The use of a 19-gauge coaxial guide needle significantly decreases the risk of pneumothorax and chest tube placement compared with an 18-guage needle.
Background. The aim of this study was to assess the frequency of potentially actionable genomic alterations in breast cancer that could be targeted with approved agents or investigational drugs in clinical trials using a next-generation sequencingbased genomic profiling assay performed in a Clinical Laboratory Improvement Amendments-certified and College of American Pathologists-accredited commercial laboratory. Methods. Fifty-one breast cancers were analyzed, including primary tumor biopsies of 33 stage I-II and 18 stage IV cancers (13 soft tissue, 3 liver, and 2 bone metastases). We assessed 3,230 exons in 182 cancer-related genes and 37 introns in 14 genes often rearranged in cancer for base substitutions, indels, copy number alterations, and gene fusions. The average median sequencing depth was 1,1543. Results. We observed 158 genomic alterations in 55 genes in 48 of 51 (94%) tumors (mean 3.1, range 0-9). The average number of potentially therapeutically relevant alterations was similar in primary (1.6, range 0-4) and in heavily pretreated metastatic cancers (2.0, range 0-4) (p 5 .24). The most common actionable alterations were in PIK3CA (n 5 9,
BackgroundIntratumoral delivery of immunotherapeutics represents a compelling solution to directly address local barriers to tumor immunity. However, we have previously shown that off-target delivery is a substantial problem during intratumoral injections; this can lead to diminished drug efficacy and systemic toxicities. We have identified three variables that influence intratumoral drug delivery: injection technique, drug formulation and tumor microenvironment. The purpose of this study was to characterize the impact of modifications in each variable on intratumoral drug delivery and immunotherapy efficacy.MethodsIntratumoral injections were performed in a hybrid image-guided intervention suite with ultrasound, fluoroscopy and CT scanning capabilities in both rat and mouse syngeneic tumor models. Intratumoral drug distribution was quantified by CT volumetric imaging. The influence of varying needle design and hydrogel-based drug delivery on the immune response to a stimulator of interferon genes (STING) agonist was evaluated using flow cytometry and single cell RNA sequencing. We also evaluated the influence of tumor stiffness on drug injection distribution.ResultsVariations in needle design, specifically with the use of a multiside hole needle, led to approximately threefold improvements in intratumoral drug deposition relative to conventional end-hole needles. Likewise, delivery of a STING agonist through a multiside hole needle led to significantly increased expression of type I interferon-associated genes and ‘inflammatory’ dendritic cell gene signatures relative to end-hole STING agonist delivery. A multidomain peptide-based hydrogel embedded with a STING agonist led to substantial improvements in intratumoral deposition; however, the hydrogel was noted to generate a strong immune response against itself within the target tumor. Evaluation of tumor stroma on intratumoral drug delivery revealed that there was a greater than twofold improvement in intratumoral distribution in soft tumors (B16 melanoma) compared with firm tumors (MC38 colorectal).ConclusionsInjection technique, drug formulation and tumor stiffness play key roles in the accurate delivery of intratumoral immunotherapeutics.
Fistulas of the lower urinary tract are uncommon conditions that may occur spontaneously or after therapy in patients with various pelvic abnormalities. When present, these fistulas are associated with urine leakage, which is often socially distressing and disabling. Unfortunately, factors that lead to the formation of genitourinary fistulas often increase their complexity or preclude surgical repair. A high failure rate is associated with surgical repair, and many patients are not optimal surgical candidates. For such patients, a percutaneous treatment approach is highly desirable. Percutaneous ureteral occlusion combined with insertion of a functioning nephrostomy tube allows complete diversion of urine in those patients in whom nephrostomy alone does not provide adequate relief. Many approaches to percutaneous ureteral occlusion have been used with variable success, including coils and gelatin sponge, isobutyl-2-cyanoacrylate, detachable balloons, radiofrequency electrocautery, ureteral clipping, and solid and soft polymer agents. Furthermore, percutaneous or retrograde ureteral stents may be used to preserve antegrade urine flow, and surgical options are also available. It is essential that the interventional radiologist involved in the care of these patients be familiar with these different techniques as well as with the limitations, pitfalls, and possible complications of their use.
The treatment of liver injuries or hepatocellular carcinoma (HCC) with has been hindered by the lack of efficient drug delivery. Even with the help of nanoparticles or other synthetic delivering agents, a large portion of the dose is still sequestered in the reticuloendothelial system (RES). As an alternative, adipose-derived mesenchymal cells (AD-MSCs), which have the capability of homing to the injured liver, can be used as a unique carrier for theranostic agents. Theranostic agents must have the capacity for being non-toxic to host cells during transportation, and for timely activation once they arrive at the injury sites. In this study, we loaded AD-MSCs with superparamagnetic iron oxide-coated gold nanoparticles (SPIO@AuNPs) and tested their effects against liver injury and HCC in cells and in mice. SPIO@AuNP is a non-toxic MRIactive contrast agent that can generate heat when irradiated with near-infrared laser. Our results showed that SPIO@AuNPs were successfully transfected into AD-MSCs without compromising either cell viability (P > 0.05) or cell differentiability. In vivo MRI imaging and histologic analysis confirmed the active homing of AD-MSCs. Upon laser irradiation, the SPIO@AuNPloaded AD-MSCs could thermally ablate surrounding HCC tumor cells. SPIO@AuNP–loaded AD-MSCs proved a promising theranostic approach for injured liver and HCC.
BackgroundCurrently, there are no imaging predictors of immunotherapy outcome in hepatocellular carcinoma (HCC). The study aim was to determine if stiffness changes measured by magnetic resonance elastography (MRE) can be a predictor of immunotherapy response in patients with advanced HCC.Materials and methodsThis was a prospective study of 15 patients with biopsy proven-advanced HCC treated with Pembrolizumab. All patients had liver MRE and liver biopsy at baseline and at 6 weeks of therapy. Change in HCC stiffness on MRE was compared with overall survival (OS), time to disease progression (TTP), and number of intratumoral CD3+ T lymphocytes. Analysis was performed using descriptive statistics and Spearman correlation (R); p-value < 0.05 was considered statistically significant.ResultsNine patients were evaluable. Median age was 71 years (range, 54–78). Etiology of liver disease was HCV (n = 4), HBV (n = 1) and NASH (n = 4). Median OS and TTP were 44 weeks and 13 weeks, respectively. Average baseline HCC stiffness and change in HCC stiffness were 5.0 kPa and 0.12 kPa, respectively. In contrast, average non-tumor liver stiffness was 3.2 kPa, and did not significantly change at 6 weeks (p = 0.42). Average size of measured tumor and change in size were 4 cm and − 0.32 cm, respectively. Change in HCC stiffness at 6 weeks correlated significantly with OS (R = 0.81), and TTP (R = 0.88,p < 0.01). Abundance of intratumoral T lymphocytes on tumor biopsy correlated significantly with HCC stiffness (R = 0.79,p = 0.007).ConclusionOur pilot MRE data suggests early change in tumor stiffness may be an indicator of immunotherapy response in patients with advanced HCC.
Portal vein embolization (PVE) is used to induce preoperative liver hypertrophy in patients with anticipated marginal future liver remnant (FLR) volumes who are otherwise potential candidates for resection. PVE can be performed utilizing the transhepatic contralateral and ipsilateral approaches. The transhepatic contralateral approach is the most commonly used technique worldwide, largely owing to its technical ease. However, the contralateral approach risks injuring the FLR, thereby compromising the planned surgical resection. The transhepatic ipsilateral approach offers a potentially safer alternative because the complications associated with this approach affect only the hepatic lobe that will be resected and are usually not serious enough to preclude surgery. This article discusses PVE using the transhepatic ipsilateral and contralateral approaches, including patient selection criteria, anatomical and technical considerations, and patient complications and outcomes.
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