Lung radiofrequency ablation in patients with pulmonary metastases from musculoskeletal sarcomas

BACKGROUND:

The authors retrospectively evaluated the impact of lung radiofrequency (RF) ablation on survival in patients with lung metastases from musculoskeletal sarcomas.

METHODS:

Lung RF ablation was done under the real‐time computed tomography (CT) fluoroscopy. Safety, local tumor progression, and survival were evaluated in 2 institutions.

RESULTS:

Lung RF ablation was performed in 20 consecutive patients. The mean maximum tumor diameter was 14 ± 9 mm (range, 5‐40 mm) and the mean tumor number 7 ± 6 (range, 1‐18) per patient. Pneumothorax requiring chest tube placement developed in 24 of 63 RF sessions (38%). During the mean follow‐up period of 18 months (range, 7 months to 54 months), 9 of 20 patients died of lung tumor progression. The 1‐ and 3‐year survival rates from RF ablation were 58% (95% confidence interval [CI], 33.3‐82.6%) and 29% (95% CI, 0‐59.9%) with a median survival time of 12.9 months in all patients. Ablation of all lung tumors was the only significantly better prognostic factors in both the univariate analysis and the multivariate analyses. The 1‐ and 3‐year survival rates were 88.9% (95% CI, 69.3%‐100%) and 59.2% (95% CI, 10.2%‐100%) in 11 patients with complete tumor ablation.

CONCLUSIONS:

Lung RF ablation is a safe and useful therapeutic option for selected patients. (R#1) Prognostic factors identified in our study will help to stratify those patients who may benefit from lung RF ablation. Cancer 2009. © 2009 American Cancer Society.     

Perioperative Allogeneic Blood Transfusion and Serum Levels of Immunosuppressive Acidic Protein in Patients Undergoing Resection of Colorectal Carcinoma

Serum levels of immunosuppressive acidic protein(IAP) were determined in 68 patients undergoingresection of colorectal cancer and 21 healthy subjects.Eighteen patients had perioperative transfusion of allogeneic blood (transfused patients) and 50patients had no blood transfusion (nontransfusedpatients). Transfused patients had a higher incidence ofnodal involvement, advanced disease, and noncurative surgery compared to nontransfused patients, butthe difference did not reach a statistical significance.Hemoglobin concentration and serum albumin level werelower in transfused patients, although there was no statistically significant difference.Preoperative serum IAP level was higher in the patientswith nodal involvement and advanced disease and thosewith moderately or poorly differentiated tumor, though this was not statistically significant.The preoperative serum IAP level was higher in patientsthan in controls, but the difference did not reachstatistical significance. Serum IAP level roseimmediately after the operation. In nontransfused patients,the serum IAP level returned to the preoperative valueby three months after the operation. In contrast, theserum IAP level of transfused patients remained significantly higher than the preoperativevalue (P < 0.05) at three months after the operation.These findings indicated that perioperative transfusionof allogeneic blood elevated the serum IAP level for a considerable period after theoperation.     

Arginyl-tRNA-protein transferase activities in crude supernatants of rat tissues.

A fluorescent HPLC method for the assay of arginyl-tRNA-protein transferase (R-Transferase) activity was applied to obtain quantitative data of the enzyme activity in rat tissues for the first time. In this assay, the major problem was a significant hydrolysis of the substrate, N-aspartyl-N'-dansylamido-1,4-butanediamine, and the product, N-arginylaspartyl-N'-dansylamido-1,4-butanediamine (ArgAsp(4)DNS) by aminopeptidases in crude samples such as 105000g supernatants (105S) of tissue homogenates. As bestatin inhibited the hydrolysis of ArgAsp(4)DNS, a standard-addition method in the presence of bestatin, using a partially purified R-Transferase preparation from hog kidney as a standard, made it possible to measure directly R-Transferase activities in 105S with a short incubation time and sufficient reliability. It was found by the established method that of 14 tissues examined, stomach was rich in the R-Transferase activity with the highest specific activity, suggesting a target tissue for the future studies on R-Transferase to elucidate its physiological significance.     

Kinetics of sequential metabolism from D-leucine to L-leucine via alpha-ketoisocaproic acid in rat.

D-Leucine is considered to be converted into the L-enantiomer by two steps: oxidative deamination to form alpha-ketoisocaproic acid (KIC) and subsequent stereospecific reamination of KIC. We investigated the pharmacokinetics of leucine enantiomers and KIC in rats to evaluate how deamination of D-leucine, reamination of KIC, and decarboxylation of KIC were affected to the overall extent that converted D-leucine into the L-enantiomer. After intravenous administrations of D-[(2)H(7)]leucine, L-[(2)H(7)]leucine, or [(2)H(7)]KIC, their plasma concentrations together with endogenous L-leucine and KIC were determined by gas chromatography-mass spectrometry. The rapid appearances of [(2)H(7)]KIC and L-[(2)H(7)]leucine were observed after administration of D-[(2)H(7)]leucine, whereas no detectable amount of D-[(2)H(7)]leucine was found after administrations of [(2)H(7)]KIC or L-[(2)H(7)]leucine. The fraction of conversion from D-[(2)H(7)]leucine into [(2)H(7)]KIC (F(D-->KIC)) was estimated by using the area under the curve (AUC) of [(2)H(7)]KIC on the D-[(2)H(7)]leucine administration [AUC(KIC(D))] and that of [(2)H(7)]KIC on the [(2)H(7)]KIC administration (AUC(KIC)) to yield 70.1%. The fraction of conversion from [(2)H(7)]KIC to L-[(2)H(7)]leucine (F(KIC-->L)) was 40.2%. The fraction of conversion from D-leucine to the L-enantiomer (F(D-->L)) was considered to be the product of F(D-->KIC) and F(KIC-->L), indicating that 28.2% of D-[(2)H(7)]leucine was metabolized to L-[(2)H(7)]leucine via [(2)H(7)]KIC. These results suggested that the relatively low conversion of D-leucine into the L-enantiomer might depend on irreversible decarboxylation of KIC. Regardless of [(2)H(7)]KIC, F(D-->L) was also calculated directly using AUC(L(D)) and AUC(L) to yield 27.5%. There were no differences between the two F(D-->L) values, suggesting that almost all of the formation of L-[(2)H(7)]leucine from D-[(2)H(7)]leucine occurred via [(2)H(7)]KIC as an intermediate.     

Pharmacokinetics of 1-phthalidyl-5-fluorouracil (PH-FU)

The blood level of PH-FU following oral administration to rabbits and tumor-bearing mice was considerably lower than that of Tegafur, HCFU or 5'DFUR, and decreased more rapidly. The t1/2 beta was 0.48 h (rabbits) and 1.74-1.91 h (mice). The blood level of 5-FU derived from PH-FU was higher at an earlier time after administration than that derived from other 5-FU derivatives, but it disappeared more rapidly. The tissue level of PH-FU in S-180-and Lewis lung carcinoma-bearing mice was detected at a low level in various tissues of mice, except for a higher level in the digestive tract and a lower level in the brain and muscle. The tissue level of 5-FU in both types of mice was high in the digestive tract and kidney. The 5-FU level in the 2 kinds of tumor tissues was relatively high and persisted for several hours. After incubating PH-FU and tissue homogenates from humans and mice at 37 degrees C for 2 h, PH-FU was converted to 5-FU very strongly in the liver and kidney, and considerably strongly in the muscle, heart, tongue and testis. In conclusion, PH-FU seems to be characterized by a low blood and tissue level of unchanged drug, a high production of 5-FU and a short duration of the level.     

Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a calcium antagonist: beyond the renoprotective effects of ACE inhibitor monotherapy in a spontaneous hypertensive rat with renal ablation.

To assess the renal benefits of combined angiotensin-converting enzyme inhibition and calcium antagonism, we studied the antihypertensive and renoprotective effects of temocapril (TMP) alone or in combination with azelnidipine (AZN) in a spontaneously hypertensive rat (SHR) remnant kidney model of chronic renal failure. Male 5/6-nephrectomized SHR/Izumo rats were randomly assigned to receive vehicle (control group), TMP (TMP group; 10 mg x kg(-1) x day(-1)), AZN (AZN group; 3 mg x kg(-1) x day(-1)), or both (TMP+AZN group) orally for 12 weeks. Systolic blood pressure (SBP) and urinary excretion of albumin (UalbV) were measured every 2 weeks. At the end of the experiment, serum creatinine (Scr), heart weight (HW), and blood urea nitrogen (BUN) levels were measured and the remnant kidneys were examined to determine the index of glomerular sclerosis (IGS). SBP and UalbV in the control group increased progressively throughout the experimental period. TMP, AZN, and TMP+AZN blocked the development of hypertension. TMP+AZN did not enhance the antihypertensive effects of either TMP or AZN used singly. TMP, AZN, and TMP+AZN all significantly decreased the UalbV, Scr, BUN, and HW/body weight (BW) ratio. The level of UalbV and the HW/BW ratio in the TMP+AZN group were significantly lower than those in the TMP and AZN groups, and the level of Scr in the TMP+AZN group was significantly lower than that in the TMP group. TMP, AZN, and TMP+AZN all significantly protected against an increase in the IGS. The IGS in the TMP+AZN group was significantly lower than that in the TMP and AZN groups. These results indicate that both TMP and AZN have antihypertensive and renoprotective effects in this model. They also suggest that simultaneous administration of TMP and AZN provides greater renoprotective effects than TMP alone.     

The effect of maternal hyperglycemia on insulin secretion by monolayer-cultured B cells of neonatal rats--a perifusion study

To evaluate the effect of maternal hyperglycemia on insulin secretion by neonatal rat B cells, perifusion was conducted on monolayer cultures of rat neonates from normoglycemic (C) mothers or those made slightly (SH) and highly (HH) hyperglycemic by the injection of streptozotocin. In the C, SH and HH groups, B cells responded to 16.7 mM glucose, 10 mM leucine, 10 mM 2-ketoisocaproate and 10 mM arginine in a biphasic manner, although these nutrients provided stimuli so feeble that insulin secretion in the second phase was slightly raised above basal levels. However, quantitative relationships differed. Compared with the C group, B cells in the SH group showed a significant increase in the secretion of the second phase in response to glucose, 2-ketoisocaproate and arginine but not to leucine, whereas there was no difference in the secretion of the first phase between these two groups. In the HH group, a lower insulin secretion of the first and second phase was observed. These results are compatible with hyperglycemia-hyperinsulinaemia theory concerning the function of B cells in neonates born to slightly hyperglycemic mothers and with a defect in insulin secretion by neonates from highly hyperglycemic females.     

Real-time quantitative polymerase chain reaction for MDR1, MRP1, MRP2, and CYP3A-mRNA levels in Caco-2 cell lines, human duodenal enterocytes, normal colorectal tissues, and colorectal adenocarcinomas.

The expression levels of mRNAs for MDR1 (P-glycoprotein), multidrug resistance-associated proteins (MRP1, MRP2), and cytochrome P450 3A (CYP3A) in Caco-2 cells were quantitatively compared with those in human duodenal enterocytes, normal colorectal tissues, and colorectal adenocarcinomas. Caco-2 cells (passages 36-88) were kindly supplied by several laboratories in Japan. Human duodenal enterocytes were obtained from five healthy male volunteers. Normal colorectal tissues and colorectal adenocarcinomas were simultaneously obtained from seven patients with primary colorectal adenocarcinoma. MDR1, MRP1, MRP2, and CYP3A mRNA levels were determined by real-time quantitative polymerase chain reactions (PCR). Relative concentrations of mRNAs for target proteins (MDR1, MRP1, MRP2, and CYP3A) and glyceraldehyde-3-phosphate dehydrogenase in Caco-2 cells were 1.00 +/- 0.15, 1.02 +/- 0.06, 0.94 +/- 0.10, and 0.68 +/-0.60, respectively, and those in human enterocytes were about 12-, 3-, 7-, and 8000-fold higher than in the Caco-2 cells, respectively. In contrast, MDR1, MRP1, and CYP3A mRNA levels in Caco-2 cells were comparable to those in normal colorectal tissue and colorectal adenocarcinoma.     

Intensive individualized induction therapy with behenoyl cytarabine, daunorubicin and 6-mercaptopurine followed by intensive consolidation including intermediate-dose continuous cytarabine, mitoxantron, etoposide and vinca alkaloids in acute myeloid leukemia in adults.

Forty-one consecutive adult patients with acute myeloid leukemia (AML) were treated with an intensive individualized induction therapy of behenoyl cytarabine, daunorubicin, and 6-mercaptopurine, 29 patients (71%) achieved complete remission (CR). Patients then received three courses of intensive consolidation therapy, including intermediate-dose continuous cytarabine (400 mg/m2, for 5 days) and non-cross resistant drugs such as mitoxantron, etoposide and vincristine. During the course of the consolidation therapy, three patients died of infections and one died of myocardial infarction. Four patients underwent allogeneic bone marrow transplantation. The patients then received six courses of moderately intensive maintenance therapy for 1 year. The predicted 5-year continuing CR and disease-free survival rates of the CR patients were 62% (95% confidence limit, 41% to 83%) and 53% (33% to 73%), respectively. Although the number of patients in this study is small, the present study indicated that it may be possible to cure a fairly large proportion of AML patients by chemotherapy alone, if intensive induction therapy is followed by intensive consolidation therapy.     

Inhibitory effect of bestatin on the growth of human leukemic cells

We examined the effect of bestatin (Ubenimex) on the growth of human leukemic cells (i.e, HL-60, K562, MT-1, MT-2, Molt-4, and Raji cells). The growth of each cell line was inhibited by the cocultivation with bestatin at higher concentrations than employed for clinical use in Japan. [3H]TdR incorporation was also inhibited in MT-1 and MT-2 cells by treatment with bestatin. Degenerated cell-to-cell adhesion was observed among the treated cells. These findings suggest that the inhibitory effect on some leukemic cells, especially on MT-1 cells, results from the inhibition of DNA synthesis.