Biomedical subjects

M E Burt

Publications and source records attributed to M E Burt.

At least 37 records · Page 2Linked to original sources

PubMed1997

Sequential bilateral isolated lung perfusion in the rat: an experimental model.

BACKGROUND: A model of isolated single-lung perfusion in the rat has been established in our laboratory to study the chemotherapeutic treatment of pulmonary metastases. A sequential bilateral isolated lung perfusion model was designed to investigate the feasibility of staged perfusions in the rat. METHODS: Twenty-four Fischer rats were randomized into three experimental groups of 8 rats each. All rats underwent left isolated lung perfusion. One, 2, or 3 weeks later, the rats in groups I, II, and III, respectively, underwent contralateral (right) perfusion. Five control animals (group IV) underwent sequential bilateral sham thoracotomies 1 week apart. Arterial blood gas analysis was performed 1 week after the second operation in the rats in groups I and IV. RESULTS: All animals survived the first operation, with 100% (8/8), 75% (6/8), and 100% (8/8) of the animals in perfusion groups I, II, and III, respectively, surviving the second operation. All control animals (group IV) survived the second sham thoracotomy. Arterial blood gas analysis did not show a significant difference in the oxygen or carbon dioxide partial pressure or the pH between group I and IV (p = 0.32, 0.96, and 0.76, respectively). CONCLUSIONS: Our experiments demonstrate that sequential bilateral isolated lung perfusion is safe in and well tolerated by the rat. This model can be used to investigate the safety and efficacy of staged perfusions with chemotherapeutic agents in the treatment of bilateral pulmonary metastases in the rat.

Animals↗

PubMed1997

Establishment of an experimental intrapulmonary tumor nodule model.

BACKGROUND: A pulmonary tumor model is necessary to study the biology and therapy of lung cancer. Methods to establish a solitary intrapulmonary nodule are not well defined. Two methods for solitary intrapulmonary tumor nodule development in the Fischer rat are described. METHODS: Methylcholanthrene-induced sarcoma cell suspensions were introduced into lung parenchyma of Fischer rats via limited thoracotomy and lung puncture, or instilled into a distal airway after tracheal puncture and catheterization. Intrapulmonary tumor location, implantation mortality, procedure length, and animal survival were recorded. RESULTS: Single pulmonary nodules developed at the implanted position in 100% (n = 320) and 95% (62/65) of animals after direct injection into the pulmonary parenchyma or via tracheal puncture and instillation. Operative mortality was 2% and 5% via lung or tracheal implantation, respectively. Less than 5 minutes was required for each implantation. Mean survival time was 24 +/- 2 and 26 +/- 6 days after lung or tracheal implantation in animals allowed to survive until tumor-induced death. CONCLUSIONS: These easily performed, reproducible methods of establishing solitary intrapulmonary tumors are useful tools for lung cancer research.

Animals↗

PubMed1997

Isolated lung perfusion with doxorubicin prolongs survival in a rodent model of pulmonary metastases.

BACKGROUND: We developed a rodent model of unilateral pulmonary metastases to evaluate long-term survival after isolated lung perfusion with doxorubicin. METHODS: In the model development study, on day 0, two groups of F344 rats (n = 15) underwent transient right pulmonary artery occlusion for either 5 or 10 minutes at the time of intravenous injection of methylcholantrene-induced sarcoma cells. On day 14, all animals were sacrificed and lung nodules counted. In the survival study, on day 0, 21 rats received intravenous injection of sarcoma cells with concomitant 10-minute right pulmonary artery occlusion. On day 7, eight rats underwent left isolated lung perfusion with doxorubicin (6.4 mg/kg); five rats underwent perfusion with buffered Hespan; six untreated rats were studied as controls. RESULTS: Ten of fifteen animals (67%) in the model study with 5-minute pulmonary artery occlusion had right-sided tumor nodules. Ten-minute occlusion resulted in a tumor-free right lung in all animals. In the survival study, all animals in the Hespan and control groups died of massive tumor replacement of the left lung, with median survival times of 20 and 18 days, respectively. The median survival time of 36 days for the animals undergoing isolated lung perfusion with doxorubicin was significantly longer (p < 0.00001). The left lung of two of the doxorubicin perfused rats was tumor-free at 6 weeks. CONCLUSIONS: Isolated lung perfusion with doxorubicin results in a durable response and prolongs survival in the treatment of experimental sarcoma pulmonary metastases.

Animals↗

PubMed1997

Mediastinal growing teratoma syndrome.

BACKGROUND: The growing teratoma syndrome refers to the phenomenon whereby germ cell tumors enlarge after chemotherapy despite complete eradication of malignant cells and normalization of serum tumor markers. This clinical scenario must be differentiated from that in which germ cell tumors maintain their malignant characteristics with elevated levels of serum tumor markers. METHODS: Hospital record review was conducted of 2 cases. RESULTS: Two male patients are presented, 1 with a metastatic germ cell tumor of both the retroperitoneum and mediastinum (with elevated alpha-fetoprotein level) and 1 with a primary germ cell tumor of the mediastinum (with elevated alpha-fetoprotein and beta-human chorionic gonadotropin levels). After completion of chemotherapy and normalization of tumor markers, both patients presented with pulmonary symptoms attributable to their massively enlarging mediastinal teratomas. The clinical and roentgenographic features of patients with thoracic manifestations of the growing teratoma syndrome, as well as its management, are reviewed. CONCLUSIONS: After chemotherapy in patients with primary or metastatic mediastinal germ cell tumors whose tumor markers normalize, a growing mass in the mediastinum may represent the growing teratoma syndrome.

Adult↗

PubMed1997

Atraumatic gastric transposition after transhiatal esophagectomy.

Transhiatal esophagectomy using the stomach for esophageal replacement requires that the gastric "neoesophagus" be transferred from the peritoneal cavity through the posterior mediastinum into the neck under blind conditions. This process is associated with stretching, tearing, and hematoma formation in the most critical portion of the gastric tube, that to be used for the anastomosis. A technique is described for this procedure that is simple to perform and, most importantly, completely atraumatic to the gastric conduit.

Anastomosis, Surgical↗

PubMed1997

Pericardiocentesis and intrapericardial sclerosis: effective therapy for malignant pericardial effusions.

BACKGROUND: Pericardial effusions remain a formidable problem in patients with an advanced malignancy. We reviewed our experience with pericardiocentesis and intrapericardial sclerotherapy versus open surgical drainage as the treatment for these effusions. METHODS: A retrospective review was performed of one surgeon's experience (M.E.B.) with the surgical treatment of malignant pericardial effusions at a tertiary-care cancer center. RESULTS: Sixty patients underwent 72 procedures during 8 years. Thirty-seven (51%) pericardiocenteses and 35 (49%) open procedures were performed in patients with effusions. There was no significant difference in the complication rates seen between those effusions drained via pericardiocentesis (n = 5; 13%) and those drained in an open surgical procedure (n = 5; 14%). Similar results were seen with respect to the development of a recurrent effusion. There were no procedure-related deaths. The median survival for all patients was 97 days. Patients with breast cancer as their primary malignancy survived significantly longer after drainage than did all others (p = 0.01). The type of procedure did not influence survival. Costs of surgical drainage exceed those of pericardiocentesis by nearly fortyfold. CONCLUSIONS: Pericardiocentesis with intrapericardial sclerotherapy is as effective as open surgical drainage for the management of malignant pericardial effusions.

Actuarial Analysis↗

PubMed1997

Magnetic resonance imaging of the postpneumonectomy chest: normal and abnormal findings.

To determine the normal findings at magnetic resonance imaging (MRI) of the postpneumonectomy space (PPS), and to evaluate the utility of MRI in detection of recurrent tumor in the postpneumonectomy chest, 32 MRI scans were performed in 31 patients at varying time intervals after pneumonectomy. Eleven patients also had 12 computed tomography (CT) scans performed at the same time to evaluate possible tumor recurrence. Of the 32 scans, 5 demonstrated complete obliteration of the fluid containing PPS, and 4 showed gas in the PPS; the remainder (n = 23) demonstrated persistence of fluid-filled spaces of varying size. The presence of a fibrotic rim of tissue was constant. In 11 patients with clinically suspected tumor recurrences, both CT and MRI were obtained: the two modalities performed with similar accuracy in diagnosing tumor recurrence at 16 sites; CT detected opposite-lung metastatic nodules not seen on MRI in one patient, and a rib metastasis described as "indeterminate" on MRI in a second patient. MRI detected a focus of recurrence in the PPS that was indeterminate on CT. There is considerable variability in the amount of fluid seen in the PPS on MRI. CT remains the procedure of choice for routine follow-up or in suspected tumor recurrence in the postpneumonectomy patient; MRI can be helpful if the CT scan is nondiagnostic or equivocal.

Adult↗

PubMed1997

Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy.

BACKGROUND: This prospective study was designed to determine whether diltiazem is superior to digoxin for the prophylaxis of supraventricular dysrhythmias (SVD) after pneumonectomy or extrapleural pneumonectomy (EPP) and to assess the influence of these drugs on perioperative cardiac function. METHODS: Seventy consecutive patients without previous SVD were randomly allocated immediately after pneumonectomy or EPP to receive diltiazem (n = 35) or digoxin (n = 35). Diltiazem-treated patients received a slow intravenous loading dose of 20 mg, followed by 10 mg intravenously every 4 hours for 24 to 36 hours, then 180 to 240 mg orally daily for 1 month. Digoxin-treated patients received a 1-mg intravenous loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1 month. A concurrent prospective cohort of 40 patients without previous SVD, who did not participate in the study and underwent pneumonectomy or EPP without prophylaxis, served as a comparison group for SVD occurrence. Serial Doppler echocardiograms were performed to assess cardiac function and all patients were continuously monitored with Holter recorders for 3 days. Data were analyzed by intent-to-treat. RESULTS: In patients undergoing standard or intrapericardial pneumonectomy, diltiazem prevented the overall incidence of postoperative SVD when compared with digoxin, 0 of 21 patients versus 8 of 25 patients, respectively, p < 0.005. When EPP patients were included in the analysis, diltiazem decreased the incidence of all SVD from 11 of 35 patients (31%) to 5 of 35 patients (14%) when compared with digoxin, p = 0.09. Digoxin-treated patients had a similar incidence of all SVD (31%) as concurrent controls (11 of 40 patients [28%]). The two treated groups did not differ in right or left atrial size, left ventricular ejection fraction, or right heart pressure. When all patients were combined, those in whom SVD developed were significantly older (65 +/- 12 years versus 55 +/- 11 years, p = 0.004) and had a longer median hospital stay (9 versus 6 days, p = 0.03), when compared with those in whom SVD did not develop, respectively. The subset of patients undergoing EPP had a greater incidence of atrial fibrillation and electrocardiographic changes suggestive of postoperative pericarditis than all other pneumonectomy patients. CONCLUSIONS: Diltiazem was both safe and more effective than digoxin in reducing the overall incidence of SVD after standard or intrapericardial pneumonectomy. Digoxin therapy had no effect on the incidence of postoperative SVD and is not recommended for prophylaxis of SVD. Dysrhythmias after pneumonectomy or EPP occur in older patients and are associated with a greater length of hospital stay.

Aged↗

PubMed1996

gamma-Glutamyl transpeptidase mediation of tumor glutathione utilization in vivo.

BACKGROUND: Glutathione is a tripeptide used by cells to protect against oxidative and free radical damage. It may also be involved in biochemical mechanisms that cause some tumors to become resistant to anticancer drugs. gamma-Glutamyl transpeptidase (GGTP) is a membrane-bound enzyme that cleaves extracellular glutathione, providing cells with amino acids necessary for intracellular synthesis of this compound. Increased expression of GGTP has been found in a number of human tumors; however, few studies have examined the contribution of GGTP to tumor glutathione metabolism in vivo. PURPOSE: Our goals were to study the utilization of host glutathione by 3-methylcholanthrene (MCA)-induced sarcomas grown in rats and to evaluate the involvement of tumor GGTP in this process. METHODS: The left ovaries of 21 female Fischer 344 rats were isolated by laparotomy and placed in subcutaneous positions through stab wounds in the abdominal wall. A 3-mm cube of MCA sarcoma was then sutured to each of the isolated ovaries. The MCA implants obliterated the ovarian tissue, yielding isolated tumors with one arterial supply (the ovarian artery) and one draining vein (the ovarian vein, referred to as the tumor vein). After 2 weeks of tumor growth, blood was drawn from the tumor vein, the inferior vena cava (IVC), and the aorta of 16 animals. Glutathione and cysteine concentrations in plasma samples from this blood were determined by high-performance liquid chromatography and used to calculate glutathione and cysteine utilization ratios for the tumor and the systemic circulations ([(concentration aorta-concentration tumor vein)/concentration aorta] x 100 and [(concentration aorta-concentration IVC)/concentration aorta ] x 100, respectively). The utilization ratios from these control animals were compared with those from acivicin (AT-125; an irreversible GGTP inhibitor)-treated rats (the remaining five animals). Data are presented as mean +/- standard deviation; reported P values are from two-tailed tests of statistical significance. RESULTS: In the control animals, glutathione and cysteine concentrations were significantly lower in the tumor vein (3.55 +/- 1.9 and 5.69 +/- 2.8 microM, respectively) and in the IVC (5.65 +/- 2.3 and 7.17 +/- 2.4 microM, respectively) than in the artery (12.48 +/- 5.7 and 12.33 +/- 5.9 microM, respectively; all P values < .05). In addition, the glutathione utilization ratio was significantly higher for the tumor circulation than for the systemic circulation (69% +/- 14% versus 52% +/- 14%; P < .003). The combined glutathione and cysteine utilization ratio was also significantly higher for the tumor circulation than for the systemic circulation (116% +/- 35% versus 88% +/- 28%; P < .02). Treatment with AT-125 lowered the tumor glutathione utilization ratio significantly (45% +/- 12% for treated animals versus 69% +/- 14% for control animals; P < .005). CONCLUSIONS: Our results show that glutathione and cysteine in the host circulation are used by MCA sarcomas. The significant reduction in tumor utilization of serum glutathione after treatment with AT-125, a GGTP inhibitor, indicates that GGTP is important in tumor glutathione metabolism.

Animals↗

PubMed1996

Oral L-2-oxo-4-thiazolidine reduces bacterial translocation after radiation in the Fischer rat.

Glutathione (GSH) is important in protecting rapidly dividing intestinal cells against free radicals generated following radiation. L-2-Oxo-thiazolidine (OTZ) promotes GSH synthesis through increased cysteine delivery. We hypothesize that oral supplementation with OTZ will augment GSH levels and decrease the incidence of bacterial translocation after abdominal radiation, and these effects will be abrogated by treating with a blocker of GSH synthesis, buthionine sulfoximine (BSO). Fischer rats received by oral gavage either OTZ (OTZ/rad), OTZ plus BSO (OTZ/BSO/rad), or saline (sal/rad) 4 hr prior to and 18 hr after radiation. One group underwent saline gavage and no radiation (ctl/sal). On Day 4, animals were sacrificed and mesenteric lymph nodes (MLN) were cultured. Liver and jejunum were removed for GSH analysis by HPLC. Nonradiated, ctl/sal had higher levels of hepatic and jejunal GSH than ctl/rad (13.0 +/- 1.2 vs 9.7 +/- 1.5, 11.2 +/- 1.0 vs 7.8 +/- 2.5 micromol/g dry wt, P < 0.05). Supplementation with OTZ (OTZ/rad) increased hepatic and jejunal GSH levels but treatment with OTZ and BSO (OTZ/BSO/rad) eliminated this benefit (12.0 + 2.6 vs 9.5 + 1.7, 10.1 + 2.4 vs 5.9 + 1.3 micromol/g dry wt, P < 0.05). Ctl/rad had a high rate of positive MLN cultures (80%) compared to ctl/sal and OTZ/rad (10 and 30%, P < 0.05). Treatment with OTZ and BSO (OTZ/BSO/rad vs OTZ/rad, 70 and 30%, P < 0.05) reversed the benefit of OTZ supplementation. This study demonstrated whole abdominal radiation depleted both hepatic and jejunal levels of GSH. Uniquely, OTZ supplementation restored hepatic and jejunal levels of GSH and decreased rate of bacterial translocation.

Administration, Oral↗

PubMed1996

Value of perioperative Doppler echocardiography in patients undergoing major lung resection.

BACKGROUND: The effects of major lung resection on right heart function have not been well established. Our goal was to evaluate these effects using serial Doppler echocardiography in the perioperative period. METHODS: In 86 patients undergoing lobectomy (n = 47) and pneumonectomy (n = 39), we examined the effects of pulmonary resection on perioperative changes in right heart function by transthoracic echocardiography. Serial echocardiograms were performed preoperatively, on postoperative day 1, and again between postoperative days 2 and 6 (median, 3 days) to evaluate cardiovascular function and to estimate right ventricular systolic pressure by the tricuspid regurgitation jet Doppler velocity method. RESULTS: Right or left atrial size, right atrial pressure, and estimated right ventricular systolic pressure did not differ between groups on the preoperative or postoperative day 1 examinations. However, on postoperative days 2 through 6 patients who underwent pneumonectomy had higher (mean +/- standard deviation) right ventricular systolic pressure values than lobectomy patients (31 +/- 15 versus 25 +/- 10 mm Hg, respectively; p < 0.05 by analysis of variance). In the subset of patients with percent predicted forced expiratory volume in 1 second less than 60% undergoing pneumonectomy (9/39), preoperative right ventricular systolic pressure was inversely correlated with percent predicted forced expiratory volume in 1 second values (r = -0.78; p < 0.04). This correlation was not significant in corresponding lobectomy patients. Postoperative right ventricular enlargement determined by echocardiography occurred with similar frequency in both groups and was associated with poor short-term prognosis in patients in whom severe respiratory failure developed. CONCLUSIONS: Preoperative indices of right heart function were within the normal range in both groups. Pneumonectomy but not lobectomy was associated with mild postoperative pulmonary hypertension that was not accompanied by significant right ventricular systolic dysfunction. Postoperative echocardiography may be useful to evaluate right heart function in critically ill patients after lung resection.

Adult↗

PubMed1996

Isolated lung perfusion with doxorubicin reduces cardiac and host toxicities associated with systemic administration.

BACKGROUND: For patients with malignant neoplasms metastatic to lung, systemic chemotherapy in doses high enough to achieve significant survival improvement is often limited by host toxicity. Isolated single-lung perfusion offers the advantage of delivering high-dose organ-specific chemotherapy while minimizing systemic toxicity. We compared the cardiac and systemic toxicities associated with intravenous administration versus isolated single-lung perfusion with doxorubicin. METHODS: Thirty-three male Fischer 344 rats weighing 275 to 300 g were randomized into three groups: normal control rats (n = 11), intravenous doxorubicin (7/mg/kg) (n = 11), and isolated left lung perfusion with 320 micrograms doxorubicin/mL (n = 11). Animals undergoing isolated single-lung perfusion were anesthetized with pentobarbital, intubated, and ventilated, and then had left thoracotomy with cannulation of the pulmonary artery and a pulmonary venotomy; pulmonary artery and vein were clamped proximally. Animals were perfused for 10 minutes at a rate of 0.5 mL/min, followed by a 5 minute rinse with buffered hespan solution. Arteriotomy and venotomy were repaired and circulation was restored. Daily weights were recorded. On day 24, cardiac output was determined in all groups by injection of radiolabeled chromium 51 microspheres. RESULTS: Animals treated with 7 mg/kg intravenous doxorubicin had a significant weight loss as compared with those treated with isolated lung perfusion (209.2 +/- 29.9 g versus 302.3 +/- 10.1 g; p < 0.01). Animals treated with isolated single-lung perfusion, after recovering from surgical stress, resumed normal growth pattern. Significant cardiac toxicities were seen in intravenously treated animals; cardiac index (27.4 +/- 6.9 versus 39.4 +/1 6.3 mL/min/100g body weight and heart weights (0.56 +/- 0.04 versus 0.88 +/- 0.09 g) were reduced in the intravenously treated group as compared with the group treated with isolated single-lung perfusion. In addition, severe hematologic toxicities are associated with intravenous doxorubicin administration. CONCLUSIONS: Intravenous administration of doxorubicin is associated with severe host toxicities, which include weight loss, decreased cardiac function, and hematologic toxicity. Isolated lung perfusion with high-dose doxorubicin is well tolerated and is associated with minimal host toxicity.

Animals↗

PubMed1996

Symptomatic tachydysrhythmias after esophagectomy: incidence and outcome measures.

BACKGROUND: Supraventricular tachydysrhythmias (SVT) after esophageal operations for carcinoma occur frequently and may be associated with increased morbidity. Prospective data on the etiology, incidence, and importance of these dysrhythmias are sparse. METHODS: In 100 consecutive patients undergoing esophagectomy without prior history of atrial dysrhythmias or receiving antiarrhythmics, we prospectively examined the effects of predefined risk factors by history and pulmonary function on the 30-day incidence of symptomatic postoperative SVT, need for intensive care unit admission, and mortality rate. RESULTS: Symptomatic postoperative SVT occurred in 13 (13%) of the 100 patients studied at a median of 3 days after operation and was accompanied by hypotension in 9/13 (69%). Univariate correlates of SVT were older age (p = 0.03), perioperative use of theophylline (p = 0.044), and a low carbon monoxide diffusion capacity (measured in 56% of patients) on preoperative pulmonary function. Patients in whom SVT developed had a higher rate of intensive care unit admission (p = 0.0001) and a longer hospital stay (p = 0.036). Although patients in whom SVT developed had a higher (p = 0.013) 30-day mortality rate, SVT was not the direct cause of death. CONCLUSIONS: These prospective data show that the true incidence of symptomatic SVT within 30 days of esophagectomy is lower than previously reported. Occurrence of SVT was associated with significant morbidity. Older age was the strongest predictor of SVT after esophagectomy. In high-risk patients, continued monitoring (48 to 72 hours) and early interventions to decrease the incidence of postoperative SVT may improve overall surgical outcomes.

Age Factors↗

PubMed1996

Role of video-assisted thoracic surgery in the treatment of pulmonary metastases: results of a prospective trial.

BACKGROUND: A retrospective review revealed a 42% error rate between computed tomographic scan reports and thoracotomy findings; therefore, a prospective study was designed to compare the value of computed tomographic scans, video-assisted thoracoscopic exploration, and open thoracotomy in the management of pulmonary metastases. METHODS: Eligibility included any patient with only one or two ipsilateral pulmonary metastases identified on computed tomographic scan who was being considered for surgical resection. Initially video-assisted thoracic surgery was performed and all lesions identified were resected. A thoracotomy adequate for complete lung palpation was then carried out and any additional lesions found were removed. RESULTS: Eighteen patients of a planned 50 were treated before closure of the study. Four patients (22%) had no additional lesions found at thoracotomy. The primary sites of tumor were colon (10), breast (3), and one patient each skin (squamous), cervix, kidney, melanoma, and sarcoma. Four patients (22%) did have additional lesions at thoracotomy, which were benign. In the remaining 10 patients (56%) additional malignant lesions were found at thoracotomy after video-assisted thoracoscopic exploration. After 18 patients were entered, analysis of the early results disclosed a 56% failure rate of a computed tomographic scan and video-assisted thoracic surgery to detect all lesions. Being within the 95% confidence interval (32% to 78%), the study was abandoned. CONCLUSIONS: We conclude that video-assisted thoracic surgery should be used only as a diagnostic tool in managing lung metastasis. A thoracotomy is required to achieve complete resection, which is the major survival prognosticator for satisfactory long-term results.

Breast Neoplasms↗

PubMed1996

Isolated lung perfusion with FUDR in the rat: pharmacokinetics and survival.

BACKGROUND: Although surgical resection remains the mainstay of treatment for metastatic pulmonary colorectal cancer, 5-year survival approaches only 30% to 40%. We have developed a model of isolated left lung perfusion (ILP) with FUDR (2'-deoxy-5-fluorouridine) for the treatment of pulmonary colorectal metastases. FUDR ILP toxicity and pharmacokinetics were evaluated and compared with continuous intravenous infusion in the rat. METHODS: Toxicity was first evaluated in F344 rats (n = 17) after left ILP (20-minute perfusion at 0.5 mL/min) with 21 mg/mL (n = 11), 28 mg/mL (n = 2), 35 mg/mL (n = 2), and 70 mg/mL (n = 2) of FUDR. Animals were followed up and weights recorded for 14 days postoperatively before a right pneumonectomy was performed to evaluate the effect of FUDR perfusion on left lung function. In the second study, 32 rats (n = 8/group) underwent: systemic FUDR (intravenous), or ILP with 7, 14, and 21 mg/mL respectively (ILP 7, ILP 14, and ILP 21 groups). Left lungs and serum were analyzed for FUDR and 5-fluorouracil by high-performance liquid chromatography. RESULTS: Rats perfused with doses of FUDR greater than 21 mg/mL died perioperatively. All animals perfused at 21 mg/mL survived until day 14, and 8/11 survived a right pneumonectomy. Rats that survived ILP resumed normal weight gain and grooming habits within 1 week. Pharmacokinetic evaluation demonstrated that ILP at 21 mg/mL maximally elevated total lung FUDR and 5-fluorouracil levels (508.5 +/- 96.4 micrograms/g lung) in comparison with the ILP 14, ILP 7, and intravenous groups (299.1 +/- 44.8, 116.0 +/- 21.1, and 7.5 +/- 4.1 micrograms/g lung, respectively) (p < 0.05). Serum FUDR levels were 10.5 +/- 6.8, 1.3 +/- 0.5, 2.31 +/- 1.1, and 1.2 +/- 0.4 microgram/g lung (p = not significant) for intravenous, ILP 7, ILP 14, and ILP 21 groups, respectively. CONCLUSIONS: Isolated left lung perfusion with FUDR is well tolerated to a maximum dose of 21 mg/mL and results in significantly higher FUDR and 5-fluorouracil lung levels with low serum levels compared with intravenous treatment. These higher pulmonary levels may offer advantages in the treatment of pulmonary colorectal metastases.

Animals↗

PubMed1996

Does resection of adrenal metastases from non-small cell lung cancer improve survival?

BACKGROUND: Metastatic non-small cell lung cancer (NSCLC) carries a dismal prognosis, which is minimally affected by chemotherapy. Solitary brain metastases from NSCLC have been resected with 5-year survivals of 10% to 30%. The objective of this study was to determine if resection of isolated adrenal metastases improves survival. METHODS: Isolated adrenal metastases were found in 14 patients with NSCLC. Eight patients had resection after cis-platinum-based chemotherapy, and 6 received chemotherapy alone. RESULTS: Median survival in the surgical group was significantly greater than that in the chemotherapy group (31 versus 8.5 months; p = 0.03). All patients in the chemotherapy group were dead by 22 months. Three-year actuarial survival in the surgical group was 38%. No difference in locoregional stage, size of adrenal metastases, patient age, or performance status was present between the two groups. CONCLUSIONS: Long-term disease-free survival is possible after resection of isolated adrenal metastases from NSCLC. Resection of isolated adrenal metastases should be considered if the primary NSCLC is resectable.

Adrenal Gland Neoplasms↗

PubMed1996

Isolated lung perfusion with melphalan for the treatment of metastatic pulmonary sarcoma.

OBJECTIVE: Isolated lung perfusion allows the delivery of high-dose chemotherapy to the perfused lung and is an efficacious modality in the treatment of pulmonary metastases in the rat. Melphalan activity in this model was investigated. METHODS: TOXICITY STUDY: Maximum tolerated dose of melphalan delivered by means of isolated lung perfusion was determined by survival after contralateral pneumonectomy. PHARMACOKINETICS STUDY: Nineteen rats were treated with melphalan administered either by isolated lung perfusion (2 mg) or intravenously (2 mg or 1 mg). Lung, pulmonary effluent, and serum melphalan were analyzed by high-pressure liquid chromatography. EFFICACY STUDY: On day 0, 41 rats received an intravenous injection of 5 x 10(6) methylcholanthrene induced sarcoma cells. On day 7, rats either received intravenous melphalan (2 mg [n = 10]; 1 mg [n = 8]) or underwent left isolated lung perfusion with 2 mg of melphalan (n = 12). Isolated lung perfusion with buffered hetastarch in sodium chloride (Hespan, n = 11) was used as control. On day 14, pulmonary nodules were counted. RESULTS TOXICITY: Maximum tolerated dose of melphalan delivered buy means of isolated lung perfusion was 2 mg. PHARMACOKINETICS: Left lung melphalan level was significantly higher in the isolated lung perfusion group (62.2 +/- 34.3 microg/gm lung) than in the intravenous treatment groups (6.9 +/- 1.9 microg/gm lung and 3.3 +/- 0.9 microg/gm lung, respectively) (p = 0.0002). EFFICACY: Significantly fewer left lung nodules were found in animals receiving melphalan by means of isolated lung perfusion (7 +/- 10) than in the groups receiving intravenous melphalan (60 +/- 21) or buffered hetastarch by isolated lung perfusion (84 +/- 52) (p = 0.01 and p = 0.0001, respectively). CONCLUSION: Isolated lung perfusion with melphalan is safe and effective in the treatment of pulmonary sarcoma metastases in the rat.

Animals↗

PubMed1996

Predictors of survival in malignant tumors of the sternum.

From 1930 to 1994, 54 patients with primary malignant tumors of the sternum were seen. Fifty patients were first seen with a mass, and one half of them also had pain in the sternal region. Two patients had no symptoms at presentation. Among 39 solid tumors were 26 chondrosarcomas, 10 osteosarcomas, 1 fibrosarcoma, 1 angiosarcoma, and 1 malignant fibrous histiocytoma. Of these, 25 were low-grade and 14 were high-grade tumors. Among 15 small cell tumors were 8 plasmacytomas, 6 malignant lymphomas, and 1 Ewing's sarcoma. Partial or subtotal sternectomy was done in 37 patients and total sternectomy in 3. Of the remaining 14 patients, 3 had local excision; 10 had external radiation or chemotherapy without operation, or both; and 1 had no treatment. All but one patient treated by wide resection (N = 40) had some form of skeletal reconstruction of the chest wall defect. Thirty-one (78%) underwent repair with Marlex mesh, and in 25 this was combined with methyl methacrylate. The skin edges were closed per primum in 32 patients; 8 required muscle, omentum, or skin flaps. Resection in chondrosarcomas yielded a 5-year survival (Kaplan-Meier) of 80% (median follow-up, 17 years). The 5-year survival in osteosarcomas was 14%. Resection was curative in 64% of low-grade sarcomas but in only 7% of high-grade sarcomas. In small cell tumors, resection and radiation were helpful for local control; all failures were a result of distant metastases. We conclude that primary sarcomas of the sternum though uncommon are potentially curable by wide surgical excision. With rigid prostheses to repair the skeletal defects, the surgical complication rates are low. Overall survival after complete surgical resection is related to tumor histologic type and grade.

Bone Cements↗