A novel role for the Wnt inhibitor APCDD1 in adipocyte differentiation: Implications for diet-induced obesity.

Impaired adipogenic differentiation during diet-induced obesity (DIO) promotes adipocyte hypertrophy and inflammation, thereby contributing to metabolic disease. Adenomatosis polyposis coli down-regulated 1 (APCDD1) has recently been identified as an inhibitor of Wnt signaling, a key regulator of adipogenic differentiation. Here we report a novel role for APCDD1 in adipogenic differentiation via repression of Wnt signaling and an epigenetic linkage between miR-130 and APCDD1 in DIO. APCDD1 expression was significantly up-regulated in mature adipocytes compared with undifferentiated preadipocytes in both human and mouse subcutaneous adipose tissues. siRNA-based silencing of APCDD1 in 3T3-L1 preadipocytes markedly increased the expression of Wnt signaling proteins (Wnt3a, Wnt5a, Wnt10b, LRP5, and ß-catenin) and inhibited the expression of adipocyte differentiation markers (CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ)) and lipid droplet accumulation, whereas adenovirus-mediated overexpression of APCDD1 enhanced adipogenic differentiation. Notably, DIO mice exhibited reduced APCDD1 expression and increased Wnt expression in both subcutaneous and visceral adipose tissues and impaired adipogenic differentiation in vitro Mechanistically, we found that miR-130, whose expression is up-regulated in adipose tissues of DIO mice, could directly target the 3'-untranslated region of the APCDD1 gene. Furthermore, transfection of an miR-130 inhibitor in preadipocytes enhanced, whereas an miR-130 mimic blunted, adipogenic differentiation, suggesting that miR-130 contributes to impaired adipogenic differentiation during DIO by repressing APCDD1 expression. Finally, human subcutaneous adipose tissues isolated from obese individuals exhibited reduced expression of APCDD1, C/EBPα, and PPARγ compared with those from non-obese subjects. Taken together, these novel findings suggest that APCDD1 positively regulates adipogenic differentiation and that its down-regulation by miR-130 during DIO may contribute to impaired adipogenic differentiation and obesity-related metabolic disease.

Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis.

Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs. PV adipose tissues. Although >90% of well-expressed genes were similarly regulated, we identified a signature of 307 differentially expressed genes that were highly enriched for functions associated with the regulation of angiogenesis, vascular morphology, inflammation, and blood clotting. Of the 156 PV upregulated genes, 59 associate with angiogenesis, vascular biology, or inflammation, noteworthy of which include TNFRSF11B (osteoprotegerin), PLAT, TGFB1, THBS2, HIF1A, GATA6, and SERPINE1. Of 166 PV downregulated genes, 21 associated with vascular biology and inflammation, including ANGPT1, ANGPTL1, and VEGFC. Consistent with the emergent hypothesis that PV adipocytes differentially regulate angiogenesis and inflammation, cell culture-derived adipocyte-conditioned media from PV adipocytes strongly enhanced endothelial cell tubulogenesis and monocyte migration compared with media from SQ adipocytes. These findings demonstrate that PV adipocytes have the potential to significantly modulate vascular inflammatory crosstalk in the setting of atherosclerosis by their ability to signal to both endothelial and inflammatory cells.

Histone deacetylase 9 is a negative regulator of adipogenic differentiation.

Differentiation of preadipocytes into mature adipocytes capable of efficiently storing lipids is an important regulatory mechanism in obesity. Here, we examined the involvement of histone deacetylases (HDACs) and histone acetyltransferases (HATs) in the regulation of adipogenesis. We find that among the various members of the HDAC and HAT families, only HDAC9 exhibited dramatic down-regulation preceding adipogenic differentiation. Preadipocytes from HDAC9 gene knock-out mice exhibited accelerated adipogenic differentiation, whereas HDAC9 overexpression in 3T3-L1 preadipocytes suppressed adipogenic differentiation, demonstrating its direct role as a negative regulator of adipogenesis. HDAC9 expression was higher in visceral as compared with subcutaneous preadipocytes, negatively correlating with their potential to undergo adipogenic differentiation in vitro. HDAC9 localized in the nucleus, and its negative regulation of adipogenesis segregates with the N-terminal nuclear targeting domain, whereas the C-terminal deacetylase domain is dispensable for this function. HDAC9 co-precipitates with USF1 and is recruited with USF1 at the E-box region of the C/EBPα gene promoter in preadipocytes. Upon induction of adipogenic differentiation, HDAC9 is down-regulated, leading to its dissociation from the USF1 complex, whereas p300 HAT is up-regulated to allow its association with USF1 and accumulation at the E-box site of the C/EBPα promoter in differentiated adipocytes. This reciprocal regulation of HDAC9 and p300 HAT in the USF1 complex is associated with increased C/EBPα expression, a master regulator of adipogenic differentiation. These findings provide new insights into mechanisms of adipogenic differentiation and document a critical regulatory role for HDAC9 in adipogenic differentiation through a deacetylase-independent mechanism.

Ultrasound monitoring of in vitro radio frequency ablation by echo decorrelation imaging.

OBJECTIVE: The purpose of this study was to test ultrasound echo decorrelation imaging for mapping and characterization of tissue effects caused by radio frequency ablation (RFA). METHODS: Radio frequency ablation procedures (6-minute duration, 20-W power) were performed on fresh ex vivo bovine liver tissue (n = 9) with continuous acquisition of beam-formed ultrasound echo data from a 7-MHz linear array. Echo data were processed to form B-scan images, echo decorrelation images (related to rapid random changes in echo waveforms), and integrated backscatter images (related to local changes in received echo energy). Echo decorrelation and integrated backscatter values at the location of a low-noise thermocouple were assessed as functions of temperature. Echo decorrelation and integrated backscatter images were directly compared with ablated tissue cross sections and quantitatively evaluated as predictors of tissue ablation and overtreatment. RESULTS: Echo decorrelation maps corresponded with local tissue temperature and ablation effects. Consistent echo decorrelation increases were observed for temperatures above 75 degrees C, whereas integrated backscatter maps showed a nonmonotonic temperature dependence complicated by acoustic shadowing, with high variance at large temperature elevations. In receiver operating characteristic curve analysis of echo decorrelation and integrated backscatter maps as predictors of local tissue ablation, echo decorrelation performed well (area under the receiver operating characteristic curve [AUROC] = 0.855 for ablation and 0.913 for overtreatment), whereas integrated backscatter performed poorly (AUROC < 0.6). CONCLUSIONS: Echo decorrelation imaging can map tissue changes due to RFA in vitro, with local echo decorrelation corresponding strongly to local tissue temperature elevations and ablation effects. With further development and in vivo validation, echo decorrelation imaging is potentially useful for improved image guidance of clinical RFA procedures.

Echo Decorrelation Imaging of Rabbit Liver and VX2 Tumor during In Vivo Ultrasound Ablation.

In open surgical procedures, image-ablate ultrasound arrays performed thermal ablation and imaging on rabbit liver lobes with implanted VX2 tumor. Treatments included unfocused (bulk ultrasound ablation, N = 10) and focused (high-intensity focused ultrasound ablation, N = 13) exposure conditions. Echo decorrelation and integrated backscatter images were formed from pulse-echo data recorded during rest periods after each therapy pulse. Echo decorrelation images were corrected for artifacts using decorrelation measured prior to ablation. Ablation prediction performance was assessed using receiver operating characteristic curves. Results revealed significantly increased echo decorrelation and integrated backscatter in both ablated liver and ablated tumor relative to unablated tissue, with larger differences observed in liver than in tumor. For receiver operating characteristic curves computed from all ablation exposures, both echo decorrelation and integrated backscatter predicted liver and tumor ablation with statistically significant success, and echo decorrelation was significantly better as a predictor of liver ablation. These results indicate echo decorrelation imaging is a successful predictor of local thermal ablation in both normal liver and tumor tissue, with potential for real-time therapy monitoring.

Ex Situ Perfusion of Human Limb Allografts for 24 Hours.

BACKGROUND: Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. METHODS: Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL. RESULTS: Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury. CONCLUSIONS: Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.

Outcomes among patients with end-stage liver disease who are coinfected with HIV and hepatitis C virus.

In at-risk populations, shared routes of transmission lead to high rates of concordance between infection with human immunodeficiency virus (HIV) type 1 and hepatitis C virus (HCV). In the era of highly active antiretroviral therapy (HAART), end-stage liver disease (ESLD) has emerged as a leading cause of mortality in coinfected patients. HAART-related toxicities have been implicated, especially when given to patients with viral hepatitis. Rates of response to treatment for HCV infection in coinfected patients continue to lag behind those in monoinfected patients, even with the advent of pegylated interferons. Liver transplantation has been approached with caution in this population because of concern about the sequelae of immunosuppression and HAART-related hepatotoxicity, and results have been conflicting. Clinical and serological markers of ESLD in coinfected patients, management of cirrhosis, and the appropriateness of transplantation are discussed.

Renal transplantations performed using non-heart-beating organ donors: going back to the future?

BACKGROUND: As more expanded-criteria organ donors are used to bridge the widening gap between organ supply and demand, non-heart-beating (NHB) donors will become increasingly important. The purpose of this study was to analyze renal transplant outcomes using this source of cadaveric (CAD) organs and compare the results with heart-beating organ sources. METHODS: Data from 98,698 adult CAD renal transplant recipients and 34,531 living donor renal transplant recipients registered in the U. S. Renal Data System database between January 1993 and June 2000 were analyzed. Kaplan-Meier survival curves were used to compare graft and patient survival rates between NHB, CAD, and living donor transplant recipients. Cox proportional hazards models were used to identify risk factors for NHB donor recipients, while adjusting for potential confounding variables. RESULTS: Recipients of NHB donor organs experienced nearly twice the incidence of delayed graft function (DGF) compared with heart-beating donors (42.4% vs. 23.3%, respectively). NHB donor transplants experienced comparable allograft survival when compared with CAD transplants at 6 years (73.2% vs. 72.5%, respectively; P=NS); patient survival was greater at 6 years for NHB compared with CAD renal transplant recipients (80.9% vs. 77.8%, respectively; P=NS). Significant factors for allograft loss for NHB donor organ recipients included the following: organ used for repeat transplants; DGF; donor age older than 35 years; and head trauma as a cause of initial injury (relative risk 2.74, 1.90, 1.78, and 1.41, respectively). CONCLUSIONS: Although exhibiting elevated DGF rates, allograft and patient survival rates of transplants from NHB donor sources are equivalent to those from conventional CAD sources. Donor age, recipient transplant number, female recipient, mechanism of injury, and DGF were the most pertinent variables leading to poor outcomes.

Epithelioid hemangioendothelioma of the liver disseminated to the peritoneum treated with liver transplantation and interferon alpha-2B.

Epithelioid hemangioendothelioma (EH) is a rare, low-grade, malignant neoplasm of vascular origin that may develop at different sites, such as in the soft tissue, lungs, or liver. We report the case of a 21-year-old female with primary EH of the liver treated by liver transplantation and review the available literature on EH. This patient developed symptomatic recurrence of the tumor in the pelvis 2 months posttransplant. Treatment with interferon alpha-2b resulted in substantial regression of the pelvic metastases and alleviation of symptoms, but the patient developed graft rejection and died of associated complications 16 months posttransplant. This report is the first showing the efficacy of interferon in this setting.

Evaluation of pancreatic allograft dysfunction by laparoscopic biopsy.

BACKGROUND: Histologic evaluation of a failing pancreatic allograft is necessary for accurate classification of graft dysfunction. Unlike percutaneous or transcystoscopic techniques, laparoscopic biopsy allows visualization of the allograft in addition to obtaining tissue for histologic examination. METHODS: We retrospectively reviewed all laparoscopic pancreas transplant biopsies performed over a 15-month period ending February 2002. RESULTS: There were 12 laparoscopic pancreas biopsies performed in 11 patients between 6 weeks and 8 years (mean 2.5+/-2.8 years) after transplant. Indications for biopsy were hyperglycemia (n=8), hyperamylasemia (n=3), and graft tenderness (n=1). Adequate tissue was obtained in 11 of 12 biopsies. Two patients received definitive treatment at the time of laparoscopy (pseudocyst debridement, ovarian cyst excision). CONCLUSIONS: Laparoscopic pancreas transplant biopsy allows safe visualization of the allograft and effective specimen retrieval, and in some cases provides the opportunity for therapeutic intervention.

Long-term follow-up of percutaneous transhepatic balloon cholangioplasty in the management of biliary strictures after liver transplantation.

BACKGROUND: This study evaluated the efficacy of a protocol of initial balloon dilation for biliary strictures after liver transplantation. METHODS: Complete records from 96 patients with biliary strictures were retrospectively reviewed. Seventy-six patients received percutaneous transhepatic balloon cholangioplasty (PTBC) after initial placement of biliary drainage (percutaneous transluminal cholangiography [PTC]) tube. In most cases, three dilations were performed with a 4 to 8 week interval between procedures. Follow-up ranged from 6 months to 10 years. RESULTS: PTBC successfully treated strictures in 39 of 76 (51.3%) cases. Factors favoring successful PTBC included older age at transplant, shorter cold ischemic time, and single strictures. There were nine recurrent strictures after PTBC, all of which were successfully treated by nonoperative measures. The number of dilations performed affected both the likelihood of success and the long-term risk of stricture recurrence. Of the 37 PTBC failures, 14 underwent subsequent surgical revision. When both angiographic and surgical modalities were considered, treatment success was associated with first transplants, shorter cold ischemic time and operative time, and less intraoperative transfusion requirements. Factors associated with treatment failure included multiple, central hepatic duct, and intrahepatic strictures. PTC-tube independence was achieved in 51 of 76 (67%) patients using the combined approach of PTBC and surgery for PTBC failures. CONCLUSIONS: PTBC is an effective initial modality for treating posttransplant biliary strictures. Prolonged cold ischemic and operative times and multiple or peripheral strictures predispose to treatment failure. Solitary extrahepatic strictures that fail PTBC are salvageable with surgical revision with excellent results.

Gender imbalance in living donor renal transplantation.

BACKGROUND: Previous studies have shown more women than men among living donors (LD) and more men among recipients of those kidneys. In this study, we compared the evolving demographics of LD transplants. METHODS: We retrospectively analyzed all LD transplants performed in our center between 1964 and 2000. RESULTS: Among 1182 LD cases, 1035 (88%) were biologically related (LRD) and 147 (12%) were unrelated (LURD). LURD donors and recipients were significantly older than LRD donors and recipients, respectively (P=0.0001). More LURD allograft recipients were male (71%) compared with LRD recipients (57%) (P=0.0013). The proportion of female donors was 55% in both groups. Spousal donations were predominantly wife-to-husband (69%). Compared with the LRD group, there was a greater proportion of female-to-male LURD transplants (46 vs. 30%) and a smaller proportion of female-to-female LURD transplants (10 vs. 25%) (P=0.0001). When spousal pairs were excluded from the analysis, there was a higher proportion of male-to-male (48 vs. 27%) donations and a lower proportion of male-to-female (18 vs. 9%) and female-to-female (25 vs. 17%) transplants in the LURD group (P=0.001). CONCLUSIONS: Gender disparities in LD transplantation are primarily due to a higher proportion of wife-to-husband donations and a lower incidence of male-to-female grafts among nonspousal LURD transplants. Strategies should be devised to ensure access for women to renal transplantation and to encourage and facilitate donation by men.

Interaction between donor and recipient age in determining the risk of chronic renal allograft failure.

OBJECTIVES: Donor age is a known risk factor for chronic allograft failure (CAF) in renal transplant recipients. We have recently shown that advanced recipient age is also a risk factor for CAF. To investigate the interaction between donor and recipient age, we analyzed 40,289 primary solitary Caucasian adult renal transplants registered at the United States Renal Data System (USRDS) from 1988 to 1997. DESIGN: CAF was defined as allograft loss beyond 6 months posttransplantation, censored for death, recurrent disease, acute rejection, thrombosis, noncompliance, infection, or technical problems. Cox proportional hazards models were used to investigate the risk of allograft loss secondary to CAF. All models were corrected for 15 covariates including donor and recipient demographics, ischemic time, and human leukocyte antigen match. Donor and recipient age were categorized, and relative risk for allograft loss of the interaction between the obtained categorical covariates was evaluated. SETTING: Retrospective data analysis using the USRDS. PARTICIPANTS: All primary Caucasian renal transplant recipients from 1988 to 1997. RESULTS: Patients aged 55 and older who received donor kidneys had a 110% increased risk of CAF (relative risk (RR) = 2.1, 95% confidence interval (CI) = 1.9-2.3, P< .001) and recipients aged 65 and older had a 90% increased risk for CAF (RR = 1.9, 95% CI = 1.61-2.1, P< .001), compared with the youngest reference groups. In addition, there was an additive and, in the long term, synergistic interaction between donor and recipient age in determining allograft loss. CONCLUSIONS: Donor and recipient age had an independent, equivalently detrimental effect on renal allograft survival. An overall additive and, in the long term (beyond 36 months posttransplant), synergistic deleterious effect on renal allograft survival was observed for the interaction of donor and recipient age.

An initial experience and evolution of laparoscopic hepatic resectional surgery.

BACKGROUND: The use of minimally invasive procedures has revolutionized modern surgery. Only recently has laparoscopy been introduced for use in hepatic surgery. METHODS: Patient demographics, tumor characteristics, and outcomes were evaluated for all initial cases of laparoscopic hepatic resection. RESULTS: Twenty-one resections were performed in 17 patients; 5 were performed for malignancy, of which 3 had underlying cirrhosis, and the remaining 12 for benign symptomatic disease. Mean patient age was 55.4 (range, 24-82 years). The mean number of lesions was 1.4 (range, 1-5), having an average size of 7.6 cm (range, 2-30 cm). Mean operative time was 2.8 hours (range, 2-5 hours) hours. Most resections involved 1 or more Couinaud segments. Mean blood loss was 288 cc (range, 50-150 cc). Complications included re-operation for hemorrhage (n=2), biliary leakage (n=1), and death from hepatic failure (n=1). Mean length of stay was 2.9 days (range, 1-14). When compared with our series of 100 patients who underwent open hepatic resection for benign tumors, significantly greater means ( P <.05) were noted for blood loss (485 cc), operative time (4.5 hours), and length of stay (6.5 days). CONCLUSIONS: Laparoscopic hepatic surgery, though complex, can be performed safely and efficaciously. Minimally invasive surgery appears to provide several distinct advantages over traditional open hepatic surgery. However, techniques for the laparoscopic control of bleeding and bile leak remain in their infancy.

In vivo thermal ablation monitoring using ultrasound echo decorrelation imaging.

Previous work indicated that ultrasound echo decorrelation imaging can track and quantify changes in echo signals to predict thermal damage during in vitro radiofrequency ablation (RFA). In the in vivo studies reported here, the feasibility of using echo decorrelation imaging as a treatment monitoring tool was assessed. RFA was performed on normal swine liver (N = 5), and ultrasound ablation using image-ablate arrays was performed on rabbit liver implanted with VX2 tumors (N = 2). Echo decorrelation and integrated backscatter were computed from Hilbert transformed pulse-echo data acquired during RFA and ultrasound ablation treatments. Receiver operating characteristic (ROC) curves were employed to assess the ability of echo decorrelation imaging and integrated backscatter to predict ablation. Area under the ROC curves (AUROC) was determined for RFA and ultrasound ablation using echo decorrelation imaging. Ablation was predicted more accurately using echo decorrelation imaging (AUROC = 0.832 and 0.776 for RFA and ultrasound ablation, respectively) than using integrated backscatter (AUROC = 0.734 and 0.494).

Allele-specific expression of angiotensinogen in human subcutaneous adipose tissue.

The angiotensinogen gene is genetically linked with hypertension, but the mechanistic basis for association of sequence variants in the promoter and coding region of the gene remains unclear. An E-box at position -20 has been hypothesized to control the level of angiotensinogen expression, but its mechanistic importance for angiotensinogen expression in human tissues is uncertain. We developed an allele-specific polymerase chain reaction-based assay to distinguish between angiotensinogen mRNA derived from variants at the -20 position (rs5050) in the angiotensinogen promoter in adipose tissues obtained during surgery. The assay takes advantage of linkage disequilibrium between the rs5050 (located in the promoter) and rs4762 (located in the coding region) single nucleotide polymorphisms. This strategy allowed us to assess the level of allele-specific expression in A-20C heterozygous subjects comparing the relative proportion of each allele with the total, thus eliminating the problem of variability in the level of total angiotensinogen mRNA among subjects. We show that angiotensinogen mRNA derived from the -20C allele is expressed significantly higher than that derived from the -20A allele in subcutaneous adipose tissue, and increased expression correlates with enriched chromatin binding of upstream stimulatory factor-2 to the -20C E-box compared with -20A. This may be depot selective because we were unable to detect these differences in omental adipose. This provides the first data directly comparing expression of angiotensinogen mRNA and differential transcription factor binding derived from 2 variant alleles in human tissue where the ratio of expression of one allele to another can be accurately determined.

Laparoscopic cholecystectomy in the cirrhotic patient: predictors of outcome.

BACKGROUND: We sought to determine the outcome predictors of 94 cirrhotic patients undergoing laparoscopic cholecystectomy (LC). METHODS: We performed a single-center, retrospective review of cirrhotic patients undergoing LC for symptomatic gallbladder disease. Statistical analysis was completed using the Chi-square, Wilcoxon rank-sum, and Student t tests as appropriate. RESULTS: Ninety-four procedures were completed. The median Child-Turcotte-Pugh (CTP) score was 6 (range, 5-12), and the average Model for End-Stage Liver Disease (MELD) score was 11 ± 5. Hepatitis C was the most common etiology of liver disease (50%) followed by Laennec's cirrhosis (22%). The average length of stay was 2.6 ± 4.3 days; 21% were outpatient procedures. The conversion rate was 11%. Conversion risk factors were decreased serum albumin, increased MELD score, and blood loss. Morbidity occurred in 32 patients. Predictors of morbidity were decreases in serum albumin, increases in International Normalized Ratio (INR) and CTP score, and the number of intraoperative red blood cell transfusions. Mortality occurred in 4 patients. Increased INR, CTP score, CTP class, the number of intraoperative blood and platelet transfusions were predictors of mortality. CONCLUSION: LC can be safely performed in cirrhotic patients with appropriate patient selection. Liver synthetic function, operative blood loss, transfusion requirement, CTP, and MELD scores may be used to predict outcomes in these patients.

Treatment of rabbit liver cancer in vivo using miniaturized image-ablate ultrasound arrays.

In the preclinical studies reported here, VX2 cancer within rabbit liver has been treated by bulk ultrasound ablation employing miniaturized image-ablate arrays. Array probes were constructed with 32 elements in a 2.3 × 20 mm(2) aperture, packaged within a 3.1 mm stainless steel tube with a cooling and coupling balloon for in vivo use. The probes were measured capable of 50% fractional bandwidth for pulse-echo imaging (center frequency 4.4 MHz) with >110 W/cm(2) surface intensity available at sonication frequencies 3.5 and 4.8 MHz. B-scan imaging performance of the arrays was measured to be comparable to larger diagnostic linear arrays, although nearfield image quality was reduced by ringdown artifacts. A series of in vivo ablation procedures was performed using an unfocused 32-element aperture firing at 4.8 MHz with exposure durations 20-70.5 s and in situ spatial average, temporal average intensities 22.4-38.5 W/cm(2). Ablation of a complete tumor cross-section was confirmed by vital staining in seven of 12 exposures, with four exposures ablating an additional margin >1 mm beyond the tumor in all directions. Analysis suggests a threshold ablation effect, with complete ablation of tumor cross-sections for exposures with delivery of >838 J acoustic energy. The results show feasibility for in vivo liver cancer ablation using miniaturized image-ablate arrays suitable for interstitial deployment.