Toxicity and pharmacokinetics of isolated lung perfusion with cisplatin in rat.

OBJECTIVE: This study was designed to evaluate the toxicity and the pharmacokinetics of cisplatin administered via isolated lung perfusion in Fischer 344 rat. METHODS: Toxicity study; Cisplatin dosages of 3.3, 5.0, 6.7, and 10.0 mg/kg were injected intravenously in four groups, respectively. Cisplatin dosages of 3.3, 5.0, and 6.7 mg/kg were perfused via isolated lung perfusion in a further three groups, respectively. The maximum tolerated dosage of cisplatin was determined by assessing the survival rate on day 21. Pharmacokinetics study; Animals received 6.7 mg/kg of cisplatin intravenously or 3.3 mg/kg of cisplatin via isolated lung perfusion. The cisplatin levels of the lung were measured by flameless atomic spectrometry. RESULTS: Toxicity study; The maximum tolerated dosage of cisplatin via intravenous injection was 6.7 mg/kg, and via isolated lung perfusion was 3.3 mg/kg. Pharmacokinetics study; The cisplatin level in the perfused lung was significantly higher than that in the lung of the animal treated intravenously (16.6 +/- 6.2 micrograms/g of tissue and 7.5 +/- 3.2 micrograms/g of tissue, respectively) (p = 0.0096). CONCLUSION: Isolated lung perfusion with 3.3 mg/kg of cisplatin was pharmacokinetically superior to the maximum tolerated intravenous injection of cisplatin.

Isolated lung perfusion for patients with unresectable metastases from sarcoma: a phase I trial.

BACKGROUND: In patients with unresectable pulmonary metastases from sarcoma, systemic chemotherapy has had limited efficacy possibly because of dose-limiting toxicities. Isolated lung perfusion is an alternative method of delivering high-dose chemotherapy to the lungs while minimizing systemic toxicities. We present the results of our Phase I trial of isolated lung perfusion with doxorubicin hydrochloride in such a group of patients. METHODS: From May 1995 to June 1997, 8 patients with unresectable metastases from sarcoma limited to the lungs underwent isolated lung perfusion with doxorubicin. A dose-escalation schedule starting at 40 mg/m2 was used. Seven patients were treated with a dose of 40 mg/m2 or less, and 1 patient received 80 mg/m2. Blood, tumor, and normal lung samples were obtained at various time points during the operation. Patients were evaluated for cardiac, pulmonary, and other toxicities. RESULTS: The doxorubicin concentrations in both normal lung and tumor correlated directly with the amount of doxorubicin in the perfusate. The tumors took up less doxorubicin than the lung. All patients had minimal or undetectable systemic levels of doxorubicin at the conclusion of the perfusion. There were no cardiac or other systemic toxicities. In the 7 patients perfused with 40 mg/m2 or less of doxorubicin, there was a significant decrease in the forced expiratory volume in 1 second and a trend toward a significant decrease in diffusing capacity. The patient who received 80 mg/m2 underwent lung scanning postoperatively, and scans showed no ventilation or perfusion in the perfused lung. There were no perioperative deaths. Two patients are alive with disease, and 6 patients died of disease. The median follow-up is 11 months and the longest, 31 months. There were no partial or complete responses. One patient had stabilization of disease in the perfused lung, whereas the lesions in the untreated lung progressed markedly. CONCLUSION: Isolated lung perfusion is well tolerated by patients and effectively delivers high doses of doxorubicin to the lung and tumor tissues while minimizing systemic toxicities. A single dose of 80 mg/m2 resulted in substantial injury to the lung. There were no partial or complete responses in patients perfused with doxorubicin at the maximum tolerated dose of 40 mg/m2. Isolated lung perfusion remains a model for testing new and innovative therapies for metastatic sarcoma.

Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival.

OBJECTIVE: To report the patterns of disease and postmetastasis survival for patients with pulmonary metastases from soft tissue sarcoma in a large group of patients treated at a single institution. Clinical factors that influence postmetastasis survival are analyzed. SUMMARY BACKGROUND DATA: For patients with soft tissue sarcoma, the lungs are the most common site of metastatic disease. Although pulmonary metastases most commonly arise from primary tumors in the extremities, they may arise from almost any primary site or histology. To date, resection of disease has been the only effective therapy for metastatic sarcoma. METHODS: From July 1982 to February 1997, 3149 adult patients with soft tissue sarcoma were admitted and treated at Memorial Sloan-Kettering Cancer Center. During this interval, 719 patients either developed or presented with lung metastases. Patients were treated with resection of metastatic disease whenever possible. Disease-specific survival was the endpoint of the study. Time to death was modeled using the method of Kaplan and Meier. The association of factors to time-to-event endpoints was analyzed using the log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. RESULTS: The overall median survival from diagnosis of pulmonary metastasis for all patients was 15 months. The 3-year actuarial survival rate was 25%. The ability to resect all metastatic disease completely was the most important prognostic factor for survival. Patients treated with complete resection had a median survival of 33 months and a 3-year actuarial survival rate of 46%. For patients treated with nonoperative therapy, the median survival was 11 months. A disease-free interval of more than 12 months before the development of metastases was also a favorable prognostic factor. Unfavorable factors included the histologic variants of liposarcoma and malignant peripheral nerve tumors and patient age older than 50 years at the time of treatment of metastasis. CONCLUSIONS: Resection of metastatic disease is the single most important factor that determines outcome in these patients. Long-term survival is possible in selected patients, particularly when recurrent pulmonary disease is resected. Surgical excision should remain the treatment of choice for metastases of soft tissue sarcoma to the lung.

The management of unicentric and multicentric Castleman's disease: a report of 16 cases and a review of the literature.

BACKGROUND: Castleman's disease (CD), or angiofollicular lymph node hyperplasia, creates both diagnostic and therapeutic dilemmas for most physicians. For patients with this rare and poorly understood disease, the optimal therapy is unknown. The authors report their experience during the years 1986-1997 with this uncommon clinicopathologic entity. METHODS: Sixteen patients with a histologic diagnosis of CD were identified in the pathology database. Unicentric disease was defined as a solitary mass. Multicentric disease compromised patients with widespread lymphadenectomy. Clinical, radiologic, and laboratory data were analyzed to evaluate treatment response. RESULTS: The study group consisted of 16 patients classified into 3 clinicopathologic groups: hyaline-vascular, plasma cell, and "mixed." Of those patients who underwent complete surgical excision of a unicentric hyaline-vascular CD mass (n = 8), all remain symptom free without clinical or radiographic recurrence. Two patients remain asymptomatic following partial resection or radiation therapy for an unresectable unicentric hyaline-vascular CD mass. Two patients with multicentric hyaline-vascular CD are currently in complete remission following adjuvant therapy. Multicentric plasma cell CD was present in a single patient. This patient (who underwent surgical and systemic therapy) died of disease within 4 months of presentation. Three patients with unicentric hyaline-vascular/plasma cell-CD remain symptom free following either complete resection or observation. CONCLUSIONS: The authors recommend surgical resection for patients with the unicentric variant of CD. Surgical removal of a unicentric mass of hyaline-vascular or hyaline-vascular/plasma cell type is curative. Partial resection, radiotherapy, or observation alone may avoid the need for excessively aggressive therapy. Patients with multicentric disease, either hyaline-vascular or plasma cell type, do not benefit from surgical management and should be candidates for multimodality therapy, the nature of which has yet to be defined.

Cytostatic lung perfusion by use of an endovascular blood flow occlusion technique.

BACKGROUND: Different modalities of cytostatic lung perfusion were compared regarding plasma and tissue drug concentrations to assess the efficacy of an endovascular blood flow occlusion technique. METHODS: A cytostatic lung perfusion study with doxorubicin hydrochloride was performed on large white pigs (n = 12). Plasma and tissue concentrations of doxorubicin were compared for isolated lung perfusion with open cannulation (ILP), blood flow occlusion perfusion with open cannulation of the pulmonary artery alone (BFO), and intravenous drug administration (i.v.). In a fourth group, thoracotomy-free BFO perfusion was performed by endovascular balloon catheterization of the pulmonary artery (endovascular BFO). The 3 animals in this group were used to compare the doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes after 1 month. RESULTS: The mean lung tissue doxorubicin concentration at the end of perfusion was 19.8 +/- 1.6 microg/g after ILP, 27.6 +/- 2.2 microg/g after BFO (p = not significant), and 3.0 +/- 0.8 microg/g after i.v. perfusion (p < 0.01). Whereas doxorubicin was not detectable in the plasma in the ILP group, concentrations ranged from not detectable to 0.44 microg/mL in the BFO group and from 0.31 to 0.84 microg/mL in the i.v. group (p < 0.05). Mean myocardial tissue concentration was not significantly different after BFO than i.v. perfusion (1.1 +/- 0.5 microg/g and 1.8 +/- 0.1 microg/g, respectively). In the endovascular BFO group, balloon-blocked pulmonary artery perfusion was successfully performed in all animals, and after 1 month, lung tissue showed no cytostatic-induced histologic changes. CONCLUSIONS: Compared with ILP, BFO cytostatic lung perfusion produced an insignificantly higher lung-tissue concentration, corresponding to a sixfold to ninefold higher level than after i.v. perfusion. Plasma drug levels during BFO perfusion were lower than during i.v. perfusion. Endovascular BFO may be a promising technique for repeated cytostatic lung perfusion.

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.

Isolated lung perfusion: single-pass system versus recirculating blood perfusion in pigs.

BACKGROUND: Cytostatic isolated lung perfusion has been advocated for treating pulmonary metastasis of soft tissue sarcoma. Different techniques of isolated lung perfusion have been developed. METHODS: Isolated lung perfusion with and without doxorubicin was performed on white pigs during 15 minutes either by a single-pass system (n = 7) or by a recirculating-blood perfusion system (n = 7). Three animals with endovenous drug application served as controls. Leakage was assessed using isotopic tracers. Perfusion-induced lung tissue injury was determined by postperfusion chest radiographs, by angiotensin-converting enzyme-to-protein ratio in the plasma and in the bronchioalveolar lavage fluid, and by wet-to-dry weight ratio and histologic examination of lung biopsy specimens at 20 and 50 minutes. Doxorubicin concentration in lung tissue and plasma was compared between the three study groups. RESULTS: All isolated lung perfusion studies were successfully performed without significant systemic leakage (< 0.6%). Wet-to-dry weight ratio was significantly lower after single-pass as compared with recirculating-blood perfusion and endovenous drug application at both time points (5.0 +/- 1.1 and 5.3 +/- 0.8 for single-pass versus 6.6 +/- 1.1 and 6.9 +/- 0.5 for recirculating-blood versus 6.6 +/- 0.2 and 5.9 +/- 0.7 for the control group, respectively; p < 0.05). Angiotensin-converting enzyme-to-protein plasma ratio in the single-pass group was significantly lower only at 20 minutes (6.3 +/- 2.4 versus 9.3 +/- 1.0 versus 9.7 +/- 1.9, respectively; p < 0.05) but not at 50 minutes. Angiotensin-converting enzyme-to-protein ratio in bronchoalveolar lavage fluid, histology of lung biopsy specimens, and chest radiographs did not differ significantly between the three groups. Doxorubicin lung tissue concentration was not significantly different after single-pass (17.5 micrograms/g) and recirculating-blood perfusion (21.9 micrograms/g), but was significantly higher than after endovenous drug application (3.0 micrograms/g; p < 0.01). CONCLUSIONS: Both isolated lung perfusion techniques resulted in a sixfold to sevenfold higher doxorubicin lung tissue concentration than after endovenous application. Isolated lung perfusion-induced lung injury was similar for both techniques, but recirculating-blood perfusion appeared to result in more acute lung injury and was technically more demanding than single-pass perfusion.

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.

Preoperative identification and operative management of intraatrial extension of lung tumors.

Preoperative identification of intraatrial tumor is uncommon. A 23-year-old woman presented with local recurrence and pulmonary metastases after previous resection of a clavicular sarcoma. Evaluation by computed tomography revealed bilateral pulmonary masses. Due to the size and proximal location, magnetic resonance imaging and transesophageal echocardiography were performed, revealing a large intraatrial mass. She then underwent staged surgical excision without intraoperative complications. We summarize this case and review risk factors for intracardiac extension and prevention of tumor emboli.

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.

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.

MRI as an alternative to CT-guided biopsy of adrenal masses in patients with lung cancer.

BACKGROUND: This study was performed to assess chemical shift magnetic resonance imaging (CSMRI) for characterizing adrenal masses in patients with lung cancer, and to compare charges associated with two algorithms for assessing adrenal masses in these patients. METHODS: Forty-two patients with lung cancer underwent both CSMRI (using in-phase and opposed-phase gradient echo images) and computed tomography-guided percutaneous biopsy of adrenal masses. Adrenal-to-spleen signal intensity ratios on the opposed-phase images were correlated with histopathologic results. The normalized charges for two algorithms were compared. In algorithm A, computed tomography-guided biopsy is used first to evaluate an adrenal mass; in algorithm B, CSMRI is used first, followed by computed tomography-guided biopsy only if CSMRI findings are not diagnostic of adenoma. RESULTS: Biopsy showed 24 (57%) adrenal adenomas and 18 (43%) metastases. Chemical shift magnetic resonance imaging was 96% sensitive for adenoma and 100% specific. The average normalized charges associated with algorithm A were $1,905 per patient versus $1,890 with algorithm B. CONCLUSIONS: Initial use of CSMRI in evaluating an adrenal mass in lung cancer patients can obviate biopsy in 55% of patients, and its charges are similar to those for performing computed tomography-guided biopsy in all patients.

The role of surgery in the treatment of clinically isolated adrenal metastasis.

BACKGROUND: Clinically isolated adrenal metastasis is rare. The role of surgical resection is unknown. The aim of this study was to define clinical and pathologic parameters that might predict long term survival after resection of adrenal metastasis. METHODS: The authors conducted a retrospective review of 37 patients who had undergone adrenalectomy for metastatic disease at the Memorial Sloan-Kettering Cancer Center (MSKCC) between July 1986 and October 1996. Patients who underwent resection of tumors that locally invaded the adrenal gland were excluded from the study, as were all patients with primary adrenal tumors. RESULTS: There were 24 men and 13 women, with a median age of 58 years (range, 42-77 years). Lung carcinoma was the most common primary tumor (n = 17), followed by renal cell carcinoma (n = 9), and colorectal carcinoma (n = 5). The median length of stay at MSKCC was 8 days (range, 3-21 days). There was a 19% incidence of complications (12% major). There was one perioperative death. Five-year survival for the entire group was 24% (median, 21 months). Disease free interval (DFI) of > 6 months and complete resection were the only predictors of improved survival. CONCLUSIONS: Adrenalectomy for clinically solitary, resectable lesions can be performed safely, and prolonged survival can be achieved in such selected patients. Adrenalectomy should be considered for patients with completely resectable disease and a DFI of > 6 months.

Pulmonary metastasectomy for testicular germ cell tumors: a 28-year experience.

BACKGROUND: The role of surgery in patients with pulmonary metastatic germ cell tumors has been evolving since the 1970s. To evaluate the results of pulmonary resection, we reviewed our 28-year experience. METHODS: Between July 1967 and May 1995, 157 patients with testicular germ cell tumors underwent pulmonary resections for suspected metastases. Their clinical and pathological data were reviewed. Kaplan-Meier and Cox regression models were used to analyze prognostic factors for survival after resection of metastatic disease. RESULTS: All patients were male with median age of 27 years (range 15-65). Complete resection was accomplished in 155 (99%) patients. Viable carcinoma was present in 44% (70) of the patients. Forty-one (26%) patients had metastases to other sites after pulmonary metastasectomy. The overall actuarial survival 5 years after pulmonary resection was 68% for the entire group and 82% for patients diagnosed after 1985. On multivariate analysis, the adverse prognostic factors were metastases to nonpulmonary visceral sites (p = 0.0069) and the presence of viable carcinoma in the resected specimen (p < 0.0001). CONCLUSIONS: With current chemotherapy regimens, almost 85% of the patients with testicular germ cell tumors undergoing complete resection of their pulmonary metastases can be expected to achieve long-term survival.

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.

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.

Early postoperative enteral feeding improves whole body protein kinetics in upper gastrointestinal cancer patients.

BACKGROUND: Patients with upper gastrointestinal (GI) tract malignancies are at increased risk for malnutrition, as well as postoperative morbidity and mortality. As data clearly documenting the benefit of early postoperative enteral feeding in upper GI cancer patients as compared with no feeding are sparse, we examined the protein kinetic effects of early enteral feeding and compared it with standard postoperative care (ie, intravenous fluid). METHODS: Twenty-nine patients undergoing resection of an upper GI tract malignancy were prospectively randomized to either enteral feeding (FEED, n = 12) starting on postoperative day (POD) 1 via a jejunostomy tube or intravenous fluid (IVF, n = 17). On POD 5, all patients underwent resting energy expenditure determination and a protein metabolic study using the isotope 14C-leucine to determine whole body (WB, micromol leu/kg/min) protein kinetics. RESULTS: Respiratory quotient and insulin (microU/mL) levels were significantly increased in patients receiving enteral feeding (0.85 +/- 0.02, 19.8 +/- 4.5 versus 0.78 +/- 0.02, 9.3 +/- 0.8, FEED versus IVF, P < 0.05). Free fatty acids (meq/dL) were significantly lower in FEED group (0.36 +/- 0.04) as compared with IVF group (0.85 +/- 0.07, P < 0.0001). While there were no significant differences in WB protein oxidation (0.10 +/- 0.01 versus 0.10 +/- 0.02) or synthesis (0.81 +/- 0.09 versus 0.68 +/- 0.08, IVF versus FEED), WB protein catabolism was significantly less (0.91 +/- 0.10 versus 0.37 +/- 0.09, P = 0.002), and WB protein net balance was converted to positive in FEED group (-0.10 +/- 0.01 versus 0.30 +/- 0.03, IVF versus FEED, P < 0.001). CONCLUSIONS: Early enteral feeding decreases fat oxidation and whole body protein catabolism while improving net nitrogen balance. By significantly improving protein metabolism, enteral feeding may decrease postoperative morbidity and mortality in upper GI cancer patients.

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.

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.

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.