Percutaneous Portal Vein Embolization Using a Simplified Sheathless 18-Gauge Trocar Needle Approach: Review of Efficacy and Safety.

PURPOSE: Portal vein (PV) embolization (PVE) is traditionally performed via a PV sheath with selective embolization of PV branches. Here, the efficacy and safety of PVE with the use of only an 18-gauge needle is reported. MATERIALS AND METHODS: Consecutive patients who underwent PVE from 2009 through 2017 were retrospectively reviewed. Forty-five patients (mean age, 60 y ± 7.6; 38 men) underwent 45 PVE procedures. Hepatocellular carcinoma, cholangiocarcinoma, and metastases accounted for 26 (58%), 13 (29%), and 6 (13%) patients, respectively. PVE was performed by puncturing a branch of right PV with an 18-gauge needle under US guidance. Via the same needle, direct portography was performed, followed by PVE with an N-butyl cyanoacrylate/Lipiodol mixture. Percentage increase of future liver remnant (FLR) volume and increase in ratio of FLR to total liver volume were estimated as measures of efficacy. Complications were reported according to Society of Interventional Radiology classification. Fluoroscopy time, procedure time, and dose-area product (DAP) were recorded. RESULTS: Technical success rate was 100%. The median DAP, fluoroscopy time, and procedure time were 74,387 mGy·cm2 (IQR, 90,349 mGy·cm2), 3.5 min (IQR, 2.10 min), and 24 min (IQR, 10.5 min). Among the 23 patients with complete CT volumetry data, mean increase in the ratio of FLR to total liver volume and percentage increase of FLR volume were 12.5% ± 7.7 and 50% ± 33, respectively. There were 3 minor complications (asymptomatic nonocclusive emboli in FLR) and 3 major complications (1 hepatic vein emboli, 1 subphrenic collection, and 1 hepatic infarct). CONCLUSIONS: PVE via a sheathless 18-gauge needle approach is feasible, with satisfactory FLR hypertrophy.

Endoscopic biliary drainage in patients with cholangiocarcinoma - self-expanding metal versus polyethylene stents.

Background: Endoscopic biliary drainage is the standard of care for patients with cholangiocarcinoma (CCA)-induced, obstructive jaundice. Self-expanding metal stents are supposed to be superior to polyethylene stents in terms of reduction of interventions and costs. So far, there are only few real-life data with respect to stent selection and survival in this patient cohort. Methods: In this study, we retrospectively analyzed patients with CCA treated with endoscopic biliary drainage from 2000 to 2015 at Hannover Medical School, Germany. The aim of this study was to analyze whether metal stenting reduces the frequency of interventions and influences survival in a large, real-life cohort. Results: Overall, 422 patients with CCA were included in this study. Indication for endoscopic biliary drainage was most often obstructive jaundice (n = 397; 94.1%). Among these patients, 20 patients (5%) were initially treated with a metal stent and 38 (9.6%) received a metal stent in the subsequent course. Median number of interventions per month was 2.4-fold reduced following metal stenting. Patients first treated with a metal stent had a more advanced tumor stage and a significantly shorter median overall survival (mOS) compared to patients who received a metal stent subsequently (7.5 months vs. 15.2 months; p=.019). There was no difference in mOS for metal vs. polyethylene stenting following a propensity score match for the confounders curative resection and chemotherapy (13.2 vs. 13.7 months, p=.555). Conclusions: Our data confirm that metal stenting reduces the frequency of interventions, but does not influence OS. Metal stenting should be considered specifically in younger patients who are suitable for chemotherapy.

Plasmonic photothermal therapy: Approaches to advanced strategy.

BACKGROUND: The analysis of recent studies on plasmonic photothermal therapy (PPT) after intravenous administration of gold nanorods (GNRs) has demonstrated that the effectiveness of nanoparticle-assisted laser hyperthermia depends on a correct dosage strategy of nanoparticle administration. Accumulation of GNRs in tumor tissue dramatically increases the local heating of the tumor without damage to healthy tissues. However, the optimal doses of GNR intravenous injections (IVIs) for effective accumulation in tumors, and optimal protocols of PPT are not designed yet. The current study aims to improve the efficacy of PPT in tumor-bearing rats using multiple fractional intravenous administration of GNRs. MATERIALS AND METHODS: For PPT experiments, the GNRs with aspect ratio of 4.1 were functionalized with thiolated polyethylene glycol (PEG) and their suspensions were used for multiple fractional intravenous administration in outbred albino male rats with experimental model of rat liver cancer (cholangiocarcinoma line PC-1). Doppler ultrasonography was performed to characterize the vascularity of transplanted rat tumors before any treatment. After a final injection of GNRs, tumor was irradiated during 15 minutes by 808-nm NIR diode laser at a power density 2.3 W/cm2 . The animals were withdrawn from the experiment and sampling of tissues for morphological study and gold accumulation was performed 24 hours and 3 weeks after PPT. RESULTS: The multiple IVIs of gold nanorods and further PPT of transplanted cholangiocarcinoma provided significant damage to tumor tissue resulting in pronounced necrotic mass and retardation of the tumor growth. More importantly, the proposed PPT protocol had low toxicity as evidenced by histological examination of internal organs. The efficiency of PPT depends on the presence of newly formed vasculature as revealed by the Doppler ultrasound investigation. CONCLUSION: The repeatable IVIs promote greater of GNR accumulation within the tumor thus resulting in higher PPT efficacy. Accompanying ultrasonography can be useful for prognosis and monitoring of treatment. Lasers Surg. Med. 50:1025-1033, 2018. © 2018 Wiley Periodicals, Inc.

Cost utility analysis of endoscopic biliary stent in unresectable hilar cholangiocarcinoma: decision analytic modeling approach.

BACKGROUND/AIMS: Endoscopic biliary drainage using metal and plastic stent in unresectable hilar cholangiocarcinoma (HCA) is widely used but little is known about their cost-effectiveness. This study evaluated the cost-utility of endoscopic metal and plastic stent drainage in unresectable complex, Bismuth type II-IV, HCA patients. METHODOLOGY: Decision analytic model, Markov model, was used to evaluate cost and quality-adjusted life year (QALY) of endoscopic biliary drainage in unresectable HCA. Costs of treatment and utilities of each Markov state were retrieved from hospital charges and unresectable HCA patients from tertiary care hospital in Thailand, respectively. Transition probabilities were derived from international literature. Base case analyses and sensitivity analyses were performed. RESULTS: Under the base-case analysis, metal stent is more effective but more expensive than plastic stent. An incremental cost per additional QALY gained is 192,650 baht (US$ 6,318). From probabilistic sensitivity analysis, at the willingness to pay threshold of one and three times GDP per capita or 158,000 baht (US$ 5,182) and 474,000 baht (US$ 15,546), the probability of metal stent being cost-effective is 26.4% and 99.8%, respectively. CONCLUSIONS: Based on the WHO recommendation regarding the cost-effectiveness threshold criteria, endoscopic metal stent drainage is cost-effective compared to plastic stent in unresectable complex HCA.

Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative volumetric apparent diffusion coefficient maps for assessment of tumor response.

PURPOSE: To evaluate volumetric changes in apparent diffusion coefficient (ADC) and contrast material enhancement on contrast-enhanced (CE) magnetic resonance (MR) images in hepatic arterial and portal venous phases for assessing early response in cholangiocarcinoma treated with transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Twenty-nine patients with unresectable cholangiocarcinoma, including 11 men (mean age, 60 years; standard deviation, 16.8) and 18 women (mean age, 63 years; standard deviation, 11.5) were included in this retrospective institutional review board-approved, HIPAA-compliant study; informed consent was waived. Sixty-nine TACE procedures were performed during the observational time (range, one to five TACE sessions). No patients received another form of therapy after treatment with TACE. MR Imaging was performed before and 3-4 weeks after TACE, and images were analyzed with a semiautomatic volumetric software package. Patients were stratified as responders and nonresponders on the basis of overall survival (OS) as the primary end point. Differences between responders and nonresponders were analyzed with paired t tests, and OS was calculated with the Kaplan-Meier method. Significant differences were analyzed with the log-rank test. RESULTS: Mean volumetric ADC increased from 1.54×10(-3) mm2/sec to 1.92×10(-3) mm2/sec (P<.0001), with no significant decrease in mean volumetric enhancement in hepatic arterial (40.6% vs 37.5%, P=.546) and portal venous (79.0% vs 70.0%, P=.105) phases. Patients who demonstrated improved survival of 10 months or more had a significant increase in mean volumetric ADC and volumetric ADC above the threshold level of 1.60×10(-3) mm2/sec (P<.002). Patients with 45% or greater (n=21; log-rank test, P<.02) and 60% or greater (n=12; log-rank test, P<.009) ADC changes for the whole tumor volume demonstrated better OS compared with patients in whom these ADC changes were not achieved. CONCLUSION: Patients with percentage tumor volume increase in ADC of 45% or greater and 60% or greater above the threshold level of 1.60×10(-3) mm2/sec had favorable response to therapy and improved survival.

Clinical outcomes of nitinol and stainless steel uncovered metal stents for malignant biliary strictures: is there a difference?

BACKGROUND: Self-expandable metal stents (SEMSs) made from nitinol (N) were developed as a potentially more effective alternative to conventional stainless steel (SS) stents. OBJECTIVE: To compare clinical outcomes of N versus SS stents in the management of malignant biliary strictures. DESIGN: Retrospective study. SETTING: Tertiary-care cancer center. PATIENTS: All patients with first-time N (Flexxus) and SS (Wallstent) uncovered biliary SEMSs placed between January 2006 and October 2007. INTERVENTIONS: SEMS placement. RESULTS: A total of 81 N and 96 SS stents were placed. The most common cancer diagnosis was pancreatic (80.2% N; 62.5% SS; P = .06). The most frequent site of stricture was the common bile duct (85.2% N; 86.5% SS; P = .31). Biliary decompression was achieved in 93.8% of the N group and 86.4% of the SS group (P = .22). Immediate stent manipulation was required in 4 patients in each group. Subsequent intervention for poor drainage was performed in 17 N (21%) and 26 SS (27%) stents at mean times of 142.1 days (range, 5-541 days; median, 77 days) and 148.1 days (range, 14-375; median, 158.5), respectively (P = .17). The occlusion rate between N and SS stents was not significant (P = .42). The overall durations of stent patency in the N and SS group were similar (median 129 and 137 days, respectively; P = .61), including the subgroup analysis performed on patients with pancreatic cancer (P = .60) and common duct strictures (P = .77). Complication rates were low in both groups (early: 3.7% N, 6.3% SS; late: 2.5% N, 3.1% SS). Ninety percent underwent chemotherapy and 38% radiation therapy in each group. LIMITATIONS: Retrospective design. CONCLUSION: Similar outcomes were achieved with N and SS stents regarding efficacy, duration of stent patency, occlusion rates, and complications. Our results are most applicable to patients with common duct strictures and pancreatic cancer.

Initial performance profile of a new 6F self-expanding metal stent for palliation of malignant hilar biliary obstruction.

BACKGROUND: A 6F endoscopic biliary self-expanding metal stent (SEMS) has been newly introduced for intended simultaneous side-by-side bilateral deployment in hilar malignant obstruction. OBJECTIVE: To report our initial experience with the Zilver 635 biliary SEMS. DESIGN: Retrospective chart review. SETTING: Tertiary referral medical center. PATIENTS: Sixteen consecutive malignant hilar biliary obstruction patients. INTERVENTIONS: Endoscopic palliative treatment of malignant biliary obstruction with the Zilver 635 SEMS from December 2008 to January 2010. MAIN OUTCOME MEASUREMENTS: Technical/functional success rates, early complications (within 30 days of stent placement), early/late stent occlusion, and biliary reintervention rates. RESULTS: A total of 49 Zilver SEMSs were placed in 16 patients (mean age 61 years, 6 men) for Bismuth type II (n = 4), III (n = 5), and IV (n = 7) lesions. Twelve had cholangiocarcinoma, 2 had metastatic colon cancer, 1 had lung cancer, and 1 had pancreatic cancer. The technical success rate was 100%. Side-by-side simultaneous bilateral stent deployment was required and was achieved successfully in 10 cases. Additional transpapillary stents were placed for potential future biliary access. The 30-day mortality rate was 0%. There were 1 early (6%) and 3 late (19%) stent occlusions. Successful overall biliary drainage was 75%. LIMITATIONS: Small sample size, uncontrolled retrospective study. CONCLUSIONS: Malignant hilar biliary obstruction endoscopic palliation with the Zilver 635 SEMS offers acceptable initial feasibility, safety, and efficacy profiles. The current design facilitates smaller bile duct negotiation and more precise intrahepatic placement. Expanding available lengths would allow transpapillary bridged bilateral SEMS placement for future reobstructed biliary access. Further long-term studies are required for comparative outcomes with other current SEMS technology.

Chemoembolization of hepatic malignancy.

Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization represents an essential component of interventional oncology. This article discusses patient selection, procedure technique, results, and complications associated with transarterial chemoembolization.

[Tolerance of hypofractionated stereotactic radiotherapy for hepatic tumours]. / Tolérance de l'irradiation stéréotaxique hypofractionnée des tumeurs hépatiques.

PURPOSE: The purpose of the study was to evaluate the outcomes of stereotactic radiation therapy for primary and secondary liver tumours in Jean-Perrin cancer centre (Clermont-Ferrand, France) in terms of efficacy and safety. MATERIALS AND METHODS: Between December 2013 and June 2016, 25 patients were included. Treatment was performed on a linear accelerator Novalis TX®. The prescription dose was 42 to 60Gy in three to five fractions. Local control at 1 year was evaluated with modified Response Evaluation Criteria in Solid Tumours (mRECIST) and RECIST criteria. Acute and late toxicity were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria. RESULTS: Median follow-up was 10.5 months. Treatment tolerance was good with few side effects grade 3 or above, no acute toxicity and only one late toxicity. We have highlighted that hepatic artery haemorrhage was associated with the presence of a biliary prosthesis in contact with the artery (P=0.006) and in the irradiation field. There was no correlation with the dose delivered to the artery and hepatic artery haemorrhage. CONCLUSION: Stereotactic radiation therapy for liver tumours allows a good local control with few secondary effects. Caution should be exercised when treating patients with biliary prostheses in the vicinity of the target volume because there is a risk of haemorrhage of the hepatic artery in contact with the prosthesis.

Gemcitabine-loaded DSPE-PEG-PheoA liposome as a photomediated immune modulator for cholangiocarcinoma treatment.

To improve the therapeutic efficacy of gemcitabine (GEM) as an anticancer drug for bile duct cancer, GEM-loaded liposomes (GDPPL) prepared from a photosensitizer-conjugated lipid were investigated regarding the drug release kinetics, photodynamic therapy (PDT) efficacy, and immunomodulatory effects. The release rate of GEM from the liposomes was improved approximately 2-fold compared to non-laser irradiation groups due to lipid disruption by reactive oxygen species produced from the activated photosensitizer upon laser irradiation. Through in vitro testing using a human liver bile duct carcinoma cell line (HuCCT-1), the cytotoxicity of GDPPL with laser irradiation was enhanced due to rapid GEM release and PDT effects. Furthermore, the results of in vivo tests using a HuCCT-1 tumor-bearing xenograft mice model showed that GDPPL exhibited approximately 3-fold antitumoral effects compared to control group. Additionally, immunohistochemical analysis demonstrated the recruitment of immunostimulatory cells in tumor tissues. IHC tests in BALB/c mice indicated that GDPPL under laser irradiation dramatically enhanced the quantities of various immune cells for effective antitumoral immunotherapy against biliary tract cancer. From these results, it was concluded that GDPPL with rapid drug release behavior, PDT efficacy, and immunomodulatory effects upon laser irradiation has potential as an antitumor therapeutic agent for biliary tract cancer.

Role of portal vein embolization in hepatobiliary malignancy.

BACKGROUND/AIMS: Inadequate remnant liver volume is the major cause of postoperative liver failure. Preoperative portal vein embolization (PVE) is the well accepted procedure to increase future liver remnant (FLR) volume and decrease the incidence of this complication. This study described the author's experience of preoperative PVE at King Chulalongkorn Memorial Hospital since 2002. METHODOLOGY: The clinical data of 29 patients who underwent PVE were reviewed. The FLR volumes before and after the procedure were calculated by CT volumetry. PVE was performed when estimated FLR volume was < 25% in normal liver or < 40% in damaged liver and also when major liver resection combined with major intraabdominal surgery was planned. The complications after PVE and hepatectomy were recorded. RESULTS: There were no deaths or complications after PVE. The mean growth of FLR was 11%. Power of liver regeneration was suboptimal in old age patients. Sixteen patients underwent liver resection (resectability rate 55.17%). There were 2 cases of postoperative hyperbilirubinemia (12.5%). The hospital mortality rate was 1/16 (6.25%). CONCLUSIONS: PVE is a useful and safe optional procedure to increase FLR. It not only reduces the postoperative liver failure but also increases the chance of curative resection.

Hepatic Arterial Infusion of Polyethylene Glycol Drug-eluting Beads for Primary and Metastatic Liver Cancer Therapy.

BACKGROUND/AIM: Recently, there has been the launch of the new Polyethylene glycol (PEG) drug-eluting beads (LifePearl®) for transarterial chemoembolization. Their innovation is that PEG guarantees more compressibility, elasticity and maximizes beads' suspension time. We applied these beads for hepatic intra-arterial infusion of irinotecan or doxorubicin for the therapy of primary and metastatic liver cancer. PATIENTS AND METHODS: We treated 20 consecutive patients, affected by unresectable primary liver cancer (PLC) or hepatic metastases (refractory to chemotherapy) using chemoembolization with doxorubicin or irinotecan pre-loaded Lifepearls. RESULTS: Tumor response rate was >80% in most patients with 63% of complete and 37% of partial response. We observed no complications during the chemoembolization and no severe general drug-related side-effects. CONCLUSION: Our data suggest that chemoembolization with LifePearl® is efficacious and safe for the treatment of liver cancer as indicated by good tolerability, quality of life and high tumor response.

Clinical characteristics and treatment outcomes of patients with unresectable cholangiocarcinoma in Thailand: are there differences dependent on stent type?

Cholangiocarcinoma, though very rare in Western countries, is one of the commonest liver malignancies in Southeast Asia, especially in Thailand. More than half of the patients present with advanced stage disease. Given the poor treatment outcomes of adjuvant therapeutic options, many patients undergo only biliary drainage for palliative treatment. Clinical characteristics and treatment outcomes after biliary stenting were here analyzed for a total of 224 unresectable cholangiocarcinoma cases, 58.9% in men. The mean age was 61.5 years. Hilar involvement was the most common location. The patients underwent biliary drainage using plastic and metallic stents equally, early stent occlusion being encountered in 21.4% and 10.7%, respectively. The median survival time was 4.93 months for patients who received plastic and 5.87 months for patients who received metallic stents.

Chemoembolization of intrahepatic cholangiocarcinoma with cisplatinum, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol: a 2-center study.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis, with a median survival of 5 to 8 months without treatment. Response and survival after chemoembolization were evaluated. METHODS: Lobar or segmental chemoembolization with cisplatinum, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol particles was performed at monthly intervals for 1-4 sessions until the entire intrahepatic tumor burden was treated. Cross-sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle of treatment was performed for intrahepatic recurrence. Toxicity was assessed using NCI CTC v.3.0. Response was evaluated using RECIST criteria, and survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-two patients were treated. Thirty-seven had pathologically proven cholangiocarcinoma, and 25 had poorly differentiated adenocarcinoma of unknown primary, likely cholangiocarcinoma. One hundred and twenty-two total procedures were performed during the initial cycle of treatment (mean, 2.0 per patient). Twenty patients received a second cycle, for a total of 165 procedures. There were 5 major complications. Thirty-day disease-specific mortality was 0%. Forty-five of 62 patients were evaluable for morphologic response after completion of their initial cycle: 11% (n = 5) partial responses, 64% (n = 29) stable, and 24% (n = 11) progressed. Median time to progression from first chemoembolization was 8 months, with 28% free of progression at 12 months. Median survival from time of diagnosis was 20 months, with 1-, 2-, and 3-year survival of 75%, 39%, and 17%, respectively. Median survival from time of first chemoembolization was 15 months, with 1-, 2-, and 3-year survival of 61%, 27%, and 8%, respectively. There was no statistically significant difference in survival between patients with cholangiocarcinoma and those with poorly differentiated adenocarcinoma. Patients who also received systemic chemotherapy had improved overall survival (median 28 vs 16 months, P = .02; HR, 1.94; 95% CI, 1.13-3.33). CONCLUSIONS: Chemoembolization provided local disease control (PR + SD) of intrahepatic cholangiocarcinoma and adenocarcinoma of unknown primary in 76%. Overall survival after chemoembolization showed the best outcomes for those receiving multidisciplinary integrated liver-directed and systemic therapies.

Endoscopic bilateral metal stent placement for advanced hilar cholangiocarcinoma: a pilot study of a newly designed Y stent.

BACKGROUND: Although endoscopic stent placement is now generally accepted as a palliative method of treatment in unresectable hilar cholangiocarcinoma, exclusively endoscopic placement of bilateral metal stents has been considered very difficult and complex. OBJECTIVE: To evaluate the technical and clinical efficacy of endoscopic placement of dual, newly designed stents in a Y configuration. DESIGN: Prospective, uncontrolled, single center. SETTING: Tertiary referral university hospital. PATIENTS: Ten patients with unresectable hilar cholangiocarcinoma of Bismuth type II or higher. INTERVENTIONS: For bilateral metal stent placement, a biliary Y stent with central wide-open mesh was used exclusively at first. A second stent was placed into the contralateral hepatic duct through the central open mesh of the Y stent. MAIN OUTCOME MEASUREMENT: Technical success, functional success, early complications, and short-term clinical outcome. RESULTS: Technical success was achieved in 8 of 10 patients (80%). Among 8 patients in whom bilateral stents were successfully placed by endoscopy, functional success was 100%, the early complication rate was 0%, and the stent occlusion rate was 25%. The median stent patency period was 217 days. LIMITATIONS: Small number of patients, uncontrolled study, short-term follow-up period. CONCLUSIONS: We described a technique for endoscopic bilateral metal stent placement by using the newly designed Y stent for advanced hilar cholangiocarcinoma that resulted in a high success rate of 80%.

Preoperative portal vein embolization with a new liquid embolic agent.

PURPOSE: To evaluate the effectiveness and safety of a new liquid embolic agent in preoperative portal vein embolization. MATERIALS AND METHODS: Embol-78 was obtained by means of hydrolysis of polyvinyl acetate and was dissolved in a mixture of ethanol and nonionic water-soluble contrast medium. After percutaneous puncture of the portal vein, embolization of the right portal vein was performed in 22 patients with hepatocellular carcinoma and in 29 patients with nonhepatocellular carcinoma. In each group, changes in volume of the future liver remnant, portal venous pressure, and liver enzymes were evaluated both before and after embolization. Complications were also evaluated. RESULTS: Portal vein embolization was successful in all patients, without major complications. The mean volumes of the future liver remnant before and 2 weeks after embolization were 385 mL +/- 138 and 533 mL +/- 140, respectively, in the hepatocellular carcinoma group and 517 mL +/- 348 and 755 mL +/- 197, respectively, in the nonhepatocellular carcinoma group. There were only transient elevations in liver enzyme levels after embolization. Mean portal venous pressures before and after the procedure were 16.7 mm Hg +/- 3.8 and 20.3 mm Hg +/- 3.6, respectively, in the hepatocellular carcinoma group and 11.7 mm Hg +/- 3.5 and 14.6 mm Hg +/- 3.6, respectively, in the nonhepatocellular carcinoma group. In each group, changes in volume of the future liver remnant and portal venous pressure were statistically significant (P <.001). CONCLUSION: The liquid embolic material Embol-78 seems to be effective and safe for preoperative portal vein embolization.