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.

The enhancement of myocardial protection through an acalcemic storage solution containing nicardipine, a potent calcium channel blocker. A basic study using rat ventricular myocytes.

Adult rat ventricular myocytes were used as a model system for investigating the direct effects of nicardipine, a potent calcium-channel blocker, on preservation of the heart during periods of simple cold storage. Cells were stored at 4 degrees C for 24 hr with an acalcemic storage solution. The superfusate then was exchanged with hypoxic Tyrode solution (1.8 mmol/L CaCl2). After 2 hr of hypoxia at 20 degrees C, cells were reoxygenated and simultaneously warmed to 37 degrees C. The addition of nicardipine to both the storage solution and Tyrode solution resulted in the highest percentage of viable cells (70.5%). Using either the storage solution or Tyrode solution containing the compound, the percentages of viable myocytes were 51.9% and 52.2%, respectively. In the absence of the drug in either solution, the percentage was 38.0%. The effect of diltiazem, another potent calcium-channel blocker, was examined using the same experimental procedure. The addition of diltiazem to Tyrode solution elevated the viability of ventricular myocytes, but addition to the storage solution showed no cardioprotective effect. Moreover, the addition of 8-bromo cyclic GMP to the storage solution resulted in a cardioprotective effect. These results suggested that nicardipine exerts a direct effect on myocardial protection in hypothermic and acalcemic storage solution and that the pharmacological effect of nicardipine depends on a mechanism other than its calcium-channel blocking action.

A heparin-coated circuit maintains platelet aggregability in response to shear stress in an in vitro model of cardiopulmonary bypass.

Alterations in platelet aggregability may play a role in the pathogenesis of qualitative platelet defects associated with cardiopulmonary bypass (CPB). We circulated fresh heparinized whole blood through tubing sets coated with heparin (C group, n = 10) and through non-coated sets (N group, n = 10) as a simulated CPB circuit. Shear stress (108 dyne/cm2)-induced platelet aggregation (hSIPA), plasma von Willebrand factor (vWF) activity and platelet glycoprotein (GP) Ib expression were measured, before, during, and after this in vitro set up of circulation. In the two groups, the extent of hSIPA significantly decreased during circulation and was partially restored after circulation. Decreases in the extent of hSIPA were significantly less with use of heparin-coated circuits. There was an equivalent reduction in plasma vWF activity, in the two groups. Expression of platelet surface GP Ib decreased significantly during circulation and recovered after circulation. Reduction of surface GP Ib expression during circulation was significantly less in the C group than that in the N group. Decrease in surface GP Ib expression correlated (r = 0.88 in either group) with the magnitude of hSIPA, in the two groups. The progressive removal of surface GP Ib was mainly attributed to redistribution of GP Ib from the membrane skeleton into the cytoskeleton. Our observations suggest that use of heparin-coated circuits partly blocks the reduction of hSIPA, as a result of a lesser degree of redistribution of GP Ib.

Ultrafiltration of the priming blood before cardiopulmonary bypass attenuates inflammatory response and improves postoperative clinical course in pediatric patients.

The priming solution using in cardiopulmonary bypass (CPB) for infants undergoing cardiac surgery includes considerable amounts of stored blood. Our objective was to test the hypothesis that ultrafiltration (UF) of the stored blood before CPB reduces the unfavorable effects of stored blood and the production of inflammatory cytokines. Fifty pediatric patients with congenital heart defects took part in this study. The patients were randomly divided into two groups: the UF (27 pediatric patients who received UF) and control (23 pediatric patients who did not receive UF) groups. UF was performed with a polysulphone ultrafiltrator before CPB. Blood samples were collected immediately before, during, and 1 h after CPB. The levels of cytokines (TNF-alpha, IL-1beta, IL-8), NH3, and bradykinin were determined. The serum concentrations of NH3 and bradykinin decreased significantly after UF. Compared with the control group, the UF group had significantly lower cytokine production. Water balance in UF group was better than that of control group. The UF group received significantly less inotropic support and shorter duration of ventilator support and ICU stay. We conclude that removal of bradykinin and a decrease in the levels of NH3, potassium, and pH play a significant role in reducing water retention and postoperative lung injury. UF of the blood used to prime the circuit for CPB is a safe and efficient method for use in open heart surgery in small pediatric patients.

Left atrial myxomas. Using gross anatomic tumor types to determine clinical features and coronary angiographic findings.

PURPOSE: To our knowledge, there have been no reports focusing on differences of clinical characteristics according to two gross anatomic types of cardiac myxomas. This study evaluated the differences of clinical features, coronary arteriographic findings, and histopathologic findings. PATIENTS AND METHODS: Twenty-six patients who underwent surgical excisions for left atrial myxomas were analyzed. According to the gross anatomic types, they were divided into two groups: group 1 having solid and ovoid myxomas (n = 14), and group 2 having soft and papillary myxomas (n = 12). Differences of presenting symptoms, prevalence of brain infarction, coronary angiographic findings, and histopathologic findings were analyzed. RESULTS: An incidence of dyspnea was significantly higher in group 1 (78.6% vs 33.3%, p < 0.05) than in group 2. That of neurologic symptoms was higher in group 2 (75% vs 14.3%, p < 0.01) than in group 1. A prevalence of brain infarction was higher in group 2 (75% vs 2.5%, p < 0.05) than in group 1. On coronary angiography, an identification rate of clusters of tortuous vessels was higher in group 1 (81.8% vs 0%, p < 0.01) than in group 2. In histologic findings, most of group 1 tumors displayed many hemorrhages, small vessels, and fibrosis in the stroma, but group 2 had few such structures. CONCLUSIONS: Coronary angiographic findings of tumor-feeding arteries without clusters of tortuous tumor vessels predict a myxoma that is papillary in type. At that time, close attention should be given for the possible existence of silent brain infarction.

Erythropoietin in pediatric cardiac surgery: clinical efficacy and effective dose.

We assessed the clinical efficacy and determined the effective dose of erythropoietin (EPO) in 48 children scheduled for open heart surgery without blood transfusion. The children were divided into three groups: group 1 (n=21) was treated with 300 U/kg of EPO; group 2 (n=11) was treated with 150 U/kg of EPO; and group 3 (n=16) was not treated with EPO. EPO was administered on the day of hospital admission (6 to 7 days prior to surgery), on the following day, immediately after surgery, and on the following day. Immediately after surgery, the hemoglobin concentration in groups 1 and 2 was significantly higher than that in group 3. The reticulocyte count in groups 1 and 2 was significantly higher than that in group 3. Open heart surgery was completed without transfusion in all 21 patients in group 1 (100%), 10 of 11 in group 2 (90.9%), and 11 of 16 in group 3 (68.8%). EPO caused no adverse reactions. In conclusion, EPO was effective as an adjuvant therapy for open heart surgery without blood transfusion in children. Administration of a relatively high dose of EPO (300 U/kg) seems to be effective for pediatric patients.

New surgical method of chordal replacement for mitral valve incompetence with echocardiographic guidance. An experimental study.

Chordal replacement with expanded polytetrafluorethylene suture has become a procedure of choice for repairing anterior leaflet prolapse among certain surgeons. However, most surgeons believe that the chordal replacement is too complicated and not reproducible. This report introduces a new method of chordal replacement using intraoperative epicardial and transesophageal echocardiography. Three dogs underwent the following procedures. One major marginal chorda of an anterior mitral leaflet was resected during cardiopulmonary bypass. A specially designed 3-0 polytetrafluoroethylene suture, having straight needles, was attached to the anterior leaflet by a mattress suture. Then the needles were brought from the root of the anterior papillary muscle to the outside of the left ventricle. After the bypass flow was reduced, both ends of the polytetrafluoroethylene suture were pulled under echocardiographic guidance until valve competence was achieved. At that point, the suture was temporarily tied. When cardiopulmonary bypass was discontinued, competence was again confirmed and the suture was tied permanently. When the procedures were completed, echocardiography showed trivial regurgitation and good pliability of the anterior leaflets in all animals. Left atrial pressures were sufficiently decreased. It appears that this new technique is reproducible for all surgeons because the optimal length of polytetrafluoroethylene chordae is determined with the valve functioning.

Primary leiomyosarcoma of the pulmonary artery confirmed by catheter suction biopsy.

A patient with clinical features consistent with pulmonary embolism showed no improvement despite therapy with tissue-plasminogen activator and full-dose heparin. Transvenous catheter suction biopsy was successful in establishing an antemortem histologic diagnosis of primary pulmonary artery leiomyosarcoma. Urgent surgical intervention was performed.

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.

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.

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.

Strategy for pulmonary atresia and intact ventricular septum.

Pulmonary atresia with an intact ventricular septum is characterized by varying degrees of right ventricular cavity hypoplasia. This factor is critical in determining the most appropriate surgical approach for each patient. We describe a patient who underwent definitive biventricular surgical repair in early infancy. We used an atrial septal defect patch with a one-way valve and performed a right ventricular overhaul after a balloon valvotomy.

Synchronous primary lung carcinoma and lung metastasis from extrathoracic carcinoma.

We present the cases of 2 patients in whom primary lung cancer was found unexpectedly when pulmonary resection was performed for metastatic lung cancer. The possibility of combined primary and metastatic carcinoma should be considered in patients with a diagnosis of multiple pulmonary metastases from extrathoracic tumor.

Surgical repair of extracardiac unruptured acquired Valsalva aneurysms.

Two cases of extracardiac unruptured Valsalva aneurysms due to rare causes are reported. One patient had been suffering from hyper eosinophilic syndrome. Operative corrections consisted of total replacement of the aortic root. The other patient had an aneurysm of just noncoronary sinus of Valsalva and a dilated ascending aorta due to cystic mucoid degeneration. Replacement of the ascending aorta with patch closure for the aneurysm was successfully performed.

Is it true that cardiac operations with cardiopulmonary bypass impair the reticuloendothelial system?

Reticuloendothelial system (RES) function after cardiac operations is a controversial issue. Sequential changes in plasma fibronectin levels and RES phagocytic function were studied after a cardiac operation and a lung operation (control). In the cardiac operation group, the plasma fibronectin level decreased until the third postoperative day and increased thereafter. Reticuloendothelial system phagocytic function remained unchanged on the third postoperative day and then it increased. However, in the control group it increased significantly after operation. In the past, investigators have demonstrated a decline in plasma fibronectin levels following cardiac operation and have assumed that RES function was impaired. However, this sequential study showed that phagocytic function was not impaired, but its enhanced phase was delayed. Moreover, our previous morphologic studies demonstrated that RES function was potentially activated after cardiopulmonary bypass. It appears that the delay of the enhanced phase is caused by the overloading of substances which must be processed by the RES during cardiopulmonary bypass. Thus, we conclude that cardiac operation produces hyperactive, yet oversaturated RES function. There is no impairment of RES function after cardiac operations.

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.

Long-term follow-up after Carpentier-Edwards ring annuloplasty for tricuspid regurgitation.

BACKGROUND: Use of flexible rings for tricuspid ring annuloplasty is becoming popular. This study was undertaken to evaluate Carpentier-Edwards (C-E) rigid ring annuloplasty for tricuspid regurgitation (TR), secondary to mitral valve disease and clinical outcome on a long-term basis. METHODS: From December 1985 to March 1996, 45 patients with secondary TR underwent C-E ring annuloplasty. Thirty-nine patients (95.1%) were in New York Heart Association (NYHA) functional class III or IV. The mean follow-up was 96.7+/-48.5 months or 362.6 patient-years. RESULTS: There were three in-hospital and nine late deaths that were not related to tricuspid annuloplasty. Actuarial survival at 10 years was 68.3%. Echocardiographic studies showed that TR was well controlled within grade 2+ in all survivors. Residual pulmonary hypertension (PH) was recognized in 9 of 21 patients (42.9%) with preoperative PH, however, no TR was seen in 6 patients. A TR grade of 2+ was observed in 3 patients. Thirty of the total survivors (96.8%) were in NYHA class I and II, but 1 patient was in NYHA class III. The actuarial rate of freedom from tricuspid valve reoperation after 10 years was 97.5%. CONCLUSIONS: C-E ring annuloplasty is acceptable for repair of secondary TR and improvement in clinical status on a long-term basis.

Terminal warm blood cardioplegia improves cardiac function through microtubule repolymerization.

BACKGROUND: To elucidate the mechanisms responsible for the beneficial effects of terminal warm blood cardioplegia, we studied dynamic change in microtubules induced by cold cardioplegia followed by rewarming. Further, we investigated the relationship between cardiac function and morphologic changes in microtubules caused by hyperkalemic, hypocalcemic warm cardioplegia during initial reperfusion. METHODS: In protocol 1 isolated rat hearts were perfused at 37 degrees C with Krebs-Henseleit buffer (KHB). After 3 hours of hypothermic cardiac arrest at 10 degrees C, hearts were reperfused at 37 degrees C with one of two buffers: group C, 60-minute reperfusion with KHB (K+, 5.9 mmol/L; Ca2+, 2.5 mmol/L); and group TC, 10-minute initial reperfusion with modified KHB (K+, 15 mmol/L; Ca2+, 0.25 mmol/L), followed by 50 minutes of reperfusion with KHB. Cardiac function after reperfusion was determined as a percentage of the prearrest value. In protocol 2 hearts were perfused at 37 degrees C with KHB containing colchicine (10(-5) mol/L) for 60 minutes. RESULTS: There was spontaneous contractile recovery after 10 minutes of initial reperfusion in hearts from group TC as well as improved cardiac function after 15, 30, and 60 minutes of reperfusion compared with that in group C. Immunohistochemical staining and immunoblot analysis demonstrated microtubule depolymerization during hypothermic cardiac arrest and complete repolymerization after 10 minutes of reperfusion with warm buffers in both groups. Colchicine-induced microtubule depolymerization is associated with deterioration of cardiac function. CONCLUSIONS: One mechanism responsible for improved cardiac function mediated by terminal warm blood cardioplegia is the restart of contraction after complete microtubule repolymerization.

Coronary artery aneurysm in a patient with Marfan syndrome.

True aneurysm of the coronary artery in Marfan syndrome is very rare. We present a patient with Marfan syndrome who had aneurysms from the ascending aorta to the thoracoabdominal aorta and a large aneurysm of the left main coronary artery after an original Bentall operation. Prosthetic graft replacement of total aorta, coronary artery bypass grafting, and removal of the aneurysm of the left main coronary artery were successfully performed.