Nicholas Fidelman

Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria.

We report on the long‐term intention‐to‐treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4‐5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4‐5 tumors at presentation. The 1‐ and 2‐year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan‐Meiers 5‐year post‐transplant survival and recurrence‐free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5‐year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha‐fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Childs B versus Childs A cirrhosis (multivariate HR: 2.19; P = 0.04). Conclusion: Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post‐transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4‐5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup. (Hepatology 2015;61:1968–1977)

Mixed hepatocellular cholangiocarcinoma and intrahepatic cholangiocarcinoma in patients undergoing transplantation for hepatocellular carcinoma

Mixed hepatocellular cholangiocarcinoma (HCC‐CC) and intrahepatic cholangiocarcinoma (I‐CC) are increasingly being reported in patients with cirrhosis. The aims of this study were (1) to evaluate the incidence, imaging features, and posttransplant outcomes for patients who underwent transplantation for hepatocellular carcinoma (HCC) and were found to have HCC‐CC or I‐CC in the explant and (2) to compare the outcomes of these patients with those of controls with HCC who were matched (1:3) by the tumor size and the number of nodules in the explant. In the explant specimens of 10 of 302 patients (3.3%) who underwent liver transplantation (LT) for HCC, mixed HCC‐CC or I‐CC was identified. There were 4 additional incidental cases of HCC‐CC. After a median follow‐up period of 32 months, 8 of the 14 patients (57%) suffered from tumor recurrence, and the median disease‐free survival time was 8 months. The cumulative risk of tumor recurrence was 40% and 70% at 1 and 5 years, respectively, for these 14 patients. When the 4 incidental cases were excluded, the study group with HCC‐CC or I‐CC (n = 10) had a significantly lower incidence of well‐differentiated tumors (11.1% versus 43.3%, P < 0.02) and a higher rate of recurrence (60% versus 16.7%, P = 0.008) in comparison with the control group of patients with HCC (n = 30). The 1‐ and 5‐year cumulative risks of tumor recurrence were 42% and 65%, respectively, in the study group and 10% and 17%, respectively, in the control group (P < 0.002). The actuarial 1‐ and 5‐year patient survival rates without recurrence were also significantly lower in the study group (79% and 32% in the study group and 90% and 62% in the control group, P < 0.03). Dynamic contrast‐enhanced computed tomography or magnetic resonance imaging showed progressive contrast enhancement throughout the arterial and portal venous phases without washout in 8 of the 10 patients. In conclusion, HCC‐CC and I‐CC are associated with a poor prognosis and a high rate of tumor recurrence after LT, and both tumors exhibit radiographic features that are distinct from those observed with HCC. Liver Transpl 17:934–942, 2011.

The transjugular intrahepatic portosystemic shunt: an update.

OBJECTIVE The purpose of this article is to review the indications, outcomes, complications, patient selection, and technical aspects of creating a transjugular intrahepatic portosystemic shunt (TIPS). CONCLUSION The best available evidence supports the use of TIPS in secondary prevention of variceal bleeding and in refractory ascites, although TIPS is also commonly used for other indications such as Budd-Chiari syndrome, hepatic hydrothorax, and acute variceal hemorrhage. The TIPS procedure was revolutionized by the introduction of covered stents, which dramatically improved long-term shunt patency.

Imaging predictors of the response to transarterial chemoembolization in patients with hepatocellular carcinoma: a radiological-pathological correlation.

Transarterial chemoembolization (TACE) is one of the standard therapies for bridging patients with hepatocellular carcinoma (HCC) to transplantation. This study was designed to determine which features on pre‐ and post‐TACE imaging are associated with tumor necrosis in pathological specimens. Records of 105 patients with 132 HCC lesions who underwent liver transplantation after TACE were retrospectively reviewed. In 70% of the nodules, >90% necrosis was achieved. The development of >90% lesion necrosis upon pathological analysis was associated with avid lesion enhancement (P = 0.03) and the presence of a feeding vessel larger than 0.9 mm in diameter on the pre‐TACE visceral angiogram (P = 0.01). Near‐complete lesion necrosis was also associated with an extensive accumulation of ethiodized oil within a lesion during TACE administration (P = 0.04). On post‐TACE computed tomography imaging, a lack of residual contrast enhancement (P < 0.0001), a decrease in the lesion size (P = 0.04), a high lesion density due to an accumulation of ethiodized oil (P = 0.03), and a diffuse distribution of ethiodized oil throughout the lesion (P = 0.0001) were also correlated with near‐complete lesion necrosis upon pathological analysis. In conclusion, this study found multiple pre‐ and post‐TACE imaging characteristics of HCC that were associated with near‐complete tumor necrosis upon histopathological analysis after TACE. These findings may help to guide the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation. Liver Transpl 18:727–736, 2012.

Experimental Renal Artery Embolization in a Combined MR Imaging/Angiographic Unit

PURPOSE The purpose of this study was to use a combined x-ray angiography and MR imaging (XMR) system to manipulate intraarterial catheters and monitor the deposition of gadolinium (Gd)-impregnated embolic microspheres in vivo in a canine kidney model. MATERIALS AND METHODS Seven anesthetized dogs (18-28 kg) were studied. The renal arteries were catheterized under fluoroscopic guidance. Renal blood flow rates were assessed with velocity-encoded cine MR imaging before and after renal artery embolization with Gd-impregnated microspheres (300-500 and 500-700 micro m in size). The particles were injected in vivo into 14 canine renal arteries under fast dynamic T1-weighted MR imaging guidance at one frame per second. Postembolic microsphere distributions were assessed with MR imaging and digital subtraction angiography (DSA). RESULTS Gd-impregnated microsphere injection into the renal arteries was successful in all animals. Renal enhancement due to the deposition of the particles persisted for at least 1 hour after the injection. The distribution of MR signal enhancement in the kidneys differed for the smaller versus the larger microspheres. The 300-500- micro m microspheres deposited preferentially in the outer cortical regions, whereas the 500-700- micro m microspheres preferentially deposited in the medulla and inner cortex. Renal blood flow was significantly reduced after the administration of both the 300-500- micro m microspheres (from 3.9 to 1.0 mL/min/g) and the 500-700- micro m microspheres (from 3.5 to 0.2 mL/min/g). CONCLUSION MR imaging permits real-time guidance of arterial embolization with Gd-impregnated microspheres.

Morbidity and mortality following transarterial liver chemoembolization in patients with hepatocellular carcinoma and synthetic hepatic dysfunction

The purpose of this study was to determine the rate and risk factors for the development of irreversible hepatotoxicity after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and synthetic hepatic dysfunction. Two hundred fifty‐one consecutive patients with HCC and hepatic dysfunction who underwent 443 TACE procedures from 2005 to 2010 were retrospectively reviewed. The included patients met one of the following criteria: a pre‐TACE bilirubin level ≥ 2 mg/dL, an international normalized ratio (INR) > 1.5, a creatinine level > 1.2 mg/dL, a platelet count ≤ 60,000/mL, a Model for End‐Stage Liver Disease (MELD) score > 15, Child‐Turcotte‐Pugh class B or C, ascites, or portal vein thrombosis. Hepatotoxicity was defined as new or worsening ascites, encephalopathy, or grade 3 or 4 toxicity (bilirubin, aspartate aminotransferase, alanine aminotransferase, creatinine, or INR) according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The rate and risk factors for death or urgent liver transplantation within 6 weeks of TACE and irreversible hepatotoxicity were determined with a generalized estimating equation analysis. Reversible hepatotoxicity developed after 90 procedures (20%) in 78 patients (31%). Irreversible hepatotoxicity developed after 41 procedures (9%) in 37 patients (15%). Six patients (2%) underwent urgent liver transplantation, and 11 (4%) died within 6 weeks of TACE. Patients at increased risk for procedure‐related mortality or urgent liver transplantation within 6 weeks of TACE had a baseline serum bilirubin level ≥ 4.0 mg/dL (P = 0.01), an elevated INR (P < 0.001), hypoalbuminemia with an albumin level < 2.0 g/L (P = 0.01), a serum creatinine level > 2.0 mg/dL (P = 0.02), large ascites (P = 0.002), encephalopathy (P = 0.005), or a MELD score ≥ 20 (P < 0.001). In conclusion, TACE can be performed safely in patients with baseline hepatic dysfunction. However, a poor hepatic reserve increases the risk of irreversible hepatotoxicity, which may lead to death or the need for urgent liver transplantation. Liver Transpl 19:164–173, 2013.

Hepatic Arterial Injuries after Percutaneous Biliary Interventions in the Era of Laparoscopic Surgery and Liver Transplantation: Experience with 930 Patients

PURPOSE To retrospectively determine if patients with a history of intraoperative bile duct injury or liver transplantation have an increased risk for arterial injury (AI) during percutaneous transhepatic cholangiography (PTC) and percutaneous transhepatic biliary drainage (PTBD) compared with the risk of AI established in the 1970s and 1980s. MATERIALS AND METHODS This study was approved by the committee on human research and was deemed compliant with the Health Insurance Portability and Accountability Act. The informed consent requirement was waived. Records of 1394 procedures (307 PTCs, 1087 PTBDs) performed in 930 patients (445 male, 485 female; age range, 4 months to 99 years) over the past 13 years were retrospectively reviewed. The rate of AI was determined, and demographic, pathologic, technical, and laboratory variables were tested for association with increased risk of AI by using generalized estimating equation analysis. RESULTS AIs were encountered after 30 (2.2%) biliary procedures. No significant difference in the rate of AI was seen among the groups of patients with malignant biliary obstruction (1.8%), history of bile duct injury (2.2%), or complications of liver transplantation (2.6%). Patients who underwent PTBD had a higher risk of AI than did patients who underwent PTC (2.6% vs 0.7%); however, this difference was not significant (P = .06). Ongoing hemobilia was seen in 26 (87%) of the patients, which made it the most common sign of AI, and it had a 94% positive predictive value for AI. A postprocedure decrease in the hematocrit level of more than 13% was seen only in the setting of AI, and it occurred in only three (10%) of patients with AIs. CONCLUSION PTC and PTBD performed for management of bile duct injury and complications of liver transplantation are not associated with an increased risk of hepatic AIs compared with the risk of AI reported in the 1970s and 1980s.

Reassessing the boundaries of liver transplantation for hepatocellular carcinoma: Where do we stand with tumor down-staging?

Down‐staging of hepatocellular carcinoma prior to liver transplantation (LT) has generated a lot of interest in recent years and has been identified in two recent national conferences on hepatocellular carcinoma as one of the priorities for research. Down‐staging is defined as reduction in the tumor burden using local regional therapy specifically to meet acceptable criteria for LT. The rationale behind down‐staging of tumors initially exceeding conventional criteria for LT is to select a subgroup of tumors with favorable biology and prognosis for LT as assessed by their response to local regional therapy. The expectation is to achieve comparable posttransplant survival between patients who achieve successful tumor down‐staging before LT and those whose tumors meet LT criteria at the outset without needing down‐staging. The application of tumor down‐staging requires a highly structured approach using a treatment protocol that includes five essential components: eligibility criteria, down‐staging endpoints, selection of the type of local regional therapy, minimal observation period from successful tumor down‐staging to LT, and criteria for treatment failure and exclusion from LT. This review article summarizes published data on down‐staging and addresses key questions related to each of the components of the down‐staging protocol as well as treatment efficacy. Conclusion: Based on a review of published data and recommendations from recent national and international conferences on hepatocellular carcinoma and LT, a standardized down‐staging protocol is proposed to further evaluate the feasibility and efficacy of applying tumor down‐staging on a broader scale. (Hepatology 2016;63:1014–1025)

Reperfusion of Pulmonary Arteriovenous Malformations after Successful Embolotherapy with Vascular Plugs

Amplatzer vascular plugs (AVPs) are among the embolic agents currently used for occlusion of pulmonary arteriovenous malformations (PAVMs). The authors encountered a patient with multiple PAVMs who developed spontaneous reperfusion of two PAVMs within 7 weeks of initially successful embolization with AVPs. Reperfused PAVMs were effectively occluded by coils deposited proximal to the vascular plugs. AVPs do not provide consistent long-term occlusion of the PAVMs. Deposition of coils proximal to the AVP may decrease the chance of PAVM reperfusion after the embolization.

Reducing the Rate of Repeat Imaging: Import of Outside Images to PACS

OBJECTIVE Repeat imaging at the transfer of care between institutions is a potential source of overutilization. The purpose of this study was to assess whether importing images obtained at one institution to the PACS at another institution reduces the number of repeat imaging examinations performed, sparing patients unnecessary cost and radiation. MATERIALS AND METHODS Informed consent was waived for this retrospective study, which included 267 patients who had undergone CT or MRI of the abdomen at our or another institution within 4 months before transarterial chemoembolization. Patients were divided into the following four groups based on the availability of their images from institutions other than ours (outside images): outside imaging performed but images not available; outside images available on CD or film but not imported; outside images imported to PACS; and no outside imaging, that is, all imaging performed at our institution. The rates of repeat imaging in the four groups were compared. RESULTS When outside images were not available, 72% (13/18) of patients underwent repeat imaging; when outside images were available but not imported, 52% (14/27); when outside images were imported to PACS, 11% (9/79); and when imaging was performed only at our institution, 13% (18/143). Patients whose outside images were imported were significantly less likely to undergo repeat imaging than were both groups whose outside images were not imported (p < 0.001), and their rate of repeat imaging was similar to that of patients who did not undergo outside imaging (p = 0.79). After adjustment for potential confounders, including age, sex, referring institution, and size and number of lesions, the odds that a patient whose images were imported would undergo repeat imaging were significantly lower than those of a patient whose outside images were not imported (odds ratios, 31 for images not available and 9.0 for images available but not imported; both p < 0.001) and were similar to those of a patient who underwent all imaging at our institution (odds ratio, 0.71; p = 0.51). CONCLUSION Importing outside images to PACS reduces the rate of repeat imaging.