Tumor Ablation Using 3-Dimensional Electromagnetic-Guided Ultrasound Versus Standard Ultrasound in a Porcine Model.

Introduction. The objective of this study was to compare the placement of ablation needles using 3-dimensional electromagnetic-guided ultrasound (guided) to standard ultrasound guidance (standard) in both laparoscopic surgery and open surgery. Endpoints for this study included targeting accuracy and number of required needle withdrawals and reorientations. Methods. Using a porcine model, fiducial markers were placed into the kidney and liver to represent tumors. Navigation and identification of target sites was achieved using standard or guided ultrasound. Intraprocedural observations as well as the number of needle placement attempts per target were recorded. Three board-certified general surgeons performed the navigation and ablation procedures. After completion of the navigation and ablation procedures, necropsy was performed. The position of the ablation zones relative to the fiducial markers was recorded. Results. A total of 48 procedures were performed across 6 animals (50% open and 50% laparoscopic). Overall, the guided ablations required 50% fewer attempts to successfully target the marker (P = .01). There was a 62% reduction of attempts for guided laparoscopic ablation (P = .006). On subgroup analysis of laparoscopic ablation, the benefit remained for liver (P = .041) ablations, but not for renal ablations (P = .093). There was no significant difference between the groups with regard to targeting accuracy (91.3% guided vs 95.4% standard, P = .58). Conclusions. The number of targeting attempts required during laparoscopic ablation procedures was significantly less with guided than with standard ultrasound, particularly for laparoscopic ablation of liver lesions. These findings suggest that the guided ultrasound can potentially reduce complications during laparoscopic ablation procedures.

The effect of alcohol on Sirt1 expression and function in animal and human models of hepatocellular carcinoma (HCC).

INTRODUCTION: Chronic heavy alcohol use is an independent risk factor for developing hepatocellular carcinoma (HCC). Sirtuin-1 (Sirt1) is a NAD+-dependent deacetylase implicated in alcohol-induced liver injury and overexpressed in human HCC. The aims of this study were to investigate Sirt1 expression in mouse models of HCC and chronic EtOH-feeding, and in human HCC cells expressing alcohol metabolizing enzymes. METHODS: C57BL/6 and B6C3 mice were injected with DEN and randomized to receive drinking water (DW) or EtOH-DW for 8 weeks at 36 weeks. Livers were analyzed for HCC incidence, size, and Sirt1 expression. In parallel, human HepG2 cells or HepG2 cells transfected to express ADH and CYP2E1 (VL-17a cells) were treated with alcohol (0-50 mM) and/or CAY10591 (Sirt1 activator) or EX-527 (Sirt1 inhibitor). RESULTS: B6C3 mice exhibited significantly elevated Sirt-1 expression vs. C57BL/6 mice and Sirt-1 expression was elevated in HCC vs. non-tumor liver. However, EtOH-feeding did not further affect Sirt1 expression in mice of either background despite EtOH increasing HCC size and incidence in B6C3 mice. In vitro, EtOH treatment significantly decreased Sirt1 expression in VL-17a-cells and stimulated cell growth, an effect not observed in HepG2 cells. The effects of ethanol on VL-17a cells were abrogated by pretreatment with CAY10591. CONCLUSIONS: Sirt1 expression correlates with susceptibility to form HCC, but is not further affected by alcohol feeding. Conversely Sirt1 expression and function is impacted by alcohol metabolism capacity in human HCC cells in vitro. These discrepancies in Sirt1-expression-function may reflect differences in enzyme expression compared to activity, or more complex changes in genes targeted for deacetylation during tumor progression in the setting of chronic alcohol ingestion.

Optimal ablation volumes are achieved at submaximal power settings in a 2.45-GHz microwave ablation system.

INTRODUCTION: Local ablative therapies, including microwave ablation (MWA), are common treatment modalities for in situ tumor destruction. Currently, 2.45-GHz ablation systems are gaining prominence because of the shorter application times required. The aims of this study were to determine optimal power and time to ablation volume (AbV) ratios for a new 1.8-mm-2.45-GHz antenna using ex vivo tissue models. METHODS: The 1.8-mm-2.45-GHz Accu2i MWA system was employed to perform ablations in bovine liver, porcine muscle, and porcine kidney ex vivo. Whole tissues were prewarmed (35°C) and multiple ablations performed at power settings of 60 to 180 W for 2- to 6-minute time intervals. Postablation, tissues were dissected, AbVs calculated, and correlations to power and time settings made. RESULTS: Significant increases in AbV were measured between each of the time points for a constant power setting in all 3 tissues. Increasing power settings led to significant increases in AbV at power settings ≤140 W. However, no significant increase in AbV was obtained at power settings >140 W. CONCLUSIONS: Optimal efficiency for MWA using a new 1.8-mm-2.45-GHz system is achieved at settings of ≤140 W for 6 minutes in a range of ex vivo tissue and no additional benefit occurs by increasing the power setting to 180 W in these tissues.

Laparoscopic microwave ablation of human liver tumours using a novel three-dimensional magnetic guidance system.

BACKGROUND: Accurate antenna placement is essential for effective microwave ablation (MWA) of lesions. Laparoscopic targeting is made particularly challenging in liver tumours by the needle's trajectory as it passes through the abdominal wall into the liver. Previous optical three-dimensional guidance systems employing infrared technology have been limited by interference with the line of sight during procedures. OBJECTIVE: The aim of this study was to evaluate a newly developed magnetic guidance system for laparoscopic MWA of liver tumours in a pilot study. METHODS: Thirteen patients undergoing laparoscopic MWA of liver tumours gave consent to their participation in the study and were enrolled. Lesion targeting was performed using the InnerOptic AIM™ 3-D guidance system to track the real-time position and orientation of the antenna and ultrasound probe. RESULTS: A total of 45 ablations were performed on 34 lesions. The median number of lesions per patient was two. The mean ± standard deviation lesion diameter was 18.0 ± 9.2 mm and the mean time to target acquisition was 3.5 min. The first-attempt success rate was 93%. There were no intraoperative or immediate postoperative complications. Over an average follow-up of 7.8 months, one patient was noted to have had an incomplete ablation, seven suffered regional recurrences, and five patients remained disease-free. CONCLUSIONS: The AIM™ guidance system is an effective adjunct for laparoscopic ablation. It facilitates a high degree of accuracy and a good first-attempt success rate, and avoids the line of site interference associated with infrared systems.

The impact of regionalization of pancreaticoduodenectomy for pancreatic Cancer in North Carolina since 2004.

Pancreaticoduodenectomy (PD) carries a significant risk. High-volume centers (HVCs) provide improved outcomes and regionalization is advocated. Rapid regionalization could, however, have detrimental effects. North Carolina has multiple HVCs, including an additional HVC added in late 2006. We investigated regionalization of PD and its effects before, and after, the establishment of this fourth HVC. The North Carolina Hospital Discharge Database was queried for all PDs performed during 2004 to 2006 and 2007 to 2009. Hospitals were categorized by PD volume as: low (one to nine/year), medium (10 to 19/year), and high (20/year or more). Mortality and major morbidity was assessed by comparing volume groups across time periods. Number of PDs for cancer increased 91 per cent (129 to 246 cases) at HVCs, whereas decreasing at low-volume (62 to 58 cases) and medium-volume (80 to 46 cases) centers. Percentage of PD for cancer performed at HVCs increased significantly (47.6 to 70.3%) while decreasing for low- and medium-volume centers (P < 0.001). Mortality was significantly less at HVCs (2.8%) compared with low-volume centers (10.3%) for 2007 to 2009. Odds ratio for mortality was significantly lower at HVCs during 2004 to 2006 (0.31) and 2007 to 2009 (0.34). Mortality for PD performed for cancer decreased from 6.6 to 4.6 per cent (P = 0.31). Major morbidity was not significantly different between groups within either time period; however, there was a significant increase in major morbidity at low-volume centers (P = 0.018). Regionalization of PD for cancer is occurring in North Carolina. Mortality was significantly lower at HVCs, and rapid regionalization has not detracted from the superior outcomes at HVCs.

Microwave ablation for hepatic malignancies: a call for standard reporting and outcomes.

BACKGROUND: Clinical standards of reporting microwave ablation outcomes have not been defined with regard to ablation success, 90-day morbidity, local recurrence after ablation, and nonablation hepatic recurrence. We propose recommendations for microwave ablation reporting and quality standards. METHODS: Literature review of clinical studies focusing on microwave ablation of primary and metastatic hepatic tumors was reported. RESULTS: Ablation success remains the highest quality reporting standard with variations in nomenclature, but with a universal agreement of complete destruction of the target lesion within 1 month after initial microwave ablation. Local recurrence after ablation remains highly variable, with reports as low as 2.2% to as high as 22%; standards lack a common, clearly defined distance from the initial target ablated lesion and the requirement that the target lesion be defined as an ablation success before it can be called a recurrence. Nonablation hepatic recurrence, nonhepatic recurrence, and 90-day morbidity and mortality remain limited in the current literature. CONCLUSIONS: Standardization of hepatic microwave ablation reporting standards are proposed. Current reporting standards in microwave ablation of hepatic malignancies are suboptimal and lack standardization for comparison across institutions.

Comparison of culture and molecular techniques for microbial community characterization in infected necrotizing pancreatitis.

BACKGROUND: Infected necrotizing pancreatitis is associated with significant morbidity and mortality. Peripancreatic fluid cultures may fail to identify all the infecting organisms. The aim of this study was to compare the bacterial biome of peripancreatic fluid from infected necrotizing pancreatitis patients using 16S ribosomal RNA (rRNA) DNA deep sequencing and quantitative polymerase chain reaction (qPCR) targeting the 16S rRNA gene versus standard laboratory culture. MATERIALS AND METHODS: Peripancreatic fluid was collected during operative or radiologic intervention and samples sent for culture. In parallel, microbial DNA was extracted, qPCR targeting the 16S rRNA gene and 16S rRNA PCR amplification followed by Illumina deep sequencing were performed. RESULTS: Using culture techniques, the bacterial strains most frequently identified were gram-negative rods (Escherichia coli, Klebsiella pneumoniae) and Enterococcus. Samples in which culture results were negative had copy numbers of the 16S rRNA gene close to background in qPCR analysis. For samples with high bacterial load, sequencing results were in some cases in good agreement with culture data, whereas in others there were disagreements, likely due to differences in taxonomic classification, cultivability, and differing susceptibility to background contamination. Sequencing results appeared generally unreliable in cases of negative culture where little microbial DNA was input into qPCR sequencing reactions. CONCLUSIONS: Both sequencing and culture data display their own sources of bias and potential error. Consideration of data from multiple techniques will yield a more accurate view of bacterial infections than can be achieved by any single technique.

Altered lysophosphatidic acid (LPA) receptor expression during hepatic regeneration in a mouse model of partial hepatectomy.

BACKGROUND: Hepatic regeneration requires coordinated signal transduction for efficient restoration of functional liver mass. This study sought to determine changes in lysophosphatidic acid (LPA) and LPA receptor (LPAR) 1-6 expression in regenerating liver following two-thirds partial hepatectomy (PHx). METHODS: Liver tissue and blood were collected from male C57BL/6 mice following PHx. Circulating LPA was measured by enzyme-linked immunosorbent assay (ELISA) and hepatic LPAR mRNA and protein expression were determined. RESULTS: Circulating LPA increased 72 h after PHx and remained significantly elevated for up to 7 days post-PHx. Analysis of LPAR expression after PHx demonstrated significant increases in LPAR1, LPAR3 and LPAR6 mRNA and protein in a time-dependent manner for up to 7 days post-PHx. Conversely, LPAR2, LPAR4 and LPAR5 mRNA were barely detected in normal liver and did not significantly change after PHx. Changes in LPAR1 expression were confined to non-parenchymal cells following PHx. CONCLUSIONS: Liver regeneration following PHx is associated with significant changes in circulating LPA and hepatic LPAR1, LPAR3 and LPAR6 expression in a time- and cell-dependent manner. Furthermore, changes in LPA-LPAR post-PHx occur after the first round of hepatocyte division is complete.

Laparoscopic transgastric endolumenal cystogastrostomy and pancreatic debridement.

BACKGROUND: Cystogastrostomy is commonly performed for internal drainage of pancreatic pseudocysts (PP) and concomitant debridement of walled-off pancreatic necrosis (WOPN). While an open approach to cystogastrostomy is well established, an optimal minimally invasive technique continues to evolve. This laparoscopic transgastric endolumenal cystogastrostomy presented here allows for a large cystogastrostomy with complete debridement of necrosis and internal drainage through a minimally invasive approach. METHODS: We performed a retrospective review of 22 patients with symptomatic PP/WOPN treated with attempted laparoscopic transgastric endolumenal cystogastrostomy (Lap-TEC) and pancreatic debridement. Short- and long-term outcomes were assessed. RESULTS: From November 2006 to March 2013, a total of 22 Lap-TEC/pancreatic debridement procedures were attempted; 15 were completed laparoscopically. The median age of the cohort was 49.5 ± 12 years (range = 18-71), average body mass index = 29.1 kg/m(2), 77 % had an ASA score ≥ 3, and 10 were female. Gallstones were the most common etiology (50 %), and median time between initial presentation and surgery was 86 days (range = 0-360). Median operative time and estimated blood loss were 213 min and 100 cc, respectively. Forty-one percent of the patients were admitted to the ICU postoperatively and the average length of stay was 14 days (range = 4-50). Median follow-up was 2 months (range = 0-62.5), with one patient having a procedure-related complication. No other reoperations, late complications, or mortalities occurred. All patients had resolution of their symptoms and fluid collections. CONCLUSION: This technique of internal drainage via Lap-TEC and pancreatic debridement has been successful in achieving primary drainage and relieving symptoms of PP/WOPN with no mortality and minimal morbidity.

Microwave ablation for hepatic malignancies: a multiinstitutional analysis.

OBJECTIVE: This study hypothesized that tumor size, number of tumors, surgical approach, and tumor histology significantly affected microwave ablation (MWA) success and recurrence-free survival. BACKGROUND: Although many hepatobiliary centers have adopted MWA, the factors that influence local control are not well described. METHODS: Consecutive patients with hepatic malignancy treated by MWA were included from 4 high-volume institutions (2003-2011) and grouped by histology: hepatocellular carcinoma (HCC), colorectal liver metastases, neuroendocrine liver metastases, and other cancers. Independent significance of outcome variables was established with logistic regression and Cox proportional hazards models. RESULTS: Four hundred fifty patients were treated with 473 procedures (139 HCC, 198 colorectal liver metastases, 61 neuroendocrine liver metastases, and 75 other) for a total of 875 tumors. Median follow-up was 18 months. Concurrent hepatectomy was performed in 178 patients (38%), and when performed was associated with greater morbidity. Complete ablation was confirmed for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (10 were unevaluable). A surgical approach (open, laparoscopic, or percutaneous) had no significant impact on complication rates, recurrence, or survival. The local recurrence rate was 6.0% overall and was highest for HCC (10.1%, P = 0.045) and percutaneously treated lesions (14.1%, P = 0.014). In adjusted models, tumor size 3 cm or more predicted poorer recurrence-free survival (hazard ratio: 1.60, 95% CI: 1.02-2.50, P = 0.039). CONCLUSIONS: In this large data set, patients with 3 cm or more tumors showed a propensity for early recurrence, regardless of histology. Higher rates of local recurrence were noted in HCC patients, which may reflect underlying liver disease. There were no significant differences in morbidity or survival based on the surgical approach; however, local recurrence rates were highest for percutaneously ablated tumors.

Does a calculated "NAFLD fibrosis score" reliably negate the need for liver biopsy in patients undergoing bariatric surgery?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease in the USA. Biopsy has been the standard for determining fibrosis but is invasive, costly, and associated with risk. Previous studies report a calculated "NAFLD fibrosis scores" (cNFS) as a means to overcome the need for biopsy. We compared cNFS versus biopsy-pathological scoring for patients undergoing bariatric surgery. METHODS: We retrospectively reviewed patients with available preoperative labs and patient information undergoing Roux-en-Y gastric bypass (RYGBP) surgery at a single institution over a 5.5-year period. Biopsy samples were blind scored by a single hepatopathologist and compared with scores calculated using a previously reported cNFS. RESULTS: Of the 225 patients that met the inclusion criteria, the mean body mass index was 44.6 ± 5.4 kg/m(2) and 85 % were female. Using the cNFS, 39.6 % of patients were categorized into low fibrosis, 52 % indeterminate, and 8.4 % high fibrosis groups. Analysis of fibrosis by pathology scoring demonstrated 2 of 89 (2.2 %) and 7 of 110 (3.4 %) had significant fibrosis in the low and intermediate groups, respectively. Conversely, in the high fibrosis group calculated by cNFS, only 6 of 19 (31.6 %) exhibited significant fibrosis by pathology scoring. CONCLUSIONS: No definitive model for accurately predicting presence of NAFLD and fibrosis currently exits. Furthermore, under no circumstances should a clinical "NAFLD fibrosis score" replace liver biopsy at this time for RYGBP patients.

Microwave ablation using 915-MHz and 2.45-GHz systems: what are the differences?

OBJECTIVES: This study was conducted to evaluate differences between 915-MHz and 2.45-GHz microwave ablation (MWA) systems in the ablation of hepatic tumours. METHODS: A retrospective analysis of patients undergoing hepatic tumour MWA utilizing two different systems over a 10-month period was carried out. RESULTS: Data for a total of 48 patients with a mean age of 58 ± 1.24 years were analysed. A total of 124 tumours were ablated; 72 tumours were ablated with a 915-MHz system and 52 with a 2.45-GHz system. Mean tumour diameters were 1.7 ± 0.1 cm in the 915-MHz group and 2.5 ± 0.2 cm in the 2.45-GHz group (P < 0.01). Mean ablation time per burn was 8.1 ± 0.3 min in the 915-MHz group and 4.0 ± 0.1 min in the 2.45-GHz group (P < 0.01). The mean number of burns per lesion was 2.0 ± 0.1 in the 915-MHz group and 1.7 ± 0.1 in the 2.45-GHz group (P < 0.05). The mean ablation time per lesion was 9.7 ± 0.7 min in the 915-MHz group, and 6.6 ± 0.6 min in the 2.45-GHz group (P < 0.01). The 2.45-GHz system demonstrated a better correlation between ablation time and tumour size (r(2) = 0.6222) than the 915-MHz system; (r(2) = 0.0696). Mean total energy applied per lesion, and energy applied per cm, were greater with the 915-MHz system (P < 0.05 and P < 0.01, respectively). Total energy applied per lesion was similarly correlated for the 2.45-GHz (r(2) = 0.6263) and 915-MHz (r(2) = 0.7012) systems. Mean total energy applied per cm/min was greater with the 2.45-GHz system (P < 0.05). CONCLUSIONS: Both 915-MHz and 2.45-GHz MWA systems achieve reproducible hepatic tumour ablation. The 2.45-GHz system achieves equivalent, but more predictable and faster ablations using a single antenna system.

Robotic hepatobiliary and pancreatic surgery: lessons learned and predictors for conversion.

BACKGROUND: The use of surgical robots has slowly gained an increasing presence in the realm of hepatobiliary and pancreatic (HPB) surgery. With additional experience, anecdotal evidence has been useful in guiding patient selection for complex robotic procedures. In the following analysis, we reviewed our case series and looked for predictors of conversion in robotic HPB surgery. METHODS: We retrospectively reviewed all patients who underwent robotic HPB procedures by a single surgeon at two institutions during March 2006-June 2012. Patient demographics, operative data, procedure type and conversion information were recorded. Trends were analysed for indications for conversion. A subset analysis of robotic-assisted laparoscopic distal pancreatomy was performed and compared with laparoscopic and open distal pancreatectomy during the same time period by the same surgeon. RESULTS: During this time period, 77 patients underwent robotic hepatobiliary and pancreatic procedures. All procedures were performed by a single surgeon (J.M.) and included 38 males (49%) and 39 females (51%). Median age was 59 and the majority of patients were ASA class III. There were 24 conversions, which decreased in frequency from 2009 (7) to 2011 (3). Reasons for conversion included significant obesity and technical difficulty. Patients with conversions had more intraoperative blood loss (966 vs 176 ml), more frequently received transfusion (29% vs 2%) and were more likely to have postoperative intensive care. Overall length of stay was longer following conversion (8.3 vs 5.6 days). CONCLUSIONS: Robotic-assisted hepatobiliary and pancreatic procedures are often extremely complex, with a significant learning curve. Recognizing factors that prohibit successful completion of a robotic-assisted surgical procedure is key for patient safety. Careful patient selection in the appropriate settings facilitates the maximal benefit of robotic-assisted complex HPB surgery.

Obesity, but not ethanol, promotes tumor incidence and progression in a mouse model of hepatocellular carcinoma in vivo.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major global health burden. Although chronic, heavy alcohol abuse is an established risk factor for HCC, obesity is emerging as an increasingly important factor in HCC development. Given that other risk factors for HCC act synergistically to promote tumorigenesis, we investigated the effects of diet-induced obesity and chronic ethanol consumption on tumor progression. METHODS: A diethylnitrosamine (DEN) mouse model of HCC was established and mice randomized to control (CD; 10 % kcal% fat) or high fat (HFD; 60 % kcal% fat diet) at 5 weeks of age. At 35 weeks, mice were randomized to 10/20 % ethanol (EtOH) in drinking water (alternate days), or drinking water (H2O) alone. Tumor incidence/size were measured and confirmed. Liver tissue was analyzed for oxidative stress and EtOH-metabolizing enzymes and serum analyzed for liver function and nutritional status. RESULTS: DEN treatment induced HCC formation in 60 % CD-H2O mice (6 of 10), an effect exacerbated by HFD (89 %). Tumors in HFD animals occupied significantly more of the liver than mice on CD. EtOH-feeding did not impact HCC incidence or tumor size. HFD resulted in increased liver injury and liver:body weight ratio regardless of EtOH consumption. Increased tumor incidence was associated with elevated hepatic oxidative stress in the absence of changes in intrinsic antioxidant (glutathione) levels. CONCLUSIONS: Obesity independently promoted HCC formation in the absence or presence of a known hepatocarcinogen (DEN), and enhanced both number and size of hepatic tumors independent of chronic EtOH consumption in mice.

Operative microwave ablation for hepatocellular carcinoma: complications, recurrence, and long-term outcomes.

BACKGROUND: Treatment of hepatocellular carcinoma (HCC) in the setting of cirrhosis is limited by tumor size/location and underlying liver disease. Radiofrequency ablation is utilized in selected patients; however, local recurrence remains a concern. Microwave ablation (MWA) delivers energy to tissue in a unique fashion, reducing local recurrence. A minimally invasive operative approach allows for mobilization/protection of adjacent structures, intra-operative ultrasound, and assessment of ablation progress. STUDY DESIGN: Retrospective review of operative MWA performed for HCC in patients with cirrhosis over a 4-year period at a single center. Complications were stratified by Clavien-Dindo classification. Incomplete ablation and local, regional, and metastatic recurrence was assessed on follow-up imaging. Survival was assessed in months. RESULTS: Fifty-four patients with 73 tumors underwent MWA. Median tumor size was 2.6 cm (range 0.5-8.5 cm). Cirrhosis was present in 92.6 % of patients, with a Child-Pugh score of B/C in 27.8 % and hepatitis C present in 59.3 %. A minimally invasive approach was used in 94.5 % of patients. There were no deaths within 30 days. Thirty-day morbidity was 28.9 %, with grade III complications present in 11.5 %. Delayed complications occurred in 7.8 % of patients, with a 5.6 % 90-day mortality. Incomplete ablation was identified in 5.9 % of tumors with local recurrence of 2.9 % at 9 months median follow-up. Regional and metastatic recurrence occurred in 27.5 and 11.8 % at 9 months median follow-up. Median survival was not reached at 11 months median follow-up. One- and 2-year survival was 72.3 and 58.8 %. CONCLUSION: Operative, preferably minimally invasive, MWA can be performed in cirrhotic patients with HCC with acceptable morbidity and low recurrence rates. High regional and metastatic recurrence rates in these patients underscore the need for minimally invasive, low morbidity approaches to liver-directed therapy.

Evaluation of an innovative, cordless ultrasonic dissector.

Ultrasonic thermal energy is commonly used for dissection and vessel ligation. This study compared HARMONIC ACE and Sonicision Cordless Ultrasonic Dissector (SCUD). The devices were used in an in vivo porcine model to coagulate 189 arteries up to 5 mm. Seal times were similar: SCUD, 5.2 ± 1.7 s; ACE, 4.9 ± 1.5 s (P = .20). Burst pressures for SCUD and AVE were 578 ± 284 and 605 ± 288 mm Hg, respectively (P = .48). Stratification by vessel diameter yielded similar results. In all, 17 applications resulted in seal failure on either the proximal or distal side, with no difference between SCUD (4.4%) and ACE (6.6%; P = .37). Histological examination of 48 specimens showed similar thermal spreads: 1.06 ± 0.05 versus 1.08 ± 0.05 mm for SCUD and ACE, respectively (P = .82). In 41 timed mesenteric transections, SCUD required 24.8 ± 4.9 s, which was significantly less than the 33.8 ± 5.4 s for ACE (P < .0001), with no bleeding in either group. SCUD and ACE showed similar vessel seal times, burst pressures, thermal spreads, and seal failure rates. SCUD was more efficient than ACE in mesenteric transection.

The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer.

BACKGROUND AND OBJECTIVES: MUC1 is over-expressed and aberrantly glycosylated in >60% of human pancreatic cancer (PC). Development of novel approaches for detection and/or targeting of MUC1 are critically needed and should be able to detect MUC1 on PC cells (including cancer stem cells) and in serum. METHODS: The sensitivity and specificity of the anti-MUC1 antibody, TAB 004, was determined. CSCs were assessed for MUC1 expression using TAB 004-FITC on in vitro PC cell lines, and on lineage(-) cells from in vivo tumors and human samples. Serum was assessed for shed MUC1 via the TAB 004 EIA. RESULTS: In vitro and in vivo, TAB 004 detected MUC1 on >95% of CSCs. Approximately, 80% of CSCs in patients displayed MUC1 expression as detected by TAB 004. Shed MUC1 was detected serum in mice with HPAF-II (MUC1(high) ) but not BxPC3 tumors (MUC1(low)). The TAB 004 EIA was able to accurately detect stage progression in PC patients. CONCLUSIONS: The TAB 004 antibody may be explored as a therapeutic targeting agent for CSCs in PC. The TAB 004 EIA detected circulating MUC1 in a stage-dependent manner in patients with PC and thus may be explored as a PC stage diagnostic biomarker.

Diet-induced obesity and ethanol impair progression of hepatocellular carcinoma in a mouse mesenteric vein injection model.

BACKGROUND: Hepatocellular carcinoma (HCC) is a rapidly increasing cancer whose known risk factors are chronic ethanol abuse, viral hepatitis infection, and aflatoxin exposure. Obesity, an emerging HCC risk factor, is reaching epidemic proportions in developed nations. This study investigated the effects of diet-induced obesity (DIO) and chronic ethanol consumption on HCC progression in mice in vivo. METHODS: In this study, C57BL/6 DIO mice and lean litter mates were maintained on a 60% (high-fat diet [HFD]) diet or a 10% (control diet [CD]) kcal% fat diet for 7 weeks before they were weaned to 10/20% ([v/v], alternating days) ethanol in drinking water (EtOH) or maintenance on drinking water (H(2)O) alone. Hepatic tumor formation was initiated by intrahepatic Hepa1-6 cell (6 × 10(6) cells) inoculation 6 weeks later via the mesenteric vein. RESULTS: The animals receiving the HFD showed decreased tumor incidence and area of hepatic foci versus the CD animals maintained on H(2)O alone. The action of EtOH suppressed tumor incidence further in both the CD and the HFD mice. Serologic analysis showed no significant differences in liver enzymes among the groups. Protein analysis demonstrated increased P450 2E1 (CYP2E1) in the groups maintained on EtOH, an effect exacerbated by HFD. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated increased tumor necrosis factor-alpha (TNF-α) expression in HFD HCC mice (H(2)O and EtOH) concomitant with decreased transforming growth factor-beta (TGF-ß) expression. CONCLUSIONS: Although obesity and EtOH consumption are known risk factors for HCC initiation and development, the data in this study suggest that these factors impair progression of established tumors within the liver.

Lysophosphatidic acid receptor expression and function in human hepatocellular carcinoma.

BACKGROUND: Lysophosphatidic acid (LPA) is a ubiquitously expressed phospholipid that regulates diverse cellular functions. Previously identified LPA receptor subtypes (LPAR1-5) are weakly expressed or absent in the liver. This study sought to determine LPAR expression, including the newly identified LPAR6, in normal human liver (NL), hepatocellular carcinoma (HCC), and non-tumor liver tissue (NTL), and LPAR expression and function in human hepatoma cells in vitro. METHODS: We determined LPAR1-6 expression by quantitative reverse transcriptase polymerase chain reaction, Western blot, or immunohistochemistry in NL, NTL, and HCC, and HuH7, and HepG2 cells. Hepatoma cells were treated with LPA in the absence or presence of LPAR1-3 (Ki16425) or pan-LPAR (α-bromomethylene phosphonate) antagonists and proliferation and motility were measured. RESULTS: We report HCC-associated changes in LPAR1, 3, and 6 mRNA and protein expression, with significantly increased LPAR6 in HCC versus NL and NTL. Analysis of human hepatoma cells demonstrated significantly higher LPAR1, 3, and 6 mRNA and protein expression in HuH7 versus HepG2 cells. Treatment with LPA (0.05-10 µg/mL) led to dose-dependent HuH7 growth and increased motility. In HepG2 cells, LPA led to moderate, although significant, increases in proliferation but not motility. Pretreatment with α-bromomethylene phosphonate inhibited LPA-dependent proliferation and motility to a greater degree than Ki16425. CONCLUSIONS: Multiple LPAR forms are expressed in human HCC, including the recently described LPAR6. Inhibition of LPA-LPAR signaling inhibits HCC cell proliferation and motility, the extent of which depends on LPAR subtype expression.

Feasibility and value of a procedural workshop for surgery residents based on phase II of the APDS/ACS national skills curriculum.

OBJECTIVES: The Association of Program Directors in Surgery/American College of Surgeons national skills curriculum provides residency programs with a great educational tool for their residents. Our objective was to assess the feasibility, value, and cost required to administer a procedural workshop for general surgery residents based on phase II of the national skills curriculum. DESIGN, SETTING, AND PARTICIPANTS: Surgery faculty instructed residents on a variety of level-appropriate surgical procedures during a procedural workshop using 4 training models (2 cadaver torsos and 2 pigs). The educational value of the workshop, the quality of teaching, the instruction and feedback received, and the training models used were evaluated by participants on a 10-point Likert scale. Resident performance and workshop cost were also assessed. RESULTS: Seven faculty instructed 16 residents (postgraduate year 1-4) on 23 surgical procedures (median 4 procedures per resident). Participants rated the overall value of the workshop as 8 (range, 7-10). Residents rated the quality of teaching as 9 (range, 6-10) and the quality of instruction and feedback received as 8.5 (range, 6-10). Overall resident performance was rated as 8 (range, 5-10) by faculty. The factors most positively impacting the quality of the workshop were reported to be the close interaction between residents and faculty, the training models, and the protected time. Sixty-eight percent of participants indicated that both cadaver and pig models were necessary for this course, and all participants believed that such workshops should be part of the general surgery curriculum. Overall cost reached just under $10,000 excluding supplies and faculty time. CONCLUSIONS: The feasibility of a cadaveric and animal-based procedural workshop for surgery residents based on phase II of the national skills curriculum was demonstrated. While very resource-intensive and costly, the educational value of this workshop was rated highly by residents and faculty because of their close interaction in a relaxed environment. Such workshops should be incorporated into the surgical curriculum.