Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Gap-App: A sex-distinct AI-based predictor for pancreatic ductal adenocarcinoma survival as a web application open to patients and physicians.

In this study, using RNA-Seq gene expression data and advanced machine learning techniques, we identified distinct gene expression profiles between male and female pancreatic ductal adenocarcinoma (PDAC) patients. Building upon this insight, we developed sex-specific 3-year survival predictive models, which achieved accuracies of 88.47% for males and 88.94% for females, respectively. These models outperformed a single general model despite the smaller sample sizes, highlighting the value of sex-specific analysis. Based on these findings, we created Gap-App, a web application that enables the use of individual gene expression profiles combined with sex information for personalized survival predictions. Gap-App, the first online tool aiming to bridge the gap between complex genomic data and clinical application and facilitating more precise and individualized cancer care, marks a significant advancement in personalized prognosis. The study not only underscores the importance of acknowledging sex differences in personalized prognosis, but also sets the stage for the shift from traditional one-size-fits-all to more personalized and targeted medicine. The GAP-App service is freely available at www.gap-app.org.

Circumstances and implications of conversion from minimally invasive to open liver resection: a multi-center analysis from the AMILES registry.

BACKGROUND: Minimally invasive approaches to liver resection (MILR) are associated with favorable outcomes. The aim of this study was to determine the implications of conversion to an open procedure on perioperative outcomes. METHODS: Patients who underwent MILR at 10 North American institutions were identified from the Americas Minimally Invasive Liver Resection (AMILES) database. Outcomes of patients who required conversion were compared to those who did not. Additionally, outcomes after conversion due to unfavorable findings (poor visualization/access, lack of progress, disease extent) versus intraoperative events (bleeding, injury, cardiopulmonary instability) were compared. RESULTS: Of 1675 patients who underwent MILR, 102 (6.1%) required conversion. Conversion rate ranged from 4.4% for left lateral sectionectomy to 10% for right hepatectomy. The primary reason for conversion was unfavorable findings in 67 patients (66%) and intraoperative adverse events in 35 patients (34%). By multivariable analysis, major resection, cirrhosis, prior liver surgery, and tumor proximity to major vessels were identified as risk factors for conversion (p < 0.05). Patients who required conversion had higher blood loss, transfusion requirements, operative time, and length of stay, (p < 0.05). They also had higher major complication rates (23% vs. 5.2%, p < 0.001) and 30-day mortality (8.8% vs. 1.3%, p < 0.001). When compared to those who required conversion due to unfavorable findings, patients who required conversion due to intraoperative adverse events had significantly higher major complication rates (43% vs. 14%, p = 0.012) and 30-day mortality (20% vs. 3.0%, p = 0.007). CONCLUSIONS: Conversion from MILR to open surgery is associated with increased perioperative morbidity and mortality. Conversion due to intraoperative adverse events is rare but associated with significantly higher complication and mortality rates, while conversion due to unfavorable findings is associated with similar outcomes as planned open resection. High-risk patients may benefit from early conversion in a controlled fashion if difficulties are encountered or anticipated.

Marginal Ulcer Following Completion Pancreatectomy Complicated by Portal Vein Erosion.

Marginal ulcers, defined as ulcers at the duodenojejunostomy or gastrojejunostomy, are a known late-onset complication of pancreaticoduodenectomy (PD) and total pancreatectomy (TP) with mean incidence ranging from 5.4% to 36% per the literature. These ulcers carry a risk of complications including hemorrhage or perforation which can result in significant mortality. Marginal ulcers from PD and TP causing portal vein erosion are extremely rare and given the high incidence of mortality, it is important to have a multimodal approach to the treatment with awareness that early operative management should be considered if other modalities fail. We discuss the case of a 57-year-old female with history of pancreatic tail intraductal papillary mucinous neoplasm (IPMN) status post distal pancreatectomy/splenectomy and subsequent completion pancreatectomy for pancreatic head IPMN who presented with acute gastrointestinal bleed. The patient was successfully managed operatively with primary repair of the marginal ulcer after multiple failed endoscopic attempts.

Minimally Invasive Versus Open Liver Resections for Hepatocellular Carcinoma in Patients With Metabolic Syndrome.

OBJECTIVE: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). BACKGROUND: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. MATERIAL AND METHODS: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. RESULTS: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival. CONCLUSIONS: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Drug-Eluting Bead, Irinotecan Therapy of Unresectable Intrahepatic Cholangiocarcinoma (DELTIC) with Concomitant Systemic Gemcitabine and Cisplatin.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (ICC) carries a poor prognosis, and currently there are moderately established chemotherapeutic [gemcitabine/cisplatin (Gem/Cis)] treatments to prolong survival. The purpose of this study was to assess the efficacy of irinotecan drug-eluting beads (DEBIRI) therapy by transarterial infusion in combination with systemic therapy in unresectable ICC. PATIENTS AND METHODS: This is a prospective, multicenter, open-label, randomized phase II study (Clin Trials: NCT01648023-DELTIC trial) of patients with ICC randomly assigned to Gem/Cis with DEBIRI or Gem/Cis alone. The primary endpoint was response rate. RESULTS: The intention-to-treat population comprised 48 patients: 24 treated with Gem/Cis and DEBIRI and 22 with Gem/Cis alone (2 screen failures). The two groups were similar with respect to the extent of liver involvement (35% versus 38%) and presence of extrahepatic disease (29% versus 14%, p = 0.12). Median numbers of chemotherapy cycles were similar (6 versus 6), as were rates of grade 3/4 adverse events (34% for the Gem/Cis-DEBIRI group versus 36% for the Gem/Cis group). The overall response rate was significantly greater in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm at 2 (p < 0.04), 4 (p < 0.03), and 6 months (p < 0.05). There was significantly more downsizing to resection/ablation in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm (25% versus 8%, p < 005), and there was improved median progression-free survival [31.9 (95% CI 8.5-75.3) months versus 10.1 (95% CI 5.3-13.5) months, p = 0.028] and improved overall survival [33.7 (95% CI 13.5-54.5) months versus 12.6 (95% CI 8.7-33.4) months, p = 0.048]. CONCLUSION: Combination Gem/Cis with DEBIRI is safe, and leads to significant improvement in downsizing to resection, improved progression-free survival, and overall survival.

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.

Multimodality treatment of intrahepatic cholangiocarcinoma: A review.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary hepatic cancer in the United States. Currently, curative treatment involves aggressive surgery. Chemotherapy and radiation treatments have been used for unresectable tumors with some success. Optimizing the use of current and developing novel multimodality treatment for iCCA is essential to improving outcomes.

Suprahepatic Gallbladder.

INTRODUCTION: Suprahepatic gallbladders have been reported in the literature dating back to 1965. However, their etiology and consequences remain unclear. METHODS: A case of a patient being treated for biliary dyskinesia with an incidental finding of suprahepatic gallbladder is presented along with a literature review on the causes, effects, and management of a suprahepatic gallbladder. DISCUSSION: Patient underwent a robotic-assisted laparoscopic cholecystectomy without complications and had an uneventful recovery. Vigilance must be used to rule out ectopic gallbladder location in a patient with atypical biliary symptoms.

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.

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 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.

Ablation therapy for hepatocellular carcinoma: past, present and future perspectives.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and is most commonly found in the setting of liver cirrhosis. Treatment of HCC must consider both the tumors present, as well as the remaining dysfunctional liver that both hinders treatment and can produce additional HCC over time. Ablation is an evolving part of the multimodality treatment approach to HCC that can effectively destroy tumors while preserving surrounding liver parenchyma. New technologies have made ablation an indispensable tool in the treatment of all stages of HCC. This review presents the history, present technologies and future potential of ablation in the treatment of HCC.

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.

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.

Invasive biliary mucinous cystic neoplasm: a review.

OBJECTIVES: Biliary mucinous cystic neoplasms (BMCNs) are recently redefined rare liver tumours in which insufficient recognition frequently leads to an incorrect initial or delayed diagnosis. A concise review of the subtle, sometimes non-specific, clinical, serologic and radiographic features will allow for a heightened awareness and more comprehensive understanding of these entities. METHODS: Literature relating to the presentation, diagnosis, treatment, pathology and outcomes of BMCNs and published prior to March 2012 was reviewed. RESULTS: Biliary mucinous cystic neoplasms most commonly occur in females (≥60%) in the fifth decade of life. Clinical symptoms, serologic markers and imaging modalities are unreliable for diagnosis of BMCNs, which leads to misdiagnosis in 55-100% of patients. Perioperative cyst aspiration is not recommended as invasive BMCNs can only be differentiated from non-invasive BMCNs by microscopic evaluation for the presence of ovarian-type stroma. Intraoperative biopsy and frozen section(s) are essential to differentiate BMCNs from other cystic liver lesions. The treatment of choice is complete excision and can result in excellent survival with initial correct diagnosis. CONCLUSIONS: A low threshold for considering BMCN in the differential diagnosis of cystic liver lesions and increased attentiveness to its subtle diagnostic characteristics are imperative. The complete surgical resection of BMCNs and the use of appropriate nomenclature are necessary to improve outcomes and accurately define prognosis.