Drug-Eluting Porous Embolic Microspheres for Trans-Arterial Delivery of Dual Synergistic Anticancer Therapy for the Treatment of Liver Cancer.

Blockage of blood supply while administering chemotherapy to tumors, using trans-arterial chemoembolization (TACE), is the most common treatment for intermediate and advanced-stage unresectable Hepatocellular carcinoma (HCC). However, HCC is characterized by a poor prognosis and high recurrence rates (≈30%), partly due to a hypoxic pro-angiogenic and pro-cancerous microenvironment. This study investigates how modifying tissue stress while improving drug exposure in target organs may maximize the therapeutic outcomes. Porous degradable polymeric microspheres (MS) are designed to obtain a gradual occlusion of the hepatic artery that nourishes the liver, while enabling efficient drug perfusion to the tumor site. The fabricated porous MS are introduced intrahepatically and designed to release a combination therapy of Doxorubicin (DOX) and Tirapazamine (TPZ), which is a hypoxia-activated prodrug. Liver cancer cell lines that are treated with the combination therapy under hypoxia reveal a synergic anti-proliferation effect. An orthotopic liver cancer model, based on N1-S1 hepatoma in rats, is used for the efficacy, biodistribution, and safety studies. Porous DOX-TPZ MS are very effective in suppressing tumor growth in rats, and induction tissue necrosis is associated with high intratumor drug concentrations. Porous particles without drugs show some advantages over nonporous particles, suggesting that morphology may affect the treatment outcomes.

A novel technology for reversible fallopian tubal occlusion using a reverse thermo-responsive polymer-Preliminary results from a rabbit animal study.

OBJECTIVES: To determine if PF-88, a reverse thermo-responsive polymer designed to create a gel at body temperature and liquefy at a lower temperature (21°C) can reversibly occlude the fallopian tubes in rabbits. STUDY DESIGN: Mature female New Zealand White rabbits underwent laparotomy and placement of 22-gage catheter into the lumen of the distil uterine horns for evaluation of tubal patency by fluoroscopy using radio opaque contrast and treatment with PF-88. In the Acute Phase group (n = 5) after PF-88 treatment we immediately cooled the serosal surface of the tube with ice for 90 seconds to liquify the gel then reassessed patency. In the Survival Phase groups, animals recovered from the initial surgery and then underwent a second procedure for evaluation of tubal occlusion and reversibility at 4 (n = 3), 14 (n = 2), and 28 (n = 3) weeks after the initial procedure. We compared the histologic appearance of the treated fallopian tubes to untreated controls (n = 3). RESULTS: In the Acute Phase, we found all 10 fallopian tubes patent on initial evaluation, occluded following treatment with PF88, and patent following re-liquification by chilling. Animals in the Survival Group, all but one of the treated tubes appeared blocked at follow-up and patent following chilling. The treatment failure occurred in an animal in the 4-week group. Tubes treated with PF88 showed no histologic evidence of residual material or damage after removal of the polymer. CONCLUSION: The PF-88 reverse thermo-responsive polymer demonstrated the ability to reversibly block fallopian tubes for up to 28 weeks. IMPLICATIONS: The demonstration of reversible occlusion of the fallopian tube of rabbits using PF-88, a thermo-responsive reverse polymer, support additional studies to evaluate the potential of this polymer as a contraceptive in women.

Diagnostic and Management Difficulty of Bleeding Aorto-Duodenal Fistula Associated with Hodgkin's Lymphoma.

Primary aorto-enteric fistula (AEF) resulting from abdominal malignancy is a rare and often fatal complication. The few reports to date are mostly secondary to solid tumors. We present a case of a patient with refractory Hodgkin's lymphoma who developed life-threatening AEF. We describe the diagnostic and therapeutic efforts, requiring a multi-disciplinary team of interventional radiology, gastroenterology, and transfusion medicine, resulting in a favorable outcome. Importantly, we offer several insights regarding the identification and management of high-risk patients, with an emphasis on pre-treatment considerations and urgent diagnosis and intervention.

Retrievable inferior vena cava filter utilization in obstetric patients.

Objectives: The objective of this study is to evaluate patterns of use and outcomes of retrievable inferior vena cava filters (rIVCF) in obstetric patients. Methods: A single center review of consecutive patients who underwent rIVCF placement during pregnancy/postpartum in 2005-2016. A pooled analysis of the relevant cases in the English literature was conducted. Results: The current cohort comprised 24 women, median age 27 [interquartile range 24-30] years. Among 10 filters placed during pregnancy, the most common indication (n = 4) was the need to withhold anticoagulation therapy before delivery, in the presence of acute thrombosis. In the postpartum period, most filters (64%, 9/14) were an adjunct to catheter-directed thrombolytic therapy. Inferior vena cava filters (IVCF)-related complications occurred in seven (29.2%). Retrieval was attempted in 21 patients (87.5%), and was technically successful in 19 (90.5%), for an overall removal rate of 79.1%. Pooled analysis of the literature (n = 98) showed comparable rates for filter removal and complications (81.6%, p = .78 and 24.2%, p = .60, respectively). Suprarenal placement (p = .12) and elective cesarean section (p = .19) did not reduce overall complication and retrieval rates. The estimated radiation dose among pregnant patients who underwent rIVCF placement without adjunct catheter directed thrombolysis (CDT) (mean 695 Gy cm2) was significantly lower than the radiation dose used in postpartum patients (1863 Gy cm2) or in pregnant patients in whom adjunct CDT was utilized (4059 Gy cm2) (p = .001 for both comparisons). Conclusions: Frequent rIVCF-related complications, radiation exposure, and removal failure call for their cautious utilization in obstetric patients. The role of suprarenal placement and elective cesarean section to improve outcomes has yet to be established.

The Role of Transcatheter Arterial Embolization in the Management of Nonvariceal Upper Gastrointestinal Bleeding.

Nearly 50 years ago, catheter angiography was introduced as a means of both diagnosing and treating nonvariceal upper gastrointestinal bleeding. Technological advances and innovations have resulted in the introduction of microcatheters that, using a coaxial technique, are capable of selecting third-order arterial branches and of delivering a wide array of embolic agents. This article reviews the imaging diagnosis of nonvariceal upper gastrointestinal bleeding, the techniques of diagnostic and therapeutic angiography, the angiographic appearance of the various etiologies of nonvariceal upper gastrointestinal bleeding, the rationale behind case-specific selection of embolic agents as well as the anticipated outcome of transcatheter arterial embolization.

Implementation of an institutional protocol to improve inferior vena cava utilization and outcomes.

To evaluate the impact of an institutional protocol on patterns of use and outcomes of inferior vena cava filters (IVCF). Following a multidisciplinary effort, an institutional protocol involving dedicated follow-up of patients receiving IVCF and a physician education program regarding IVCF utilization, was established. We prospectively collected data of patients who received IVCF during 2015-2016, following protocol implementation (POST group). For comparison, we reviewed records of patients who received IVCF during 2009-2014, before implementation of the institutional protocol (PRE group). In the PRE and POST groups, 76 and 38 IVCF per year were inserted respectively, with an overall decrease of 50%. IVCF were more likely to be placed for therapeutic rather than prophylactic indications in the POST compared to the PRE group (P = 0.003). Follow-up rates at our coagulation clinic were significantly higher in the POST than the PRE group (100 vs. 22.9%, P < 0.0001), as were rates of attempted retrieval: 60.5% (23/38) vs. 16.7% (76/455), P < 0.0001. Failed retrieval occurred at similar rates: 15.8% (12/76) vs. 18.2% (4/22), P = 0.75. There was a trend towards a lower thrombotic complication rate in the POST than the PRE group: 2.6 vs. 11.2%, P = 0.16. Implementation of an institutional protocol significantly decreased the use of IVCF and increased the retrieval rate. Such intervention could potentially lead to lower rates of IVCF-related complications in the future.

Indications, complications and outcomes of elderly patients undergoing retrievable inferior vena cava filter placement.

AIM: The utilization of inferior vena cava filter placement for pulmonary embolism prevention in elderly patients has not been well characterized. The present study aimed to review indications, complications and follow-up data of elderly patients undergoing inferior vena cava filter placement. METHODS: A retrospective review was carried out of consecutive admitted patients who underwent inferior vena cava filter insertion at a large university hospital with a level I trauma center. RESULTS: Overall, 455 retrievable filters were inserted between 2009 and 2014. A total of 133 patients (29.2%) were aged ≥70 years. Elderly patients were less likely to have their filter retrieved compared with non-elderly patients (5.3% vs 21.4%, P < 0.001). Filter-related complications occurred in 13% of non-elderly patients and 14.3% of elderly patients (P = 0.72), most of them occurring in the first 3 months after filter placement. Survival among elderly patients with no evidence of active malignancy was similar to the non-elderly patients with a 1-year survival rate of 76.3% versus 82% in non-elderly patients (P = 0.22), and a 2-year survival rate of 73.1% versus 78.6% in non-elderly patients (P = 0.27). Although decreased, survival rates among elderly patients with active cancer were still substantial, with a 1-year survival rate of 45% and 2-year survival rate of 40%. CONCLUSIONS: Elderly patients had significantly lower rates of filter retrieval with similar complication rate. Survival rates among elderly patients were substantial, and in elderly patients with no active cancer were even comparable with non-elderly patients. When feasible, filter retrieval should be attempted in all elderly patients in order to prevent filter-related complications. Geriatr Gerontol Int 2017; 17: 1508-1514.

Inferior vena cava (IVC) filters in children: A 10-year single center experience.

BACKGROUND: Venous thromboembolism (VTE) is an increasingly recognized problem among children and adolescents. Although inferior vena cava (IVC) filter placement for pulmonary embolism prevention is well reported in adults, data regarding safety and efficacy in the pediatric age group are lacking. PROCEDURE: At a large university hospital with a level I trauma center, medical records of children and adolescents who underwent IVC filter insertion were reviewed. Appropriateness of referral for retrieval was assessed in each case. RESULTS: Fifty-nine children and adolescents (mean age 16 years) successfully underwent IVC filter insertion. All filters placed were retrievable. In 47 patients (79.7%), prophylactic filters were placed in the absence of acute VTE in the setting of trauma. In eight patients (13.5%), filters were placed due to contraindication to anticoagulation therapy with concomitant lower extremity deep vein thrombosis or pulmonary embolism. Filters were successfully retrieved in only 12 patients (20.3%), although an attempt at removal was appropriate and feasible in over 90% of cases. Mean duration of follow-up was 2.1 (range 0.4-7.3) years. A significantly higher retrieval rate was found in patients followed at our thrombosis clinic (P < 0.01). Ten patients (17%) experienced at least one filter-related complication. CONCLUSIONS: Although in most cases, IVC filters were placed for prophylactic indications, the evidence to support their role in this setting is limited. Their low retrieval rate and high filter-related complication rate question their extensive utilization in children. Dedicated follow-up is necessary to detect complications and to ensure that an attempt at retrieval is made when feasible.

Pharmacomechanical catheter-directed thrombolysis for pregnancy-related iliofemoral deep vein thrombosis.

PURPOSE: Pharmacomechanical catheter-directed thrombolysis (PCDT) is relatively contraindicated during pregnancy and postpartum. The purpose of this study was to evaluate outcomes of PCDT in this population. MATERIALS AND METHODS: Data for 11 consecutive patients (aged 21-35 y) undergoing PCDT at a tertiary center for symptomatic pregnancy-related iliofemoral deep vein thrombosis (DVT) were retrospectively reviewed. Details regarding patient presentation, location and extent of thrombus, the PCDT procedure, outcomes, frequency of postthrombotic syndrome (PTS), and subsequent pregnancies were recorded. Two patients who presented in the first trimester terminated their pregnancies after PCDT, 2 patients who presented in the third trimester delayed PCDT until after delivery, and 7 patients who presented with postpartum DVT underwent immediate PCDT. RESULTS: Thrombus extended into the inferior vena cava in 5 patients (45%) and into popliteal/tibial veins in 7 (64%). Four patients (36%) had synchronous pulmonary embolism and three had May-Thurner compression. Median interval from diagnosis to PCDT was 5 days (range, 2-68 d); median duration of urokinase infusion was 27 hours (range, 16-72 h). Greater than 90% clot lysis was achieved in 9 of 11 patients (82%). Metal stents were placed in 8 of 11 patients (73%). A self-limiting popliteal hematoma developed in 1 patient, and 2 had early recurrent thrombosis requiring repeat PCDT. At median 20-month follow-up, nonocclusive thrombus was seen in 5 patients. No patient developed PTS. Three patients, all with stents, had uneventful pregnancies after PCDT. CONCLUSIONS: Pharmacomechanical catheter-directed thrombolysis achieved encouraging initial outcomes in this series. Validation in prospective trials with larger enrollment and longer follow-up is needed.

Endovascular infection following inferior vena cava (IVC) filter insertion.

Inferior vena cava filter (IVC) placement is increasing significantly. However, due to low retrieval rates, many filters are left in place indefinitely thereby exposing patients to long-term filter-related complications. This study reports a series of three patients with IVC filter infection. Cases were identified during retrospective review of medical records of all patients undergoing an IVC filter insertion at a single tertiary care university hospital between 2009 and 2013. Clinical presentation, radiological features and management are discussed. Two patients presented within days of filter placement, while the other one presented 1 year later. In two patients, fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) was found to be a sensitive method to diagnose IVC filter infection. Endovascular infection of IVC filter is a rare event. In patients with IVC filter in place and fever of unknown origin or persistent bacteremia, this complication should be suspected. FDG PET/CT has a diagnostic value in this challenging diagnosis.

Patterns of use and outcome of inferior vena cava filters in a tertiary care setting.

BACKGROUND: Inferior vena cava (IVC) filter placement is increasing although the evidence to justify their use is limited. Many filters are left in place indefinitely, thereby exposing patients to long-term complications. OBJECTIVES: To review indications, complications, and follow-up data of patients undergoing IVC filter placement at our center. METHODS: A retrospective review of consecutive admitted patients who underwent IVC filter insertion in a large university hospital with a level I trauma center. Thrombosis specialists retrospectively assessed the appropriateness of indication for IVC filter placement as well as referral for retrieval. RESULTS: Overall, 405 filters were inserted between 2009 and 2013. All filters were retrievable. IVC filter was placed as a primary prevention in 42% of patients. Fifty-two patients (12.8%) experienced at least one filter-related complication. The most common complication was deep vein thrombosis occurring in 6.9% of cases. Almost a third of all complications occurred in filters originally placed for prophylactic indications. Only 13.6% of filters were successfully removed. Nevertheless, according to our reviewers, an attempt for filter retrieval should have been made in 57% of all cases and in 86% of trauma patients. A significantly higher retrieval rate was found in patients followed at our thrombosis clinic (P < 0.01). During follow-up, 95 patients (23.4%) died, most of them with active cancer. CONCLUSIONS: IVC filters are placed in many cases for prophylactic indications. Their low retrieval rates together with relatively high risk of long-term complications, questions their extensive utilization. Prospective trials addressing the safety and efficacy of IVC filters are still warranted.

Clinical Impact of Percutaneous Transhepatic Insertion of Metal Biliary Endoprostheses for Palliation of Jaundice and Facilitation of Chemotherapy.

OBJECTIVE: To describe the technique and report on the clinical benefit of percutaneous transhepatic metal biliary endoprosthesis (TMBE) placement for the palliation of malignant biliary obstruction (MBO). MATERIALS AND METHODS: This is a retrospective single-center case series of 31 TMBE placements between October 2007 and October 2011 in 29 patients with inoperable MBO who failed endoscopic drainage and were not candidates for surgical resection. The mean age was 66.4 years. Eastern Cooperative Oncology Group performance scores were ≤2 in all patients. Data on procedural success, clinical and radiologic markers of stent patency, procedure-related complications, return to medically treatable status, benefit from chemotherapy, and survival were recorded. RESULTS: All TMBE procedures were successful with no major procedure-related complications, and all patients improved clinically. Mean preprocedural and postprocedural bilirubin concentrations were 228.9±138.4 and 39.9.0±33.6 µmol/L, respectively (P<0.0001). Mean overall survival and occlusion-free survival were 9.355±2.425 months (95% confidence interval [4.60-14.12]) and 4.678±0.720 months (95% confidence interval [3.27-6.09]), respectively. Chemotherapy was initiated or reinstated in 16 patients (55%), 7 of whom (44%) demonstrated stable disease or partial response. Three patients were lost to follow-up. CONCLUSIONS: TMBE provides acceptable palliation for patients with inoperable MBO who have failed endoscopic drainage. Stents appear to remain patent for the remainder of the patient's life in most cases and may facilitate the first induction or reinstatement of chemotherapy with further clinical response in some patients.

Image-guided sharp recanalization of a benign J pouch anastomotic occlusion facilitates surgical repair.

A 27-year-old man with a 9-year history of ulcerative colitis who had undergone total proctocolectomy with construction of a continent pouch in 2008 presented 1 year later with occlusion of the ileal pouch-anal anastomosis precluding ileostomy closure. An attempt at surgical reconstruction at an outside hospital failed, and the patient was informed that he would have a permanent stoma. A further attempt at blind surgical recanalization of the occlusion risked sphincter damage and was deferred. In 2010, reconstruction was performed using a hybrid approach combining image-guided sharp recanalization of the occluded anastomosis with positioning of a large-diameter Foley balloon catheter across the recanalized segment, followed by immediate surgical revision of the J pouch. Ileostomy closure was performed 1 month later. Continence was preserved. Surgical repair preceded by sharp recanalization with positioning of a balloon catheter across the occluding membrane may safely regain durable patency in a chronically occluded ileal pouch-anal anastomosis.

Trans-arterial chemo-embolization is safe and effective for elderly advanced hepatocellular carcinoma patients: results from an international database.

OBJECTIVE: Hepatocellular carcinoma (HCC) incidence among elderly patients is increasing. Trans-arterial chemo-embolization (TACE) prolongs survival in selected HCC patients. The safety and efficacy of TACE in elderly patients has not been extensively studied. The objective of this study was to assess the safety and efficacy of TACE in elderly patients (older than 75) with HCC. DESIGN: Combined HCC registries (Spain, Italy, China and Israel) and cohort design analysis of patients who underwent TACE for HCC. RESULTS: Five hundred and forty-eight patients diagnosed and treated between 1988 and 2010 were included in the analysis (China 197, Italy 155, Israel 102 and Spain 94,). There were 120 patients (22%) older than 75 years and 47 patients (8.6%) older than 80. Median (95% CI) survival estimates were 23 (17-28), 21 (17-26) and 19 (15-23) months (P=0.14) among patients aged younger than 65, 65-75 and older than 75 respectively. An age above 75 years at diagnosis was not associated with worse prognosis, hazard ratio of 1.05 (95% CI 0.75-1.5), controlling for disease stage, sex, diagnosis year, HBV status and stratifying per database. No differences in complication rates were found between the age groups. CONCLUSIONS: TACE is safe for patients older than 75 years. Results were similar over different eras and geographical locations. Though selection bias is inherent, the results suggest overall adequate selection of patients, given the similar outcomes among the different age groups.

Treatment of severe steroid resistant acute GVHD with mesenchymal stromal cells (MSC).

BACKGROUND: Several studies revealed that MSC from human bone marrow can downregulate graft-versus-host disease (GVHD) after allogeneic HSCT. METHODS: Herein we present 50 patients with acute GVHD who got 74 (1-4) MSC infusions for 54 separate episodes of aGVHD. RESULTS: aGVHD was defined as steroid resistant grade IV aGVHD in 42 cases. The major presentation was gastrointestinal GVHD; two (n=18) or more (n=21) systems were involved in the majority of cases. The 1(st) infusion with MSC was given on day +27 (range, 1 to 136); d+45 (range, +11 to +150) post diagnosis of aGVHD and HSCT, respectively. In 2/3 of the cases treatment was performed with frozen stocked MSCs; in 62 cases early passages (1-3) were used. The median number of infused cells was 1.14±0.47 million per kg in the first injection and up to 4.27 (1.70±1.10) millions in total. The two patients with aggressive liver GVHD received MSCs injections intra hepatic arteries without changes of blood flow or evidence cytolysis, but also without a visible effect. Disease free survival at 3.6 years was 56%. We observed better overall survival in patients with GVHD grade < 4, in responders to the 1(st) treatment with MSC, and in pediatric group. The multivariate analysis demonstrated independent influence on survival of initial response and younger age. There were no immediate or late toxicity or side effects. CONCLUSION: Injection of MSCs seems to be a promising and safe treatment of GVHD. The encouraging results obviously should be confirmed in a randomized prospective study.

Patient radiation exposure during percutaneous endovascular revascularization of the lower extremity.

BACKGROUND: Percutaneous endovascular revascularization is emerging as the first line treatment for peripheral artery disease for both intermittent claudication and chronic critical limb ischemia. Radiation doses for these interventions have not been well documented. METHODS: A single center retrospective study of therapeutic endovascular lower extremity interventions performed between September 2006 and December 2011 was undertaken. Collected data included patient demographics, procedure indication, procedural access, anatomic location of occlusive disease (pelvis, thigh, below-knee, or multilevel), and radiation exposure parameters including dose area product (DAP) and fluoroscopy time. RESULTS: Data was available for 382 procedures performed in 313 patients. Eighteen procedures bilateral procedures were excluded. Access site and complete anatomic data were available for 346 procedures. DAP was significantly higher for procedures performed in the pelvis compared with thigh procedures (179.6 vs 63.2 Gy*cm(2); P < .0001) and below-knee procedures (179.6 vs 28.9 Gy*cm(2); P < .0001), despite shorter fluoroscopy times (11.8 vs 16.4 minutes; P < .0001 and 11.1 vs 31.06 minutes; P < .0001, respectively). Procedure access-site affected radiation dose as well; contralateral up-and-over access resulted in a higher DAP than antegrade access (112.2 vs 42.6 Gy*cm(2); P < .0001). In a multivariable analysis, anatomic location of the procedure showed the strongest association with radiation dose (P < .0001). CONCLUSIONS: Percutaneous endovascular revascularization for lower extremity peripheral artery disease involves a substantial radiation dose, comparable, on average, to a computed tomography scan of the abdomen and pelvis. Procedures performed in the pelvis for intermittent claudication involve more radiation than thigh or below-knee procedures for chronic critical limb ischemia. Radiation dose should be considered when planning these procedures.

Endovascular management of blunt renal artery trauma.

BACKGROUND: Renal artery injuries are rarely encountered in victims of blunt trauma. However, the rate of early diagnosis of such injuries is increasing due to increased awareness and the liberal use of contrast-enhanced CT. Sporadic case reports have shown the feasibility of endovascular management of blunt renal artery injury. However, no prospective trials or long-term follow-up studies have been reported. OBJECTIVES: To present our experience with endovascular management of blunt renal artery injury, and review the literature. METHODS: We conducted a retrospective study of 18 months at a level 1 trauma center. Search of our electronic database and trauma registry identified three patients with renal artery injury from blunt trauma who were successfully treated endovascularly. Data recorded included the mechanism of injury, time from injury and admission to revascularization, type of endovascular therapy, clinical and imaging outcome, and complications. RESULTS: Mean time from injury to endovascular revascularization was 193 minutes and mean time from admission to revascularization 154 minutes. Stent-assisted angioplasty was used in two cases, while angioplasty alone was performed in a 4 year old boy. A good immediate angiographic result was achieved in all patients. At a mean follow-up of 13 months the treated renal artery was patent in all patients on duplex ultrasound. The mean percentage renal perfusion of the treated kidney at last follow-up was 36% on DTPA renal scan. No early or late complications were encountered. CONCLUSIONS: Endovascular management for blunt renal artery dissection is safe and feasible if an early diagnosis is made. This approach may be expected to replace surgical revascularization in most cases.

Trans-arterial chemo-embolization is safe and effective for very elderly patients with hepatocellular carcinoma.

AIM: To assess the safety and efficacy of trans-arterial chemo-embolization (TACE) in very elderly patients. METHODS: A prospective cohort study, from 2001 to 2010, compared clinical outcomes following TACE between patients ≥ 75 years old and younger patients (aged between 65 and 75 years and younger than 65 years) with hepatocellular carcinoma (HCC), diagnosed according to the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases criteria. The decision that patients were not candidates for curative therapy was made by a multidisciplinary HCC team. Data collected included demographics, co-morbidities, liver disease etiology, liver disease severity and the number of procedures. The primary outcome was mortality; secondary outcomes included post-embolization syndrome (nausea, fever, abdominal right upper quadrant pain, increase in liver enzymes with no evidence of sepsis and with a clinical course limited to 3-4 d post procedure) and 30-d complications. Additionally, changes in liver enzyme measurements were assessed [alanine and aspartate aminotransferase (ALT and AST), gamma-glutamyl transpeptidase and alkaline phosphatase] in the week following TACE. Analysis employed both univariate and multivariate methods (Cox regression models). RESULTS: Of 102 patients who underwent TACE as sole treatment, 10 patients (9.8%) were > 80 years old at diagnosis; 13 (12.7%) were between 75 and 80 years, 45 (44.1%) were between 65 and 75 years and 34 (33.3%) were younger than 65 years. Survival analysis demonstrated similar survival patterns between the elderly patients and younger patients. Age was also not associated with the adverse event rate. Survival rates at 1, 2 and 3 years from diagnosis were 74%, 37% and 31% among patients < 65 years; 83%, 66% and 48% among patients aged 65 to 75 years; and 86%, 41% and 23% among patients ≥ 75 years. There were no differences between the age groups in the pre-procedural care, including preventive treatment for contrast nephropathy and prophylactic antibiotics. Multivariate survival analysis, controlling for disease stage at diagnosis with the Barcelona Clinic Liver Cancer score, number of TACE procedures, sex and alpha-fetoprotein level at the time of diagnosis, found no significant difference in the mortality hazard for elderly vs younger patients, and there were no differences in post-procedural complications. Serum creatinine levels did not change after 55% of the procedures, in all age groups. In 42% of all procedures, serum creatinine levels increased by no more than 25% above the baseline levels prior to TACE. Overall, there were 69 post-embolization events (23%). Hepatocellular enzymes often increased following TACE, with no association with prognosis. In 40% of the procedures, ALT and AST levels rose by at least 100%. The increases in hepatocellular enzymes occurred similarly in all age groups. CONCLUSION: TACE is safe and effective in very elderly patients with HCC, and is not associated with decreased survival or increased complication rates.

A sequential treatment algorithm for infants with stage 4s neuroblastoma and massive hepatomegaly.

Infants with 4s neuroblastoma (NB) and massive hepatomegaly have a guarded prognosis and mortality approaches 30%. We report on eight patients with 4s NB and massive hepatomegaly treated with multiple modalities. One patient had spontaneous tumor regression. Three patients had progressive disease and responded to chemotherapy. Four patients progressed despite intravenous chemotherapy, of whom two died, and two were salvaged with hepatic intra-arterial chemoembolization. Treatment of infants with stage 4s NB with massive hepatomegaly should be individualized based on disease course. A sequential approach with observation, intravenous chemotherapy, and intra-arterial chemoembolization, may improve the outcome of these infants.

Complications of high grade liver injuries: management and outcomewith focus on bile leaks.

BACKGROUND: Although liver injury scale does not predict need for surgical intervention, a high-grade complex liver injury should alert the physician to expect an increased risk of hepatic complications following trauma. The aim of the current study was to define hepatic related morbidity in patients sustaining high-grade hepatic injuries that could be safely managed non-operatively. PATIENTS AND METHODS: This is a retrospective study of patients with liver injury admitted to Hadassah-Hebrew University Medical Centre over a 10-year period. Grade 3-5 injuries were considered to be high grade. Collected data included the number and types of liver-related complications. Interventions which were required for these complications in patients who survived longer than 24 hours were analysed. RESULTS: Of 398 patients with liver trauma, 64 (16%) were found to have high-grade liver injuries. Mechanism of injury was blunt trauma in 43 cases, and penetrating in 21. Forty patients (62%) required operative treatment. Among survivors 22 patients (47.8%) developed liver-related complications which required additional interventional treatment. Bilomas and bile leaks were diagnosed in 16 cases post-injury. The diagnosis of bile leaks was suspected with abdominal CT scan, which revealed intraabdominal collections (n = 6), and ascites (n = 2). Three patients had continuous biliary leak from intraabdominal drains left after laparotomy. Nine patients required ERCP with biliary stent placement, and 2 required percutaneous transhepatic biliary drainage. ERCP failed in one case. Four angioembolizations (AE) were performed in 3 patients for rebleeding. Surgical treatment was found to be associated with higher complication rate. AE at admission was associated with a significantly higher rate of biliary complications. There were 24 deaths (37%), the majority from uncontrolled haemorrhage (18 patients). There were only 2 hepatic-related mortalities due to liver failure. CONCLUSIONS: A high complication rate following high-grade liver injuries should be anticipated. In patients with clinical evidence of biliary complications, CT scan is a useful diagnostic and therapeutic tool. AE, ERCP and temporary internal stenting, together with percutaneous drainage of intra-abdominal or intrahepatic bile collections, represents a safe and effective strategy for the management of complications following both blunt and penetrating hepatic trauma.