Common design and data elements on rectal artery embolization for treatment of symptomatic internal hemorrhoidal disease: an interactive systematic review of clinical trials.

BACKGROUND: Internal hemorrhoids (IH) is a common medical condition that can result in morbidity secondary to bleeding and discomfort. Treatment for IH has traditionally consisted of dietary and conservative medical management, focal treatments including banding and sclerotherapy or hemorrhoidectomy. Recently, rectal artery embolization (RAE) has been studied as a potential treatment for bleeding predominant IH. We performed a common design and data element analysis of studies that report on RAE. MATERIALS AND METHODS: We conducted a qualitative systematic literature review for rectal artery embolization (RAE) for symptomatic hemorrhoidal disease. The screening process involved five online databases (PubMed, Embase, Google Scholar, DOAJ, and Scopus). Additionally, ClinicalTrials.gov was examined for active, unpublished completed studies. The initial search yielded 2000 studies, with 15 studies meeting the inclusion criteria after screening and assessment. The included studies comprised one RCT, one case series, one pilot study and 12 cohort studies. RESULTS: The population analysis revealed a male predominance across all studies, with varying cohort sizes. The baseline Goligher hemorrhoid grade was utilized in 80% of studies. The majority (73.3%) employed a transfemoral approach, and coils were the primary embolic material in 60% of studies, 26.6% were combination of coils and particles, and 6.6% were particles only. Patient selection criteria highlighted RAE's applicability for high surgical risk patients and those with anemia, chronic hematochezia, or treatment-refractory cases. Exclusion criteria emphasized factors such as previous surgeries, colorectal cancer, rectal prolapse, acute hemorrhoidal complications, and contrast allergy. Study designs varied, with cohort studies being the most common (12/15; 80%). Procedural details included the use of metallic coils and detachable micro-coils, with a high technical success rate reported in most studies ranging from 72 to 100%. The follow-up ranged from 1 to 18 months. The majority of studies reported no major immediate or post-procedural complications. CONCLUSION: While all studies focused on RAE as a treatment for IH, there was a great degree of heterogeneity among included studies, particularly regarding inclusion criteria, exclusion criteria, outcomes measures and timeframe. Future literature should attempt to standardize these design elements to help facilitate secondary analyses and increase understanding of RAE as a treatment option.

Update on Percutaneous Ablation for Sarcoma.

PURPOSE OF REVIEW: To provide an update on the current state of percutaneous thermal ablation in the treatment of sarcoma. RECENT FINDINGS: Data continue to accrue in support of ablation for local control and palliation of specific sarcoma subtypes such as extra-abdominal desmoid fibromatosis and for broader indications such as the treatment of oligometastatic disease. The synergistic possibilities of various combination therapies such as cryoablation and immunotherapy represent intriguing areas of active investigation. Histotripsy is an emerging non-invasive, non-thermal ablative modality that may further expand the therapeutic arsenal for sarcoma treatment. Percutaneous thermal ablation is a valuable tool in the multidisciplinary management of sarcoma, offering a minimally invasive adjunct to surgery and radiation therapy. Although there remains a paucity of high-level evidence specific to sarcomas, ablation techniques are demonstrably safe and effective for achieving local tumor control and providing pain relief in select patients and are of particular benefit in those with metastatic disease or requiring palliative care.

cAMP-dependent protein kinase signaling is required for (2R,6R)-hydroxynorketamine to potentiate hippocampal glutamatergic transmission.

(2R,6R)-Hydroxynorketamine (HNK) is a ketamine metabolite that shows rapid antidepressant-like effects in preclinical studies and lacks the adverse N-methyl-d-aspartate receptor (NMDAR) inhibition-related properties of ketamine. Investigating how (2R,6R)-HNK exerts its antidepressant actions may be informative in the design of novel pharmacotherapies with improved safety and efficacy. We sought to identify the molecular substrates through which (2R,6R)-HNK induces functional changes at excitatory synapses, a prevailing hypothesis for how rapid antidepressant effects are initiated. We recorded excitatory postsynaptic potentials in hippocampal slices from male Wistar Kyoto rats, which have impaired hippocampal plasticity and are resistant to traditional antidepressants. (2R,6R)-HNK (10 µM) led to a rapid potentiation of electrically evoked excitatory postsynaptic potentials at Schaffer collateral CA1 stratum radiatum synapses. This potentiation was associated with a decrease in paired pulse facilitation, suggesting an increase in the probability of glutamate release. The (2R,6R)-HNK-induced potentiation was blocked by inhibiting either cyclic adenosine monophosphate (cAMP) or its downstream target, cAMP-dependent protein kinase (PKA). As cAMP is a potent regulator of brain-derived neurotrophic factor (BDNF) release, we assessed whether (2R,6R)-HNK exerts this acute potentiation through a rapid increase in cAMP-dependent BDNF-TrkB signaling. We found that the cAMP-PKA-dependent potentiation was not dependent on TrkB activation by BDNF, which functionally delimits the acute synaptic effects of (2R,6R)-HNK from its sustained BDNF-dependent actions in vivo. These results suggest that, by potentiating glutamate release via cAMP-PKA signaling, (2R,6R)-HNK initiates acute adaptations in fast excitatory synaptic transmission that promote structural plasticity leading to maintained antidepressant action.NEW & NOTEWORTHY Ketamine is a rapid-acting antidepressant and its preclinical effects are mimicked by its (2R,6R)-(HNK) metabolite. We found that (2R,6R)-HNK initiates acute adaptations in fast excitatory synaptic transmission by potentiating glutamate release via cAMP-PKA signaling at hippocampal Schaffer collateral synapses. This cAMP-PKA-dependent potentiation was not dependent on TrkB activation by BDNF, which functionally delimits the rapid synaptic effects of (2R,6R)-HNK from its sustained BDNF-dependent actions that are thought to maintain antidepressant action in vivo.

Vaginal stenosis treatment using computed tomography and fluoroscopy guidance.

INTRODUCTION: Vaginal stenosis is a common complication following construction of a neovagina with vascularized myocutaneous flaps. This is primarily because of inconsistent or inappropriate vaginal dilator use. Image-guided recanalization, especially for obstructed genitourinary tracts, is an emerging idea in interventional radiology. Although multiple surgical techniques have been reported to treat vaginal agenesis or obstruction, the idea of image-guided recanalization of vaginal stenosis is a relatively new management strategy for vaginal stenosis. CASE: We present a challenging case of a patient who initially presented with the complaint of increasing pelvic pressure after the creation of a neovagina via vaginoplasty. She had a distal neovagina created after extensive surgical resection for a large infiltrating pelvic rectal adenocarcinoma. A computed tomography scan revealed a fluid-filled neovaginal abscess. Examination under anesthesia revealed complete stenosis of the neovagina with no identifiable tract for dilation. INTERVENTION: A computed tomography scan and fluoroscopy-guided sharp recanalization of the stenosed neovagina was performed, followed by serial fluoroscopic balloon angioplasty to dilate the stenosed neovagina. Finally, the patient underwent a gynecologic surgery for the excision of remaining granulation tissue to produce a more permanent patent neovagina, followed by regular and proper use of vaginal dilators to ensure patency. CONCLUSION: This case report demonstrates that image-guided techniques can be used to aid in vaginal recanalization in the postoperative setting.

Nodular Fasciitis: False Positive on 18F-Piflufolastat and 11C-Choline PET/CT.

ABSTRACT: PET/CT plays a crucial role in the management of prostate cancer with several emerging and established radiopharmaceuticals, including 18 F-piflufolastat and 11 C-choline. These radiotracers are thought to be relatively specific to prostate cancer; however, uptake has also been demonstrated in other benign and malignant lesions. Nodular fasciitis is a rapidly growing benign soft tissue neoplasm that is typically self-limiting. Although a few case reports describe 68 Ga-PSMA uptake in nodular fasciitis, uptake of 11 C-choline and other PSMA-targeted PET probes, including 18 F-piflufolastat, have not previously been reported. We present a novel case of nodular fasciitis demonstrating both 18 F-piflufolastat and 11 C-choline avidity.

Radiofrequency Ablation of Benign and Malignant Thyroid Nodules.

Thyroid nodule treatment has significantly evolved over recent years with attempts to individualize treatment on the basis of the cause of the nodule and patient performance status. The risks and complications associated with surgery and radioactive iodine have promoted interest in additional therapies such as radiofrequency ablation (RFA). RFA creates an electrical current through a target tissue (thyroid nodule) with resultant tissue heating causing coagulative necrosis. National and international groups are beginning to recognize the role of RFA as a viable therapeutic option in the treatment of thyroid nodules. Based on numerous guidelines, RFA is indicated in the treatment of symptomatic benign nodules and autonomously functioning nodules when surgery is refused or when the patient would not tolerate surgery. The treatment of thyroid malignancy with RFA is controversial, with some groups advocating for its use in the treatment of small papillary thyroid cancers in specific scenarios. The most important aspect of RFA is the preprocedural workup and adequate patient selection. Procedural technique varies among centers. However, RFA is typically performed as a single-day-admission outpatient procedure. Methods such as hydrodissection and a moving shot technique are employed to ensure adequate coverage of the nodule without overtreating the peripheries and damaging sensitive structures. As a result, the procedure is well tolerated, and major complications such as recurrent laryngeal nerve injury and nodule rupture are very rare. In the proper patient cohort, thyroid RFA offers an efficacious and safe option in the management of thyroid nodules. An invited commentary by Filippiadis and Vrachliotis is available online. ©RSNA, 2022.

Ablation for oligometastatic colorectal carcinoma in extrahepatic, extrapulmonary sites.

Treatment of metastatic colorectal carcinoma has evolved in the era of increasingly effective systemic therapies. Increasing survival rates provide opportunities for repeated focal therapies to be directed at limited metastatic disease. Surgical resection and other ablative therapies to eliminate oligometastases in the most common sites, namely liver and lung, have been proven to prolong survival. As such, patients develop additional sites of metastasis in the course of their disease, including adrenal, peritoneal, nodal, and skeletal metastases. Data supporting aggressive focal therapy for extrahepatic, extrapulmonary metastases are limited. This manuscript summarizes findings of surgical studies of cytoreduction in these patients, describes limited data from ablation case series that include these metastases, and presents a rationale for further investigation of thermal ablation within this patient population.

MELD-Na > 16 is associated with high peri-procedural and short-term mortality in patients with ruptured hepatocellular carcinoma treated with emergent transarterial embolization.

PURPOSE: To evaluate prognostic factors associated with peri-procedural (30 days) and short-term (90 days) mortality in the United States cohort of patients following emergent transarterial embolization for ruptured hepatocellular carcinoma. METHODS: Patients with ruptured hepatocellular carcinoma treated with emergent TAE between January 2001 and December 2019 were retrospectively identified (n = 24). Average age was 62 years (range, 23-78 year); 15 (62.5%) were men. Univariate and Cox proportional hazard modeling were used to determine independent predictors of overall survival (OS) following TAE. OS stratified by Model for End-Stage Liver Disease-Sodium score was assessed using Kaplan-Meier analysis. RESULTS: Twenty-one patients (88%) died during a mean clinical follow-up period of 328 ± 139 days. MELD-Na score (HR 1.22 per 1-unit increase; 95% CI 1.06-1.46; p = 0.005) and pre-rupture ECOG PS score (HR 8.1; 95% CI 1.28-51.2; p = 0.026) were independent predictors of decreased overall survival. There was no significant association between overall survival and presence of cardiovascular co-morbidities (p = 0.60), hemorrhagic shock on presentation (p = 0.16), portal vein thrombus (p = 0.08), vasopressor support required (p = 0.79), intubation required (p = 0.40), acute kidney injury (p = 0.58), and number of packed red blood cell transfusions (p = 0.22). The median OS was 64 days. Median OS was significantly greater in patients with a MELD-Na score ≤ 16 as compared to those with a MELD-Na score > 16 (166.5 days vs 9 days, p = 0.011). Cumulative OS rates in those with a MELD-Na score ≤ 16 at 30, 60, 90, and 360 days were 79%, 64%, 64%, and 25%, respectively, vs 33%, 33%, 11%, and 0%, respectively, in those with a MELD-Na score > 16. CONCLUSION: MELD-Na > 16 is associated with very high peri-procedural (67% at 30 days) and short-term (89% at 90 days) mortality in patients with ruptured HCC treated with emergent transarterial embolization. A better understanding of these prognostic factors may help guide treatment decisions and provide realistic expectations when counseling patients and their families.

PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68 Ga-PSMA-11 PET Using Cyclotron-Produced 68 Ga.

Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68 Ga-PSMA-11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68 Ga-PSMA-11 PET was prospectively performed in patients with treatment-naïve HCC on a digital PET scanner using cyclotron-produced 68 Ga. Uptake was graded qualitatively and semi-quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor-associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10-5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = -0.753; P = 1.58 × 10-6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68 Ga-PSMA-11 standardized uptake value: SUVmax (median [range] 9.2 [4.9-28.4]), SUVmean 4.7 (2.4-12.7), and tumor-to-liver background ratio 2 (1.1-11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68 Ga-PSMA-11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

Body Interventional MRI for Diagnostic and Interventional Radiologists: Current Practice and Future Prospects.

Clinical use of MRI for guidance during interventional procedures emerged shortly after the introduction of clinical diagnostic MRI in the late 1980s. However, early applications of interventional MRI (iMRI) were limited owing to the lack of dedicated iMRI magnets, pulse sequences, and equipment. During the 3 decades that followed, technologic advancements in iMRI magnets that balance bore access and field strength, combined with the development of rapid MRI pulse sequences, surface coils, and commercially available MR-conditional devices, led to the rapid expansion of clinical iMRI applications, particularly in the field of body iMRI. iMRI offers several advantages, including superior soft-tissue resolution, ease of multiplanar imaging, lack of ionizing radiation, and capability to re-image the same section. Disadvantages include longer examination times, lack of MR-conditional equipment, less operator familiarity, and increased cost. Nonetheless, MRI guidance is particularly advantageous when the disease is best visualized with MRI and/or when superior soft-tissue contrast is needed for treatment monitoring. Safety in the iMRI environment is paramount and requires close collaboration among interventional radiologists, MR physicists, and all other iMRI team members. The implementation of risk-limiting measures for personnel and equipment in MR zones III and IV is key. Various commercially available MR-conditional needles, wires, and biopsy and ablation devices are now available throughout the world, depending on the local regulatory status. As such, there has been tremendous growth in the clinical applications of body iMRI, including localization of difficult lesions, biopsy, sclerotherapy, and cryoablation and thermal ablation of malignant and nonmalignant soft-tissue neoplasms. Online supplemental material is available for this article. ©RSNA, 2021.

Percutaneous MR Imaging-Guided Laser Ablation and Cryoablation for the Treatment of Pediatric and Adult Symptomatic Peripheral Soft Tissue Vascular Anomalies.

PURPOSE: To evaluate the safety and effectiveness of percutaneous magnetic resonance (MR) imaging-guided laser ablation and cryoablation for the treatment of symptomatic soft tissue vascular anomalies (VAs) of the trunk and extremities. MATERIALS AND METHODS: An institutional review board-approved retrospective review was undertaken of all pediatric and adult patients who underwent MR imaging-guided and monitored laser ablation and/or cryoablation for the treatment of symptomatic peripheral soft tissue VA. Preablation and postablation MR imaging was independently reviewed. Pain scores on the visual analog scale (0 to 10) and self-reported subjective symptomatic improvement were assessed. Change in VA size and pain scores were compared using a paired t test. RESULTS: Thirty patients (24 females; age, 10-75 years) with 34 VAs were treated for moderate to severe pain (n = 27) or swelling/mass effect (n = 3) with 60 total ablation sessions. The baseline maximum VA diameter was 9.5 cm ± 8.6. At baseline, all VAs (100%) demonstrated variable T2-weighted signal hyperintensity and enhancement. The baseline pain score was 6.4 ± 1.6. Clinical follow-up was available for 23 patients. At a mean follow-up time of 12.2 months ± 10.1, 19 of 20 (95%) patients treated for pain and 2 of 3 (67%) patients treated for swelling/mass effect reported partial or complete symptomatic relief. There was a significant decrease in the postablation pain scores (-5.7 ± 1.0, P < .001) and maximum VA size (-2.3 cm ± 2.7, P = .004), with >50% reduction in VA T2 signal (59%) and enhancement (73%). Nine of 30 (30%) patients experienced minor complications. CONCLUSIONS: MR imaging-guided and monitored percutaneous laser ablation and cryoablation appear to be safe and effective for the treatment of symptomatic peripheral soft tissue VAs.

Long-term renal function outcomes after renal cryoablation complicated by major hemorrhage requiring selective transarterial embolization.

PURPOSE: To determine long-term renal function outcomes after renal cryoablation complicated by major hemorrhage requiring transarterial embolization compared to patients who underwent uncomplicated renal cryoablation without major hemorrhage. METHODS: Utilizing a matched cohort study design, retrospective review identified 23 patients who underwent percutaneous image-guided renal cryoablation complicated by major hemorrhage requiring ipsilateral transarterial embolization (TAE group) and a control group of 23 patients who underwent uncomplicated renal cryoablation matched 1:1 by age, gender and RENAL Nephrometry score at a single institution from 1/1/2005 to 12/31/2019. Primary outcome parameters included change in creatinine (mg/dl) and estimated glomerular filtration rate (ml/min/1.73 m2; eGFR) from baseline and were compared between TAE and control group using a paired t-test. RESULTS: There was a significantly higher proportion of patients on pre-ablation anticoagulation in the TAE v. control group (30% v. 4%; p = 0.047), but all patients were off anticoagulation and with normal coagulation parameters at the time of cryoablation. Otherwise there were no significant differences in clinical, renal tumor, Charlson co-morbidity index, baseline renal function or cryoablation parameters between the TAE and control group. In the post-ablation period, there was trend toward greater increase in creatinine from baseline to worst post-ablation creatinine in the TAE v. the control group (+ 0.5 ± 0.7 mg/dl v. 0.2 ± 0.1 mg/dl; p = 0.056). However, at a mean follow-up of 42.7 ± 35.7 months, there was no significant difference between the TAE and control group in creatinine (p = 0.68), eGFR (p = 0.60) or change from baseline in creatinine (p = 0.28), eGFR (p = 0.80) or CKD stage (p = 0.74). No patient required initiation of hemodialysis. CONCLUSION: Selective transarterial embolization for post-renal cryoablation hemorrhage does not significantly affect long-term renal function compared to cryoablation alone. Pre-ablation anticoagulation despite normal coagulation at time of ablation may be a risk factor for post-ablation hemorrhage, and warrants further evaluation when considering pre-ablation embolization.

Thoracic positron emission tomography: 18F-fluorodeoxyglucose and beyond.

Ongoing technologic and therapeutic advancements in medicine are now testing the limits of conventional anatomic imaging techniques. The ability to image physiology, rather than simply anatomy, is critical in the management of multiple disease processes, especially in oncology. Nuclear medicine has assumed a leading role in detecting, diagnosing, staging and assessing treatment response of various pathologic entities, and appears well positioned to do so into the future. When combined with computed tomography (CT) or magnetic resonance imaging (MRI), positron emission tomography (PET) has become the sine quo non technique of evaluating most solid tumors especially in the thorax. PET/CT serves as a key imaging modality in the initial evaluation of pulmonary nodules, often obviating the need for more invasive testing. PET/CT is essential to staging and restaging in bronchogenic carcinoma and offers key physiologic information with regard to treatment response. A more recent development, PET/MRI, shows promise in several specific lung cancer applications as well. Additional recent advancements in the field have allowed PET to expand beyond imaging with 18F-flurodeoxyglucose (FDG) alone, now with the ability to specifically image certain types of cell surface receptors. In the thorax this predominantly includes 68Ga-DOTATATE which targets the somatostatin receptors abundantly expressed in neuroendocrine tumors, including bronchial carcinoid. This receptor targeted imaging technique permits targeting these tumors with therapeutic analogues such as 177Lu labeled DOTATATE. Overall, the proper utilization of PET in the thorax has the ability to directly impact and improve patient care.

Portomesenteric Venous Complications after Pancreatic Surgery with Venous Reconstruction: Imaging and Intervention.

Pancreatic surgery with en bloc venous resection and reconstruction is becoming increasingly common in the current era of expanding neoadjuvant oncologic therapies and advanced surgical techniques for patients with more anatomically complex tumors. However, patients who have alterations in their venous outflow are at increased risk for postoperative portomesenteric venous stenosis and/or thrombosis. Cross-sectional imaging for postoperative surveillance, including multiphase CT or MRI, is critical for recognizing portomesenteric venous complications and thus implementing early intervention and preventing complications related to portomesenteric venous hypertension. Hypertension-related complications include ascites, variceal or gastrointestinal bleeding, postprandial abdominal pain, intestinal edema, protein-losing enteropathy, malabsorptive diarrhea, and splenomegaly. Percutaneous transhepatic, transsplenic, and transjugular portomesenteric interventions, including venoplasty, stent placement, and thrombectomy or thrombolysis, are safe and effective options for restoring patency to the portomesenteric venous system. Preintervention CT or MRI and diagnostic catheter venography are important for procedural planning, while postintervention CT or MRI surveillance is critical for detecting recurrent stenosis or thrombosis, or de novo portomesenteric venous disease. Online supplemental material is available for this article. ©RSNA, 2020.

Evaluation of Technical Success, Efficacy, and Safety of Portomesenteric Venous Intervention following Nontransplant Hepatobiliary or Pancreatic Surgery.

PURPOSE: To evaluate technical success, efficacy and safety of portomesenteric venous (PMV) intervention for PMV stenosis or occlusion following nontransplant hepatobiliary or pancreatic (HPB) surgery. MATERIALS AND METHODS: A retrospective review identified 42 patients (mean age 60 y) with PMV stenosis (n = 33; 79%) or occlusion (n = 9; 21%) who underwent attempted PMV intervention following HPB surgery between June 1, 2011, and April 1, 2018. Main outcomes were technical success, primary patency rates, and complications. Technical success was compared by venous pathology and primary PMV patency based on anticoagulation status after the procedure using Fisher exact test. Rates of primary patency by stent group were estimated using Kaplan-Meier method. RESULTS: Technical success was 91% (n = 38/42) and significantly higher in patients with stenosis (n = 33/33; 100%) vs occlusion (n = 5/9; 56%) (P = .001). Primary presenting symptom resolved in 28 (87%) patients, including 6 (100%) patients with gastrointestinal bleeding. At mean imaging follow-up of 8.6 months ± 8.8, primary stent patency was 76%. There was no significant difference in primary stent patency based on anticoagulation status after the procedure (P = .48). There were 2 (4.8%) periprocedural complications. CONCLUSIONS: Portomesenteric venoplasty and stent placement following nontransplant HPB surgery is safe with a high rate of technical success if performed before chronic occlusion.

Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model.

BackgroundLocal recurrence following thermal ablation of hepatocellular carcinoma (HCC) larger than 2-3 cm remains a challenging clinical problem. Prior studies suggest that phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-dependent protein kinase B (AKT) signaling mediates HCC cell survival caused by moderate heat stress in vitro, but these findings need in vivo validation.PurposeTo test the hypothesis that neoadjuvant inhibition of PI3K/mTOR/AKT signaling reduces HCC tumor growth in vivo after laser ablation and to evaluate the effects of moderate heat stress on molecular signaling and cellular function in HCC cells in vitro.Materials and MethodsHCC tumor-bearing mice were randomized to neoadjuvant PI3K/mTOR inhibitor (BEZ235) or control groups followed by an intentional partial laser ablation or sham ablation; there were at least nine mice per group. Postablation tumor growth was monitored up to 7 days. Tumor volumes were compared for drug or ablation groups by using two-way analysis of variance. N1S1 HCC cells pretreated with BEZ235 or control and subjected to moderate heat stress (45°C for 10 minutes) or control (37°C for 10 minutes) were analyzed by using mass spectrometry. Protein interaction networks were derived from protein expression analysis software, and cellular function activation state (Z-score) and fold-change in AKT phosphorylation were calculated.ResultsThere was a 37%-75% reduction in HCC tumor volume by day 7 after ablation in the BEZ235 plus ablation group (713 mm3 ± 417) compared with vehicle plus sham (1559 mm3 ± 552), vehicle plus ablation (1041 mm3 ± 591), and BEZ235 plus sham (1108 mm3 ± 523) groups (P < .001, P = .04, and P = .005, respectively). PI3K/mTOR inhibition prevented moderate heat stress-induced AKT signaling (Z-score, -0.2; P < .001) and isoform-specific AKT phosphorylation compared with the vehicle plus heat stress group. PI3K/mTOR inhibition prevented moderate heat stress-induced global effects on HCC molecular signaling and cellular function, including decreased cell survival, growth, and proliferation (Z-score, -0.3 to -3.2; P < .001) and increased apoptosis and cell death (Z-score, 0.4-1.1; P < .001).ConclusionModerate heat stress induces PI3K/mTOR/AKT-dependent global effects on hepatocellular carcinoma (HCC) cell survival, function, and death. Neoadjuvant PI3K/mTOR/AKT inhibition reduces postablation HCC tumor growth.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by White in this issue.

Introduction of Microwave Ablation Into a Renal Ablation Practice: Valuable Lessons Learned.

OBJECTIVE: The purpose of this study was to evaluate the early outcomes of percutaneous microwave ablation (MWA) for clinical stage T1 (cT1) renal masses when performed within a high-volume ablation practice with critical emphasis on procedural safety. MATERIALS AND METHODS: A retrospective review of a percutaneous renal ablation registry identified 26 patients with a total of 27 cT1 renal masses treated with MWA between 2011 and 2017. Mean patient age was 63.8 years and 16 (61.5%) patients were male. Mean renal mass size ± SD was 2.3 ± 0.8 cm (range, 1.1-4.7 cm). The main outcome parameters investigated were technical success, local tumor progression, survival rates, and complications. Complications were categorized using the Clavien-Dindo classification system. Rates of local progression-free and cancer-specific survival (PFS and CSS, respectively) were estimated using the Kaplan-Meier method. RESULTS: Technical success was 100% on contrast-enhanced CT or MRI performed immediately after renal MWA. Twenty-four patients (92%) with 25 tumors had follow-up imaging for 3 months or longer (mean, 20.6 ± 11.6 months), with no local tumor recurrences identified. Estimated 3-year local PFS and CSS were 96% and 94%, respectively. The overall complication rate was 19.2%; two patients (7.7%) experienced minor complications (grade I or II) and three patients (11.5%) experienced major bleeding or urinary-related complications (grade III or higher), including one death. CONCLUSION: This study suggests that percutaneous MWA is a promising minimally invasive treatment option for cT1 renal masses. Nonetheless, major bleeding and urinary-related complications can occur, and further studies are needed to determine optimal patient and tumor selection for renal MWA.

Non-alcoholic fatty liver disease-associated hepatocellular carcinoma: effect of hepatic steatosis on major hepatocellular carcinoma features at MRI.

OBJECTIVE:: To evaluate the effect of hepatic steatosis on LI-RADS® major features at MRI in patients with non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC). METHODS:: HCC and liver parenchyma features at MRI from 48 consecutive patients with NAFLD and histology proven HCC (mean ± SD; 4.5 ± 3.4 cm) were independently reviewed by three radiologists. Inter-rater agreement was determined by prevalence/bias-adjusted kappa. Hepatic fat signal fraction (FS%) was independently calculated. HCC features were compared by FS% at MRI using logistic regression analysis and histologic steatosis grade using Cochran-Armitage test for trend, stratified by cirrhotic liver morphology or histologic fibrosis stage. Receiver operating characteristic curves were generated to determine the sensitivity and specificity for major HCC features by FS%. RESULTS:: Major HCC features included arterial phase hyperenhancement (APHE) in 45 (93%), portal venous phase washout (PVWO) in 30 (63%), delayed phase washout (DPWO) in 38 (79%) and enhancing "capsule" in 34 (71%). Cirrhotic morphology was present in 22 (46%). Inter-rater agreement was 0.75 for APHE, 0.42-0.58 for PVWO, 0.58-0.71 for DPWO and 0.38-0.67 for enhancing "capsule". There was an 18%, 14% and 22% increase in the odds of absent PVWO, DPWO and capsule appearance for every 1% increase in hepatic FS% in patients with non-cirrhotic liver morphology (p = 0.011, 0.040 and 0.029, respectively). Hepatic FS% ≥ 14.8% had a sensitivity and specificity of 64 and 100% for absent PVWO and 71 and 90% for absent DPWO in patients with non-cirrhotic liver morphology. CONCLUSION:: Absent washout and capsule appearance are associated with increasing hepatic steatosis in patients with non-cirrhotic, NAFLD-associated HCC. ADVANCES IN KNOWLEDGE:: In patients with non-cirrhotic, non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC), absent HCC washout and capsule appearance are associated with increasing hepatic steatosis, thereby potentially impacting the noninvasive imaging diagnosis of HCC in these patients. Lack of washout or capsule appearance in steatotic livers at MRI may require alternative criteria for the diagnosis of HCC in patients with non-cirrhotic NAFLD.

Heat Stress and Thermal Ablation Induce Local Expression of Nerve Growth Factor Inducible (VGF) in Hepatocytes and Hepatocellular Carcinoma: Preclinical and Clinical Studies.

The purposes of this study were to test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Hepatocytes and HCC cells were subjected to moderate (45°C) or physiologic (37°C) heat stress for 10 min and assessed for VGF expression at 0-72 h post-heat stress (n ≥ 3 experiments). Orthotopic N1S1 HCC-bearing rats were randomized to sham or laser thermal ablation (3 W × 90 s), and liver/serum was harvested at 0-7 days postablation for analysis of VGF expression (n ≥ 6 per group). Serum was collected from patients undergoing thermal ablation for HCC (n = 16) at baseline, 3-6, and 18-24 h postablation and analyzed for VGF expression. Data were analyzed using ordinary or repeated-measures one-way analysis of variance and post hoc pairwise comparison with Dunnett's test. Moderate heat stress induced time-dependent VGF mRNA (3- to 15-fold; p < 0.04) and protein expression and secretion (3.1- to 3.3-fold; p < 0.05). Thermal ablation induced VGF expression at the hepatic ablation margin at 1 and 3 days postablation but not remote from the ablation zone or distant intrahepatic lobe. There was no detectable serum VGF following hepatic thermal ablation in rats and no increase in serum VGF following HCC thermal ablation in patients at 3-6 and 18-24 h postablation compared to baseline (0.71- and 0.63-fold; p = 0.27 and p = 0.16, respectively). Moderate heat stress induces expression and secretion of VGF in HCC cells and hepatocytes in vitro, and thermal ablation induces local intrahepatic but not distant intrahepatic or systemic VGF expression in vivo.

Heat Stress and Hepatic Laser Thermal Ablation Induce Hepatocellular Carcinoma Growth: Role of PI3K/mTOR/AKT Signaling.

Purpose To determine if heat stress and hepatic laser thermal ablation induce hepatocellular carcinoma (HCC) growth and to identify growth factors induced by heat stress. Materials and Methods Non-heat-stressed HCC cells were cocultured with HCC cells or hepatocytes that were heat stressed at 37°C (physiologic), 45°C (moderate), or 50°C (severe) for 10 minutes and proliferation monitored with bioluminescence imaging for up to 6 days after heat stress (three experiments). Rats bearing orthotopic N1S1 HCC were randomly assigned to undergo immediate sham or laser thermal (3 W for 60 or 90 seconds; hereafter, 3W×60s and 3W×90s, respectively) ablation of the median (local) or left (distant) hepatic lobe, and tumor growth was monitored with magnetic resonance imaging for up to 18 days after ablation (six or more rats per group). Experiments were repeated with rats randomly assigned to receive either the adjuvant phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor (NVP-BEZ235) or the vehicle control. Heat-stressed HCC cells and hepatocytes were analyzed by using microarray or quantitative real-time polymerase chain reaction analysis for growth factor expression (three or more experiments). Groups were compared by using one- or two-way analysis of variance, and post hoc pairwise comparison was performed with the Dunnett test. Results There were more non-heat-stressed HCC cells when cells were cocultured with cells subjected to moderate but not physiologic or severe heat stress (P < .001 for both). Local intrahepatic N1S1 tumors were larger at day 18 in the 3W×60s (mean, 3102 mm3 ± 463 [standard error]; P = .004) and 3W×90s (mean, 3538 mm3 ± 667; P < .001) groups than in the sham group (mean, 1363 mm3 ± 361) but not in distant intrahepatic tumors (P = .31). Adjuvant BEZ235 resulted in smaller N1S1 tumors in the BEZ235 and laser thermal ablation group than in the vehicle control and laser thermal ablation group (mean, 1731 mm3 ± 1457 vs 3844 mm3 ± 2400, P < .001). Moderate heat stress induced expression of growth factors in HCC cells and hepatocytes, including heparin-binding growth factor, fibroblast growth factor 21, and nerve growth factor (range, 2.9-66.9-fold; P < .05). Conclusion Moderate heat stress and laser thermal ablation induce hepatocellular carcinoma growth, which is prevented with adjuvant PI3K/mTOR/protein kinase B inhibition.