Surgical treatment of primary lung cancer in patients less than 40 years of age.

PURPOSE AND METHODS: The major purpose of this study was to determine whether the survival rate in young lung cancer patients after surgical treatment differs from that in older patients. An analysis was performed for all patients with bronchogenic carcinoma who underwent surgery at Mie University Hospital from 1965 to 1990. RESULTS: Of 803 patients, 24 (2.99%) were 33 to 39 years old. At the time of surgery, the disease was diagnosed as stage I in seven patients (29%), stage II in four (17%), stage IIIa in seven (29%), stage IIIb in two (8%), and stage IV in four (17%), while 46.3% of the patients older than 40 years of age had either stage IIIa, IIIb, or IV disease. All of the 24 patients less than 40 years of age underwent thoracotomy: curative resection in 14 cases, palliative resection in sex, and probe-thoracotomy in four. The 5-year survival rate for all stages of disease was 31.4% in these 24 patients, and 41.9% in 603 patients greater than 40 years of age. The 5-year survival rate for stage I disease was 35.7% in the seven younger patients and 78.0% in the 207 older patients; for stage II, it was 25.5% in the four younger patients and 40.6% in the 98 older patients; for stage III, it was 33.3% in the nine younger patients and 15.6% in the 250 older patients; and for stage IV, it was 25% in the four younger patients and 6.6% in the 48 older patients. There were no significant differences in survival rate between the two age groups for all patients or for those with each stage of disease. CONCLUSION: Although younger patients tended to have more advanced disease, long-term survival in these patients did not differ from that of older patients.

New diagnostic method for pulmonary allograft rejection by measurement of bronchial mucosal blood flow.

We investigated the relationship between the rejection of lung allografts and the bronchial mucosal blood flow with a laser flowmeter. Nineteen mongrel dogs underwent left lung allotransplantation and were given daily oral immunosuppressive therapy with azathioprine and cyclosporine. The bronchial mucosal blood flow at the carina and the bifurcation of left upper and lower bronchi were measured on days 14, 21, and 28 after left lung transplantation. The bronchial mucosal blood flow of the transplanted lungs was expressed as the ratio of bronchial mucosal blood flow at the bifurcation of left upper and lower bronchi to the bronchial mucosal blood flow at the carina (L/C ratio) instead of the absolute value because bronchial mucosal blood flow was affected by the depth of anesthesia of the dogs. We classified the histologic appearance of the transplanted lung tissue into one of five grades: 0, 1a, 1b, 2, and 3. No rejection was in grade 0, and as the rejection process progressed the higher grades were used in order. The mean L/C ratios for grades 0, 1a, 1b, 2, and 3 were 0.95 +/- 0.03, 0.82 +/- 0.05, 0.68 +/- 0.04, 0.58 +/- 0.07, and 0.30 +/- 0.07, respectively. Thus the L/C ratio decreased as the rejection process progressed. The histologic changes of the donor main bronchus in each rejection grade were investigated. Mononuclear cell infiltration and edema around the small vessels was seen in early rejection. These same histologic changes appeared in muscular arteries as rejection progressed, and the damage to the small vessels and muscular arteries was more severe in late rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Histologic changes in donor bronchi may explain the reduced mucosal blood flow seen during acute lung allograft rejection.

We assessed the histologic changes in donor and recipient bronchi from 15 dogs that had received a lung transplant and related these changes to the severity of acute rejection seen in the parenchyma of these same lungs. Minimal rejection was associated with no abnormal change in either the donor or the recipient bronchi. In mild lung rejection, mononuclear cell cuffings were seen around bronchial arteries in donor bronchial adventitia, although few mononuclear cell infiltrates were seen in the submucosa. Moderate lung rejection was associated with more prominent mononuclear cell cuffings in the donor bronchial adventitia and mucosal infiltrates of mononuclear cells in the membranous portion. In cases of severe lung rejection, the mononuclear cell infiltrates were also apparent in the cartilaginous portion of the donor bronchial mucosa. Moreover, submucosal edema and detachment of bronchial epithelium were seen. These histologic changes were not observed in the recipient bronchi during acute rejection, nor were they seen in the donor and the recipient bronchi during lung infection without rejection. They might, therefore, reflect acute rejection in the donor bronchus. These results might provide the histologic support for our previous observation of decreased bronchial mucosal blood flow measured by the laser Doppler flowmeter in relation with the extent of acute lung rejection.

Significance of bronchial mucosal blood flow for the monitoring of acute rejection in lung transplantation.

Bronchial mucosal blood flow (BMBF) was measured with a laser-Doppler flowmeter in a canine model (n = 20), and the measurement was evaluated to see if it was a useful method for diagnosing allografted lung rejection. The ratio of the value of BMBF at the level of the donor second carina against that at the level of carina (the L/C ratio, an index of BMBF of donor bronchus) decreased in accordance with the extent of lung rejection, and it increased and entered the normal range with the reversal of lung rejection. Compared with the L/C ratio and the rejection grade by histologic changes in open-lung biopsy, the L/C ratio at grade 0 (latent phase) was 0.91 +/- 0.07; at grade Ia (early vascular phase), 0.86 +/- 0.05; at grade Ib (late vascular phase), 0.68 +/- 0.10; at grade II (early alveolar phase), 0.60 +/- 0.14; and at grade III (late alveolar phase), 0.50 +/- 0.15. A significant difference was noted between grades Ia and Ib (p less than 0.01) and between grades Ib and III (p less than 0.01). The sensitivity and the specificity in the detection of early rejection before grade Ib were 96% and 92%, with only one false-negative and two false-positives resulting from 51 measurements of BMBF. In three cases of serious lung infections, the L/C ratio did not fall, and the rejection could be distinguished from infection. These results suggest that measurement of the BMBF is useful for detecting the early rejection of transplanted lungs.

Effects of inhaled nitric oxide in single lung transplantation in rats with monocrotaline-induced pulmonary hypertension.

BACKGROUND: The edema of grafted lungs during the early postoperative period is one of the serious complications of single lung transplantation for primary pulmonary hypertension. METHODS: The effectiveness of inhaled nitric oxide in single lung transplantation for primary pulmonary hypertension during the early postoperative period was evaluated with the use of rats with monocrotaline-induced pulmonary hypertension. In the inhaled nitric oxide group, rats were given 60 parts par million of nitric oxide for 24 hours just after left lung transplantation; in the no inhaled nitric oxide group, rats were kept without nitric oxide inhalation; in the control group, normal rats received left isografts. RESULTS: Three hours after transplantation, the mean pulmonary artery pressure of the no inhaled nitric oxide group (28.0 +/- 4.6) was significantly higher than that of the control group (23.3 +/- 0.9, p < 0.05) and the inhaled nitric oxide group (22.7 +/- 1.7, p < 0.05). On the first postoperative day, the mean left-to-right pulmonary blood flow ratio in the inhaled nitric oxide group was 0.34 +/- 0.03; it showed no significant difference to those of the other two groups, whereas that of the no inhaled nitric oxide group (0.42 +/- 0.14) was significantly elevated compared with that of the control group (0.14 +/- 0.03, p < 0.05). Histopathologically, the edema of the grafted lungs 24 hours after operation in the inhaled nitric oxide group was less severe than that in the no inhaled nitric oxide group. CONCLUSIONS: The postoperative use of inhaled nitric oxide is effective to reduce the pulmonary edema of the grafts in single lung transplantation for pulmonary hypertension by reducing acute pulmonary blood flow shift toward grafts after transplantation.

Rupture of a benign mediastinal teratoma into the right pleural cavity.

A 27-year-old woman with a ruptured mediastinal cystic teratoma had high levels of amylase and carcinoembryonic antigen in cystic fluid. The activity of the amylase is thought to be the most likely cause of the rupture. High levels of carcinoembryonic antigen in pleural fluid are not necessarily indicative of a malignant lesion but may suggest the presence of a ruptured teratoma in patients with mediastinal tumors.

Ongoing prospective study of segmentectomy for small lung tumors. Study Group of Extended Segmentectomy for Small Lung Tumor.

BACKGROUND: Lesser resection for small lung tumors remains an unresolved problem. This study was conducted to see whether this type of operation is acceptable or not. METHODS: From 1992 to 1994, 55 patients were enrolled in a multicenter trial of limited surgical resection for peripheral tumors of less than 2 cm diameter. The procedure consisted of segmentectomy with exploration of lymph nodes by examining frozen sections. The operation was modified if the report was positive. The intersegmental plane was identified by keeping the resected segments inflated and the preserved segments collapsed. To divide the plane, stapling or electrocauterization on the edge of the collapsed area was used. In this way the resection line was delivered beyond the burdened segment; this was called extended segmentectomy. RESULTS: There were no perioperative deaths, but there were eight postoperative deaths. In 1 patient who died because of local recurrence, it had been known that the margin to the lesion had been narrow (15 mm); 1 had bilateral intrapulmonary nodules, 1 had nodules in the side that was not operated on, and another succumbed to a second neoplasm of small cell lung cancer 4 years after the first operation. The remaining 4 died of nonpulmonary diseases. Almost all other patients are alive and free from recurrence, except for 1 in whom N2 disease was not detected intraoperatively but was confirmed after the operation. CONCLUSIONS: The interim results suggest that extended segmentectomy is applicable in patients with a small peripheral lung cancer. However, a wide margin and aggressive intraoperative pathologic examinations are mandatory.

Fulminant myasthenia gravis manifested after removal of anterior mediastinal tumor.

Myasthenia gravis developed in a 35-year-old man after removal of an encapsulated anterior mediastinal tumor that was preoperatively diagnosed as a teratoma based on a computed tomographic image. Postoperative pathologic diagnosis of the excised tumor was thymoma. The patient was in crisis after the initiation of immunosuppressive treatment. The therapy was changed to immunoadsorbent perfusion therapy because of concurrent severe pneumonia and an extremely high serum concentration of anti-acetylcholine receptor antibodies. Respiratory support was necessary for 2 months after reoperation.

[Surgical treatment of T4 primary lung cancer].

We investigated 257 T4 primary lung cancer patients who received operation in 30 hospitals of a lung cancer surgical therapy group of Chubu and present the results of questionnaires on the outcomes of surgical treatment for the T4 cases. T4 cases were classified as follows; 147 resections (57.4%); 110 exploratory thoracotomies (42.8%) ; 90 pleural dissemination and pleural effusions; 33 aorta; 30 left atrium and 17 superior vena cava. Survival rate of the T4 lung cancer patients in resection group and exploratory thoracotomy group were respectively 49.1% and 37.8% for one-year survival rate, and 15.1% and 4.7% for three-year survival rate. P of these two groups was 0.06 from Logrank test. Thirty three patients (21 resection and 12 exploratory thoracotomies) survived for two years and more. The number of cases by invasive organ was 17 pleural disseminations and effusion, 4 aorta, 4 left atrium and 3 mediastinum. We questionnaire on surgical operation for T4 cases with poor prognosis and obtained the result that half of the hospitals were positively performing surgery and the other half revealed a policy avoiding surgery.

[Successful treatment of a giant bulla by thoracoscopic excision and laser ablation].

A 39-year-old male complaining of shortness of breath on mild exertion. Radiographs revealed that a giant bulla occupied more than half the area of the right lung field. Thoracoscopic excision of the giant bulla was performed using some autosutures. After the emphysematous lesion was consolidated by laser ablation, it was sutured using PDS thread. The bulla in the left lung was similarly excised 3 weeks after the first procedure. The FEV1.0% improved from 72% to 89% after excision and laser ablation of a giant bulla and bullae. Thoracoscopic excision and laser ablation of a giant bulla appears to be an effective alternative to conventional thoracotomy.

[Application and limitation of laser pulmonary resection].

A new type of laser handpiece, bipolar Nd-YAG laser dissector, was experimentally applied for laser pulmonary resection of the dogs. The lung was completely and easily divided by the use of the bipolar laser dissector without scissors. The dissected edge without cartilages was completely sealed and additional stitches by threads was not required. But massive leakage of air was obvious from the dissected bronchus. The cause of unsuccessful sealing of the bronchus was supposed to be an unequal tissue remodeling, because of a very high melting point of cartilages compared with other tissue. We conclude that the bipolar Nd-YAG laser dissector contributes segmental pulmonary resection at the level without bronchi and it should not be applied for pulmonary resection containing bronchial cartilages.

[Long-term follow-up study of the surgical treatment of pulmonary adenocarcinoma].

The surgical treatment of pulmonary adenocarcinoma was studied on the basis of the postoperative long-term results in 211 cases. The overall five-year survival rate was 42% for adenocarcinoma and 48% for squamous cell carcinoma, and there was no significant difference. In stage I, as the degree of differentiation became lower, the prognosis became poorer. In stage III, the five-year survival rate was 50% for the alveolar cell type and 32% for the well differentiated type. The prognosis was better than in the moderately or poorly differentiated types. The prognosis of T1N0 cases was 79% in T1, but it was significantly lower 39% for T2 cases. Among T3 or T4 cases other than N2, the two-year survival rate was 15%, and the longest survival recorded was 32 months. The results were also poor in 9 cases undergoing extensive surgery, with the two-year survival rate being only 10%. Of the N2 cases undergoing extensive surgery all died within a year, except for one case surviving two years following panpleuro-pneumonectomy. In N2, the prognosis was significantly worse if there were two or more foci of mediastinal lymph node metastasis or if subcarinal lymph node metastasis was present. In the long surviving cases, cancer-bearing survivors were about twice as common as with squamous cell carcinoma. Recurrence was usually by distant metastasis (mainly to the brain), being twice as common as local recurrence. Therefore, in adenocarcinoma the significance of postoperative adjuvant therapy was considered to be greater than in squamous cell carcinoma.

[Localized fibrous mesothelioma with bloody pleural effusion; report of a case].

Diffuse malignant mesothelioma with bloody pleural effusion is not rare, but a localized fibrous mesothelioma with bloody pleural effusion is relatively rare. A 45-year-old woman presented with a localized fibrous mesothelioma causing a bloody pleural effusion. Her chief complaint was right-sided lateral chest pain. A chest roentgenogram demonstrated a right-sided pleural effusion, so a chest tube was inserted, and the bloody fluid drained. A preoperative diagnosis of localized fibrous mesothelioma was made based on chest computed tomography and examination of computed tomographic guided percutaneous needle biopsy specimen. At operation, the tumor seemed to have originated from the right lung parenchyma or had invade the right lower lobe because tumor had penetrated deeply in the lung. Tumor and part of the parietal pleura were resected by right lower lobectomy. Final pathology established that the tumor was adherent to the right lung and was only encapsulated by the lung.

[Surgical treatment of the so-called "galloping type" small size carcinoma of the lung].

We experienced twelve cases of non-small cell carcinoma of the lung of the so-called "galloping type" small size carcinoma (less than or equal to 2 cm). Ten cases presented with mediastinal lymph node metastasis and two cases with distant metastasis. Solitary lymph node metastasis observed in almost half of the cases and lymph node metastasis in peculiar lymphatic regions (#3 a) seen in two cases, were the prominent characteristics of the lymphatic pathway dissemination showed by this type of cancer in advanced clinical stage. The prognosis was good, with 3 years and 5 years survival rate of 72.2% and 54.1% respectively. According to these results, we consider that, if the clinical stage is favorable, the surgical treatment must be indicated in all cases of these advanced small size carcinoma of the lung.

[A case of thymoma with pure red cell aplasia].

A 71-year-old man was admitted to the hospital because of general fatigue. There were few reticulocytes in the peripheral blood and no erythroblasts in the bone marrow. Chest CT revealed an anterior mediastinal tumor. Under a diagnosis of thymoma with PRCA, extended thymothymectomy was performed. Histological diagnosis was mixed type thymoma with no invasive growth beyond the capsule. Administration of predonisolone following surgery was not effective for PRCA. Otherwise, peripheral blood counts were significantly improved following occasional onset of acute bronchitis.

[Selection criterion of limited operation for lung cancer as a radical operation].

We reviewed partial resection and segmentectomy for 75 cases (6.5%) out of 1,212 cases treated surgically for primary lung cancer between 1957 and 1996. The surgical results of limited operation in radicality group and risk group was comparable to that of standard operation for the stage I lung cancer. Five-year survival of clinical stage I non-small cell lung cancer patients that tumor size is 2.0 cm or less was excellent (88.9%). Although risk group may be the best candidates for limited surgery, careful patient selection and theoretical operative procedure could make limited operation a standard procedure in radicality group.

[Surgical treatment for primary lung cancer in octogenarians: the role of limited operations].

34 octogenarians out of 1,214 cases treated surgically for primary lung cancer in our unit between 1957 and 1996. 12 patients underwent limited operation because they had one or more risk factors besides their age actor. We could suppress postoperative complications in octogenarians. 5-year survival rate in octogenarians was comparable to that in younger patients. The octogenarians underwent limited operations were better than those had lobectomies in 5-year survival rate and postoperative quality of life. So our surgical strategy for primary lung cancer in octogenarians was evaluated to be appropriate. However, we should improve the radicality of limited operation furthermore because 5-year survival rate for stage I non-small cell lung cancer was poor in octogenarians than in younger patients.

[A rational approach of limited resection for small peripheral lung adenocarcinoma with curative intent; analyses of multiple primary adenocarcinomas].

Hundred and forty-one small peripheral adenocarcinomas 2 cm or less in diameter were retrospectively studied to determine the rationale of limited resection with curative intent. We used a conventional computed tomography (CT) which used 2.5 mm thick sections to examine only the main tumor during from March 1985 to May 1999 and a spiral CT which produced 2.5 mm thick sections of the entire lung field during from June 1999 to July 2003. The incidence of small peripheral adenocarcinoma significantly increased from 12.6% to 29.1%, suggesting an increase in the rate of detection with spiral CTs. During the spiral CT era, the percentage of females, pathological stage I a tumors, predominant ground-glass opacity (GGO) tumors and limited resection were significantly higher. The incidence of multiple adenocarcinomas 2 cm or less in diameter significantly increased 2.6% to 14.1%. It increases to 21.9% in small adenocarcinomas and 63.6% in predominant GGO type, when minute GGO lesion which have been followed in 5 patients by a watch and wait policy would be bronchioloalveolar carcinoma (BAC). In conclusion, a paradigm shift of the treatment for small peripheral adenocarcinoma should be warrant, because localized BAC as noninvasive cancer is not rare and often found as multiple BACs.

[Treatments for T4 advanced lung cancer with invasion to the superior vena cava].

We discussed on the treatments for T4 lung cancer with invasion to the superior vena cava, whose prognosis has been poor. However, surgical resection may improve the prognosis compared with radiation therapy. The prosthetic replacement of superior vena cava can be done safely, and its patency is good in cases of ring-enforced ePTFE graft. Although superior vena caval obstruction syndrome had been a hard issue in the advanced cases, stenting in superior vena using the interventional radiological technique is a safe and reliable method. We should consider the stenting as the first choice for superior vena cava obstruction syndrome, because it makes the QOL improve so much.

[Asynchronus rejection of intrathoracic heart-lung transplantation rats].

We have reported intrathoracic heart-lung transplantation in rats could be made easily by using Internal Shunt Method as described elsewhere. In this study, we examined the rejection of intrathoracic heart-lung allografts in this model to determine whether acute pulmonary rejection precedes cardiac rejection following heart-lung transplantation or not. Ten heart-lung allografts (no immunosuppressive agent was given) and four isografts were examined pathologically. There was no pathologic change except perivascular or peribronchiolar edema in isografts, which was attributed to operative damage. Acute pulmonary rejection apparent pathologically 3 days after transplantation and lung allografts lost its function 6 days after transplantation. Otherwise, acute cardiac rejection first became apparent pathologically 5 days after transplantation. And their pulsation appeared well 6 days after it. It is concluded that pulmonary rejection precedes cardiac rejection following heart-lung transplantation.