Friend or Foe? Locoregional Therapies and Immunotherapies in the Current Hepatocellular Treatment Landscape.

Over the last several decades, a number of new treatment options for patients with hepatocellular carcinoma (HCC) have been developed. While treatment decisions for some patients remain clear cut, a large numbers of patients have multiple treatment options, and it can be hard for multidisciplinary teams to come to unanimous decisions on which treatment strategy or sequence of treatments is best. This article reviews the available data with regard to two treatment strategies, immunotherapies and locoregional therapies, with a focus on the potential of locoregional therapies to be combined with checkpoint inhibitors to improve outcomes in patients with locally advanced HCC. In this review, the available data on the immunomodulatory effects of locoregional therapies is discussed along with available clinical data on outcomes when the two strategies are combined.

Gallbladder Cryoablation for Chronic Cholecystitis in High-Risk Surgical Patients: 1-Year Clinical Experience with Imaging Follow-up.

PURPOSE: To assess the short-term safety and efficacy of gallbladder cryoablation in high-risk patients. MATERIALS AND METHODS: A single-center, retrospective review of clinical and imaging follow-up from patients who were referred for gallbladder cryoablation between August 2018 and July 2019 was performed. All patients had serious pre-procedural comorbidities and were unacceptable surgical candidates (mean age, 52.5 years; mean American Society of Anesthesiologists score, 3.67). Primary efficacy measures included technical success, absence of symptoms after cholecystostomy tube removal, and imaging evidence of cystic duct obstruction and gallbladder involution. The primary safety measure was the absence of Society of Interventional Radiology moderate or greater adverse events. RESULTS: Technical success was 86%, with 1 of 7 patients unable to undergo cryoablation because of adhesions preventing hydrodissection of the colon away from the gallbladder. Mean duration of clinical follow-up after discharge was 278 days (range, 59-498 days). Abdominal pain was absent in all patients after ablation. Cholecystostomy tubes were removed immediately after ablation (n = 5) or on post-procedure day 11 (n = 1). Computed tomography or magnetic resonance imaging was obtained at 1-3 months (n = 6), 4-6 months (n = 4), and 6-12 months (n = 5) after the procedure and demonstrated gallbladder involution in 5 of 6 patients. One patient had asymptomatic distention of the gallbladder on follow-up imaging. Hepatobiliary iminodiacetic acid scans were completed in 5 of 6 patients 1 month after ablation and demonstrated cystic duct occlusion in all 5 patients. One moderate adverse event (infection) and 1 life-threatening adverse event (hemorrhage) occurred. CONCLUSIONS: Gallbladder cryoablation might be a viable treatment option for high-risk patients with gallbladder disease and warrants further investigation.

Predictability of Pelvic Tilt During Total Hip Arthroplasty Using a Traction Table.

BACKGROUND: Pelvic positioning during total hip arthroplasty (THA) affects functional position of the acetabular component. We sought to evaluate whether preoperative pelvic tilt correlated with intraoperative pelvic tilt while positioned on a traction table for direct anterior THA and furthermore to evaluate whether there was a consistent and predictable effect on pelvic tilt while positioned for surgery. METHODS: We evaluated the sagittal spinopelvic preoperative standing and supine pelvic tilt radiographic measurements as compared with intraoperative measurements of 25 patients. Changes in pelvic tilt were analyzed for statistical significance and interobserver reliability. RESULTS: The mean standing pelvic tilt was 13.5° ± 5.7°. The mean supine pelvic tilt was 13.3° ± 6.1°. There was no statistically significant difference between standing and supine pelvic tilt (P = .866). The mean intraoperative pelvic tilt was 3.0° ± 6.2°. There was a statistically significant decrease in pelvic tilt between both standing to intraoperative comparison and supine to intraoperative comparison (P < .0001 for both). Difference in mean between these comparisons was 10.5° ± 4.6° (95% confidence interval, 8.7°-12.3°) and 10.3° ± 6.3° (95% confidence interval, 7.8°-12.8°), respectively. CONCLUSION: Patient positioning on a traction table for direct anterior THA has a reliable effect on pelvic tilt in the magnitude of approximately 10° decreased pelvic tilt. This effect on pelvic tilt correlates to approximately 7.4° and 3° altered anteversion and inclination, respectively. Taking into account this change in pelvic tilt at the time of surgery will allow the hip arthroplasty surgeon to more accurately place acetabular components in the desired functional position.

Preoperative thrombocytopenia and outcomes of hepatectomy for hepatocellular carcinoma.

BACKGROUND: Platelet count is known to be an indirect indicator of portal hypertension but is not a part of the model for end-stage liver disease (MELD) score or the Child-Pugh score for risk stratification in hepatobiliary surgery. METHODS: Data from 2097 hepatic resections for hepatocellular carcinoma (HCC) were evaluated from 2005-2012 using the National Surgical Quality Improvement Program database. Patient demographics, morbidity, and mortality were evaluated. RESULTS: Median age and body mass index were 64 y and 26.5 kg/m(2), respectively. Majority of the patients had American Society of Anesthesiologists ≥3 (78.1%) and median MELD score was 7. On multivariate analysis, thrombocytopenia (platelet count <150/nL) and severe thrombocytopenia (platelet count <100/nL) were independently associated with an increased risk of mortality (odds ratio [OR], 1.79; P = 0.024 and OR, 4.19; P < 0.001), cardiopulmonary complications (OR, 1.61; P = 0.009 and OR, 1.96; P = 0.018), need for blood transfusion (OR, 1.35; P = 0.05 and OR, 1.60; P = 0.05), septic complications (OR, 1.53; P = 0.025 and OR, 1.96; P = 0.016), reintubation (OR, 1.91; P = 0.004 and OR, 2.64; P = 0.003), and renal insufficiency and/or failure (OR, 2.48; P = 0.001 and OR, 4.96; P < 0.001), respectively. CONCLUSIONS: Thrombocytopenia, which is an indirect indicator for portal hypertension, is significantly associated with adverse outcomes after hepatectomy, independent of the MELD score. Platelet count should be integrated into the selection criteria for hepatic resections for HCC.

Interventional Radiology Locoregional Therapies for Intrahepatic Cholangiocarcinoma.

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.

Cryoablation in the liver: how accurately does the iceball predict the ablation zone?

PURPOSE: To evaluate the accuracy with which the iceball predicts the realized ablation zone in patients undergoing cryoablation of the liver. MATERIALS AND METHODS: Continuous patients who underwent cryoablation of primary or secondary malignancies of the liver were retrospectively reviewed. Iceball and ablation zone dimensions on 1 month follow up imaging were collected in three orientations, the long axis (LA), perpendicular transverse (PTR), and perpendicular craniocaudal (PCC). Factors which may predict differences in the measurements were evaluated with regression analysis. Oncologic outcomes were also collected. RESULTS: The mean size of the iceball was 5.5 ± 1.1 cm, 3.9 ± 1.1 cm, and 4.4 ± 1.4 cm in the LA, PTR, and PCC orientations, respectively. The mean size of the one-month ablation cavity was 4.3 ± 1.3 cm, 3 ± 1.1 cm, and 3 ± 1.3 cm in the LA, PTR, and PCC orientations, respectively. The iceball was significantly larger than the ablation zone in all orientations (p < 0.001). When comparing HCC and non-HCC patients the Kaplan-Meier analysis of TTLP, the Kaplan Meier curves deviated significantly (p = 0.015, HR 2.26 (95%CI 1.17-4.37)). When a similar analysis was performed looking at TTP again the curves diverged significantly (p = 0.002, HR 2.4 (95%CI 1.37-4.19)). CONCLUSION: The iceball seems to overestimate the realized ablation zone by about 1 cm in all orientations during hepatic cryoablation.

Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis.

PURPOSE: Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. MATERIALS AND METHODS: Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan-Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. RESULTS: 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32-3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58-2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52-3.16, p = 0.595) by log-rank analysis. CONCLUSION: TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted.

Role of the Interventional Radiologist in the Treatment of Desmoid Tumors.

Desmoid tumors are locally aggressive soft tissue tumors with variable clinical presentation. As is the case with most relatively rare tumors, a multidisciplinary team approach is required to best manage these patients. Surgical resection, systemic therapy, and radiation therapy have classically been mainstays of treatment for desmoid tumors; however, a more conservative "wait-and-see" approach has been adopted given their high recurrence rates and significant morbidity associated with the aforementioned therapies. Given the challenges of classical treatment methods, interventional radiologists have begun to play a significant role in minimally invasive interventions for desmoid tumors. Herein, the authors review imaging characteristics of desmoid tumors, current management recommendations, and minimally invasive therapeutic intervention options.

Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions.

In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.

Systematic evaluation of split-fluorescent proteins for the direct detection of native and methylated DNA.

In order to directly detect nucleic acid polymers, we have designed biosensors comprising sequence-specific DNA binding proteins tethered to split-reporter proteins, which generate signal upon binding a predetermined nucleic acid target, in an approach termed SEquence-Enabled Reassembly (SEER). Herein we demonstrate that spectroscopically distinct split-fluorescent protein variants, GFPuv, EGFP, Venus, and mCherry, function effectively in the SEER system, providing sensitive DNA detection and the ability to simultaneously detect two target oligonucleotides. Additionally, a methylation-specific SEER-Venus system was generated, which was found to clearly distinguish between methylated versus non-methylated target DNA. These results will aid in refinement of the SEER system for the detection of user defined nucleic acid sequences and their chemical modifications as they relate to human disease.

The Effect of Stents in Cerebral Aneurysms: A Review.

The etiology of up to 95% of cerebral aneurysms may be accounted for by hemodynamically-induced factors that create vascular injury. The purpose of this review is to describe key physical properties that stents have and how they affect cerebral aneurysms. We performed a two-step screening process. First, a structured search was performed using the PubMed database. The following search terms and keywords were used: "Hemodynamics," "wall shear stress (WSS)," "velocity," "viscosity," "cerebral aneurysm," "intracranial aneurysm," "stent," "flow diverter," "stent porosity," "stent geometry," "stent configuration," and "stent design." Reports were considered if they included original data, discussed hemodynamic changes after stent-based treatment of cerebral aneurysms, examined the hemodynamic effects of stent deployment, and/or described the geometric characteristics of both stents and the aneurysms they were used to treat. The search strategy yielded a total of 122 articles, 61 were excluded after screening the titles and abstracts. Additional articles were then identified by cross-checking reference lists. The final collection of 97 articles demonstrates that the geometric characteristics and configurations of deployed stents influenced hemodynamic parameters such as aneurysmal WSS, inflow, and pressure. The geometric characteristics of the aneurysm and its position also had significant influences on intra-aneurysmal hemodynamics after treatment. In conclusion, changes in specific aneurysmal hemodynamic parameters that result from stenting relate to a number of factors including the geometric properties and configurations of deployed stents, the geometric properties of the aneurysm, and the pretreatment hemodynamics.

The minipterional approach for ruptured and unruptured anterior circulation aneurysms: Our initial experience.

OBJECTIVE: To report our experience with the minipterional (MPT) craniotomy approach for anterior circulation aneurysms and to discuss the clinical outcomes as well as to evaluate the advantages of this unique approach. MATERIALS AND METHODS: Single-center retrospective review of 57 cases involving anterior circulation aneurysms both ruptured and unruptured aneurysms treated with the MPT. We analyzed the clinical and patient demographic data, aneurysm characteristics, surgical outcomes, and complications in these individuals. RESULTS: Between July 2008 and March 2014, of the 57 patients reviewed: 45 had middle cerebral artery (MCA), 6 had internal carotid artery terminus, and 7 had posterior communicating artery aneurysms. 20 of the 57 patients presented with a ruptured aneurysm. The average aneurysm size was 5.8 mm. The length of hospitalization for unruptured aneurysm cases ranged between 3 and 5 days. The average follow-up for all cases was 21.5 months. Successful clipping of the aneurysms was obtained in all patients. None of the cases required additional skin incisions or craniotomy extensions. The overall surgical outcomes were favorable. There was no postoperative facial nerve damage, temporalis muscle wasting, or symptoms of paresthesias around the incision line. Two patients developed a postoperative stroke manifested as symptoms of unilateral arm and facial weakness, receptive aphasia, and dysarthria. CONCLUSION: The MPT provides a reliable and less invasive alternative to the standard pterional craniotomy. Furthermore, ruptured and unruptured anterior circulation aneurysms can safely and effectively be treated with limited bone removal which provides better cosmetic outcomes and excellent postoperative temporalis muscle function.

Driving Safety after Spinal Surgery: A Systematic Review.

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving.

Comprehensive literature review: recent advances in diagnosing and managing patients with poorly differentiated thyroid carcinoma.

Poorly differentiated thyroid carcinomas are a rare form of thyroid carcinomas; they display an intermediate behavior between well-differentiated and anaplastic thyroid carcinomas. PDTCs are more aggressive than the well-differentiated, but less aggressive than the undifferentiated or anaplastic, forms. No clinical features can accurately diagnose poorly differentiated thyroid carcinomas. Thus, the results of histocytology, immunohistochemistry, and molecular genetics tests aid in diagnosis. Given the aggressiveness of poorly differentiated thyroid carcinomas and the poor survival rates in patients who undergo surgery alone, a multimodality treatment approach is required. We conducted a comprehensive review of the current diagnostic and therapeutic tools in the management of patients with poorly differentiated thyroid carcinomas.

Postoperative pain assessment and analgesic administration in Native American patients undergoing laparoscopic cholecystectomy.

Ethnic disparities in pain assessment and analgesic administration following surgery have received little attention in the surgery literature. We noted that our Native American patients were less likely than others to complain of pain. A retrospective chart review of 21 Native American patients and a control group who underwent outpatient, elective laparoscopic cholecystectomy was performed. Native American patients had a statistically lower numeric pain score (mean, 6.5; 95% CI, 3.6-9.4) than non-Native American patients (mean, 8.1; 95% CI, 6.3-9.9; t38 = 2.63; P < .05). Native American patients also received less postsurgical analgesic (mean, 7.4; 95% CI, 4.0-10.8) than non-Native American patients (mean, 11.2; 95% CI, 7.2-15.2; t38 = 3.07; P < .01). Medical staff attending Native American patients should be aware that response to some scales to assess pain may not reflect accurately the degree of pain experienced.