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.

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.

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.

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.

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.

Pyogenic hepatic abscess secondary to endolumenal perforation of an ingested foreign body.

INTRODUCTION: Pyogenic hepatic abscess induced by foreign body perforation of the gastrointestinal tract is an increasing phenomenon. Pyogenic liver abscess in itself is a challenge to treat without the complication of a foreign body. METHODS: A case of a patient who developed a pyogenic hepatic abscess after unknown ingestion of a toothpick that subsequently perforated the duodenum is presented, and a literature review of pyogenic hepatic abscesses secondary to ingestion of foreign bodies and their causes, diagnosis, and treatment was performed. DISCUSSION: Even with a thorough workup, often the diagnosis of a pyogenic hepatic abscess secondary to an endolumenal foreign body perforation is not obtained until the time of operation.

Laparoscopic-assisted microwave ablation for hepatocellular carcinoma: safety and efficacy in comparison with radiofrequency ablation.

BACKGROUND: Thermal ablation techniques are increasingly important in the search for improved locoregional therapy of hepatocellular carcinoma (HCC) in patients with cirrhosis. This study reports the largest US series using laparoscopic-assisted microwave ablation (Lap-MWA) with a 915-MHz generator for HCC and compares it with a contemporary laparoscopic-assisted radiofrequency ablation (Lap-RFA) experience. METHODS: Thirty-five patients with HCC underwent laparoscopic-assisted ablation utilizing either MWA or RFA. Medical records, radiographic imaging, and histology were reviewed and outcomes analyzed. RESULTS: Twenty-two patients underwent Lap-RFA (27 tumors) and 13 received Lap-MWA (15 tumors). Average ablation volumes were similar for Lap-RFA and Lap-MWA at 23.43 and 28.99 cm(3), respectively (=0.69). Average operative times for Lap-RFA were 149 ± 35 min versus 112 ± 40 min with Lap-RFA (P = 0.004). Mean follow-up was 19 months in the Lap-RFA group: 50% alive without evidence of disease, 9% alive with disease, 36% deceased and 5% lost to follow-up. Mean follow-up in the Lap-MWA group was 7 months: 54% alive without evidence of disease, 31% alive with disease and 15% deceased. CONCLUSION: Lap-MWA is a safe and efficacious locoregional therapy for HCC which achieves outcomes comparable to Lap-RFA. Shorter operative times were realized with this modality and complete coagulative necrosis was confirmed histologically on explanted livers.

Medical epidemiology of patients surviving ten years after liver transplantation.

The transition into extended long-term follow-up after liver transplantation raises a new series of issues with respect to continuing care of this population. A retrospective study was performed, analyzing patients who underwent orthotopic liver transplant (OLT) and survived ≥10 yr at a single institution. Long-term comorbidities such as diabetes mellitus (DM), hypertension (HTN), chronic kidney disease (CKD), coronary artery disease (CAD), and obesity were identified and standardized prevalence ratios ([SPR]) utilized to compare with the general US population. There was an increased prevalence of HTN ([SPR] = 2.25 ± 0.61), DM ([SPR] = 2.67 ± 0.72), and CKD ([SPR] = 15.3 ± 4.04) but not CAD or obesity. In multivariate analysis, non-viral etiology of end-stage liver disease was associated with CKD (OR 3.42 CI 1.11-10.53), and an initial glomerular filtration rate (GFR) <60 mL/min per 1.73 m(2) (CKD stages III-V) was associated with HTN (OR 4.62 CI 1.14-18.73) after OLT. Creatinine ≥ 1.5 mg/dL at 10 yr was associated with an initial GFR <60 mL/min per 1.73 m(2) (p = 0.000) and CAD after OLT (p = 0.012). Patients, 10 yr after OLT, have a significantly higher prevalence of HTN, DM, and CKD than the general population, which is not confounded by obesity. Increased vigilance and proactive management are required to further improve long-term outcomes.