Management of hepatocellular carcinoma in patients who are 70 years or older.

Background: Although liver transplantation has been done successfully in elderly patients with hepatocellular carcinoma, these are likely well-selected patients. This study uses a large database of patients with hepatocellular carcinoma to explore treatment and potential candidacy for liver transplantation in the elderly. Methods: Retrospective review of 1,533 hepatocellular carcinoma cases identified 2 groups: 475 patients 70 years or older (70 +) and 1,058 patients < 70 years. Demographics, risk factors, tumor characteristics, treatments, and survival were compared. Three- and 5-year survival rates were determined, and logistic regression was used to identify factors predictive of 3-year survival. Results: Patients 70 + were more likely to have metabolic factors and less likely to have viral hepatitis, cirrhosis, hepatocellular carcinoma found with surveillance (21.7% vs 28.4%, P = .005), and hepatocellular carcinoma within Milan criteria (37.3% vs 43.8%, P = .019). Model for End-stage Liver Disease score was similar, but patients 70 + had higher mean creatinine and lower mean bilirubin. Patients 70 + were equally likely to undergo liver resection but less likely to undergo liver transplantation (0.4% vs 10.2%, P < .001). Three- and 5-year survival rates were significantly worse in 70 +, and predictors of 3-year survival included hepatocellular carcinoma found with surveillance, meeting Milan criteria, and normal alpha fetoprotein. Discussion: Elderly patients with hepatocellular carcinoma were less likely to undergo liver transplantation potentially due to metabolic factors and advanced disease. Although there is no age cutoff for liver transplantation, elderly patients should be given realistic expectations of liver transplantation candidacy. Continued surveillance for hepatocellular carcinoma in elderly patients may allow for earlier diagnosis and improved liver transplantation candidacy. Key Message: Hepatocellular carcinoma in patients who are 70 years or older can be managed with liver transplantation in select cases, but more patients will be managed with liver resection and nonoperative therapies.

Should a homeless person become a deceased organ donor?

Efforts to increase deceased donation have included the use of US Public Health Service (PHS) high-risk donors. The homeless have high rates of medical and substance abuse issues that are often unrecognized. This study investigates whether the homeless should become suitable organ donors. We retrospectively reviewed 193 brain-dead prospective donors from Hawaii's organ procurement organization (OPO; 2013-2018) and compared two groups: homeless (n = 13) and non-homeless (n = 180) prospective donors. The homeless prospective donors were older (48.0 vs 40.7 years, P = .009) and had more substance abuse (30.8% vs 10%, P = .046), methamphetamine use (53.8% vs 12.2%, P = .001), cocaine use (23.1% vs 3.9%, P = .022), and urine with amphetamines (54.5% vs 17.9%, P = .049). The homeless prospective donors trended toward more PHS high-risk designation (50% vs 19%, P = .062). There was no difference in medical history, gender/race, hepatitis serologies, authorization for donation, and organs procured/transplanted between prospective donors. We have provided evidence that the homeless should become prospective organ donors; however, they have more high-risk behaviors and often have limited information. Larger studies from OPOs are needed to better characterize organ donation and track disease transmission in this population.

The changing characteristics of hepatocellular cancer in Hawaii over time.

BACKGROUND: The incidence of hepatocellular cancer (HCC) is increasing, and we sought to characterize the differences and trends in HCC over 2 decades in Hawaii. METHODS: This retrospective study of 821 HCC cases analyzed risk factors, diabetes, alpha-fetoprotein (AFP), tumor characteristics, and treatment, comparing 5-year eras (1993 to 2012). RESULTS: With succeeding eras, there were fewer Asians, immigrants, and hepatitis B-related HCC. Hepatitis C, diabetes, hyperlipidemia, and body mass index have increased. Over time, more patients had normal AFP, and normal AFP was seen more often in nonviral HCC (49.6% vs 33.2%, P = .007). Over time, the proportion of patients who underwent resection or transplant was stable, but fewer patients underwent no therapy. CONCLUSIONS: Characteristics of HCC are changing, and diagnosis may be more difficult as metabolic factors are becoming more important than viral factors. AFP seems to be a less important biomarker, and clearly, better diagnostic tools will be necessary to identify HCC in the future.

Ultrasound safety with midfrequency transcranial sonothrombolysis: preliminary study on normal macaca monkey brain.

We investigated the safety of transcranial-targeting midfrequency (0.1 to 1 MHz) ultrasonic thrombolysis for acute ischemic stroke. We applied a new therapeutic and imaging transducer to healthy Macaca monkey brains via sonication of the ipsilateral middle cerebral artery through an acoustic temporal window. Young adult cynomolgus monkeys (Macaca fascicularis) were assigned to a group without sonication (control), a group maintained for 1 d after sonication (C1) and a group maintained for 7 d after sonication (C7; n = 3 for each). Two elder rhesus monkeys (Macaca mulatta) were ultrasonicated under transvenous injection of the recombinant tissue plasminogen activator alteplase (0.9 mg/kg), and maintained for 7 d (R). An automatic switching circuit alternately operated a therapeutic ultrasound beam (T-beam) generator for thrombolysis (frequency = 490 kHz; intensity = 0.72 W/cm(2)) and a diagnostic color-flow imaging ultrasound beam (D-beam; frequency = 2.5 MHz; intensity = 0.20 W/cm(2)). A 15-min protocol, comprising four repeats of a sequence of 120-s T-beam activation followed by 30-s D-beam activation and then 5-min T-beam deactivation together with D-beam activation, was repeated four times over 60 min. After confirmation of neurologic deficits, the brains were removed and investigated histologically and immunohistochemically. Three skull samples were subjected to 494-kHz continuous waveform ultrasound, the transcranial intensity was measured and the mechanical index was calculated. None of the monkeys showed neurologic deficits after ultrasonication. The transskull ultrasound intensity rate was 48 ± 12%. The intracranial mechanical index value was 0.15. The novel system did not cause tissue damage in the primate brain and no cavitation effect was detected intracranially.

Dual-frequency ultrasound imaging and therapeutic bilaminar array using frequency selective isolation layer.

A new ultrasound array transducer with two different optimal frequencies designed for diagnosis and therapy integration in Doppler imaging-based transcranial sonothrombolysis is described. Previous studies have shown that respective frequencies around 0.5 and 2 MHz are suitable for sonothrombolysis and Doppler imaging. Because of the small acoustic window available for transcranial ultrasound exposure, it is highly desirable that both therapeutic and diagnostic ultrasounds pass through the same aperture with high efficiency. To achieve such a dual-frequency array transducer, we propose a bilaminar array, having an array for imaging and another for therapy, with a frequency selective isolation layer between the two arrays. The function of this layer is to isolate the imaging array from the therapy array at 2 MHz without disturbing the 0.5-MHz ultrasound transmission. In this study, we first used a 1-D model including two lead zirconate titanate (PZT) layers separated by an isolation layer for intuitive understanding of the phenomena. After that, we optimized the acoustic impedance and thickness of the isolation layer by analyzing pulse propagation in a 2-D model by conducting a numerical simulation with commercially available software. The optimal acoustic impedance and thickness are 3 to 4 MRayI and lambda/10, respectively. On the basis of the optimization, a prototype array transducer was fabricated, and the spatial resolutions of the Doppler images it obtained were found to be practically the same as those obtained through conventional imaging array transducers.

Outcomes of transplantation in children with primary hepatic malignancy.

HBL and HCC are the most common hepatic malignancies in children. The role of OLT in children with HCC is still a matter of debate. The aim of this study was to review our experience of OLT for HCC. Medical records of patients (<18 yr) who underwent OLT for HCC were reviewed and compared to children who underwent OLT for HBL and for indications other than malignancy. There were 25 patients: HCC (10 cases) and HBL (15 cases). The actuarial patient survival for HCC at one and five yr was 100% and 83.3%, for the HBL group the survival was 86.7% at both one and five yr, and for indications (n=377) other than malignancy the patient survival for pediatric OLT at our center was 87.7% and 84.7% at one and five yr, respectively. The actuarial recurrence free survival at five yr was 83.3% for HCC and 66.8% for HBL. In conclusion, OLT is a good therapeutic modality for children with HCC and HBL.

Overexpression of heat shock proteins in pallido-nigral axonal spheroids of nonhuman aged primates.

The occurrence of spheroids has been described in the globus pallidus (GP) and substantia nigra pars reticulata (SNr) of aged rhesus monkeys. Opinions vary as to the origin of spheroids. Ultrastructural and immunohistochemical analysis suggested that spheroids originate from degenerating axons or astroglia. In the present study, we have investigated the GP and SNr of aged monkeys (Macaca fascicularis and Macaca mulatta). Although immunoreactive for microtubule-associated protein (MAP) 1A, tau, amyloid precursor protein, synaptophysin and phosphorylated neurofilament, spheroids were not immunoreactive for MAP1B and MAP2. We confirmed the axonal nature of pallido-nigral spheroids in aged rhesus monkeys. Pallido-nigral spheroids have been reported to overexpress stress proteins, such as ubiquitin, alphaB-crystallin, and heat shock protein (Hsp) 27. We further evaluated the expression of Hsps in pallido-nigral spheroids. As well as being intensely immunoreactive for ubiquitin, alphaB-crystallin, Hsp27, and Hsp70, spheroids were immunoreactive for Hsp32 (heme oxygenase-1), Hsp40, Hsp60, and Hsp90. On the basis of these findings, we speculate that Hsp32-immunoreactive spheroids might be expressed as an oxidative stress response. Induction of other Hsps might play a role in protection of axons from the aggregation of neurofilament, MAPs and other proteins, and failure to protect degenerating axons might result in their proteolysis by the ubiquitin-proteasome system.

Radiofrequency ablation versus surgical resection for single nodule hepatocellular carcinoma: long-term outcomes.

BACKGROUND: Radiofrequency ablation (RFA) has been increasingly utilized for treatment of hepatocellular carcinoma (HCC). Long-term results of RFA, especially in comparison to surgical resection, have not been well described. METHODS: Eighty-seven patients with single nodule HCC underwent surgical resection (N=47) or RFA (N=40) during a 9-year period. RFA was performed for 36 unresectable disease and 4 surgical refusals. Each group was further divided based on tumor size for analysis; Group 1: resection, 5 cm (N=29) and Group 4: RFA, >5 cm (N=14). Follow-up ranged from 2 to 72 months (median 16 months). Patients' characteristics, local recurrences and overall and disease-free survivals were compared. RESULTS: Patients who underwent RFA were older (69 versus 60, p=0.0006), had more advanced Child-Pugh class and TNM stage (p=0.0002 and p=0.016, respectively), and had smaller tumors (4.6 versus 7.4 cm, p=0.0032). Local recurrence rates were 2% for resection and 10% for RFA (p=0.12). These local and other recurrences were subsequently treated with multimodal therapies as indicated. The median overall and disease-free survivals were equivalent both between Groups 1 and 2 (49 versus 51 months, p=0.44, 36 versus 22 months, p=0.84), and Groups 3 and 4 (47 versus 463 months, p=0.94, 28 versus 20 months, p=0.67). DISCUSSION: Although the groups were not truly comparable, this retrospective study suggests that RFA may offer similar long-term results to surgical resection for single nodule HCC when combined with multimodal treatments.