Society of Radiologists in Ultrasound Consensus Conference Recommendations for Incidental Gallbladder Polyp Management: Interreader Agreement Among Ten Radiologists.

Background: The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations support less-aggressive management of small gallbladder polyps on ultrasound versus earlier approaches and may help standardize polyp evaluation by radiologists. Objective: To assess radiologists' interreader agreement in applying the SRU recommendations for management of incidental gallbladder polyps on ultrasound. Methods: This retrospective study included 105 patients (median age, 52 years; 75 women, 27 men) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003 and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using SRU recommendations, assessed one polyp per patient for risk category (extremely low-risk, low-risk, or indeterminate risk) and possible recommendation for surgical consultation. Five radiologists were considered less-experienced (<5 years), and five more-experienced (≥5 years). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. Results: For risk category assignments, interreader agreement was substantial among all readers (k=0.710), less-experienced readers (k=0.705), and more-experienced readers (k=0.692). For surgical consultation recommendations, interreader agreement was substantial among all readers (k=0.795) and more-experienced readers (kappa=0.740), and almost perfect among less-experienced readers (k=0.811). Of ten readers, a median of 5 (IQR, 2-8), 4 (IQR, 2-7), and 0 (IQR, 0-0) classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the fraction of polyps classified as extremely low risk ranged from 32-72%, as low risk from 24-65%, and as indeterminate risk from 0-8%. Of ten readers, a median of 0 (IQR, 0-1) recommended surgical consultation; the fraction of polyps receiving a surgical consultation recommendation ranged from 4-22%. A total of 102/105 polyps were nonneoplastic; 3/105 were neoplastic (all benign). Based on readers' most-common assessments for the nonneoplastic polyps, the risk category was extremely low risk in 53, low risk in 48, and indeterminate risk in 1; surgical consultation was recommended in 16. Conclusion: Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. Clinical Impact: The findings support overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.

Body and Extremity MR Venography: Technique, Clinical Applications, and Advances.

Magnetic resonance venography (MRV) represents a distinct imaging approach that may be used to evaluate a wide spectrum of venous pathology. Despite duplex ultrasound and computed tomography venography representing the dominant imaging modalities in investigating suspected venous disease, MRV is increasingly used due to its lack of ionizing radiation, unique ability to be performed without administration of intravenous contrast, and recent technical improvements resulting in improved sensitivity, image quality, and faster acquisition times. In this review, the authors discuss commonly used body and extremity MRV techniques, different clinical applications, and future directions.

COVID-19 associated spontaneous hemorrhagic cholecystitis.

Hemorrhagic cholecystitis is a rare disorder associated with considerable morbidity and mortality. The clinical presentation of hemorrhagic cholecystitis is non-specific and imaging findings can be difficult to accurately interpret without a high level of suspicion. Most recent reports of hemorrhagic cholecystitis have been associated with concurrent therapeutic anticoagulation. Here, we report imaging findings of a case of acute, spontaneous hemorrhagic cholecystitis in a 67-year-old male patient admitted for hypoxic respiratory failure secondary to COVID-19 pneumonia.

Pulmonary and coronary arterial abnormalities in patients with IgG4-related disease.

IgG4-related disease (IgG4-RD) is an immune-mediated multiorgan fibroinflammatory disorder with variable clinical presentations. IgG4-RD cardiovascular involvement is considered rare, with pulmonary arterial involvement reported in a small subset of cases. Known pulmonary artery manifestations include pulmonary arteritis, pulmonary artery stenoses and central pulmonary artery aneurysms. Here we report 2 different patients with multifocal dilatation of the segmental and subsegmental pulmonary arteries with differing degrees of severity. Both patients also had coronary arterial abnormalities.

Microwave Ablation as Bridging Therapy for Patients with Hepatocellular Carcinoma Awaiting Liver Transplant: A Single Center Experience.

PURPOSE: To determine the pathologic response of computed tomography-guided percutaneous microwave ablation as bridging therapy for patients with hepatocellular carcinoma awaiting liver transplant, and its subsequent effect on survival. MATERIALS AND METHODS: A single-center retrospective analysis was conducted on 62 patients (M:F = 50:12) with mean age of 59.6 years ± 7.2 months (SD). Sixty-four total MWA procedures were performed for hepatocellular carcinomas within Milan criteria as bridging therapy to subsequent orthotopic liver transplant between August 2014 and September 2018. The pathology reports of the explanted livers were reviewed to assess for residual disease. Residual disease was categorized as complete or incomplete necrosis. Patient demographics, tumor/procedural characteristics, and laboratory values were evaluated. Survival from time of ablation and time of transplantation were recorded and compared between cohorts using log rank tests. RESULTS: The mean tumor size was 2.4 cm ± 0.7 cm (SD), (range = 1-4.6 cm). 32 (50%) cases required hydrodissection. Histopathologic necrosis was seen in 66% of cases at time of liver transplantation. Median time to liver transplant post-MWA was 12.6 months. [IQR = 8.6-14.8 months]. The median survival from ablation was 60.8 months [IQR = 45.5-73.7 months], and the median survival from transplant was 49.3 months [IQR = 33.7-60.1 months]. There was no significant difference in survival for patients with complete versus incomplete necrosis from ablation or liver transplant (p = 0.49, p = 0.46, respectively). CONCLUSIONS: Computed tomography-guided percutaneous microwave ablation is an effective bridge to orthotopic liver transplantation for patients with hepatocellular carcinoma. CEBM LEVEL OF EVIDENCE: Level 3, non-randomized controlled cohort study/follow-up study.

Insulin-Dependent Status Influences Post-Procedural Outcomes in Diabetic Patients Following Lower Extremity Endovascular Intervention for Peripheral Arterial Disease.

PURPOSE: Diabetic patients are at increased risk of developing lower extremity peripheral arterial disease (PAD) requiring revascularization. This study assessed the effect of insulin dependence in diabetics on post-procedural outcomes following infra-inguinal endovascular intervention. MATERIALS AND METHODS: The American College of Surgeon's National Surgical Quality Improvement Program database was used to identify 8022 patients undergoing infra-inguinal endovascular interventions between 2014 and 2017. Thirty-day post-procedural outcomes for patients without diabetes, with non-insulin-dependent diabetes mellitus (NIDDM), and with insulin-dependent diabetes mellitus (IDDM) were compared. RESULTS: At presentation, IDDM patients were more likely to present with critical limb ischemia compared to NIDDM and non-diabetic patients. In propensity score-weighted logistic regression analysis, IDDM status was an independent predictor for increased renal complication (odds ratio [OR] = 3.08, confidence interval [CI] = 1.44-6.65), sepsis (OR = 1.68, CI = 1.13-2.48), wound complication (OR = 1.57, CI = 1.09-2.25, p = 0.006), UTI (OR = 2.07, CI = 1.09-3.94, p = 0.03), and readmission (OR = 1.21, CI = 1.03-1.42). NIDDM status was an independent predictor for increased risk of renal complications (OR = 2.80, CI = 1.18-6.63). CONCLUSIONS: IDDM status is an independent predictor for increased risk of 30-day post-procedural complications and readmission compared to both NIDDM and non-diabetic status in patients undergoing lower extremity endovascular interventions for PAD.

Infection Control in Interventional Radiology During the COVID-19 Era.

The COVID-19 pandemic has challenged the capacity of interventional radiology departments worldwide to effectively treat COVID-19 and non-COVID-19 patients while preventing disease transmission among patients and healthcare workers. In this review, we describe the various data driven infection control measures implemented by the interventional radiology department of a large tertiary care center in the United States including the use and novel re-use of personal protective equipment, COVID-19 testing strategies, modifications in procedural workflows and the leveraging of telehealth visits. Herein, we provide effective triage, procedural, and management algorithms that may guide other interventional radiology departments during the ongoing COVID-19 pandemic and in future infectious disease outbreaks.

Biotinylated amplicon sequencing: A method for preserving DNA samples of limited quantity.

BACKGROUND: Genomic testing is often limited by the exhaustible nature of human tissue and blood samples. Here we describe biotinylated amplicon sequencing (BAmSeq), a method that allows for the creation of PCR amplicon based next-generation sequencing (NGS) libraries while retaining the original source DNA. DESIGN AND METHODS: Biotinylated primers for different loci were designed to create NGS libraries using human genomic DNA from cell lines, plasma, and formalin-fixed paraffin embedded (FFPE) tissues using the BAmSeq protocol. DNA from the original template used for each BAmSeq library was recovered after separation with streptavidin magnetic beads. The recovered DNA was then used for end-point, quantitative and droplet digital PCR (ddPCR) as well as NGS using a cancer gene panel. RESULTS: Recovered DNA was analyzed and compared to the original DNA after one or two rounds of BAmSeq. Recovered DNA revealed comparable genomic distributions and mutational allelic frequencies when compared to original source DNA. Sufficient quantities of recovered DNA after BAmSeq were obtained, allowing for additional downstream applications. CONCLUSIONS: We demonstrate that BAmSeq allows original DNA template to be recovered with comparable quality and quantity to the source DNA. This recovered DNA is suitable for many downstream applications and may prevent sample exhaustion, especially when DNA quantity or source material is limiting.

Prophylactic Internal Iliac Artery Occlusion Balloon Placement to Reduce Operative Blood Loss in Patients with Invasive Placenta.

PURPOSE: To evaluate efficacy and safety of prophylactic internal iliac occlusion balloon placement before cesarean hysterectomy for invasive placenta. MATERIAL AND METHODS: A retrospective analysis was performed of patients with invasive placenta treated with and without occlusion balloon placement. Preoperative occlusion balloons were placed in 90 patients; 61 patients were treated without balloon placement (control group). Baseline demographics, including patient age, gestational age at delivery, gravidity, parity, and number of previous cesarean sections, were not significantly different (P > .05). Of the balloon placement group, 56% had placenta percreta compared with 25% in the control group (P < .001), and 83% had placenta previa compared with 66% in the control group (P = .012). RESULTS: Median blood loss was 2 L (range, 1.5-2.5 L) in the balloon placement group versus 2.5 L (range, 2-4 L) in the control group (P = .002). Patients with occlusion balloons were transfused a median of 2 U (range, 0-5 U) of packed red blood cells versus 5 U (range, 2-8 U) in patients in the control group (P = .002). In the balloon placement group, 34% had large volume blood loss > 2,500 mL versus 61% in the control group (P = .001), and 21% required blood transfusion > 6 U versus 44% in the control group (P = .002). Eight complications (9%) were attributed to occlusion balloon placement. CONCLUSIONS: Prophylactic internal iliac artery occlusion balloon placement reduces operative blood loss and transfusion requirements in patients undergoing hysterectomy for invasive placenta.

Whole-Exome Sequencing of Metaplastic Breast Carcinoma Indicates Monoclonality with Associated Ductal Carcinoma Component.

Purpose: Although most human cancers display a single histology, there are unusual cases where two or more distinct tissue types present within a primary tumor. One such example is metaplastic breast carcinoma, a rare but aggressive cancer with a heterogeneous histology, including squamous, chondroid, and spindle cells. Metaplastic carcinomas often contain an admixed conventional ductal invasive or in situ mammary carcinoma component, and are typically triple-negative for estrogen receptor, progesterone receptor, and HER-2 amplification/overexpression. An unanswered question is the origin of metaplastic breast cancers. While they may arise independently from their ductal components, their close juxtaposition favors a model that postulates a shared origin, either as two derivatives from the same primary cancer or one histology as an outgrowth of the other. Understanding the mechanism of development of these tumors may inform clinical decisions.Experimental Design: We performed exome sequencing for paired metaplastic and adjacent conventional invasive ductal carcinomas in 8 patients and created a pipeline to identify somatic variants and predict their functional impact, without having normal tissue. We then determined the genetic relationships between the histologically distinct compartments.Results: In each case, the tumor components have nearly identical landscapes of somatic mutation, implying that the differing histologies do not derive from genetic clonal divergence.Conclusions: A shared origin for tumors with differing histologies suggests that epigenetic or noncoding changes may mediate the metaplastic phenotype and that alternative therapeutic approaches, including epigenetic therapies, may be required for metaplastic breast cancers. Clin Cancer Res; 23(16); 4875-84. ©2017 AACR.

PIK3CA mutations and TP53 alterations cooperate to increase cancerous phenotypes and tumor heterogeneity.

BACKGROUND/PURPOSE: The combined contributions of oncogenes and tumor suppressor genes toward carcinogenesis remain poorly understood. Elucidation of cancer gene cooperativity can provide new insights leading to more effective use of therapies. EXPERIMENTAL DESIGN/METHODS: We used somatic cell genome editing to introduce singly and in combination PIK3CA mutations (E545K or H1047R) with TP53 alterations (R248W or knockout), to assess any enhanced cancerous phenotypes. The non-tumorigenic human breast epithelial cell line, MCF10A, was used as the parental cell line, and resultant cells were assessed via various in vitro assays, growth as xenografts, and drug sensitivity assays using targeted agents and chemotherapies. RESULTS: Compared to single-gene-targeted cells and parental controls, cells with both a PIK3CA mutation and TP53 alteration had increased cancerous phenotypes including cell proliferation, soft agar colony formation, aberrant morphology in acinar formation assays, and genomic heterogeneity. Cells also displayed varying sensitivities to anti-neoplastic drugs, although all cells with PIK3CA mutations showed a relative increased sensitivity to paclitaxel. All cell lines remained non-tumorigenic. CONCLUSIONS: This cell line panel provides a resource for further elucidating cooperative genetic mediators of carcinogenesis and response to therapies.

Detection fidelity of AR mutations in plasma derived cell-free DNA.

Somatic genetic alterations including copy number and point mutations in the androgen receptor (AR) are associated with resistance to therapies targeting the androgen/AR axis in patients with metastatic castration resistant prostate cancer (mCRPC). Due to limitations associated with biopsying metastatic lesions, plasma derived cell-free DNA (cfDNA) is increasingly being used as substrate for genetic testing. AR mutations detected by deep next generation sequencing (NGS) of cfDNA from patients with mCRPC have been reported at allelic fractions ranging from over 25% to below 1%. The lower bound threshold for accurate mutation detection by deep sequencing of cfDNA has not been comprehensively determined and may have locus specific variability. Herein, we used NGS for AR mutation discovery in plasma-derived cfDNA from patients with mCRPC and then used droplet digital polymerase chain reaction (ddPCR) for validation. Our findings show the AR (tTC>cTC) F877L hotspot was prone to false positive mutations during NGS. The rate of error at AR (tTC>cTC) F877L during amplification prior to ddPCR was variable among high fidelity polymerases. These results highlight the importance of validating low-abundant mutations detected by NGS and optimizing and controlling for amplification conditions prior to ddPCR.

Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer.

PURPOSE: The clinical utility of next-generation sequencing (NGS) in breast cancer has not been demonstrated. We hypothesized that we could perform NGS of a new biopsy from patients with metastatic triple-negative breast cancer (TNBC) in a clinically actionable timeframe. EXPERIMENTAL DESIGN: We planned to enroll 40 patients onto a prospective study, Individualized Molecular Analyses Guide Efforts (IMAGE), to evaluate the feasibility of obtaining a new biopsy of a metastatic site, perform NGS (FoundationOne), and convene a molecular tumor board to formulate treatment recommendations within 28 days. We collected blood at baseline and at time of restaging to assess cell-free circulating plasma tumor DNA (ptDNA). RESULTS: We enrolled 26 women with metastatic TNBC who had received ≥1 line of prior chemotherapy, and 20 (77%) underwent NGS of a metastatic site biopsy. Twelve (60%) evaluable patients received treatment recommendations within 28 days of consent. The study closed after 20 patients underwent NGS, based on protocol-specified interim futility analysis. Three patients went on to receive genomically directed therapies. Twenty-four of 26 patients had genetic alterations successfully detected in ptDNA. Among 5 patients, 4 mutations found in tumor tissues were not identified in blood, and 4 mutations found in blood were not found in corresponding tumors. In 9 patients, NGS of follow-up blood samples showed 100% concordance with baseline blood samples. CONCLUSIONS: This study demonstrates challenges of performing NGS on prospective tissue biopsies in patients with metastatic TNBC within 28 days, while also highlighting the potential use of blood as a more time-efficient and less invasive method of mutational assessment. Clin Cancer Res; 23(2); 379-86. ©2016 AACR.

Ki-67 is required for maintenance of cancer stem cells but not cell proliferation.

Ki-67 expression is correlated with cell proliferation and is a prognostic marker for various cancers; however, its function is unknown. Here we demonstrate that genetic disruption of Ki-67 in human epithelial breast and colon cancer cells depletes the cancer stem cell niche. Ki-67 null cells had a proliferative disadvantage compared to wildtype controls in colony formation assays and displayed increased sensitivity to various chemotherapies. Ki-67 null cancer cells showed decreased and delayed tumor formation in xenograft assays, which was associated with a reduction in cancer stem cell markers. Immunohistochemical analyses of human breast cancers revealed that Ki-67 expression is maintained at equivalent or greater levels in metastatic sites of disease compared to matched primary tumors, suggesting that maintenance of Ki-67 expression is associated with metastatic/clonogenic potential. These results elucidate Ki-67's role in maintaining the cancer stem cell niche, which has potential diagnostic and therapeutic implications for human malignancies.

ESR1 Mutations in Circulating Plasma Tumor DNA from Metastatic Breast Cancer Patients.

PURPOSE: Mutations in the estrogen receptor (ER)α gene, ESR1, have been identified in breast cancer metastases after progression on endocrine therapies. Because of limitations of metastatic biopsies, the reported frequency of ESR1 mutations may be underestimated. Here, we show a high frequency of ESR1 mutations using circulating plasma tumor DNA (ptDNA) from patients with metastatic breast cancer. EXPERIMENTAL DESIGN: We retrospectively obtained plasma samples from eight patients with known ESR1 mutations and three patients with wild-type ESR1 identified by next-generation sequencing (NGS) of biopsied metastatic tissues. Three common ESR1 mutations were queried for using droplet digital PCR (ddPCR). In a prospective cohort, metastatic tissue and plasma were collected contemporaneously from eight ER-positive and four ER-negative patients. Tissue biopsies were sequenced by NGS, and ptDNA ESR1 mutations were analyzed by ddPCR. RESULTS: In the retrospective cohort, all corresponding mutations were detected in ptDNA, with two patients harboring additional ESR1 mutations not present in their metastatic tissues. In the prospective cohort, three ER-positive patients did not have adequate tissue for NGS, and no ESR1 mutations were identified in tissue biopsies from the other nine patients. In contrast, ddPCR detected seven ptDNA ESR1 mutations in 6 of 12 patients (50%). CONCLUSIONS: We show that ESR1 mutations can occur at a high frequency and suggest that blood can be used to identify additional mutations not found by sequencing of a single metastatic lesion.