Selective fetal reduction in complicated monochorionic twin pregnancies: A comparison of techniques.

OBJECTIVE: To compare perinatal outcomes associated with three methods of selective reduction in complicated monochorionic (MC) twin pregnancies: bipolar cord coagulation (BC), fetoscopic or ultrasound guided laser cord occlusion and radiofrequency ablation (RFA). METHODS: Retrospective cohort study of complicated MC twin pregnancies undergoing selective fetal reduction at a tertiary fetal center over a 20-year period. Obstetric and perinatal outcomes were compared. RESULTS: 105 procedures met inclusion criteria: 74 RFAs, 17 lasers and 14 BCs. Procedure duration was significantly shorter for RFA (27.4 ± 15.8 minutes) compared to BC (91.7 ± 38.7 minutes) and laser (83.4 ± 40.4 minutes), P < .0001). The incidence of preterm prelabor rupture of membranes (PPROM) and co-twin demise did not differ between groups, however preterm delivery <34 weeks occurred less frequently following RFA (29.7%), compared to laser (64.7%) or BC (42.9%) (P = .02); delivery <37 weeks was also less frequent following RFA (45.9%), compared to laser (76.5%) or BC (78.6%)(P = .01). The difference in preterm birth<34 weeks between RFA and laser was maintained after adjusting for cord occlusion indication and amnionicity (OR 3.96, 95% CI 1.27-12.31). CONCLUSIONS: In our experience, RFA procedures were simpler, faster and associated with a lower risk of preterm delivery <34 and <37 weeks, compared to laser or BC.

Hepatic Arterial Blood Flow Modulation in Patients with Hepatocellular Carcinoma: A Pilot Study of the Influence of Intraarterial Norepinephrine Assessed with CT Perfusion.

PURPOSE: This pilot study aims to evaluate the effect of hepatic intraarterial norepinephrine injection in vasculature modulation for hepatocellular carcinoma (HCC) tumors. MATERIALS AND METHODS: This is a single-center prospective study of patients with HCC with proven single-lobe tumors > 3 cm. Eight patients were included, with a mean age of 63 y ± 8. All patients had Barcelona Clinic Liver Cancer stage B HCC and an Eastern Cooperative Oncology Group performance status of 0. Mean tumor size was 6.1 cm ± 1.8; all tumors were hypervascular. Patients underwent CT hepatic perfusion before and after injection of 24 µg of norepinephrine intraarterially (4 µg/mL; total 6 mL injected at a rate of 1 mL/s). Color-coded perfusion maps were used to assess the effects of local therapy on hepatic perfusion values. Tumor-to-liver ratio (TLR) was calculated from the ratio of tumor perfusion to background liver perfusion value. RESULTS: Seven of 8 patents had significant (P = .04) absolute increase in tumor perfusion vs background liver, varying from incremental (-2 mL/min/100 mL) to 290 mL/min/100 mL. There was a nonsignificant increase in TLR from 2.7 ± 1.3 to 2.9 ± 1.4 after norepinephrine injection (P = .8). Mean peak time to maximal increase in tumor perfusion after injection was 6.1 s (range, 4.5-9.1 s). Norepinephrine injection was well tolerated without major adverse events. CONCLUSIONS: Norepinephrine causes increased blood flow toward HCC tumors, but with a corresponding smaller increase in blood flow to noncancerous liver tissue, with no observed systemic side effects.

Management of primary hepatic malignancies during the COVID-19 pandemic: recommendations for risk mitigation from a multidisciplinary perspective.

Around the world, recommendations for cancer treatment are being adapted in real time in response to the pandemic of COVID-19. We, as a multidisciplinary team, reviewed the standard management options, according to the Barcelona Clinic Liver Cancer classification system, for hepatocellular carcinoma. We propose treatment recommendations related to COVID-19 for the different stages of hepatocellular carcinoma (ie, 0, A, B, and C), specifically in relation to surgery, locoregional therapies, and systemic therapy. We suggest potential strategies to modify risk during the pandemic and aid multidisciplinary treatment decision making. We also review the multidisciplinary management of intrahepatic cholangiocarcinoma as a potentially curable and incurable diagnosis in the setting of COVID-19.

Patterns and Predictors of Mortality After Waitlist Dropout of Patients With Hepatocellular Carcinoma Awaiting Liver Transplantation.

BACKGROUND: There is a lack of information about survival after dropout from the liver transplant waiting list. Therefore, we aimed to assess the overall survival, and risk factors for death, after waiting list dropout due to hepatocellular carcinoma (HCC) progression. METHODS: We assessed patients who dropped out of the liver transplant waiting list between 2000 and 2016 in a single, large academic North American center. Patients were divided into 3 groups according to the types of HCC progression: locally advanced disease (LAD), extrahepatic disease (EHD), and macrovascular invasion (MVI). The primary outcome was overall survival. Survival was assessed by the Kaplan-Meier method. Predictors of death after dropout were assessed by multivariable Cox regression. RESULTS: During the study period, 172 patients dropped out due to HCC progression. Of those, 37 (21.5%), 74 (43%), and 61 (35.5%) dropped out due to LAD, EHD, and MVI, respectively. Median survival according to cause of dropout (LAD, EHD, or MVI) was 1.0, 4.4, or 3.3 months, respectively (P = 0.01). Model for End-stage Liver Disease (MELD) score (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.08), alcoholic liver disease (HR, 1.66; 95% CI, 1.02-2.71), and α-fetoprotein >1000 ng/mL (HR, 1.86; 95% CI, 1.22-2.84) were predictors of mortality after dropout. Dropout due to EHD (HR, 0.61; 95% CI, 0.38-0.98) and undergoing treatment after dropout were protective factors (HR, 0.32; 95% CI, 0.21-0.48) for death. CONCLUSIONS: Patient prognosis after dropout is dismal. However, a subgroup of patients may have longer survival. The present study identifies the patterns of waitlist dropout in patients with HCC and provides evidence for the effectiveness of treatment strategies offered to HCC patients after dropout.

Effect of portal vein embolization on treatment plan prior to major hepatectomy for hepatocellular carcinoma.

BACKGROUND: Portal vein embolization (PVE) is used before major hepatectomy for hepatocellular carcinoma (HCC) to increase future liver remnant (FLR) volume. However, this may increase tumour growth rate, leading to more extensive resections. This study aimed to determine the effect of tumour growth, following PVE, on treatment plan. METHOD: Retrospective cohort study conducted on patients treated from 2008 to 2015 with PVE before major hepatectomy for HCC. Liver and tumour volumetry was performed on pre- and post-PVE CT scans. Image-based and actioned plans were compared before and after PVE. RESULTS: Thirty-one patients received PVE. Non-tumour total liver volume decreased (median 1440 to 1394 cm3; p = 0.031), while tumour (median 161-240 cm3; p < 0.001) and FLR volumes (median 430-574 cm3; p < 0.001) increased. The treatment plan changed in 15/31 patients: more extensive resection (n = 6), less extensive resection (n = 1), no resection as scheduled (n = 8). Tumour progression accounted for a clinically relevant change in treatment plan in 8/31 patients. CONCLUSION: Following PVE in the setting of HCC, tumour progression accounts for a change in treatment plan in approximately a quarter of patients. Further research is warranted to determine whether additional liver directed therapy should routinely be used to slow the growth of HCC post-PVE.

Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3 cm in potentially transplantable patients.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy. METHODS: We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged <70 years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2 cm vs. HCC >2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria. RESULTS: We included 301 patients (167 HCC ≤2 cm and 134 HCC >2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC >2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2 cm group (p = 0.01). Tumor size >2 cm (hazard ratio 1.94; 95%CI 1.25-3.02) and alpha-fetoprotein levels at the time of ablation (100-1,000 ng/ml: hazard ratio 2.05; 95%CI 1.10-3.83) were found to be predictors of post-RFA recurrence outside Milan criteria. CONCLUSION: RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA. LAY SUMMARY: Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients.

Clinical Case Panel: Treatment Alternatives for Inoperable Hepatocellular Carcinoma.

Surgical resection or liver transplantation offers the best chance of cure for patients with hepatocellular carcinoma (HCC). Unfortunately, most patients are not good candidates for liver resection due to locally advanced disease or compromised liver function. Moreover, liver transplantation waiting lists are long. For those cases not amenable for resection, a variety of local treatment modalities are available, such as image-guided ablative procedures, transarterial chemoembolization, and radioembolization, as well as external beam radiation. HCC presentation can vary considerably in size, number, and location of lesions. The management of inoperable HCC is, therefore, quite complex, and there is a lack of consensus on the best local treatment modality for each type tumor presentation. Here, we present 4 clinical case scenarios representative of commonly seen cases in the clinical setting, with different therapeutic perspectives from institutions with high expertise in the management of HCC.

Transabdominal Direct Sac Puncture Embolization of Type II Endoleaks after Endovascular Abdominal Aortic Aneurysm Repair.

PURPOSE: To determine the efficacy and safety of transabdominal direct sac puncture embolization of type II endoleaks after endovascular abdominal aortic aneurysm repair (EVAR). MATERIALS AND METHODS: This retrospective review included 30 patients (4 women, 26 men; mean age = 79.1 years) who underwent 33 transabdominal direct sac puncture embolization procedures for type II endoleaks after EVAR. Embolization agents included cyanoacrylate glue only (45.5%), glue/coils (36.4%), and Onyx with or without glue/coils (18.1%). Technical success was defined as complete endoleak embolization on intraprocedural fluoroscopy. The primary outcome was freedom of aneurysm growth, which was defined as ≤ 5% aneurysm sac volume change on follow-up computed tomography (CT) imaging or ≤ 5 mm aneurysm sac diameter change on ultrasound without definite endoflow. Aneurysm sac volumes before and after embolization were manually segmented from CT images. The procedural complication rate was calculated. RESULTS: Technical success was achieved in 97% of patients (29/30). Follow-up imaging was available in 27 patients (25 CT; 2 ultrasound), and mean imaging follow-up duration was 15.5 months. Freedom of aneurysm growth was achieved in 85.2% of patients (23/27) after 1 or more embolization procedures. Median fluoroscopic and procedure times were 11.3 minutes and 90 minutes, respectively. The complication rate was 9.1% (3/33) and included 1 case of nontarget embolization with transient neuropraxia and 2 self-limiting rectus sheath hematomas relating to the percutaneous puncture site. No aneurysm-related mortality occurred during the follow-up period. CONCLUSIONS: Percutaneous transabdominal embolization is a safe and efficacious treatment for type II endoleak, with a short procedure time.

Retrospective Single-Arm Cohort Study of Patients with Hepatocellular Adenomas Treated with Percutaneous Thermal Ablation.

PURPOSE: To assess the safety and efficacy of percutaneous thermal ablation for the treatment of hepatocellular adenomas. MATERIALS AND METHODS: This is an ethics board-approved, single-arm, retrospective, cohort study of patients with pathologically proven hepatocellular adenomas treated with percutaneous thermal ablation at a tertiary referral center from 1999 to 2016. Demographic, procedural, and outcome data were collected and summarized with appropriate measures of central tendency and dispersion. Complications were graded per the Society of Interventional Radiology reporting guidelines. Determination of primary and secondary technique efficacies was based on post-procedural imaging. RESULTS: Thirty-six patients (4 male, 32 female) with a median age of 35 years had 44 procedures for the treatment of 58 tumors. Twenty-two percent of patients had prior history of adenoma-related hemorrhage. The median tumor size was 2.1 cm (range 0.6-6.0). The majority of treatments were done on an outpatient basis, under moderate sedation, using radiofrequency ablation with ultrasound guidance. The median procedure time was 85 min. There were two immediate post-procedural hemorrhages (4.5% per procedure). During a median follow-up of 1.7 years (95% CI 0.2-8.0), there were no instances of malignant transformation, adenoma-related hemorrhages, or deaths. The primary and secondary technique efficacy rates were 88 and 100%, respectively. CONCLUSION: Thermal ablation for the treatment of hepatocellular adenoma had a primary and secondary efficacy of 88 and 100%, respectively. The major complication rate was 4.5%. The clinical efficacy during a median follow-up of 1.7 year was 100%.

Effectiveness of stent-graft placement for salvage of dysfunctional arteriovenous hemodialysis fistulas.

PURPOSE: To determine the clinical effectiveness of stent-graft placement in dysfunctional autogenous hemodialysis fistulas. MATERIALS AND METHODS: Between September 2006 and June 2008, 24 Fluency Plus stent-grafts were inserted in 17 patients with failing autogenous hemodialysis fistulas (two radiocephalic, 12 brachiocephalic, and three brachiobasilic). Six fistulas were thrombosed at presentation. Indications for stent-graft insertion included 10 residual stenoses, six pseudoaneurysms, and one fistuloplasty-induced rupture. Fistula function before and after intervention was assessed with ultrasound dilution technique. RESULTS: The technical success rate was 100%, as were the anatomic and clinical success rates. Via Kaplan-Meier method, the primary access patency rates were 94.1% at 3 months (95% CI, 0.461-0.995) and 88.2% at 6 and 12 months (95% CI, 0.468-0.980). The primary lesion patency rate was 94.1% (95% CI, 0.650-0.992) at 3, 6, and 12 months. The secondary access patency rate had a point estimate of 100% at 3 months, and was 93.8% (95% CI, 0.632-0.991) at 6 and 12 months. Univariate analysis suggested that male sex and left-sided accesses were associated with a longer primary access patency rate (P = .02). The binary restenosis rate at 6 months was 5.9%. Mean transonic flow rates were 667.5 mL/min before intervention and 2,076.0 mL/min after intervention (P = .03, Wilcoxon signed-rank test). No patients were lost to follow-up. CONCLUSIONS: Stent-graft placement in dysfunctional autogenous hemodialysis fistulas is technically feasible and effective in preserving function and preventing access abandonment, with patency rates that exceed historical patency rates with angioplasty and/or uncovered stents.

Intraretinal RGMa is involved in retino-tectal mapping.

The repulsive guidance molecule (RGMa) is involved in controlling the topography of retinal ganglion cell axons along the anterioposterior axis of the tectum. Here, we generated a new RGMa-monoclonal antibody and show that it is expressed in the developing retina, suggesting that it may regulate retinal axon pathfinding. We tested this hypothesis by using in ovo electroporation to either overexpress or downregulate RGMa in the eye. Anterograde labeling of retinal axons entering the optic tecta revealed abnormal phenotypes when RGMa expression is perturbed. These included the absence of terminal zone, the premature stalling of arborization of fibers, overshooting of terminal zone, aberrant axonal turns in the optic tectum and abnormal projections into deeper tectal layers. Moreover, RGMa overexpression frequently leads to intraretinal pathfinding errors. Thus, these data suggest that RGMa expression on retinal axons is a major determinant of topographic targeting in the retino-tectal projection and in the retina.