Benny Weksler

Thymoma: A multivariate analysis of factors predicting survival

BACKGROUND Despite complete surgical excision, malignant thymomas often recur with resultant death. We reviewed our series to determine which factors independently predict survival after surgical resection. METHODS A retrospective analysis of patients operated on for thymoma between 1949 and 1993 at Memorial Sloan-Kettering Cancer Center was performed. Clinical data were collected from chart review. Only patients with a pathology report confirming the diagnosis of thymoma were included in this analysis. Kaplan-Meier survival curves were generated and comparisons of survival analyzed by log rank test. Multivariate analysis was performed by the Cox proportional hazard model. RESULTS One hundred eighteen patients with thymoma underwent operation. There were 86 complete resections (73%), 18 partial resections (15%), and 14 biopsies (12%). By Masaoka staging, 25 patients were stage I (21%), 41 stage II (35%), 43 stage III (36%), and 9 stage IVa (8%). Overall survival was 77% at 5 years and 55% at 10 years. Tumor recurred in 25 (29%) of 86 completely resected thymomas. Stage of disease (p = 0.03) was the only independent prognostic factor affecting recurrence. By multivariate analysis, stage (p = 0.003), tumor size (p = 0.0001), histology (p = 0.004), and extent of surgical resection (p = 0.0006) were independent predictors of long-term survival. CONCLUSIONS Patients with stage I disease require no further therapy after complete surgical resection. Neoadjuvant therapy should be considered for patients with large tumors and invasive disease.

Isolated Single-Lung Perfusion With Doxorubicin Is Pharmacokinetically Superior to Intravenous Injection

To investigate new modalities in the treatment of pulmonary metastases we developed a model of isolated single-lung perfusion in the rat. In this study we compare the pharmacokinetics of isolated lung perfusion and intravenous doxorubicin. In the first experiment, designed to evaluate lung tissue levels of doxorubicin, 35 rats were randomized into seven groups (n = 5). The first five groups underwent isolated lung perfusion with 72.1 +/- 6.9, 118.4 +/- 12.1, 255.2 +/- 12.8, 384.1 +/- 46.2, and 457.6 +/- 32.5 micrograms/mL of doxorubicin, respectively, for 10 minutes. Groups 6 and 7 received 5 mg/kg and 7 mg/kg of intravenous doxorubicin, respectively. A second study was designed to measure heart tissue level of doxorubicin in 3 groups of 5 rats each. Two groups received 5 or 7 mg/kg of intravenous doxorubicin and a third group underwent isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL of doxorubicin for 10 minutes. A third study, designed to evaluate toxicity in vivo, had a similar design, and the animals were followed up for 21 days after treatment. Lung doxorubicin concentration after isolated lung perfusion was significantly higher than after intravenous doxorubicin (p < 0.01). Tissue doxorubicin concentration was 25 and 20 times higher after isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL than after 5 or 7 mg/kg of intravenous doxorubicin, respectively. Heart concentration of doxorubicin was significantly lower after isolated lung perfusion with 255.2 +/- 12.8 micrograms/mL of doxorubicin as compared with 5 or 7 mg/kg of intravenous doxorubicin (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Resection of lung cancer invading the diaphragm

Each year, stage III non-small-cell lung cancer (NSCLC) is diagnosed in approximately 30,000 patients. Locally advanced NSCLC (stage IliA) includes a group of biologically diverse tumors with subgroups of truly locally advanced disease--T3 tumors and advanced locoregional disease with the presence of N2 disease. The prognosis of patients with a diagnosis of stage III lung cancer is mainly dependent on the status of the mediastinal nodes. Good long-term results are achieved in patients with NO disease, whereas patients with N2 disease are poor candidates for resection as a primary treatment. 1-3 Information is not available on results of surgical treatment of patients with stage III disease and tumors involving the diaphragm. Patients and methods. From January 31, 1974, to August 17, 1995, a total of 4668 patients underwent exploration for resection of NSCLC at Memorial Hospital. By analyzing our database we identified eight patients (0.17%) who had exploratory thoracotomy for resection of NSCLC invading the diaphragm. The medical records of these eight patients were retrospectively analyzed. Data are reported as mean -+ standard deviation. Survival data are reported as mean and 95% confidence interval (CI) for the mean. The Kaplan-Meier method was used to calculate actuarial survival. Results. The demographics of these eight patients are shown in Table I. The mean age at diagnosis was 65.8 + 10.2 years, ranging from 52.6 to 82.4 years. The most common symptoms were cough in four patients, hemoptysis in two patients, and chest pain in one patient. One patient had clubbing of the fingers. Three patients were free of symptoms. All patients smoked. The mean time from first symptoms to referral for treatment was 25.1 -+ 16.6 weeks, ranging from 5.3 to 49 weeks. The histologic diagnosis was made by bronchoscopic examination in four patients and by fluoroscopic guided needle biopsy in two. In two patients the diagnosis was made in the operating room. Four tumors were on the right side and four on the left side. Two patients underwent mediastinoscopy, both studies yielding negative results. The other six did not undergo preoperative mediastinoscopy. Among the eight patients, diaphragmatic invasion was not suspected at exploration in six and it was suspected before the opera-

Isolated single-lung perfusion with TNF-α in a rat sarcoma lung metastases model☆

Abstract 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 μg/mL of either human or murine TNF. Controls were incubated with Hanks 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 μg of murine TNF, 5 animals were perfused with 420 μg of murine TNF, 10 animals underwent isolated lung perfusion with 420 μg of human TNF, and 4 animals were injected systemically with 420 μg 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 P = 0.07). Animals perfused with 420 μg/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

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.

Effect of growth hormone on tumor and host in an animal model

Background: The relative effects of growth hormone on tumor versus host growth and protein metabolism are not known. This study examines the influence of recombinant rat growth hormone (r-rGH) on host and tumor growth, host body composition, and protein synthesis of tumor and host in tumor-bearing rats.Methods: After left flank implantation of methylcholanthrene-induced sarcoma, 28 Fischer rats with palpable tumor were treated with s.c. saline or 1 mg/kg/day r-rGH for 11 days. At death, fractional protein synthetic rates (FSRs) of tumor, liver, and gastrocnemius muscle were determined. In a separate experiment, 27 tumor-bearing rats received saline or 1 mg/kg/day r-rGH for 2 weeks. Tumor and host growth and host body composition were analyzed.Results: Animals treated with r-rGH had significantly higher liver FSR than did controls (233 ± 27%/day vs. 110 ± 4%/day, respectively). No significant differences were associated with growth hormone administration with respect to tumor growth, host composition, or FSR of tumor or muscle.Conclusions: Growth hormone stimulates liver protein synthesis, without changing tumor growth, protein synthesis, or host composition in this rat sarcoma model. Further investigation of growth hormone as an anticachectic agent is warranted.

The merit of oxygen insufflation during one-lung ventilation

T H O R opening of the DLT without employing pre-OLV apnea (lung collapse) would significantly impair the surgical field. Bussieres and colleagues used the BB after applying pre-OLV apnea. Blocking the opening of the DLT during the lung inflation state will slow lung collapse and be beneficial in terms of PaO2 without doubt. Blocking the opening of the DLTafter employing pre-OLVapnea is not known yet for its effect on PaO2 and therefore needs to be compared with the contemporary method of leaving it open or our AOI technique for better oxygenation in future studies.