PET, CT, and MRI with Combidex for mediastinal staging in non-small cell lung carcinoma.

BACKGROUND: To determine the relative utility of positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging with Combidex (MRI-C) in the non-invasive staging of non-small cell lung cancer (NSCLC) mediastinal lymph nodes (MLN), we compared the three tests' individual performance with surgical mediastinal sampling. In contrast to prior studies, cytology was not used. METHODS: The MLN were evaluated using PET and CT in 64 NSCLC patients. MRI-C was performed in 9 of these patients. MLN with a PET standard uptake value greater than or equal to 2.5, or greater than 1 cm in the short axis by CT or lack of MRI-C signal change were considered positive for metastatic disease. All MLN were sampled and subjected to standard pathologic analysis. PET, CT, and MRI-C scans were interpreted blinded to the histopathological results. Sensitivity, specificity, and accuracy for each scan type to appropriately stage MLN was determined using pathologic results as the standard. RESULTS: Thirty patients had stage I disease, 8 stage II, 9 stage IIIA, 7 stage IIIB, and 10 stage IV. Two-hundred-and-thirty MLN were sampled. Sixteen patients had metastatic mediastinal disease. Compared to the pathological results, PET, CT, and MRI-C had a sensitivity, specificity, and accuracy of 70%, 86%, 84%; 65%, 79%, 76%; 86%, 82%, and 83%, respectively. PET and MRI-C were statistically more accurate than CT (p<0.001). In cases where PET and CT did not identify MLN involvement with NSCLC, 8% (2/25) were pathologically positive. CONCLUSIONS: PET and MRI-C are statistically more accurate than CT. However, the differences are small and may not be clinically relevant. No technique was sensitive or specific enough to change the current recommendation to perform mediastinoscopy for MLN staging in NSCLC.

Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma.

The purpose of this study was to evaluate the clinical efficacy of ultrasmall superparamagnetic iron oxide particles as a magnetic resonance (MR) contrast agent in differentiating metastatic from benign lymph nodes. Eighteen patients with primary lung malignancy and suspected regional lymph node metastases underwent MR imaging before and after Combidex(R) infusion in a multi-institutional study. All MR sequences were interpreted by one or more board-certified radiologists experienced in imaging thoracic malignancy. Each patient was evaluated for the number and location of lymph nodes, homogeneity of nodal signal, and possible change of MR signal post contrast. All patients underwent resection or sampling of the MR-identified lymph node(s) 1-35 day(s) post contrast MR imaging. In all, 27 lymph nodes or nodal groups were available for histopathologic correlation. Combidex had a sensitivity of 92% and a specificity of 80% in identifying pathologically confirmed metastatic mediastinal lymph nodes. Based on our preliminary data, Combidex MR imaging may provide additional functional information useful in the staging of mediastinal lymph nodes.

Failure of cryopreserved saphenous vein allografts following coronary artery bypass surgery.

Internal mammary arteries and saphenous vein grafts are the most satisfactory conduits for coronary artery bypass. However, at times these conduits are not available, due to previous use or poor quality. This paper reports our experience with 6 patients who underwent coronary artery bypass operations using 10 cryopreserved saphenous veins and internal mammary arteries. Postoperative graft patency was assessed with ultra fast computed tomography or cardiac catheterization. At operation, venous graft patency was 100% (10/10), at 1-8 weeks was 60% (6/10), and at 6-30 months was 0% (0/9). Alternately, all seven internal mammary artery grafts were patent at 2 to 18 months following surgery. One patient died 6 months following operation. Poor graft patency may be related to destruction of the cellular components or fibrosis resulting from the cryopreservation process or from immunologic factors. Because of poor patency compared to autologous conduits, we conclude the use of cryopreserved saphenous veins for coronary artery bypass should be severely restricted.

Allograft vein patency in a canine model. Additive effects of cryopreservation and cyclosporine.

Autogenous saphenous vein is the preferred conduit for many cardiovascular operations. Attempts to use allograft veins for arterial reconstruction have had poor results. To define circumstances under which allograft veins might prove to be acceptable vascular conduits, dogs underwent femoral artery bypass using reversed saphenous veins. Veins were transplanted fresh or after cryopreservation. Group I dogs received a fresh autograft to replace one femoral artery (group I F) and a cryopreserved (CP) autograft (group I C) to replace the other. Group II dogs received fresh allograft veins, and group III received CP allograft veins, neither group receiving additional treatment. Group IV received fresh allograft veins and Group V received CP allograft veins; both groups received cyclosporine 15 mg/kg. Animals were maintained until grafts occluded or until six months elapsed. Patency was observed in all group I F grafts throughout the observation period. Six-month patency rates in the other groups were: group I C, 9/10 (P = NS vs. group I F); group II, 0/10 (P less than 0.01), group III, 0/10 (P less than 0.01), group IV, 1/10 (P less than 0.01), group V, 7/11 (P = NS). In a separate series of observations 10 cryopreserved allograft veins were implanted in 10 dogs that received CsA for 30 days. CsA was then discontinued. All of these grafts occluded within 30 days of discontinuing the CsA. Long-term patency of saphenous vein allografts was achieved only with the combination of cryopreservation and immunosuppression with continued CsA.

Hemangiopericytoma of the sternum.

Hemangiopericytoma of the chest wall is a rare tumor. We describe a patient with malignant hemangiopericytoma of the sternum who was treated with primary surgical resection and discuss the clinical, radiographic, and histologic features of the case. Surgical resection is the primary mode of therapy. High-dose radiotherapy and chemotherapy with a doxorubicin hydrochloride-containing combination may be warranted in certain cases.

Clinical outcome of emergency repeat coronary artery bypass surgery.

To determine the clinical outcome of patients requiring emergency repeat coronary artery bypass graft (CABG) procedures, we reviewed 23 such procedures performed for ongoing myocardial ischemia refractory to medical management. The operative mortality was 17%. On follow-up, an average of 24.9 months after emergency reoperation, 14 of the 19 survivors (74%) had recurrent angina. As compared to a randomly selected group of 25 patients who underwent elective repeat CABG procedures during the same time period, the incidence of late cardiac events was significantly higher (79% in the emergency group, 30% in the elective surgery group) and fewer patients had received internal mammary artery (IMA) grafts (9% vs 52%). Emergency repeat CABG operations have considerable operative mortality and poor postoperative functional results with the majority of survivors developing recurrent ischemic syndromes within a short period of time.

Limited lateral thoracotomy. Improved postoperative pulmonary function.

A prospective randomized controlled study was designed to determine differences in early postoperative pulmonary function, pain, and complications between patients undergoing limited lateral muscle-sparing thoracotomy. Fifteen patients underwent standard thoracotomy and 13 underwent limited incision with the same anesthetic technique. During the first 24 hours after operation, there were large decreases in the results of spirometric tests of pulmonary reserve (forced expiratory volume in 1 second and forced vital capacity), but these decrements were consistently significantly smaller in the limited-incision group. Other tests of pulmonary function (mid-expiratory phase forced expiratory flow, alveolar-arterial oxygen gradient, and PaCO2), however, demonstrated similar postoperative changes in both groups. Similarly, there were no differences in pain scores, postoperative morphine requirements, complications, or length of hospital stay. Use of the limited muscle-sparing incision resulted in improved postoperative pulmonary reserve, but this did not translate into differences in other measures of postoperative convalescence.

Cryopreserved saphenous vein homografts for femoral-distal vascular reconstruction.

Cryopreserved saphenous vein homografts may serve as an alternative for femoral distal bypass conduits when suitable endogenous vein is not available. In a preliminary study, 6 patients underwent femoral distal bypass for limb salvage with cryopreserved saphenous vein with patency in 2 patients at 18 and 20 months, respectively. One graft, occluded at 14 months, was salvaged with thrombolytic therapy and percutaneous angioplasty, and is patent 7 months post intervention. Occlusion occurred in 3 grafts at 1 day, 7 days and 4 months, respectively. Reasons for reduced patency of cryopreserved grafts are related to destruction of the cellular components and fibrosis as a result of the cryopreservation and poor distal run-off present in these patients. Due to lower patency as compared to autogenous vein grafts, cryopreserved veins should be reserved for limb salvage when no autogenous vein is available for revascularization.

Intrapleural bupivacaine--technical considerations and intraoperative use.

The authors evaluated the incidence and type of technical problems associated with blind insertion of intrapleural catheters placed in 21 anesthetized patients and then injected in a double-blind fashion with 0.5% bupivacaine (1.5 mg/kg) or isotonic saline. The patients' chests were then opened, catheter positions located, and the lungs inspected. Eleven of the catheters were located with the tips intrapleurally, three extrapleurally, and seven actually in lung tissue. Eight patients had holes in the lung surface. Three patients had a pneumothorax, two of which were under tension. Plasma bupivacaine levels reached maximal concentrations at about 20 minutes in those with intrapleurally placed catheters, but not until 60 minutes when the catheter had actually penetrated the lung. Significant variations in plasma bupivacaine levels were achieved when the catheter entered lung tissue, with potentially toxic levels in one patient. To evaluate intraoperative analgesic effects, all patients were given a standard anesthetic with isoflurane, oxygen, and a muscle relaxant. There was no significant difference in isoflurane requirement between the groups who had bupivacaine v saline injected into their intrapleural catheters before surgery. It is concluded that blind insertion of intrapleural catheters can be hazardous, especially if followed by positive-pressure ventilation. In addition, catheter placement in lung tissue, which was not uncommon, delays the time for peak plasma concentrations and may increase risk of toxicity. Intrapleural bupivacaine was not found to be a useful adjunct to general anesthesia during thoracotomies.

Left ventricular-coronary sinus fistula after mitral valve replacement.

One of the more rare complications after mitral valve replacement is the development of a left ventricular-coronary sinus fistula, which has been reported only twice before. In the reported cases a common feature has been multiple valve replacements. Our case was one of the late development (8 years) of a fistula in a patient who had only one previous replacement but in whom a murmur was detected 3 months after the operation.

A combined surgical approach to non-oat-cell pulmonary carcinoma with single cerebral metastasis.

Eighty consecutive patients with pulmonary non-oat-cell carcinoma and a single cerebral metastasis were followed for at least 5 years after therapy. Forty were treated by surgical excision at both sites of disease plus whole-brain irradiation in most cases (group 1). The remaining 40 patients, an observational cohort, were treated either by surgery at only one site of disease (usually craniotomy), whole-brain irradiation, chemotherapy, or some combination of these modalities (group 2). The 1-year survival in group 2 was 15%, and all were dead at 2 years. In group 1, hospital mortality was 1.5%, the 1-year survival rate 35%, the 2-year survival rate 25%, and the 5-year survival rate 12.5%. All the five year survivors were patients with N0 disease. In this subgroup of group 1, the five year survival was 20%. All patients surviving for more than 2 years were in group 1 and had a Karnofsky rating greater than 50 and N0 disease after staging. These data indicate that a combined surgical approach can be accomplished with low morbidity, low mortality, and increased survival rates, especially for patients with N0 disease who are vigorous enough to undergo the combined treatment.

Coronary artery bypass grafting in dialysis patients.

Cardiac disease continues to be a major cause of death in patients undergoing long-term hemodialysis. The results of coronary artery bypass grafting (CABG) for severe coronary artery disease in long-term hemodialysis patients have been studied in a group of 12 patients who underwent CABG between January 1979 and December 1983. Hospital mortality was 8% (1 of 12 patients). This patient died of ventricular arrhythmia. Two late deaths occurred, 1 from peritonitis in a patient undergoing long-term peritoneal hemodialysis and 1 from metastatic renal cell carcinoma. The two postoperative complications (morbidity 17%) consisted of a sternal dehiscence secondary to mediastinitis and a perioperative cerebrovascular accident. Ten of the 11 hospital survivors experienced complete relief from angina. In the other patient the angina became easier to control with medication. Combining this series of patients with those previously reported in the literature allows determination of actuarial survival in a group of 25 patients followed up for 1 to 79 months (mean, 33 months). Actuarial survival was 83% at one year, 69% at three years, and 48% at five years. This is not significantly different from the survival of long-term hemodialysis patients who have coronary disease but have not undergone CABG. It appears that CABG, when performed in long-term hemodialysis patients, is associated with an only slightly greater risk of mortality and morbidity than CABG performed in routine patients. Although CABG provides considerable symptomatic relief of angina, no statistically significant change in actuarial survival can be demonstrated.

Establishment and characterization of four new human non-small cell lung cancer cell lines.

Four new human non-small cell lung cancer cell lines have been established in vitro. These cell lines have been characterized by (a) growth of a tumor in nude mice with histopathology similar to that of the primary, (b) isoenzyme patterns phenotypically human and distinct from each other, (c) distinguishing karyotypic findings, (d) growth rate determinations, and (e) presence of epidermal growth factor receptors. Each of the cell lines will form colonies when directly seeded into a flask without soft agar. The development and availability of the four cell lines may facilitate in vitro studies of the biology of this common cancer. Their clonogenic potential may be of value in the study of sensitivity to antineoplastic agents. Their low passage level may mean that their antigens still resemble those of the primary tumor.

Coronary artery bypass surgery in the elderly.

One hundred fifteen patients over 65 years of age were operated on at our institution for coronary artery bypass grafting (CABG). The operative mortality was 5% compared with an overall operative mortality of 2.5% in the last five years for 1,500 persons with CABG. Increased risk factors included qualification for New York Heart Association (NYHA) class IV, ejection fraction of less than 35%, diffuse disease requiring more than five grafts, and age over 75 years. At one year after operation, 81% of the patients were clinically improved, and the survival rate was 91%. Patients over 65 years of age in NYHA classes II and III with good left ventricular function requiring four or less bypass grafts appeared to have an excellent prognosis both acutely and during a one-year follow-up period.

Cellular retinoic acid-binding protein in human lung carcinomas.

Cellular retinoic acid-binding protein (CRABP) was detected in the cytosol of 11 human non-small-cell lung cancer specimens. Neither normal lung nor a small-cell lung cancer specimen contained this binding protein. The quality of CRABP per milligram of cytosol protein ranged from 48.3 to 426.5 fmol.

Operation for aortic arch anomalies.

Forty-two patients with aortic arch anomalies resulting in tracheoesophageal compression were treated during the period 1948 through 1978. These anomalies are important causes of upper respiratory and esophageal obstruction in babies and small children and can be corrected safely with excellent relief of symptoms. Nineteen patients (45%) had a right aortic arch with a ligamentum arteriosum, 17 patients (40%) had double aortic arches, and 6 patients (15%) had aberrant right subclavian arteries. Other associated congenital malformation and mental retardation were seen in 15 patients (36%). Diagnosis was accurately made in 38 patients (90%) by barium esophagogram. Basic surgical principles include exposure through a left thoracotomy, complete identification of the aortic arch anatomy, and division of the constricting ring. Surgical treatment resulted in 2 deaths (5%), and 1 patient died late. Early postoperative respiratory complications were common. All survivors were relieved of their symptoms late (median, 94 months) postoperatively.

Esophageal and gastroesophageal junction carcinoma: an evolved philosophy of management.

One hundred eleven patients with esophageal and gastroesophageal junction carcinoma were treated in the last 12 years. Fifty-seven (52%) underwent resection for cure (38%) or for palliation (14%). Overall operative mortality was 32% (18/57), being greatest with colon interposition (71%) or gastric tube (67%) and least with esophagogastrectomy (11%). Major complications--anastomotic leak being the most important--were strikingly more prevalent (71 and 66%) with the first two procedures than with esophgoastrectomy (14%). The mean survival time in patients resected for cure was 17 months compared to seven in those treated primarily by radiation. In addition, radiation therapy was accompanied by a 20% major complication rate and by less subjective palliation. In the surgically-resected group, there was a two, three, and five year survival of 26, 9, and 5%. Incomplete removal of tumor did not improve survival above that attained with untreated patients. Morbidity and mortality associated with use of endoprostheses in an additional 27 patients was 65%. This experience has led us to espouse the following approach: 1) The main thrust of treatment should be to resect gross tumor completely. 2) The use of the stomach in reconstruction at all levels offers the safest, most expeditious means of immediate rehabilitation. This is best accomplished by first an abdominal approach followed by a right thoracotomy, as outlined by Lewis (Br J Surg, 1946). 3) Radiation therapy should be used as post-resection adjunctive therapy or when surgery primarily is not applicable for medical reasons or refused.