Noninvasive Diagnosis of Hepatocellular Carcinoma on Sonazoid-Enhanced US: Value of the Kupffer Phase

The aim of this study was to compare the diagnostic performance of Contrast-Enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) version 2017, which includes portal- and late-phase washout as a major imaging feature, with that of modified CEUS LI-RADS, which includes Kupffer-phase findings as a major imaging feature. Participants at risk of hepatocellular carcinoma (HCC) with treatment-naïve hepatic lesions (≥1 cm) were recruited and underwent Sonazoid-enhanced US. Arterial phase hyperenhancement (APHE), washout time, and echogenicity in the Kupffer phase were evaluated using both criteria. The diagnostic performance of both criteria was analyzed using the McNemar test. The evaluation was performed on 102 participants with 102 lesions (HCCs (n = 52), non-HCC malignancies (n = 36), and benign (n = 14)). Among 52 HCCs, non-rim APHE was observed in 92.3% (48 of 52). By 5 min, 73.1% (38 of 52) of HCCs showed mild washout, while by 10 min or in the Kupffer phase, 90.4% (47 of 52) of HCCs showed hypoenhancement. The sensitivity (67.3%; 35 of 52; 95% CI: 52.9%, 79.7%) of modified CEUS LI-RADS criteria was higher than that of CEUS LI-RADS criteria (51.9%; 27 of 52; 95% CI: 37.6%, 66.0%) (p = 0.0047). In conclusion, non-rim APHE with hypoenhancement in the Kupffer phase on Sonazoid-enhanced US is a feasible criterion for diagnosing HCC.

Histopathology of hepatocellular carcinoma - when and what

When do you need to take biopsies of the liver, and what information will you get is the topic of this review on hepatocellular carcinoma (HCC). If, clinically, the differential diagnosis of HCC after imaging is suggested, a biopsy has become obligatory as a diagnostic confirmation of HCC in the non-cirrhotic liver prior to definitive therapeutic interventions, as well as in a palliative therapy concept. In the case of hepatic lesions with an uncharacteristic contrast uptake, a biopsy should be performed immediately to confirm the diagnosis of HCC. After diagnosing HCC, a treatment strategy is evaluated. Further, the biopsy, or in case of surgical treatment, the resected tissue, shows us the different subtypes of HCC, with the steatohepatitic subtype being the most common and the lymphocyte-rich subtype being the least common. Further, the histological grade of HCC is determined according to the grading system of the WHO or the Edmonson and Steiner System. Through biopsies, HCC can be differentiated from intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma or metastases of other malignant tumors, especially metastases of the gastrointestinal tract. In summary, biopsies are fundamental in the diagnosis of HCC.

Neurological aspects of COVID-19

The coronavirus disease COVID-19 began to spread worldwide in December 2019 from the city of Wuhan (China). COVID-19 is often accompanied by fever, hypoxemic respiratory failure and systemic complications (for example, gastrointestinal, renal, cardiac, neurological, and hepatic lesions), thrombotic phenomena. Central nervous system damage is caused by the primary effect on it, direct neuroinvasion of the virus, and more often by secondary effect due to systemic hyperinflammation. Neurological manifestations include fatigue, headache, insomnia, and olfactory/taste disorders. Neurological manifestations and complications of COVID-19 are diverse: (1) cerebral circulatory disorders, including ischemic stroke and macro/microhemorrhages; (2) encephalopathy; (3) para/postinfectious autoimmune complications, such as GuillainBarre syndrome; (4) meningoencephalitis; (5) neuropsychiatric complications (psychosis and mood disorders). In terms of pathogenesis, neurological disorders in COVID-19 can be caused by neurotropicity and neurovirulence of SARS-CoV-2, cytokine storm, hypoxemia, homeostasis disorders, as well as their combined effects. COVID-19 adversely affects the course and prognosis of chronic neurological disorders in comorbid patients. The review highlights the need for vigilance to early neurological complications in patients infected with SARS-CoV-2 and other coronaviruses, especially since some neurological complications may precede respiratory manifestations.

Primary infection by E. multilocularis induces distinct patterns of crosstalk between hepatic regulatory T and natural killer T cells in mice

The larval stage of the helminthic cestode Echinococcus multilocularis can inflict tumor-like hepatic lesions that cause the parasitic disease alveolar echinococcosis in humans, with high mortality in untreated patients. Recently, opportunistic properties of the disease have been proposed based on the increased incidence in immunocompromised patients and mouse models, indicating that an appropriate adaptive immune response is required for the control of the disease. However, little is known about how the local hepatic immune responses modulate the infection with E. multilocularis. In a mouse model of oral infection that mimics the normal infection route in human patients, the adaptive immune response in the liver was assessed using single-cell RNA sequencing of isolated hepatic CD3+ T cells at different infection stages. We observed an early significant increase in regulatory T and natural killer T cells in parallel with an active downregulation of CD4+ and CD8+ T cells. Early interactions between regulatory T cells and natural killer T cells indicate a promotion of the formation of hepatic lesions and later contribute to suppression of the resolution of parasite-induced pathology. The obtained data provides a fresh insight on the adaptive immune responses and local regulatory pathways at different infection stages of E. multilocularis in mice.

Treatment of multiple huge liver cysts in a hybrid operating room: a case report

Background Liver cysts are common, with most cases being asymptomatic. In symptomatic cases, the disease is amenable to treatment. However, huge or multiple liver cysts with vascular narrowing and associated systemic symptoms are extremely rare. Furthermore, the performance of a reliable and effective surgery in such cases remains a major problem. Here, we report a case of multiple giant liver cysts with impaired blood flow surgically treated in a hybrid operating room. Case presentation A 73-year-old male presented to a previous doctor with leg edema and dyspnea on exertion; computed tomography revealed that the cause complaint was right lung and heart compression and inferior vena cava (IVC) stenosis due to huge liver cysts in the caudal lobe. The patient was referred to our hospital because of disease recurrence despite percutaneous aspiration of the cyst. Multiple liver cysts were observed in addition to the drained cysts, two of which were located on both sides of the IVC and caused IVC stenosis. We performed open surgery for the liver cysts and used the hybrid operating room for intraoperative IVC angiography and measuring the hepatic vein and portal vein (PV) pressure. We performed unroofing of the hepatic cyst and cauterization of the cyst wall on the hepatic side. Angiography was performed before and after unroofing of the liver cysts, and IVC stenosis release was confirmed. IVC pressure measured at the peripheral side of the stenosis and PV pressures were continuously measured during surgery and were confirmed to have decreased during the opening of the liver cysts. The patient had a good postoperative course and was discharged on the 10th postoperative day. No recurrence was observed 6 months postoperatively. Conclusions Cyst unroofing surgery using angiography in a hybrid operating room is a useful treatment for deep hepatic lesions in that vascular stenosis improvement can be intraoperatively confirmed. Moreover, in cases wherein the cyst compresses the vasculature, intraoperative monitoring of IVC and PV pressures can be used to prove that the liver cyst is hemodynamically involved.

Usefulness of ultrasound fusion technology for hepatocellular carcinoma localisation, pre- and post-thermal ablation

Introduction Percutaneous thermal ablation of inconspicuous lesions can be challenging. Fusion ultrasound (FUS) allows the use of previously performed diagnostic imaging like computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET–CT) to localise hepatocellular carcinoma (HCC) for treatment. This paper illustrates FUS case studies of pre-, intra- and post-ablation imaging of inconspicuous HCC, supplemented by use of contrast-enhanced ultrasound (CEUS). Method Four prospective cases during September 2014 to October 2018, with HCC amenable to ablation, which were poorly identified on ultrasound, underwent FUS. FUS pre-screening was scheduled within three months of the previous CT or MRI, and between one to four weeks prior to the scheduled ablation date. Post-ablation imaging with FUS was performed between four to six weeks to coincide with their routine follow-up CT or MRI. Findings There were potential benefits observed in the cases with combined techniques of FUS and CEUS for limiting circumstances such as heat sink effect, multiple lesions targeting, inconspicuous lesion detection and pre-ablation technical feasibility assessment. Discussion The combined use of FUS and CEUS improves tumour visibility, increases operator imaging confidence and reduces heat sink effect during percutaneous thermal ablation. Conclusion FUS imaging is helpful in targeting poor conspicuity lesions that cannot be detected on grey-scale ultrasound. It facilitates in ensuring optimal treatment of hepatic lesions for improvement of patient prognosis and follow-up imaging.

Automated liver lesion detection in 68Ga DOTATATE PET/CT using a deep fully convolutional neural network

Background Gastroenteropancreatic neuroendocrine tumors most commonly metastasize to the liver; however, high normal background 68Ga-DOTATATE activity and high image noise make metastatic lesions difficult to detect. The purpose of this study is to develop a rapid, automated and highly specific method to identify 68Ga-DOTATATE PET/CT hepatic lesions using a 2D U-Net convolutional neural network. Methods A retrospective study of 68Ga-DOTATATE PET/CT patient studies (n = 125; 57 with 68Ga-DOTATATE hepatic lesions and 68 without) was evaluated. The dataset was randomly divided into 75 studies for the training set (36 abnormal, 39 normal), 25 for the validation set (11 abnormal, 14 normal) and 25 for the testing set (11 abnormal, 14 normal). Hepatic lesions were physician annotated using a modified PERCIST threshold, and boundary definition by gradient edge detection. The 2D U-Net was trained independently five times for 100,000 iterations using a linear combination of binary cross-entropy and dice losses with a stochastic gradient descent algorithm. Performance metrics included: positive predictive value (PPV), sensitivity, F1 score and area under the precision–recall curve (PR-AUC). Five different pixel area thresholds were used to filter noisy predictions. Results A total of 233 lesions were annotated with each abnormal study containing a mean of 4 ± 2.75 lesions. A pixel filter of 20 produced the highest mean PPV 0.94 ± 0.01. A pixel filter of 5 produced the highest mean sensitivity 0.74 ± 0.02. The highest mean F1 score 0.79 ± 0.01 was produced with a 20 pixel filter. The highest mean PR-AUC 0.73 ± 0.03 was produced with a 15 pixel filter. Conclusion Deep neural networks can automatically detect hepatic lesions in 68Ga-DOTATATE PET. Ongoing improvements in data annotation methods, increasing sample sizes and training methods are anticipated to further improve detection performance.