Biomedical subjects

M E Burt

Publications and source records attributed to M E Burt.

At least 55 records · Page 3Linked to original sources

PubMed1996

Vocal cord medialization for unilateral paralysis associated with intrathoracic malignancies.

Patients with unilateral vocal cord paralysis from intrathoracic malignancies may have significant dysfunctions of speech, swallowing, ventilation, and effective coughing as a result of inadequate compensation of the nonparalyzed cord. In patients with already compromised pulmonary function, aspiration can be a life-threatening event. Sixty-three patients with intrathoracic malignancies required surgical correction of vocal cord paralysis. Primary pathology included lung cancer (49), esophageal cancer (nine), and miscellaneous tumors (five). Symptoms included hoarseness (62), dyspnea (21), aspiration (26), weight loss (19), dysphagia (14), and pneumonia (14). The surgical procedures included medial displacement of the vocal cord with silicone elastomer (48), temporary Gelfoam injection (seven), and Teflon (polytetrafluoroethylene) injection (eight) to move the affected cord to a medial position. In 11 patients, the operation was performed in the acute postoperative setting to improve pulmonary toilet. Symptomatic improvement was noted in the following proportions of affected patients: hoarseness, 92%; dyspnea, 90%; dysphagia, 93%; aspiration, 92%; pneumonia, 93%; and weight loss, 47%. Overall success rate of the intervention was 57 of 63 patients (90%). All 11 patients treated in the acute setting had immediate improvement. A variety of complications occurred in 17% of patients. Surgical management of vocal cord paralysis in patients with intrathoracic malignancies prevents life-threatening pulmonary complications in the acute postoperative setting. In chronic situations, it provides patients with improved speech, swallowing, and pulmonary function, resulting in improved quality of life, even for patients not cured of their disease.

Adult↗

PubMed1995

Isolated lung perfusion with FUDR is an effective treatment for colorectal adenocarcinoma lung metastases in rats.

Currently, the only treatment capable of significantly prolonging survival in patients with isolated pulmonary metastases from colorectal adenocarcinoma is complete resection. Systemic chemotherapy has been shown to provide little benefit. We evaluated the efficacy of highdose, organ-specific 2'-deoxy-5-fluorouridine (FUDR) using a model of isolated single-lung perfusion (ILP) in the rat. On day 0, 28 BDIX rats were inoculated intravenously with 10(6) viable Sp-5 colorectal adenocarcinoma cells. On day 10 after-tumor inoculation, animals were randomized into five treatment groups. Group I received a continuous intravenous infusion of FUDR (1 mg.kg-1.d-1) for 7 days administered by an osmotic minipump. Group II underwent isolated left lung perfusion with a buffered Hespan solution, groups III to V underwent ILP with 3.5, 7, and 14 mg of FUDR per milliliter of the buffered Hespan solution, respectively. Animals undergoing ILP were anesthetized with pentobarbital, intubated, and ventilated, and then underwent left thoracotomy with cannulation of the pulmonary artery; the pulmonary artery and vein were clamped proximally. Groups II to V were perfused for 20 minutes at a rate of 1 mL/min, followed by a 5-minute washout with FUDR-free buffered Hespan solution. On day 26 after tumor inoculation, the animals in all groups were sacrificed and their lungs were stained and counted. Animals that underwent ILP with 14 mg of FUDR per milliliter of the buffered Hespan solution showed a significant decrease in the number of tumor nodules on the treated side versus the number on the untreated side (455.2 +/- 87.3 versus 11 +/- 6.4; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1995

Buthionine sulfoximine pretreatment potentiates the effect of isolated lung perfusion with doxorubicin.

BACKGROUND: Although surgical resection remains the mainstay of treatment for metastatic pulmonary sarcoma, 5-year survival approaches only 25%. Chemotherapy has been limited by tumor resistance and systemic toxicity. We assessed the efficacy of L-buthionine-SR-sulfoximine, an inhibitor of glutathione synthesis, as a sensitizer for isolated lung perfusion. METHODS: In experiment 1, sarcoma-bearing rats (n = 20) received either buthionine sulfoximine via intraperitoneal injection or Hespan. After the last injection, tumor glutathione levels were measured. In experiment 2, rats (n = 60) were injected with sarcoma intravenously. On day 6, animals were pretreated with either buthionine sulfoximine or Hespan intraperitoneally. On day 7, rats underwent isolated lung perfusion (Hespan or doxorubicin) or intravenous therapy (Hespan or doxorubicin). On day 14, tumor nodules were counted. RESULTS: Buthionine sulfoximine effectively depleted tumor glutathione. Animals treated with intravenous therapy had no response to therapy, whereas those animals treated with doxorubicin isolated lung perfusion alone had a limited response. Buthionine-sulfoximine pretreatment in combination with doxorubicin isolated lung perfusion led to a 13-fold reduction in tumor nodules and 5 complete responses. CONCLUSIONS: Buthionine-sulfoximine pretreatment in combination with doxorubicin isolated lung perfusion is superior to intravenous doxorubicin and doxorubicin isolated lung perfusion alone for the treatment of metastatic pulmonary sarcoma.

Animals↗

PubMed1995

Isolated single-lung perfusion: a study of the optimal perfusate and other pharmacokinetic factors.

BACKGROUND: Isolated single-lung perfusion with doxorubicin hydrochloride was shown to be effective in clearing experimental sarcoma lung metastases in the rat. The best perfusate to be used for isolated lung perfusion and factors affecting the final lung concentration of doxorubicin are the subject of the present study. METHODS: In experiment 1, 60 animals were randomized to undergo isolated left lung perfusion with doxorubicin with six different perfusates (n = 10 per group): saline, low-potassium-dextran, 5% albumin, 6% hetastarch, 5% buffered albumin, and 6% buffered hetastarch. Five animals served as negative controls. After perfusion, the lung wet to dry ratio and final lung doxorubicin concentration were determined. In experiment 2, 60 animals underwent isolated left lung perfusion with either 80 micrograms/mL or 320 micrograms/mL of doxorubicin. Animals were perfused at either 0.5 mL/min or 1 mL/min and for 2, 6, or 10 minutes. At the end of the perfusion period, the left lung doxorubicin concentration was measured. Statistical analysis included analysis of variance, the Duncan test for multiple comparisons, and multiple linear regression analysis. Significance was defined as a p value of less than 0.05. RESULTS: In experiment 1, perfusion with 6% buffered hetastarch resulted in the lowest lung wet to dry ratio, significantly different from all groups except the controls. Perfusion with low-potassium-dextran solution led to the highest final lung concentration of doxorubicin. In experiment 2, a model to predict final lung doxorubicin concentration was constructed: Log (final lung concentration) = 1.9 + 0.0071.P + 0.186.T, where P is the measured perfusate concentration of doxorubicin, and T is the time of perfusion in minutes. The R2 was 0.91 and p, less than 0.001. The dose of doxorubicin per kilogram of animal body weight, the dose of doxorubicin per square meter of body surface area, the total amount of doxorubicin delivered, and the rate of perfusion did not meet the criteria to enter the equation. CONCLUSIONS: Isolated lung perfusion experiments should use 6% buffered hetastarch as the perfusate. The perfusate doxorubicin concentration and the duration of perfusion are the only factors determining the final lung concentration of doxorubicin. In lung perfusion experiments, the dose of chemotherapy is not as important as the perfusate concentration and the duration of the perfusion. Animals should be perfused at a lower rate so the lungs are exposed to less doxorubicin without changing the final lung concentration.

Albumins↗

PubMed1995

Successful treatment of solitary extracranial metastases from non-small cell lung cancer.

BACKGROUND: Recurrence after resection of non-small cell lung carcinoma is generally associated with a poor outcome and is treated with either systemic agents or palliative irradiation. Recently, long-term survival has been reported after resection of isolated brain metastases from non-small cell lung carcinoma, but resection of other metastatic sites has not been explored fully. METHODS: We have identified 14 patients who had solitary extracranial metastases treated aggressively after curative treatment of their non-small cell lung carcinoma. The histology was squamous carcinoma in 5, adenocarcinoma in 8, and large cell carcinoma in 1. Initially, 3 patients had stage I, 5 stage II, and 6 stage IIIa disease. RESULTS: The sites of metastases included extrathoracic lymph nodes (six), skeletal muscle (four), bone (three), and small bowel (one). The median disease-free interval before metastases was 19.5 months (range, 5 to 71 months). Complete surgical resection of the metastatic site was the treatment in 12 of 14 patients. Two patients received only curative irradiation to the metastatic site, with complete response. The overall 10-year actuarial survival (Kaplan-Meier) was 86%. To date, 11 patients are alive and well after treatment of their metastases (17 months to 13 years), 1 has recurrent disease, 1 died of recurrent widespread metastases, and 2 died of unrelated causes. CONCLUSION: Long-term survival is possible after treatment of isolated metastases to various sites from non-small cell lung carcinoma, but patient selection is critical.

Actuarial Analysis↗

PubMed1995

Pulmonary artery perfusion of doxorubicin with blood flow occlusion: pharmacokinetics and treatment in a metastatic sarcoma model.

BACKGROUND: We compared pharmacokinetics, toxicity, and treatment efficacy of pulmonary artery perfusion of low-dose doxorubicin with blood flow occlusion to intravenous doxorubicin injection in a metastatic sarcoma model in the rat. METHODS: Animals received left pulmonary artery perfusion with 0.1, 0.2, or 0.5 mg/kg doxorubicin at a rate of 0.1 mL/min for 1 minute with 20 minutes of blood flow occlusion. Doxorubicin levels of the lung, heart, and serum were assayed. Body weights after treatment were recorded and right pneumonectomy was performed. The results were compared with those in rats that received 5 mg/kg doxorubicin by intravenous injection or the saline group. Pulmonary sarcoma metastases were treated with 0.5 mg/kg doxorubicin through lung perfusion or intravenously, or with saline solution. RESULTS: Doxorubicin levels in the lung, heart, and serum were 112.1 +/- 9.2 micrograms/g, 1.7 +/- 0.2 microgram/g, and 0.3 +/- 0.1 microgram/mL in the group with 0.5 mg/kg doxorubicin perfusion, versus 24.8 +/- 1.9 microgram/g, 10.1 +/- 1.3 microgram/g, and 0.7 +/- 0.2 microgram/mL in the intravenous group (p < 0.05). Animals had normal growth patterns and survived after right pneumonectomy in the perfused group, whereas the intravenous group failed to thrive. No tumors were found or a significant reduction in nodules was noted in the lungs treated with perfusion as compared with untreated right lungs or the intravenous and saline groups. CONCLUSION: This chemotherapy model has important pharmacokinetic advantages and causes an increased treatment response for pulmonary metastatic sarcoma with minimal systemic and local toxicity as compared with systemic doxorubicin administration.

Animals↗

PubMed1995

Incidence of local recurrence and second primary tumors in resected stage I lung cancer.

From 1973 to 1985, 598 patients underwent resection for stage I non-small-cell lung cancer. There were 291 T1 lesions and 307 T2 lesions. The male/female ratio was 1.9:1. The histologic type was squamous carcinoma in 233 and nonsquamous carcinoma in 365. Lobectomy was performed in 511 patients (85%), pneumonectomy in 25 (4%), and wedge resection or segmentectomy in 62 (11%). A mediastinal lymph node dissection was carried out in 560 patients (94%) and no lymph node dissection in 38 (6%). Fourteen postoperative deaths occurred (2.3%). Ninety-nine percent of the patients were observed for a minimum of 5 years or until death with an overall median follow-up of 91 months. The overall 5- and 10-year survivals (Kaplan-Meier) were 75% and 67%, respectively. Survival in patients with T1 N0 tumors was 82% at 5 years and 74% at 10 years compared with 68% at 5 years and 60% at 10 years for patients with T2 tumors (p < 0.0004). The overall incidence of recurrence was 27% (local or regional 7%, systemic 20%) and was not influenced by histologic type. Second primary cancers developed in 206 patients (34%). Of these, 70 (34%) were second primary lung cancers. Despite complete resection, 31 of 62 patients (50%) who had wedge resection or segmentectomy had recurrence. Five- and 10-year survivals after wedge resection or segmentectomy were 59% and 35%, respectively, significantly less than survivals of those undergoing lobectomy (5 years, 77%; 10 years, 70%). The 5- and 10-year survivals in the 38 patients who had no lymph node dissection were reduced to 59% and 32%, respectively. Apart from the favorable prognosis observed in this group of patients, three facts emerge as significant: (1) Systematic lymph node dissection is necessary to ensure that the disease is accurately staged; (2) lesser resections (wedge/segment) result in high recurrence rates and reduced survival regardless of histologic type; and (3) second primary lung cancers are prevalent in long-term survivors.

Adenocarcinoma↗

PubMed1995

Revised technique of isolated lung perfusion in the rat.

Isolated lung perfusion in the rat is a useful research tool. Pulmonary arteriotomy and venotomy repair is required for animal survival. Rat pulmonary vessels are fragile, thin, and small in caliber, making their repair the focal technical point. This technique has been improved. The arteriotomy now is closed with a single suture and the venotomy no longer requires repair. The lung is returned to its original anatomic position then compressed to stop bleeding. These improvements have improved animal morbidity and mortality markedly while reducing operating time.

Animals↗

PubMed1994

Contribution of videothoracoscopy to the management of the cancer patient.

BACKGROUND: Videothoracoscopy has rapidly become a popular procedure, but its technical feasibility has been emphasized without critically evaluating its role in the management of thoracic disease. To assess the value of videothoracoscopy in the diagnosis and staging of the cancer patient and to determine if it has added to our previous standard approach of thoracoscopy performed with a mediastinoscope without video, we established a prospective database when we initiated videothoracoscopy in January 1992. METHODS: Patients were offered videothoracoscopy as an alternative to thoracotomy only if other standard approaches (e.g., needle biopsy, mediastinoscopy) were inadequate to diagnose or stage cancer or to restage patients after therapy. Parameters entered and analyzed in a prospective database were patient name; age; sex; past history; indications for videothoracoscopy; procedure type; surgical technique; whether conversion to thoracotomy was necessary, and if so, why; complications; and pathology. A complete case list of thoracoscopies performed in 1991 before videothoracoscopy was available provided historical comparison. RESULTS: From January 1 to December 31, 1991, 82 patients underwent thoracoscopy using a mediastinoscope for diagnosis and therapy of pleural disease. From January 1 to July 31, 1992, 160 patients (male:female = 81:79; mean age 56 years) had videothoracoscopy; 72 of 160 patients (44%) had procedures that previously would have required thoracotomy: 69 lung wedge resections, one pericardial window, one pleurectomy, one mediastinal node sampling. No major resectional procedures (e.g., lobectomy, esophagectomy) were performed by videothoracoscopy. Twenty-two percent of all patients (35 of 160), and 23% of wedge resection patients (16 of 69) required conversion to thoracotomy because videothoracoscopy was inadequate for diagnosis or staging. Reasons for conversion (multiple reasons in five patients) included further resection required in 23 patients; inability to evaluate lesion in 11; adhesions in five; and inability to tolerate one lung ventilation in two. The chest tube was in place postoperatively for a mean of 2.3 days. Thirty-day postoperative complications included ventilation for > 48 h in one patient; prolonged air leak in one; pneumonia in one; arrhythmia in one; and death from progressive disease in two. CONCLUSIONS: Although the role of videothoracoscopy in the treatment of primary thoracic malignancies and pulmonary metastases is still undefined, this early experience indicates that videothoracoscopy often enhances the ability to diagnose and stage patients by obviating thoracotomy.

Adult↗

PubMed1994

Influence of surgical resection and brachytherapy in the management of superior sulcus tumor.

We analyzed the results of surgical treatment of all patients presenting with untreated superior sulcus tumors between 1974 to 1991 inclusive at our institution. Most patients received preoperative radiotherapy. We attempted to analyze the influence of surgical resection and intraoperative brachytherapy in obtaining locoregional control and disease-free survival. One hundred twenty-four patients underwent thoracotomy and 100 patients underwent resection. The overall 5-year survival rate was 26% for all patients and 30% for resected patients. Those patients receiving a complete resection achieved a 41% 5-year survival. The best single group were those patients undergoing a lobectomy (versus wedge resection) and en-bloc chest wall resection (60% 5-year survival). We were unable to demonstrate an advantage for the use of intraoperative brachytherapy in those patients with complete resection. For those patients with incomplete resection, the use of brachytherapy combined with preoperative or postoperative external radiation therapy resulted in a 9% 5-year survival. Locoregional failure was significant both in patients with complete resection and in patients with incomplete resection. Adverse prognostic factors included Horner's syndrome, N2 and N3 disease, T4 disease, and incomplete resections. In superior sulcus tumors, every attempt to completely resect the tumor by en-bloc chest wall resection combined with lobectomy and adequate nodal staging remains the surgical treatment of choice together with either preoperative, postoperative, or "sandwich" external radiation therapy.

Adult↗

PubMed1994

The clamshell incision: an improved approach to bilateral pulmonary and mediastinal tumor.

Median sternotomy has been the accepted approach for dealing with mediastinal tumors or bilateral pulmonary disease, but exposure to the lower lobes and to mediastinal tumors extensively involving a hemithorax is often limited. Based on the reported experience from double-lung transplantation, we explored the use of clamshell incisions for these difficult problems. From March 1991 to December 1993, we prospectively studied the utility of clamshell incisions in 90 patients for the following indications: bilateral pulmonary metastases (62 patients), primary lung carcinoma with mediastinal involvement (13 patients), primary tumors of the mediastinum (14 patients), and mesothelioma (1 patient). Bilateral anterior thoracotomies with a transverse sternotomy (clamshell incision) were employed in 71 patients and a unilateral anterior thoracotomy with partial or complete median sternotomy (hemiclamshell incision) was used in 19 patients. For closure, we used pericostal sutures and sternal wires, usually augmented by sternal K-wire stents or Steinmann pins to prevent sternal override. Exposure to all areas of the mediastinum, pericardium, pleura, and lung was excellent. Specifically, the clamshell incision afforded markedly better access to lower lobe disease and hemithoracic extension of mediastinal disease than that possible with median sternotomy. There were no deaths or significant morbidity, and all patients tolerated the incisions well without mechanical respiratory difficulties. There was one wound infection. There was no late sternal override and the cosmetic results were found to be excellent during a follow-up of 2 to 33 months. We conclude that clamshell incisions constitute an improved surgical approach for the management of bilateral pulmonary or combined pulmonary and mediastinal disease.

Bone Nails↗

PubMed1994

Limbic encephalitis secondary to malignant thymoma.

A 56-year-old woman presented with memory loss and an enlarging mediastinal mass on chest roentgenogram. Physical findings were normal except for an altered mental status examination consistent with dementia. Further radiologic assessment was nondiagnostic. Surgical resection of a malignant thymoma resulted in clinical improvement. Treatment for limbic encephalitis should be directed at the underlying disease, and symptoms may improve if the tumor is eradicated.

Dementia↗

PubMed1994

Chest wall neoplasms and their management.

Although uncommon, primary and metastatic neoplasms can occur in the chest wall. For malignant neoplasms, the potential for cure depends on the completeness of resection, histologic type, and tumor stage. Each patient warrants individual evaluation for chest wall resection. Operative selection is based on the potential benefits, operative feasibility, patient health, and anticipated tumor biology. The choice of reconstruction techniques is based on the tumor's location, the size of the remaining defect, and the availability of autogenous graft materials. Skeletal and soft tissue reconstruction can be performed safely in a single stage.

Humans↗

PubMed1994

Management of non-small cell lung cancer with direct mediastinal involvement.

The results of surgical treatment were analyzed for 102 patients with non-small cell lung cancer invading the mediastinum by direct extension (T3 and T4), but those who had N2 disease were excluded to eliminate the adverse prognostic effect of this nodal subset. The histologic type was squamous cell carcinoma in 55 patients, adenocarcinoma in 40, and large cell carcinoma in 7. There were 58 T3 tumors invading the mediastinal pleura or fat, phrenic nerve, vagus nerve, pericardium, or pulmonary vessels and 44 T4 lesions invading the aorta, vena cava, esophagus, trachea, spine, or atrium. Resection included lobectomy (33 patients), pneumonectomy (32 patients), and limited resection (6 patients). Complete resection was possible in 46 patients and incomplete or no resection was possible in 56. The interstitial implantation of radioactive sources to control residual tumor also was undertaken in 43 patients. The operative mortality was 6%. The overall survival (Kaplan-Meier) was 19% at 5 years (median survival time, 18 months). Factors found to be significantly affect survival were complete resectability and the histologic type. With complete resection, the 5-year survival was 30% (p = 0.005). The 5-year survival in patients with adenocarcinoma or large-cell carcinoma was 30%, compared with 14% in patients with squamous cell carcinoma (p = 0.002). The extent of mediastinal involvement (T3 versus T4) influenced resectability and survival, and this approached statistical significance (p = 0.055). We conclude that most patients with non-small cell carcinoma and mediastinal invasion do poorly with primary surgical treatment.

Adult↗

PubMed1994

Isolated single-lung perfusion with TNF-alpha in a rat sarcoma lung metastases model.

We conducted a trial of isolated lung perfusion using tumor necrosis factor (TNF) in an experimental sarcoma lung metastasis model. In an in vitro experiment, methylcholanthrene-induced sarcoma cells were incubated for 48 hours with 42 micrograms/mL of either human or murine TNF. Controls were incubated with Hank's balanced salt solution. In an in vivo experiment, 23 F344 rats were injected with 10(7) methylcholanthrene-induced sarcoma cells. On day 7, 4 animals were perfused with 210 micrograms of murine TNF, 5 animals were perfused with 420 micrograms of murine TNF, 10 animals underwent isolated lung perfusion with 420 micrograms of human TNF, and 4 animals were injected systemically with 420 micrograms of human TNF. Animals were sacrificed on day 14 and the lung nodules counted. The cells incubated with murine TNF exhibited a 21% decrease in growth (p = 0.07); cells incubated with human TNF showed a 37% decrease in growth (p < 0.05). Animals perfused with 210 micrograms/mL of murine TNF and animals treated by systemically administered human TNF showed no tumor response. Animals perfused with 420 micrograms/mL of murine TNF had 7.8 +/- 14.2 nodules on the left lung and 58.5 +/- 66.0 nodules on the right lung (p = 0.07). Animals perfused with 420 micrograms/mL of human TNF had 21.7 +/- 18.3 nodules on the left lung and 91.7 +/- 66.2 nodules on the right lung (p < 0.01). On the basis of these findings, we conclude that isolated lung perfusion with TNF can be done safely in the rat and is effective in decreasing the growth of sarcoma lung metastases.

Animals↗

PubMed1994

Treatment and prognosis in bronchial carcinoids involving regional lymph nodes.

From 1953 to 1992, 25 patients were surgically treated for bronchial carcinoids with metastases to regional lymph nodes (N1 or N2). The tumors were located centrally, involving main or lobar bronchi in 12 patients and were peripheral in 13. Histologically, 12 of the carcinoids were classified as typical and 13 as atypical (neuroendocrine carcinoma). Pneumonectomy was performed in 11 patients, sleeve lobectomy in one, lobectomy in seven and bilobectomy in six. A formal mediastinal lymph node dissection was done in 20 patients. At final staging, 10 had N1 disease and 15 had N2. No adjuvant treatment was given to the 10 patients with N1 disease. External radiation therapy was given after the operation to 9 of 15 patients with N2 disease. The overall 5-year survival (Kaplan-Meier) was 75% (median 62 months). No difference in survival was found between patients with N1 or N2 disease. However, survival and recurrence rate differed between typical and atypical carcinoids. In typical carcinoids, the 5-year survival was 92% and, in atypical carcinoids, it was 60% (p = 0.02). We conclude that complete resection for bronchial carcinoids results in long-term survival despite the presence of regional lymph node metastases. Recurrence appears to depend more on cell type than nodal status. Postoperative radiation therapy does not appear to be beneficial.

Adolescent↗

PubMed1993

Thoracotomy in the management of gestational choriocarcinoma. A clinicopathologic study.

BACKGROUND: Pulmonary metastases occur frequently in patients with gestational choriocarcinoma and most of these patients achieve remission with chemotherapy alone. Thus, the indications for surgical intervention are limited, but in appropriately selected patients, resection of a chemotherapy-resistant lung lesion can be curative. METHODS: Nine patients with choriocarcinoma metastatic to the lung underwent 11 thoracotomies. The procedure was done in two patients for diagnosis and in seven to remove a resistant focus of tumor in the lung. The excised resistant tumors in six patients were studied histopathologically, immunohistochemically, and by electron microscopic examination (one patient). RESULTS: Six (66.6%) patients achieved complete remission for periods ranging from 3 months to 18 years, and three patients died of their disease. The residual lung nodules in these patients with chemotherapy-resistant tumors were characterized by the presence of large mononucleated tumor cells that showed features intermediate between those of cytotrophoblasts and syncytiotrophoblasts but lacking ultrastructural and immunohistochemical features of the intermediate trophoblasts seen in placental site tumors. CONCLUSION: A major role for operative treatment of chemotherapy-resistant choriocarcinoma in the lung is suggested by the observation that some of the resistant tumors contain a unique variant of trophoblastic cells that show a decreased sensitivity to chemotherapy but are amenable to surgical resection.

Adult↗

PubMed1993

Tolbutamide inhibits gluconeogenesis in the tumor-influenced hepatocyte.

The tumor-bearing state is associated with an increase in gluconeogenesis which may contribute to the development of cancer cachexia. The purpose of this study was to determine if tolbutamide, a drug known to decrease gluconeogenesis in diabetes, could decrease gluconeogenesis in hepatocytes isolated from tumor-bearing rats. Hepatocytes from 24-hr fasted normal and methylcholanthrene-induced sarcoma-bearing rats (5-10% tumor burden) were isolated by in situ collagenase liver perfusion. Hepatocytes (n = 12 samples) from non-tumor-bearing (NTB) controls and tumor-bearing (TB) rats were incubated with lactate (10 mM) and alanine (10 mM) with and without 1 mM tolbutamide. Supernatant glucose concentration was measured at 30-min intervals for 2 hr. Rates of gluconeogenesis (+/- standard error) were calculated by linear regression and are expressed as nmole glucose/10(6) cells/min. Comparisons were made by two-way analysis of variance and significance defined as P < 0.05. TB hepatocytes had an increased rate of gluconeogenesis (P < 0.0001) from alanine and lactate (3.8 +/- 0.30 and 2.2 +/- 0.10, respectively) compared with NTB hepatocytes (0.66 +/- 0.10 and 1.2 +/- 0.04, respectively). TB hepatocytes treated with tolbutamide had a decreased (P < 0.0001) rate of gluconeogenesis from alanine and lactate (3.1 +/- 0.10 and 1.1 +/- 0.10, respectively) compared with untreated TB hepatocytes (5.3 +/- 0.10 and 2.1 +/- 0.10, respectively). Tolbutamide inhibits gluconeogenesis from lactate and alanine in tumor-influenced hepatocytes.

Alanine↗