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.

Glucose metabolism and the percentage of glucose derived from alanine: response to exogenous glucose infusion in tumor-bearing and non-tumor-bearing rats.

Glucose and alanine metabolism were investigated in non-tumor-bearing (NTB) and tumor-bearing (TB) male F344 rats after a 24-hr fast and during the infusion of either 0.9% NaCl solution or glucose at 0.67 or 2.35 mg per 100 g total body weight per min. During 0.9% NaCl solution infusion, the plasma glucose level was higher (98.2 +/- 4.0 versus 85.8 +/- 8.1 mg per di; p less than 0.05), the whole-blood lactate level was lower (5.8 +/- 0.8 versus 8.3 +/- 1.6 mg per di; p less than 0.05), the glucose turnover rate was lower (0.72 +/- 0.04 versus 0.88 +/- 0.13 mg per 100 g total body weight per min; p less than 0.05), alanine turnover rate and the percentage of glucose derived from alanine was measured by [14C]alanine in the NTB and compared to the TB animals. In response to glucose infusions, the whole-blood lactate level rose in both groups but remained lower (7.1 +/- 0.9 versus 10.5 +/- 2.4 mg per dl at 0.67 mg per 100 g total body weight per min, p less than 0.05; 9.1 +/- 1.1 versus 19.3 +/- 5.5 mg per dl at 2.35 mg per 100 g total body weight per min, p less than 0.05; NTB versus TB) in the NTB than in the TB animals. The endogenous production rate of glucose as measured by [3H]glucose displayed a similar response to exogenous substrate in the NTB and TB animals but required a higher plasma glucose concentration to effect a similar degree of suppression in the TB group. The alanine turnover rate rose to a similar level, and the percentage of glucose derived from alanine was similarly depressed in the NTB and TB animals at each glucose infusion rate.

Prospective evaluation of unilateral adrenal masses in patients with operable non-small-cell lung cancer.

Although adrenal metastases are frequently noted with non-small-cell lung cancer (NSCLC) at autopsy, their incidence in patients with operable NSCLC is unclear. We prospectively assessed consecutive patients with otherwise operable NSCLC for the incidence and histology of unilateral adrenal masses. Assessment included blood chemistries, lung function tests, bronchoscopy, chest x-ray, bone scan, and computed tomography (CT) of the head, chest, and upper abdomen. Of 246 patients with otherwise operable NSCLC, 10 (4.1%) had a unilateral adrenal mass. Unilateral adrenal masses were needle-aspirated under CT control. If cytology was nondiagnostic, adrenalectomy was performed. Four (40%) of 10 patients had adrenal metastases proven by needle aspiration. Of the six (60%) patients with benign unilateral adrenal masses, one was demonstrated by needle aspiration. In the other five patients, a nondiagnostic needle aspiration led to adrenalectomy, which yielded two adenomas, two hyperplastic nodules, and one hemorrhagic cyst. There was no significant difference between the patients with benign and metastatic unilateral adrenal masses with respect to patient age or stage and size of adrenal mass. Patients with benign unilateral adrenal masses underwent curative resection of their NSCLC and had significantly prolonged survival compared with patients with metastatic unilateral adrenal masses treated with chemotherapy (P = .037). Median survival of patients with benign and metastatic unilateral adrenal masses was greater than 30 months and 9 months, respectively. In conclusion, the presence of unilateral adrenal masses in patients with otherwise operable NSCLC should not preclude thoracotomy without pathologic proof of metastatic disease.

Resection of metastatic renal cell carcinoma.

PURPOSE: Resection of solitary metastases from renal cell carcinoma (RCC) is associated with a 5-year survival rate of 35% to 50%. Selection criteria are not well defined. PATIENTS AND METHODS: We retrospectively analyzed our experience with 278 patients with recurrent RCC from 1980 to 1993. RESULTS: One hundred forty-one of 278 patients underwent a curative metastectomy for their first recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent noncurative surgery (14% 5-year OS rate), and 67 patients were treated nonsurgically (11% 5-year OS rate). Favorable features for survival were a disease-free interval (DFI) greater than 12 months versus 12 months or less (55% v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5-year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n = 50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS rate; P < .05). Survival rates after curative resection of second and third metastases were not different compared with initial metastectomy (46% and 44%, respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of survival by multivariate analysis included a single site of first recurrence, curative resection of first metastasis, a long DFI, a solitary site of first metastasis, and a metachronous presentation with recurrence. CONCLUSION: Selected patients with recurrent RCC who can undergo a curative resection of their disease have a good opportunity for long-term survival, particularly those with a single site of recurrence and/or a long DFI.

Serum vitamin level maintenance in cancer patients on total parenteral nutrition.

The quantity of water and fat soluble vitamins required to maintain serum levels in cancer patients on total parenteral nutrition (TPN) has yet to be determined. A prospective evaluation of our current intravenous vitamin regimen during TPN was performed in order to define these requirements. Seventy-five patients receiving 97 TPN courses for seven to 60 days were studied. Serum levels of vitamins A (74 courses), B12 (85), folate (62), C (97), and 25-OH-cholecalciferol (25-OH-D) (9) were available for analysis. Daily vitamin intakes were recorded and serum levels were determined weekly. Restoration and maintenance of normal mean serum vitamin levels were achieved for all but 25-OH-D. However, analysis of individual courses in previously depleted patients revealed that serum levels were not restored in three patients (4%) for vitamin A and six patients (66%) for 25-OH-D. A TPN regimen designed to provide the following weekly vitamin quantities: A: 21,000 IU, D: 2100 IU, C: 3500 mg, B12: 126 micrograms, and folate: 7 mg will maintain mean serum vitamin levels for all but 25-OH-D. This regimen has the ability to uniformly restore and maintain vitamins B12, C, and folate in all patients but not in those patients previously deficient in vitamins A and D.

Cervicothoracic tumors: results of resection by the "hemi-clamshell" approach.

OBJECTIVES: Our goal was to describe the "hemi-clamshell" approach for the resection of primary and metastatic tumors of the cervicothoracic junction, evaluate its morbidity and mortality, and present survival data on a series of 42 patients who underwent resection with the use of this technique. METHODS: We conducted a retrospective review of the records of all patients of a single surgeon undergoing resection of tumors of the cervicothoracic junction. Data collected includes tumor type and involvement, type of resection, complications, and survival. RESULTS: Forty-two patients underwent resection of various primary (n = 28) and metastatic (n = 14) tumors of the cervicothoracic junction over 6.5 years by means of the hemi-clamshell approach. En bloc resection of the tumor and invaded structures was successful in all but two patients (5%), who required an additional posterolateral thoracotomy to facilitate removal of tumor invading the posterior chest wall. Invaded structures that were resected included lung (n = 22), vertebral body (n = 7), chest wall (n = 8), central veins (n = 10), thyroid (n = 3), carotid artery (n = 1), and cervical esophagus (n = 1). Four major complications occurred in three patients, and nine minor complications occurred in eight patients. There were no deaths. The overall 5-year actuarial survival was 67.4%. CONCLUSIONS: Tumors of the cervicothoracic junction are represented by a variety of histologic types and can be both primary and metastatic. The hemi-clamshell approach is a successful technique for the exposure and resection of these tumors. This approach has significant advantages over other previously reported techniques. The complication rate is low and the mortality rate is zero in this series, the largest yet reported. Long-term survival is acceptable if complete resection can be performed.

Pulmonary sequestration in the neonate.

Pulmonary sequestration is a congenital anomaly resulting in nonfunctioning lung tissue in either the "extralobar" or "intralobar" position. Both forms derive their blood supply from the systemic circulation. Large pulmonary sequestrations can present in the newborn with potentially fatal respiratory distress. Surgical resection is the treatment of choice.

Soft tissue sarcomas of the chest wall. Results of surgical resection.

UNLABELLED: Primary soft tissue sarcomas of the chest wall are uncommon, and data concerning treatment and results are sparse. Most studies have categorized these tumors as truncal sarcomas and inferred a poor prognosis. To assess the results of surgical treatment, we reviewed our 40-year experience. METHODS: Records of 189 patients admitted to our institution from 1948 to 1988 were reviewed. Pathologic material was available for review in the 149 cases (79%) that comprise this report. Survival was calculated by the Kaplan-Meier method, with comparisons by log-rank analysis and significance defined as p less than 0.05. RESULTS: Ages ranged from 3 weeks to 86 years (median, 38 years); the ratio of male to female patients was 2:1. The initial complaint was mass or pain in 97% of the cases. Ninety sarcomas (60%) were high grade and 59 (40%) were low grade. Histologic types were as follows: desmoid tumor (n = 32, 21%); liposarcoma (n = 23, 15%); rhabdomyosarcoma (n = 18, 12%); fibrosarcoma (n = 17, 11%); embryonal rhabdomyosarcoma (n = 14, 9%); malignant peripheral nerve tumor (n = 13, 9%); malignant fibrous histiocytoma (n = 11, 7%); spindle cell sarcoma (n = 4, 3%); tenosynovial sarcoma (n = 3, 3%); hemangiopericytoma (n = 3, 3%); alveolar soft part sarcoma (n = 3, 3%); and other types (n = 12, 9%). Resection was the primary treatment in 140 cases (94%). Local recurrence developed in 27%. Metastases occurred in 52 (35%) of the cases (metachronous in 42, synchronous in 10) and were more common in patients with high-grade disease (46/90, 51%) than in those with low-grade disease (6/59, 10%). Overall 5-year survival was 66%. Five-year survival rate for those with high-grade sarcomas (49%) was significantly lower than that for low-grade sarcomas (90%, p less than 0.0001). Tumor size and age of patient were not prognostic. CONCLUSIONS: Survival of patients with primary soft tissue sarcomas of the chest wall after resection is similar to that of patients with sarcomas of the extremities. Resection alone provides acceptable survival (90% at 5 years) for those with low-grade sarcomas, but adjuvant treatment should be considered for those with high-grade sarcomas.

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.

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.

Thymic carcinoma: current staging does not predict prognosis.

BACKGROUND: Thymic carcinomas are currently staged by Masaoka classification, a staging system for thymomas. We retrospectively evaluated surgical patients with thymic carcinoma to determine prognostic factors and to evaluate the usefulness of Masaoka staging in this disease. METHODS: Our computerized tumor registry yielded 118 patients with thymoma. Review of pathologic material revealed 43 cases of thymic carcinoma. Collection of data was by review of hospital and physician charts and telephone contact with patients. Analysis of prognostic factors was performed in patients undergoing complete resection by the method of Kaplan-Meier and Cox proportional hazards regression. RESULTS: Between 1949 and 1993, 43 patients underwent surgery for thymic carcinoma. Overall survival was 65% at 5 years and 35% at 10 years. Overall recurrence was 65% at 5 years and 75% at 10 years. On univariate analysis, survival was not dependent on age, sex, tumor size, or Masaoka stage but was dependent on innominate vessel invasion. By multivariate analysis, survival was dependent only on innominate vessel invasion. CONCLUSIONS: Patients with thymic carcinoma have a high rate of recurrence. Tumor invasion of the innominate vessels is associated with a particularly poor prognosis. Although Masaoka staging is useful in staging patients with thymoma, it does not appear to predict outcome for patients with thymic carcinoma.

Proposed revision of the staging classification for esophageal cancer.

OBJECTIVES: This study analyzed survival with respect to lymph node involvement to develop a new staging system for patients with esophageal cancer that accurately reflects prognosis. METHODS: The records of patients undergoing resection of primary esophageal cancer from 1989 to 1993 were reviewed. The data collected included patient age and sex, tumor histologic characteristics and location, the use of preoperative or postoperative radiation and chemotherapy, the type of resection, the depth of tumor invasion, the number and location of benign and malignant lymph nodes in the resected specimen, the disease status at last follow-up, and the first site of relapse. With an anatomically specific lymph node map, tumors designated in the current American Joint Committee on Cancer system as M1 because of extensive lymph node metastases were reclassified as N2, reserving the M1 category for visceral metastases. Survival was analyzed by the Kaplan-Meier method, and prognostic factors were assessed by log-rank and Cox regression analyses. RESULTS: There were 216 patients (159 men, 57 women) with a median age of 63.5 years. Adenocarcinoma of the distal esophagus or gastroesophageal junction was the most common tumor (127 patients, 59%) and Ivor Lewis esophagogastrectomy was the most frequently performed operation. Both lymph node location (N1 versus N2) and number (0 vs 1 to 3 vs 4 or more) significantly influenced survival. CONCLUSIONS: A new staging system that adds an N2 M0 descriptor and reclassifies stage groupings reflects prognosis more accurately than does the current American Joint Committee on Cancer staging system. The number of positive lymph nodes is also an important stratification factor.

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. 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.

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.

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.

Glucose turnover and gluconeogenesis in a patient with somatostatinoma.

Previous evidence has documented the hyperglycemia and glucose intolerance that occur during prolonged infusions of somatostatin and in patients with somatostatinoma. We studied glucose utilization and production and gluconeogenesis (from alanine) in a patient with the somatostatinoma syndrome (peripheral somatostatin levels 20,000 pg/ml) during saline (basal state) and glucose infusion (1.78 mg/kg . min). Plasma glucose levels increased from 163 to 229 mg/100 ml during glucose infusion, whereas lactate, free fatty acid, and glucagon levels did not change. Endogenous glucose production decreased from 7.34 to 0.0 mumol/kg . min, and the percentage of glucose derived from alanine also decreased from 10.5 to 7.4. Glucose clearance decreased from 0.81 to 0.74 cc/kg . min and suggests that the hyperglycemia of the somatostatinoma syndrome is secondary to reduced peripheral glucose utilization secondary to relative insulin deficiency.

The human tumor-bearing limb: an ex vivo model.

The present report describes a viable, isolated, perfused, human, tumor-bearing limb model suitable for the study of human host-tumor metabolism. The model is hemodynamically stable with high flow rates (50 cc/kg/min) and low perfusion pressures (mean, 77.2 mm Hg) which are stable over time. Metabolically, the preparation is viable with initial oxygen and glucose uptake 0.88 cc/kg/min and 0.029 mmole/kg/min, respectively. These parameters and lactate concentrations do not change significantly with time.

Incidence of hypercalcemia and malignant neoplasm.

Hypercalcemia often complicates the course of patients with malignant neoplasms. Since this metabolic derangement is potentially lethal, knowledge of the expected relative incidence of hypercalcemia in various malignant neoplasms is of importance. The incidence of hypercalcemia and malignant neoplasm at the Clinical Center, National Institutes of Health, Bethesda, Md, was reviewed. Of 17,706 admissions (multiple admissions counted once), the overall incidence of hypercalcemia for all disorders was 5.0%; of these, 38.0% (338 patients) had associated neoplasms (99.4% malignant). Primary hyperparathyroidism represented 19.6% of those admitted with hypercalcemia, and nonneoplastic disorders represented 10.7%. Of the 338 patients with hypercalcemia associated with neoplasia, 44.1% had hematologic and 41.4% had solid neoplasms. The relative incidences of hypercalcemia and neoplasia are reported for each of the solid and hematologic neoplasias evaluated.

Local recurrent mammary carcinoma failing multimodality therapy. A solution.

Chest wall recurrence following radiation and hormonal therapy is an uncommon but serious and disabling condition. A chest wall ulcer secondary to treatment for recurrence also presents the same dilemma. Over the past 35 years, the Thoracic Service at our institution has treated 35 patients for these problems by surgical resection and reconstruction. Eight patients were seen after the first recurrence, six after the second, ten after the third, and ten after the fourth. One patient had chest wall resection with mastectomy when recurrence followed radiation therapy. Following resection of the tumor, 21 patients had reconstruction using mesh or a mesh "sandwich." There were no operative deaths and no respirator need. Twenty patients are alive from five to 120 months, with a median of 50 months. One of 35 patients had chest wall recurrence. Surgical resection of recurrent mammary carcinoma resistant to all other therapy is a viable alternative for both palliation and cure.

Lung resection for colorectal metastases. 10-year results.

BACKGROUND: Metastasectomy for colorectal carcinoma to the lung is controversial. We analyzed results of this approach to justify its credibility. METHODS: We studied 144 patients by retrospective review after complete resection of lung metastases from colorectal cancer from 1965 through 1988. Patient selection and prognostic factors influencing survival were analyzed. Survival was analyzed by the Kaplan-Meier method, and comparisons were made by log-rank analysis. RESULTS: A total of 170 thoracotomies were performed in 144 patients. The overall 5- and 10-year survival was 40% and 30%, respectively. Those patients undergoing complete resection of their metastases survived significantly longer than those undergoing incomplete resections. CONCLUSION: It appears that resection of pulmonary metastases from colorectal carcinoma translates into long-term survival benefit.