2
balanced physiological response as compared to flatter (less negative) slopes. Analyses of variance on cortisol slopes were done with a within-subject factor for day and between-subject factors for group. Group attribution was based on whether women knew the diagnosis was benign (benign group), knew the diagnosis was malignant (malignant group). didn't know the biopsy result (unknown group), or needed surgery for final diagnosis or presumed benign disease (uncertain group). RESULTS: A significant difference in slopes was seen on day 4 (benign = -0.146, malignant = -0.117. unknown = -0.103, uncertain = -0.116; p = 0.0354). Supplemental ANOVAs with pairs of groups showed that there were no significant difference in slope between the benign and malignant group; but that there was a significant difference between benign and unknown result groups (p = 0.0052). Benign and uncertain groups did not differ significantly on day 4, but there was a significant result by day interaction (p = 0.0140), with benign slopes remaining around -0.14 whereas the uncertain group had less normal slopes towards the end of the week. 00 day 5 there was a significant difference among slopes (benign = -0.156, malignant = -0.1 10, unknown = -0.107, uncertain = -0.058; p= 0,0064). A supplemental Tukey test showed that it is the uncertain group that differs from the benign group on the Day 5 cortisoI slope. CONCLUSION: Waiting for a final diagnosis is associated with considerable stress as evidenced by cortisol measw-ements. Therefore all efforts should be made to provide biopsy results expeditiously. Oncology Abstract No. 246 The Anti-Thmor Effect and Toxicity of a Hexokinase II Inhibitor, 3-Bromopyruvate: In Vitro and In Vivo Investigation. J. W Chung, Seoul National University Hospital, Seoul, Republic of Korea'H.i. Jae·M.J. Lee·H.S. Park'J.H. Park PURPOSE: Hexokinase II, the first-step enzyme of the glycolytic pathway, is overexpressed in highJy malignant cells. The purpose of this study was to elucidate cytotoxic characteristics of a hexokinase II inhibitor, 3-bromopyruvate (3-BP), and to investigate antitumor effect of its intraarterial delivery. MATERIALS AND METHODS: VX2 carcinoma cells and normal rabbit hepatocytes were treated with 3-BP in various concentrations (from 0.2 to 2.0 mM) for variable exposure time (from 10 mintltes to 24 hours) until cell viability was measured with MIT assay. VX2 carcinoma was implanted in livers of21 rabbits. Transcatheter intra-arterial administration was performed using low dose 3-BP (25mL in lnu\t1, n=6), high dose 3-BP (5mM, n=6), Lipiodol-doxorubicin emulsion (1.6mg doxorubicin/OAmL Lipiodol, n=6), and normal saline (n=3) as a control. One week later, proportion of tumor necrosis was calculated based on histopathologic examination. Hepatotoxicities were evaluated by biochemical analysis. RESULTS: In vitro experiment, more than 90% of VX2 carcinoma cells were killed in every concentration and exposure time at 24 hour measurement. On the other hand, more than 50% of normal hepatocytes were viable even after 24 hour treatment with 2.0 mM concentration. There were statistically significant difference in cytotoxicities of 3-BP between VX2 carcinoma cells and nOlmal hepatocytes (p < 0.01). In vivo experiment, Tumor necrosis rate was significantly higher in high dose group (90.5%±8.7 [mean±SD]) than in the control group (63.1 %±14.9)(P=.024). However, tumor necrosis rate of high dose group was significantly lower than that of Lipiodol-doxorubicin treatment group (98.6%±3A7)(P=.0 I5). Hepatotoxicity was dose-dependent. CONCLUSION: In vitro study, 3-BP showed profound cytotoxicity in YX2 carcinoma cells even after a 2-minute exposure oflow drug concentration of 0.2 mM. Significantly, VX2 carcinoma cells were more susceptible to 3-BP than normal hepatocytes. However, even though intra-arterial delivery of 3-BP showed dose-dependent anti-tumor effect, single session treatment seems to have limited efficacy when compared with the conventional method. Abstract No. 247 Arterial Infusion Chemotherapy Followed by RF Ablation for the Treatment of Liver Metastasis from Gastric Cancer. K. Yamakado, Mie University School of Medicine, Tsu, Mie, Japan-A. Nakatsuka·M. Akeboshi'H. Takaki'K. Takeda PURPOSE: Although liver metastasis is one of the important prognostic factors in patients with gastric cancer, useful therapeutic options have not been established yet. This prospective study was undertaken to evaluate feasibility and clinical utility of arterial Infusion chemotherapy followed by radiofrequency (RF) ablation for the treatment of liver metastasis from gastric cancer. MATERIALS AND METHODS: Inclusion criteria of this prospective study were as follows; a) performance status:'S:2, b) curative gastrectomy, c) no peritoneal dissemination, d) no extrahepatic metastasis, e) maximum liver tumor size:'S: 6cm, c) number of liver tumor :'S: 6, e) normal hematological and coagulability study. Patients received hepatic arterial infusion chemotherapy using the implanted port and catheter system once a week during 3 or 6 months. The timing of RF ablation was decided as follows; a) new intra- or extra-hepatic metastases did not develop during hepatic arterial infusion chemotherapy, 2) the maximum tumor size became 3-4cm in diameter. Therapeutic response was evaluated by contrast- enhanced CT studies. Eradication of tumor enhancement was considered to be tumor necrosis. RESULTS: Six patients were included in the present study. The mean maximum tumor size shrunk from 5.0cm to 2.5 cm (p<0.05) and the tumor number decreased from 19 to 13 after arterial infusion chemotherapy. RF ablation was successfully done in all residual liver tumors, resulting in complete tumor necrosis in all liver lesions. All patients are still living without intrahepatic recurrences during the mean follow-up of 16 months. Nodal metastasis developed in one patient which was resected. CONCLUSION: The combined therapy described here is a feasible and useful therapeutic option for the treatment of liver metastasis from gastric cancer. Abstract No. 248 Diffusion Weigh ted MR Imaging after Chemoembolization for Neuroendocrine Metastases: Assessment of Thmor Response. I.R. Kamel, Johns Hopkins Medical Institutions. Baltimore, MD, USA ·E.A. Liapi·D.A. Bluemke·i.FH. Geschwind PURPOSE: To assess treatment response of hepatic neuroendocrine metastases after TACE using diffusion- weighted MR imaging. MATERIALS AND METHODS: MR imaging studies before and after TACE on 30 consecutive patients were evaluated. Patients were scanned using a 1.5-T MR scanner and a phased S87

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balanced physiological response as compared to flatter (lessnegative) slopes. Analyses of variance on cortisol slopes weredone with a within-subject factor for day and between-subjectfactors for group. Group attribution was based on whetherwomen knew the diagnosis was benign (benign group), knewthe diagnosis was malignant (malignant group). didn't knowthe biopsy result (unknown group), or needed surgery forfinal diagnosis or presumed benign disease (uncertain group).

RESULTS: A significant difference in slopes was seen on day4 (benign = -0.146, malignant = -0.117. unknown = -0.103,uncertain = -0.116; p = 0.0354). Supplemental ANOVAs withpairs ofgroups showed that there were no significant differencein slope between the benign and malignant group; but thatthere was a significant difference between benign and unknownresult groups (p = 0.0052). Benign and uncertain groups didnot differ significantly on day 4, but there was a significantresult by day interaction (p = 0.0140), with benign slopesremaining around -0.14 whereas the uncertain group had lessnormal slopes towards the end of the week. 00 day 5 therewas a significant difference among slopes (benign = -0.156,malignant = -0.1 10, unknown = -0.107, uncertain = -0.058;p= 0,0064). A supplemental Tukey test showed that it is theuncertain group that differs from the benign group on the Day5 cortisoI slope.

CONCLUSION: Waiting for a final diagnosis is associatedwith considerable stress as evidenced by cortisol measw-ements.Therefore all efforts should be made to provide biopsy resultsexpeditiously.

Oncology

Abstract No. 246

The Anti-Thmor Effect and Toxicity of a Hexokinase IIInhibitor, 3-Bromopyruvate: In Vitro and In VivoInvestigation.J. W Chung, Seoul National University Hospital, Seoul, Republicof Korea'H.i. Jae·M.J. Lee·H.S. Park'J.H. Park

PURPOSE: Hexokinase II, the first-step enzyme of theglycolytic pathway, is overexpressed in highJy malignant cells.The purpose of this study was to elucidate cytotoxiccharacteristics of a hexokinase II inhibitor, 3-bromopyruvate(3-BP), and to investigate antitumor effect of its intraarterialdelivery.

MATERIALS AND METHODS: VX2 carcinoma cells andnormal rabbit hepatocytes were treated with 3-BP in variousconcentrations (from 0.2 to 2.0 mM) for variable exposuretime (from 10 mintltes to 24 hours) until cell viability wasmeasured with MIT assay. VX2 carcinoma was implanted inlivers of21 rabbits. Transcatheter intra-arterial administrationwas performed using low dose 3-BP (25mL in lnu\t1, n=6),high dose 3-BP (5mM, n=6), Lipiodol-doxorubicin emulsion(1.6mg doxorubicin/OAmL Lipiodol, n=6), and normal saline(n=3) as a control. One week later, proportion of tumornecrosis was calculated based on histopathologic examination.Hepatotoxicities were evaluated by biochemical analysis.

RESULTS: In vitro experiment, more than 90% of VX2carcinoma cells were killed in every concentration and exposuretime at 24 hour measurement. On the other hand, more than50% of normal hepatocytes were viable even after 24 hourtreatment with 2.0 mM concentration. There were statisticallysignificant difference in cytotoxicities of 3-BP between VX2carcinoma cells and nOlmal hepatocytes (p < 0.01). In vivoexperiment, Tumor necrosis rate was significantly higher inhigh dose group (90.5%±8.7 [mean±SD]) than in the controlgroup (63.1 %±14.9)(P=.024). However, tumor necrosis rate

of high dose group was significantly lower than that ofLipiodol-doxorubicin treatment group (98.6%±3A7)(P=.0 I5).Hepatotoxicity was dose-dependent.

CONCLUSION: In vitro study, 3-BP showed profoundcytotoxicity in YX2 carcinoma cells even after a 2-minuteexposure oflow drug concentration of 0.2 mM. Significantly,VX2 carcinoma cells were more susceptible to 3-BP thannormal hepatocytes. However, even though intra-arterialdelivery of 3-BP showed dose-dependent anti-tumor effect,single session treatment seems to have limited efficacy whencompared with the conventional method.

Abstract No. 247

Arterial Infusion Chemotherapy Followed by RF Ablationfor the Treatment of Liver Metastasis from Gastric Cancer.K. Yamakado, Mie University School of Medicine, Tsu, Mie,Japan-A. Nakatsuka·M. Akeboshi'H. Takaki'K. Takeda

PURPOSE: Although liver metastasis is one of the importantprognostic factors in patients with gastric cancer, usefultherapeutic options have not been established yet. Thisprospective study was undertaken to evaluate feasibility andclinical utility of arterial Infusion chemotherapy followed byradiofrequency (RF) ablation for the treatment of livermetastasis from gastric cancer.

MATERIALS AND METHODS: Inclusion criteria of thisprospective study were as follows; a) performance status:'S:2,b) curative gastrectomy, c) no peritoneal dissemination, d) noextrahepatic metastasis, e) maximum liver tumor size:'S: 6cm,c) number of liver tumor :'S: 6, e) normal hematological andcoagulability study. Patients received hepatic arterial infusionchemotherapy using the implanted port and catheter systemonce a week during 3 or 6 months. The timing of RF ablationwas decided as follows; a) new intra- or extra-hepaticmetastases did not develop during hepatic arterial infusionchemotherapy, 2) the maximum tumor size became 3-4cm indiameter. Therapeutic response was evaluated by contrast­enhanced CT studies. Eradication of tumor enhancement wasconsidered to be tumor necrosis.

RESULTS: Six patients were included in the present study.The mean maximum tumor size shrunk from 5.0cm to 2.5 cm(p<0.05) and the tumor number decreased from 19 to 13 afterarterial infusion chemotherapy. RF ablation was successfullydone in all residual liver tumors, resulting in complete tumornecrosis in all liver lesions. All patients are still living withoutintrahepatic recurrences during the mean follow-up of 16months. Nodal metastasis developed in one patient whichwas resected.

CONCLUSION: The combined therapy described here is afeasible and useful therapeutic option for the treatment ofliver metastasis from gastric cancer.

Abstract No. 248

Diffusion Weigh ted MR Imaging afterChemoembolization for Neuroendocrine Metastases:Assessment of Thmor Response.I.R. Kamel, Johns Hopkins Medical Institutions. Baltimore,MD, USA ·E.A. Liapi·D.A. Bluemke·i.FH. Geschwind

PURPOSE: To assess treatment response of hepaticneuroendocrine metastases after TACE using diffusion­weighted MR imaging.

MATERIALS AND METHODS: MR imaging studies beforeand after TACE on 30 consecutive patients were evaluated.Patients were scanned using a 1.5-T MR scanner and a phased S87

Page 2: Oncology

S88

array torso coil. Imaging protocol included T2-weighted FSE(TR 5000; TE 1(0), BH diffusion-weighted EPI (B value 500;TR 5000-6500; TE 110), and BH unenhanced and contrast­enhanced Tl-weighted 3D FS ORE (TE 1.2; flip angle 15) inthe arterial and portal venous phases. Images were evaluatedby consensus of 2 radiologists. Mean % lipiodol depositionon CT as well as tumor size, % enhancement, and ADC valuesbefore and after treatment were recorded.

RESULTS: The study included 81 lesions in 21 males and 9females with mean age of58 years. Mean % lipiodol depositionon CT was 59% +1- 4%. Mean tumor diameter before treatmentwas 5.2 cm +1- 0.3 cm, and decreased by an average of9 mmafter treatment (t-test, p<O.OOOl). Mean tumor enhancementin the portal venous phase before treatment was 81 % +1- 3 %,and decreased to 44 % +1- 4 % after treatment (t-test,p<O.OOOl). Tumor ADC value for aU tumors before treatmentwas 0.00171 mm2/sec and remained unchanged after treatment(t-test; p=0.98). Following treatment tumors that had >25%lipiodol deposition (n=68) had a decrease in mean lesion sizeby 1.1 cm (t-test, p<O.OOOl), decrease in mean enhancementby 40% (t-test, p<O.OOOl), and decrease in mean ADC valueby 0.0003 mm2/sec (t-test, p=0.08). Tumors with lipiodoldeposition <=25% on CT (n=13) had no change in size,enhancement or ADC value (t-test, p=0.2, 0.3 and 0.4respectively), after treatment.

CONCLUSION: Following TACE, lesions with >25%lipiodol deposition demonstrate decrease in tumor size andenhancement. The ADC values increased indicating increasingnecrosis and membraneous disruption. These findings canpredict treatment response and may be used to guide therapy.

Abstract No. 249

Comparison Between Intravenous and IntraarterialContrast Injection for Dynamic 3D MRI of Liver Thmorsin Rabbits.A.c. Larson, Northwestern University, Chicago, IL, USA·T.K.Rhee'T. Mounajjed'K. T. Sato'R. Salem'RA Omary

PURPOSE: Although intravenous (IV) contrast-enhanceddynamic MRI is widely accepted for liver tumor imaging, thismethod has limited capacity to detect small «1 cm) lesions.Catheter-directed injections of gadolinium (Od) might be oneapproach to improve MRI detection of these tumors,especially in the setting of future MRI-guided oncologicinterventions, because of the potential to target contrast agentdelivery to tumors. We tested the hypothesis that catheter­based intraarterial (IA) contrast injections improve tumorenhancement in a rabbit liver tumor model.

MATERIALS AND METHODS: We used 1 New ZealandWhite rabbit for an initial dose escalation contrast study. Wethen surgically implanted VX2 carcinoma into the left liverlobe of 3 additional rabbits. After 2-4 weeks, we placed a 2-Fcatheter in the hepatic artery via femoral access and transferredanimals to a 1.5T MR scanner (Siemens Sonata). We performeddynamic 3D inversion recovery ORE MRI (10 slices, 5mmthick, 2.1 s acquisition time for each 3D volume, repeatedlysampled for 4 min) following each Od injection. Scans wereperformed after IA injection of 2 mL 20% Od solution (0.3mL/s) and after IV injection of lmL 100% Od solution (0.3mLls). Tissue intensities returned to baseline betweeninjections. At each slice position containing tumor, identicalregions were assessed in IA and IV images at peak enhancementto calculate tumor-to-liver contrast-to-noise (CNR). Wecompared mean differences in CNR between IA and IVinjections using a two-tailed t-test, with a = 0.05. Tumorswere confirmed by necropsy.

RESULTS: CNR measurements (n=31) were obtained frommultiple tumors in each of the rabbits. Mean CNR for IAinjections (20.9±6.97) was significantly higher than for IVinjections (6.32±3.29; p<0.05). Several tumors with markedIA enhancement had minimal IV enhancement. IA injectionsused 60% less Od than IV injections.

CONCLUSION: Using less overall contrast agent, IA injectionssignificantly improve tumor contrast enhancement overconventional IV techniques using dynamic 3D MRI. Thisstrategy might be employed to enhance detection of smallliver tumors or to conserve contrast agent in the setting offuture MRl-guided transcatheter liver interventions.

Abstract No. 250

Superselective Chemoembolization and RF AblationAssessed in 21 Livers Available after Transplantation.E.K. Lang, Tulane Unviersity Health Sciences Center, NewOrleans, LA, USA'S. ]oshi'M. Brammer'F.G Regenstein ·S.Florman'K. Cline, et a!.

PURPOSE: Oross and histopathologic assessment of theeffect of superselective chemoembolization, somecomplemented by RF ablation, in respect to reduction oftumor volume and remaining viable folci of HCC and CHC.

MATERIALS AND METHODS: 21 patients, (19 He), 2CHC,14 male and 7 female age 39 -57 years were treated bysuperselective chemoembolization (Doxorubicin and ethiodol)CE, (N=21) and sometimes RF ablation (N=4). Tumorresponse on CT is compared to gross and histopathologicfindings on the liver removed for transplantation.

RESULTS: In eight livers with no identifiable residual tumoron CT histopathology proved two to be free of tumor, threeshowing significant necrosis of tumor, two minimal necrosisof tumor and one extensive disseminated tumor. Four patientsshowed an 80-90% regression of tumor on CT of which twoshowed significant necrosis on histopathology, one minimalnecrosis and one disseminated tumor. Five showed 60-80%of tumor necrosis on CT, histopathology showed a significantnecrosis in one, minimal necrosis in one, but massivemicroscopic tumor folci in three. Three patients showed 40­50% tumor necrosis on CT histopathology showing minimalnecrosis in one, extensive disseminated tumor folci in two.The one patients that showed recurrence on CT had extensivedisseminated tumor folci on histopathology.

CONCLUSION: While a tumor free status was confirmed inonly two of the 21 patients significant tumor necrosis andreduction of tumor volume was present in 6, some tumornecrosis in another 5, while 8 showed widely disseminatedtumor cell nests. Curtailment of tumor volume as assessed byCT permitted segmental resection or liver transplantation inall 21 patients.

Pediatric

Abstract No. 251

Hemodialysis Central Venous Catheter (CVC) RelatedComplications in a Pediatric Population.M. Sey, Hospitalfor Sick Children, Toronto, ON, Canada'PChait']. Amaral'B. Connolly'M. Temple'G Krishnamurthy,eta!'

PURPOSE: To the incidence and type of hemodialysis CVCrelated complications in a pediatric population.

MATERIALS AND METHODS: A retrospective chart reviewof all hemodialysis CVCs placed between January 2000 and