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In patients treated nonsurgically for “limited” small cell carcinoma of the lung, the most frequent site of relapse is within the chest We have treated patients with clinical Stage III M0 disease (T3 and/or N2, M0) by two cycles of chemotherapy, surgical resection of the primary site and mediastinal nodes, and continued chemotherapy thereafter. Since May, 1979, the regimen has consisted of cyclophosphamide, doxorubicin, vincristine, and etoposide on a 3 week cycle. The first 12 patients so treated had partial or complete remission after two cycles. Resection was technically not possible in two. Residual small cell carcinoma was not identifiable in the specimens from two of the 10 patients undergoing resection. Microscopic tumor extended to a resection line in two of the eight with residual tumor. Malignant tissue appearing to have the structure of papillary adenocarcinoma was found in hilar and paratracheal nodes in one patient, but nowhere in the resected lung; some residual small cell carcinoma remained in the lung. Nuclear ballooning and eosinophilic inclusions were noted in cells still identifiable as small cell carcinoma in one case. Marked fibrotic scarring was noted in eight cases, acute and organizing bronchopneumonia in three, and multiple small parenchymal abscesses in one case. Long disease-free survival occurred in one patient, in whom residual tumor could not be found in the specimen; in at least one more in whom residual tumor was present; and even in one patient in whom tumor was present at the bronchial resection line.

Surgical resection offers distinct theoretical advantages as the “local” modality in treatment of Stage I and II small cell carcinoma of the lung. We have treated 10 such patients by initial resection since 1975; all survivors but one received adjuvant chemotherapy for the full course thereafter. One patient died of a pulmonary embolus; the other nine remain without evidence of disease from 7 to 69 months after resection. A trial was undertaken of extended indications for resection in selected patients with Stage III-MO*** disease. Criteria for patient selection have been developed gradually; these exclude patients for reasons of refusal, physiological inadequacy, disease unsuited to gross total eradication, or lack of adequate initial response to chemotherapy. Of six patients who survived the exclusion criteria and underwent resection, one has had a relapse at 26 months. All others remain without evidence of disease, 5 to 25 months after the start of treatment. We believe that systematic patient selection on the basis of defined criteria will identify a subset of patients having markedly improved chances for disease control. This group may represent as many as half of the patients first presenting with localized or MO disease. Patients excluded as candidates for resection have continued to receive standard nonsurgical combined-modality therapy.

We reviewed survival of patients with clinically localized small cell carcinoma of the lung treated by surgical resection, combination chemotherapy, and prophylactic cranial irradiation. Long-term survival was defined as continuing complete remission 30 months after the start of treatment. Initial TNM staging determined the course of treatment. Ten patients with disease in Stages I and II were treated over 30 months ago by initial resection followed by the full course of chemotherapy. Only one has had a relapse, whereas 80% remained disease-free at 30 months. Five of these patients have passed 5 years. Four patients with T3 N1 disease were treated by two cycles of chemotherapy, surgical resection, and cranial irradiation plus resumption of chemotherapy thereafter; two remained in remission at 30 months. Sixteen patients initially with N2 disease were treated according to the same schedule; 10 of the 16 underwent successful resection. All 16 patients have had a relapse, but the relapse occurred very late in three—at 27, 30, and 37 months. The reasons for the apparently poor prognosis of N2 disease are not clear. Considerations of tumor response kinetics and somatic mutation suggest that these biologic factors are fundamentally responsible. Other studies may find disease control achieved in a very few patients with N2 disease.

Long-standing pulmonary insufficiency after repair of tetralogy of Fallot may adversely affect ventricular function. We evaluated 20 patients at a mean of 9 years after repair by radionuclide ventriculography, 24 hour Holter monitoring, and M-mode echocardiography. The mean age at complete repair was 7.1 ± 2.6 years. Patients were divided into groups as follows: Group I (eight patients), no clinical pulmonary insufficiency; Group II (12 patients), moderate to severe pulmonary insufficiency. Group II was further divided: Group IIa, transannular patch (six patients): Group IIb, no transannular patch (six patients). There was no difference between groups for age at operation, duration of follow-up, right ventricular pressure, or right ventricular-pulmonary arterial gradient. No patient had a residual shunt and all were in New York Heart Association Class I. Serious ventricular dysrhythmias occurred in 38% of Group I patients and 50% of Group II (p = NS). The echocardiographic ratio of right to left ventricular end-diastolic dimension was greater in patients with pulmonary insufficiency than in those without pulmonary insufficiency: 0.83 ± 0.17 versus 0.55 ± 0.15, p < 0.01. Right ventricular ejection fraction was 0.39 ± 0.08 in Group I and 0.27 ± 0.07 in Group II, p < 0.01. Left ventricular ejection fraction was 0.64 ± 0.12 in Group I and 0.53 ± 0.07 in Group II, p < 0.02. Radionuclide angiography is a useful means of identifying right ventricular dysfunction following repair of tetralogy of Fallot. The dysfunction appears significantly worse in patients with pulmonary insufficiency.

Surgical resection has failed notably as definitive treatment for small cell carcinoma of the lung. Newer treatment programs combining intensive chemotherapy with radiation therapy achieve a significant response in about 85 percent of cases, with about 50 percent of patients showing clinically complete remission. Long-term survival without recurrence has been the outcome in a small minority of cases. A frequent mode of failure after treatment of limited disease is recurrence within the chest. The course of one patient treated early in this series suggests that exclusion of initial surgical resection from programs of combined treatment may be a serious omission. Since that time, four patients have undergone initial resection, apparently with uniformly favorable courses to date. Selection criteria based on staging factors are proposed. Admittedly, only a minority of patients will be suitable for this treatment at the time of first diagnosis. Much opportunity exists for improvement in survival rates of patients, even those with limited disease.

Supraventricular arrhythmias continue to complicate the postoperative course of patients undergoing myocardial revascularization. In a previous study, we showed a decrease in arrhythmias if patients were given digitalis prior to operation. Since that time we have made two changes—propranolol is no longer discontinued prior to operation and cold hyperkalemic cardioplegic solution is routinely used. To assess the affect of these changes on arrhythmias, we repeated the previous study. One hundred twenty patients all receiving preoperative and postoperative propranolol were randomized into a control group and a digitalis-treated group. The incidence of supraventricular arrhythmia postoperatively was 21.4% in the control group and 3.1% in the digitalis group (p < 0.005). Therefore, we continue to advise preoperative digitalization in patients requiring coronary artery bypass and continue to maintain beta blocker and digitalis therapy in the postoperative period.

The association of intraventricular conduction defects and aortic valvular disease is widely recognized. This study was undertaken to evaluate the effects on survival of left bundle conduction defects (LBCDs) as a consequence of aortic valve replacement. A total of 133 patients were followed between 1 and 70 months after operation, with a mean follow-up of 32.1 months. The incidence of intraoperative LBCDs was 31.6% or 42 patients. There were 13 deaths in the group of 42 patients with LBCDs compared to eight deaths in the group of 91 patients without such abnormalities (p < 0.01). Sudden death occurred in five of 42 patients with postoperative LBCDs and two of 91 patients with normal intraventricular conduction (p < 0.025). The survival rate in these patients with significant aortic stenosis and normal intraventricular conduction was 89.9%, whereas if LBCD had occurred after operation, the survival rate was 65.7% (p < 0.005). If the LBCD was accompanied by a left axis deviation, the survival rate was 21.7%. Sudden death may be due either to a tachyarrhythmia or perhaps to progression from LBCD to complete heart block or trifascicular block. It is important that this group of patients be monitored closely after operation. There may be an indication to insert prophylactic permanent pacemakers in this group.

The clinical, hemodynamic, and angiographic data on 92 patients with severe isolated aortic stenosis were reviewed to determine the incidence and mechanism of pulmonary hypertension. The status of each of these patients was determined 1 to 8 years after diagnosis by cardiac catheterization. Patients were divided into three groups on the basis of the pulmonary artery systolic pressure: group 1 (≤30 mm Hg), 46 patients; Group 2 (31 to 50 mm Hg), 31 patients; and Group 3 (>50 mm Hg), 15 patients. The prevalence of pulmonary hypertension was 50% (46/92) and that of severe pulmonary hypertension, 16% (15/92). There was no significant difference in age, aortic valve gradient, or valve area among the three groups. There was a significant positive correlation in left ventricular end-diastolic pressure (group 1, 15.5 ± 7.2 mm Hg; group 2, 23.3 ± 8.1 mm Hg; and group 3, 29.5 ± 5.8 mm Hg; R = 0.56, p < 0.01). There was also a significant negative correlation in left ventricular ejection fraction (group 1,67.5% ± 14%; group 2,62.3% ± 13.8%; and group 3 49.9% ± 18.3%; R = 0.43, p < 0.01). Of the 92 patients, 85 had aortic valve replacement with four (4.7%) hospital deaths. Follow-up showed excellent symptomatic relief in all three groups. Thirteen of the 15 patients in group 3, with severe pulmonary hypertension, had aortic valve replacement. There were no hospital deaths and only one noncardiac death at follow-up in Group 3 patients, and 11 of the 12 surviving patients were in New York Heart Association functional class I. We conclude that pulmonary hypertension is common in isolated aortic stenosis and is related to an elevated left ventricular end-diastolic pressure, frequently with preserved systolic function. Surgical results are excellent.

Between 1979 and 1986, 30 patients underwent replacement of the aortic valve and ascending aorta by a composite graft, with aortic wrapping of the graft. Thirteen patients had annuloaortic ectasia; six had DeBakey type I dissection (five acute, one chronic); three had DeBakey type II dissection (one acute, two chronic); three had left ventricular-aortic discontinuity caused by prosthetic valve endocarditis; three had sinus of Valsalva aneurysms after previous aortic valve procedures; and two had atherosclerotic aneurysms. Three patients died (10%). The mean duration of follow-up was 54 months. Fifteen patients consented to be restudied by intra-arterial digital subtraction angiography; studies were performed 6 to 58 months (mean 25 months) after composite graft replacement. Two patients had pseudoaneurysms at the right coronary anastomosis, which were repaired successfully. One patient showed persistent dissection beyond the distal aortic anastomosis; no reoperation has been done. One patient had pulmonary edema. Emergency study and reoperation showed disruption of the proximal aortic anastomosis and right coronary anastomosis. Anastomotic dehiscence after composite graft replacement is potentially lethal. Follow-up by means of intra-arterial digital subtraction angiography is simple and highly accurate. We suggest that dehiscences may occur early in the postoperative period and that restudy may be appropriate within a few months after operation.

Left ventricular function following aortic valve replacement has been evaluated in 15 consecutive patients. Cold potassium cardioplegia was utilized for myocardial preservation. Left ventricular function was assessed by radionuclide ventriculography performed preoperatively and 3 months postoperatively. The predominant lesion was aortic insufficiency in 10 patients and aortic stenosis in five patients. All patients demonstrated improved ejection fractions at 3 months. The mean increases of ejection fraction in the aortic insufficiency group were 20% from the anterior (Ant.) position and 12.5% from the left anterior oblique (LAO) position; in the aortic stenosis group they were 15.2% (Ant.) and 14.8% (LAO). It is our contention that cold potassium cardioplegia is an effective means of myocardial preservation and that it showed no measurable deleterious effect on left heart function in this group of patients.

The mechanisms of hypertension in coarctation remain to be clearly defined. In other hypertensive states, abnormal plasma renin activity (PRA) has been unmasked by the depletion of extracellular volume and the use of angiotensin antagonists. In a group of patients with coarctation, preoperative and postoperative evaluations of the renin-angiotensin system have been performed. Before operation, a group of patients with coarctation and a group of normal control subjects both underwent salt restriction followed by diuresis. A standard angiotensin antagonist (saralasin) test was performed on the patients with coarctation, and they demonstrated excessive renin-angiotensin activity compared to the control subjects. Following operation, paradoxical hypertension developed in all of the patients. Repeat saralasin test in these patients again revealed excessive angiotensin activity in the same patients as preoperatively. It appears that the renin-angiotensin system plays a more active role in coarctation than previously believed.