nodes, an increase in tumor size, and the development of pleural invasion. However, no such correlation could be observed between the cytostatic activity of pleural cavity macrophages and the degree of pleural invasion. The cytostatic activity of pleural cavity macrophages was found to be suppressed when the pleural invasion extended beyond the visceral pleura to the neighboring lobe or chest wall. On the other hand, the cytostatic activity of pleural cavity macrophages was markedly augmented when pleural invasion was limited to within the visceral pleura, although it was low in patients with no visceral pleural invasion. These results suggest that the pleural cavity is isolated from sites of systemic immunological response and that systemic immunological response does not strongly affect pleural cavity macrophages.

The relationship between CYP1A1 aryl hydrocarbon hydroxylase activity and lung cancer in a Japanese population.

Because aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung cancer. We investigated AHH activity in peripheral mitogen-treated lymphocytes in 108 lung cancer patients and 95 healthy control individuals. Non-induced AHH activity was detectable in all the samples. AHH inducibility (3-methylcholanthrene-induced/non-induced AHH activity) showed a very wide interindividual variation as well as non-induced AHH activity. No significant associations were found between adjusted AHH activity and histologic type of tumor among lung cancer patients. Adjusted AHH inducibility of genotype C [geometric mean and 95% confidence interval (CI); 15.56 and 11.69-20.71] in MspI polymorphism was significantly higher than those of the other two genotypes (P = 0.0001), while no significant difference was observed between genotypes A (4.76 and 3.82-5.93) and B (5.60 and 4.57-6.86). On the other hand, non-induced AHH activity of genotype Val/Val (0.121 and 0.082-0.178 pmol/min/10(6) cells) in isoleucine-valine (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.042 and 0.034-0.052 pmol/min/10(6) cells) and Ile/Val (0.040 and 0.030-0.053 pmol/min/10(6) cells) (P < 0.0001). Even after controlling for age, cigarettes smoked per day and season of the year, high AHH inducibility (7.0 < versus 0 < < or = 3.0: OR and 95 %CI, 12.4 and 2.88-53.4) was an independent risk factor for lung cancer. The data indicate that high AHH inducibility may strongly associate with the susceptibility to lung carcinogenesis.

Preoperative examination to detect distant metastasis is not advocated for asymptomatic patients with stages 1 and 2 non-small cell lung cancer. Preoperative examination for lung cancer.

The purpose of the present study was to determine whether all patients with non-small cell lung cancer, clinically defined as stage 1 or 2, should have examinations to determine the presence of distant metastatic (M1) disease. The survival rates of patients who underwent the examinations and those who did not were compared. In all groups, the examinations had in no way positively affected survival. The 33 patients in whom distant recurrence had occurred within 12 months of curative operation, were then evaluated to establish the relationship between the recurrent site and the preoperative examination: negative scans on the examination failed to predict the low incidence of early distant recurrence. Those data suggest that the routine use of radionuclide or CT scans is of no benefit to asymptomatic patients with local, early disease.

Brain metastases in patients with limited small cell lung cancer achieving complete remission. Correlation with TNM staging.

We reviewed the brain metastases, after treatment, of 45 patients with limited small cell lung cancer who achieved complete remission by radiochemotherapy or curative operation. No patient received prophylactic cranial irradiation. The incidence of subsequent brain metastases was classified according to pretreatment staging as follows: two of 13 (15 percent) patients in stage I; two of ten (20 percent) in stage II; nine of 17 (53 percent) in stage IIIa; and four of five (80 percent) in stage IIIb. The brain metastases occurred from seven to 29 months after the start of treatment, and the median time of the occurrence was 13 months. Of 17 patients who developed brain metastases and who subsequently received cranial irradiation, there were two in whom relapse had occurred at no other site except the brain and who survived 26 and 79 months after the relapse, respectively. These data indicate that not all patients with limited SCLC achieving CR due to treatment necessarily benefit from PCI.

Japanese doctors' preferred treatment choices for their hypothetical non-small cell lung cancer: how they would wish to be treated. National Chest Hospital Study Group for Lung Cancer.

We conducted a trial to clarify what Japanese clinical doctors think about the present status of therapy for non-small cell lung cancer, as well as to clarify which problems are still unresolved. One-hundred five Japanese doctors who treat lung cancer patients were asked how they would choose to be treated, if they suffered from non-small cell lung cancer. Six scenarios were presented and the doctors had to choose one treatment method for each of the six scenarios. Adjuvant chemotherapy or radiotherapy after complete resection, increase with progression of the pathological stage. Ninety-three per cent of Japanese doctors wanted surgery, even if mediastinal lymph node metastases were present. In the scenario of only one distant metastasis to the brain, 44% of doctors wanted surgery while 39% wanted chemotherapy and/or radiotherapy. In the scenario of multiple bone metastases, 33% wanted chemotherapy, 77% did not. It was concluded therefore that Japanese doctors choose surgery as the number one treatment modality when all lesions are considered resectable.

Juxta-anastomotic aneurysm in the residual infrarenal abdominal aorta.

A 72-year-old man, who had undergone an emergency operation with a tube graft for a ruptured abdominal aortic aneurysm 9 years previously presented with a recurrent true abdominal aortic aneurysm near the proximal anastomotic site. True aneurysmal formation in the juxta-anastomotic aorta proximal to the prosthetic graft as seen in this case is very rare. Since recurrent aortic aneurysms impose significant problems of diagnosis and management, procedures to prevent the recurrence of aneurysms are important in the initial operation.

Video-assisted thoracoscopic esophagomyotomy for achalasia after pulmonary lobectomy.

A 52-year-old man developed achalasia and a lung abscess due to aspiration pneumonia. We conducted a right upper lobectomy by thoracotomy for the abscess and, 2 weeks later, video-assisted thoracoscopic myotomy and fundoplication (modified Belsey Mark IV procedure) though the left thorax for achalasia. Three months after surgery, the patient was free of dysphasia and chest pain and had regained his original weight. Esophageal myotomy and fundoplication using video-assisted thoracoscopy appear to be feasible in treating achalasia involving impaired pulmonary function.

[Clinical efficacy of imipenem/cilastatin sodium for respiratory infections in patients with lung cancer].

Imipenem/cilastatin sodium (IPM/CS) was administered to 102 patients with respiratory tract infections and lung cancer. Patients with other serious diseases were excluded and a total of 73 patients were enrolled. They were divided into 12 patients who underwent surgery (operated group) and 61 who did not (non-operated group); the latter group included 28 patients treated with anticancer agents or radiation therapy (treated group) and 33 untreated patients (untreated group). IPM/CS was effective in 75% of the patients, both with and without surgery. The drug was effective in 81% of the treated group, although many of the patients had Stage III or more advanced cancer, as well as bronchial occlusion. IPM/CS was also effective in 69% of the untreated group, although many of the patients have serious infections and a PS (Performance Status) of 3 or greater. Thus, IPM/CS treatment achieved good results. Bacteriological studies showed that 3 out of 4 strains in the operated group and 16 out of 18 in the non-operated group were eliminated. Safety was evaluated in all patients. Two patients (2%) experienced side effects and two others (2%) showed abnormal clinical findings, but the symptoms were mild and resolved after discontinuation or completion of therapy. In conclusion, IPM/CS was very effective for treating respiratory infections in patients with lung cancer.

[Imipenem/cilastatin sodium and other beta-lactams for respiratory tract infections: clinical benefit and treatment days for cure].

Therapeutic efficacy and the treatment days for cure of imipenem/cilastatin sodium (IPM/CS) in treatment of pulmonary infections were prospectively determined in comparison with those of beta-lactams other than carbapenems mainly ceftazidime (CAZ) or sulbactam/cefoperazone (SBT/CPZ). The overall response rate was 84.9% (62/73) in the IPM/CS group and 74.7% (56/75) in the beta-lactam group, the difference not being significant. In the subjects having underlying respiratory diseases, the response rate was 91.1% (41/45) and 73.9% (34/46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the rate was 91.2% (31/34) in the former group and 66.7% (24/36) in the latter group, respectively. The differences were significant for both stratified analyses. The treatment days for cure judged by the attending physician were 12.9 +/- 0.6 days in the IPM/CS group, and 14.5 +/- 0.7 days in the beta-lactam group. The difference was not, however, significant. In patients with mild to moderate infections, the treatment days for cure was 12.0 +/- 0.6 days (n = 64) in the IPM/CS group and 14.3 +/- 0.7 days (n = 70) in the beta-lactam group. In patients with underlying respiratory disease, the treatment days for cure were 11.8 +/- 0.7 days (n = 45) and 14.7 +/- 0.9 days (n = 46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the days were 11.1 +/- 0.7 days (n = 34) and 14.7 +/- 1.1 days (n = 36), respectively. Thus, IPM/CS therapy significantly reduced the number of treatment days until cure. There was, however, no significant difference between the two therapy groups in treatment of the patients with severe infections, those without underlying respiratory disease, or those with pneumonia and/or lung abscess. The treatment days for cure were also assessed by the members of review committee taking into consideration of body temperature, leukocyte count, and C-reactive protein. As the result, it was 6.9 +/- 0.5 days in the IPM/ CS and 10.3 +/- 0.7 days in the beta-lactam groups; respectively, and the difference was significant. Time (days) until cure was also compared between the two groups using survival time analysis, confirming a more rapid response in the IPM/CS group. Although IPM/CS therapy was associated with a shorter response time as assessed by both the attending physicians and the review committee, there were considerable differences between the results of these judgements. Thus, the duration of treatment with injectable antibiotics requires reevaluation in the future. No significant differences were observed between the groups with respect to parameters indicating side effects and laboratory abnormalities. There were no severe symptoms or laboratory findings, and symptoms and changes in laboratory values, if any resolved during the course of therapy or after the withdrawal of treatment. In conclusion, IPM/CS seems to be very useful as first-line therapy for respiratory tract infections and for shortening the duration of treatment.

[Bronchopleural fistula following the use of automatic stapling devices for lung cancer].

We compared automatic stapling with hand suturing in the rate of bronchopleural fistula. Twenty two hundred forty one patients of 25 hospitals, who were performed lobectomy or pneumonectomy for lung cancer from the year of 1990 to 1992, were investigated about the occurrence of bronchopleural fistula. The rate of bronchopleural fistula following lobectomy were 0.9% (11/1,227 cases) in automatic stapling, and 1.1% (8/753 cases) in hand suturing; there was no difference. However, there was a higher rate of the fistula with the use of automatic stapling devices in pneumonectomy. The rate was 11.2% (11/98 cases) in automatic stapling, and 1.2% (2/166 cases) in hand suturing. Automatic stapling may lead to bronchopleural fistula in pneumonectomy. Moreover, addition of hand suturing to automatic stapling was thought to prevent the fistula.

[A case of epithelial cancer of the alveoli which responded favorably to the additional administration of UFT for refractory cancer after administration of carboplatin and docetaxel].

Epithelial cancer of the alveoli is considered to be a pulmonary non-small cell carcinoma which responds poorly to carcinostatics. In one case of epithelial cancer of the alveoli which metastasized to both lungs and caused breathing to deteriorate rapidly, chemotherapy was applied with 500 mg of carboplatin (CBDCA) and 90 mg of docetaxel (TXT). Although the tumor was reduced initially, it was found to have been aggravated again three weeks after the start of the chemotherapy. In the second and third courses of the chemotherapy, CBDCA and TXT were administered in the same dosage as in the initial course, but with the oral administration of UFT (600 mg/day). The results were favorable, as evidenced by the absence of recurring aggravation. Currently, the patient has been followed on an outpatient basis for over six months with the administration of UFT. Good QOL is being maintained without any repeated aggravation of the tumor.

[Combination chemotherapy and radiation therapy for small cell carcinoma of the lung].

From January, 1982 to March, 1983, patients with small cell carcinoma of the lung were treated at Kyushu Cancer Center. Eleven patients received combination chemotherapy-radiotherapy and one patient chemotherapy alone. The chemotherapy regimen consisted of cyclophosphamide, adriamycin and vincristine which was repeated every 4 weeks for as long as possible. Radiotherapy was administered to the primary lesion and mediastinum following 2 cycles of induction chemotherapy. The overall response rate after receiving 2 cycles of chemotherapy was 75% with 4 complete (33%) and 5 partial responses (42%). After radiotherapy, response increased to 100% with 8 complete (73%) and 3 partial responses (27%). Complete response occurred in 6 of the 7 patients with limited disease and 2 of the 5 patients with extensive disease. Overall survival rate was 73% at 1 year, 36% at 2 years and 12% at 3 years with a median survival time of 21 months. Survival was better in patients with limited disease than in those with extensive disease (median survival time, 21.5 months vs. 14 months). In the 3-Year follow-up period, all patients had recurrences consisting of 4 distant, 2 local and 5 both. Myelosuppression was mild to moderate and there were no deaths related to the side effects of treatment.

[Evaluation of prognostic factors in early lung cancer].

We evaluated the prognostic factors in 52 cases of resected early lung cancer: hilar early lung cancers 9 cases and peripheral early lung cancers 43 cases. All hilar lesions were squamous cell carcinoma, and peripheral lesions were adenocarcinoma (31 cases), squamous cell carcinoma (10 cases), large cell carcinoma (2 cases) and carcinoid (1 case). No relapse was found in hilar lesions, but 7 relapses and 5 deaths were found in peripheral lesions. Prognostic factors were examined in these cases. Location of lung cancer (hilar or peripheral) was found to be important in early lung cancer. In addition, age was a significant prognostic factor in peripheral early lung cancer with multivariate analysis. No other significant factor was found in our cases. Twelve out of 52 cases with lung cancer had other malignancies after or before operation. These were cancers of second primary lung, colo-rectal, uterus, stomach, breast, thyroid, liver and malignant melanoma. Therefore, we have to carefully observe other parts even after resection of early lung cancer.

Synchronous growth of triple lung cancer.

The case of a 75-year-old man with three synchronous carcinomas of the lung (large cell carcinoma, adenocarcinoma, and small cell carcinoma) is reported. This is the eighth well-documented case report in the literature; however, our case is the first to be reported with the newly described histological combination.

Bronchogenic carcinoma following pulmonary aspergilloma.

We have observed two cases of bronchogenic carcinoma following pulmonary aspergilloma among 25 cases of pulmonary aspergilloma. Patients with a pulmonary aspergilloma may be susceptible to bronchogenic carcinoma.

Mechanisms involved in acute lung edema induced in dogs by oleic acid.

We investigated mechanisms related to the development of acute lung edema, as induced by oleic acid in adult mongrel dogs. The intravenous injection of oleic acid (0.04 ml/kg) was considered to induce a permeability edema, as an enhancement of transvascular protein clearance was observed after the injection. The effects of oleic acid injection on systemic blood pressure (SBP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), cardiac output (CO) and airway pressure (AWP) were measured. A significant decrease in CO and increase in AWP were evident after the injection, but there were no changes in SBP, PAP and PAWP. Treatment of the animals with prostaglandin I2 (PGI2) did not alter the induction of edema by oleic acid. However, the decrease in CO and increase in AWP were normalized by treatment with PGI2. Blood platelet count was not affected by oleic acid given in a dose of 0.04 ml/kg. To determine the direct effect of oleic acid on the vascular endothelium, the agent was injected through a catheter placed in the pulmonary artery. Electron microscopic examination revealed severe vacuolation on the endothelium of the pulmonary artery after only 1 min of exposure to oleic acid. Increased permeation of Evans blue into the subendothelial tissue was also observed with oleic acid treatment, compared with findings in the controls. These results indicate that the lung edema induced by oleic acid is due to an increased protein clearance, probably through a direct toxic effect on the vascular endothelium rather than an indirect toxic effect of chemical mediators released from the aggregated platelets.

Analysis of various treatments for pulmonary aspergillomas.

The objective of this study was to analyze the results of various treatments for pulmonary aspergilloma and to determine the surgical indications. A total of 41 patients with pulmonary aspergilloma hospitalized at the National Minamifukuoka Chest Hospital between 1973 and 1999 were analyzed with regard to their response to treatment and long-term prognosis. Five asymptomatic patients who were untreated demonstrated no change in the clinical status of aspergilloma. Analysis of the short-term response revealed surgery to be the most effective treatment. Systemic and intracavitary injections of antifungal drugs were not definitely effective, although they had a positive effect in some patients. A survival analysis revealed that all eight patients who underwent surgery are still alive. Using the Cox proportional hazard model, it was found that the favorable prognostic factors were the absence of symptoms, the absence of a superimposed bacterial infection, and surgery. There were ten deaths: three from lung cancer and seven related to uncontrollable superimposed bacterial infections, often resulting in hemoptysis. We conclude that patients with asymptomatic pulmonary aspergillomas should be clinically observed for signs of the development of lung cancer, but do not require active treatment. On the other hand, patients who are symptomatic and have uncontrollable superimposed bacterial infection will benefit from surgery.

Giant extrathoracic hematoma after thoracoplasty--a case report.

A rare case of an extrathoracic giant hematoma developing after a thoracoplasty in a 67 year old man is presented herein. The patient underwent a right thoracoplasty without removal of plombage and a left thoracoplasty with removal of plombage for tuberculosis of the bilateral upper lobes 27 and 24 years prior to presentation, respectively. He presented to us in May, 1987, with a subscapular tumor which had been growing over the last 5 years. A giant tumor, measuring 23 x 17 x 12 cm and weighing 2585 g was successfully removed and the patient has since been well without any evidence of recurrence.

Influence of surgical resection before and after chemotherapy on survival in small cell lung cancer.

We attempted to define the role of surgery in the treatment of small cell lung cancer (SCLC). Of 81 patients with clinically localized SCLC, 36 underwent surgical resection: 19 underwent initial resection with postoperative chemotherapy, while the remaining 17 were treated initially with chemotherapy, then resection. The remaining 45 patients were treated with a combination of chemotherapy and radiotherapy. The 5-year survival for the 36 surgical patients was 38%; median survival time (MST) was 33 months. Nineteen patients treated with postoperative chemotherapy showed a 42% 5-year survival, while 17 patients treated with preoperative chemotherapy showed a 33% 5-year survival. This difference was not significant. However, stage III survival tended to be better in patients with preoperative chemotherapy (MST, 29 months) than in those who had had postoperative chemotherapy only (MST, 17 months). Although survival of the 45 nonsurgical patients was poor, stage I and II patients, or those with complete remission showed a 25% 5-year survival with an MST of 33 months, and a 21% 5-year survival with an MST of 25 months, respectively. We thus concluded that initial resection combined with postoperative chemotherapy is beneficial for patients with stage I, and probably stage II disease. For resectable stage III, particularly in patients with N2 disease, adjuvant resection after chemotherapy may be a favorable choice in the management of SCLC. For advanced stage III, complete remission by chemotherapy should be attempted in combination with radiotherapy.