The malignant transformation of endometriosis: Is there a left lateral predisposition of ovarian clear cell and endometrioid carcinomas?

INTRODUCTION: Endometriosis affects 10% of women of reproductive age. There is evidence for a left lateral predisposition of endometriotic lesions and a 1.9-fold greater risk of ovarian cancer in endometriosis. The aim of this study is to determine whether a left lateral predisposition of ovarian clear-cell carcinoma (CCC) and endometrioid carcinoma (EC) exists. MATERIALS AND METHODS: A retrospective cohort study of all EC and CCC patients in Northern Ireland between March-2011 and June-2018. ANOVA was used to analyse preoperative prediction of stage, chi-squared (χ2) was used to compare left- and right-sided masses. Survival was estimated using Kaplan-Meier and log-rank test. A p-value <0.05 was considered significant. RESULTS: 158 patients were identified (95 EC, 55 CCC, 8 mixed). Mean age was 57.65 years with 69% presenting at stage 1. The mean CA125 was 559 U/mL (p = 0.850) and mean abdominal mass size was 14.12 cm (p = 0.732). The most common presenting symptom was an abdominal mass (37%). Despite 67% of patients having endometriosis on final pathology, only 8.9% had a known history pre-operatively. 51% of tumours were located on the left (p = 0.036). For unilateral tumours this was significant for EC (P = 0.002) but not for CCC (P = 0.555). The 1-, 3- and 5-year overall survival for all types/stages was 85%, 78% and 71% respectively. CONCLUSION: While CCC and EC are associated with endometriosis, only EC exhibits a left lateral predisposition. There is no association between preoperative CA125 or abdominal mass size and stage of disease.

Head and Neck Cancer Segmentation in FDG PET Images: Performance Comparison of Convolutional Neural Networks and Vision Transformers.

Convolutional neural networks (CNNs) have a proven track record in medical image segmentation. Recently, Vision Transformers were introduced and are gaining popularity for many computer vision applications, including object detection, classification, and segmentation. Machine learning algorithms such as CNNs or Transformers are subject to an inductive bias, which can have a significant impact on the performance of machine learning models. This is especially relevant for medical image segmentation applications where limited training data are available, and a model's inductive bias should help it to generalize well. In this work, we quantitatively assess the performance of two CNN-based networks (U-Net and U-Net-CBAM) and three popular Transformer-based segmentation network architectures (UNETR, TransBTS, and VT-UNet) in the context of HNC lesion segmentation in volumetric [F-18] fluorodeoxyglucose (FDG) PET scans. For performance assessment, 272 FDG PET-CT scans of a clinical trial (ACRIN 6685) were utilized, which includes a total of 650 lesions (primary: 272 and secondary: 378). The image data used are highly diverse and representative for clinical use. For performance analysis, several error metrics were utilized. The achieved Dice coefficient ranged from 0.833 to 0.809 with the best performance being achieved by CNN-based approaches. U-Net-CBAM, which utilizes spatial and channel attention, showed several advantages for smaller lesions compared to the standard U-Net. Furthermore, our results provide some insight regarding the image features relevant for this specific segmentation application. In addition, results highlight the need to utilize primary as well as secondary lesions to derive clinically relevant segmentation performance estimates avoiding biases.

PET/CT Imaging in Treatment Planning and Surveillance of Sinonasal Neoplasms.

Sinonasal cancers are uncommon malignancies with a generally unfavorable prognosis, often presenting at an advanced stage. Their high rate of recurrence supports close imaging surveillance and the utilization of functional imaging techniques. Whole-body 18F-FDG PET/CT has very high sensitivity for the diagnosis of sinonasal malignancies and can also be used as a "metabolic biopsy" in the characterization of some of the more common subgroups of these tumors, though due to overlap in uptake, histological confirmation is still needed. For certain tumor types, radiotracers, such as 11C-choline, and radiolabeled somatostatin analogs, including 68Ga-DOTATATE/DOTATOC, have proven useful in treatment planning and surveillance. Although serial scans for posttreatment surveillance allow the detection of subclinical lesions, the optimal schedule and efficacy in terms of survival are yet to be determined. Pitfalls of 18F-FDG, such as post-surgical and post-radiotherapy crusting and inflammation, may cause false-positive hypermetabolism in the absence of relapse.

Fibroblast Activation Protein Inhibitor-Based Radionuclide Therapies: Current Status and Future Directions.

Metastatic malignancies have limited management strategies and variable treatment responses. Cancer cells develop beside and depend on the complex tumor microenvironment. Cancer-associated fibroblasts, with their complex interaction with tumor and immune cells, are involved in various steps of tumorigenesis, such as growth, invasion, metastasis, and treatment resistance. Prooncogenic cancer-associated fibroblasts emerged as attractive therapeutic targets. However, clinical trials have achieved suboptimal success. Fibroblast activation protein (FAP) inhibitor-based molecular imaging has shown encouraging results in cancer diagnosis, making them innovative targets for FAP inhibitor-based radionuclide therapies. This review summarizes the results of preclinical and clinical FAP-based radionuclide therapies. We will describe advances and FAP molecule modification in this novel therapy, as well as its dosimetry, safety profile, and efficacy. This summary may guide future research directions and optimize clinical decision-making in this emerging field.

Pathologic mechanobiological interactions between red blood cells and endothelial cells directly induce vasculopathy in iron deficiency anemia.

The correlation between cardiovascular disease and iron deficiency anemia (IDA) is well documented but poorly understood. Using a multi-disciplinary approach, we explore the hypothesis that the biophysical alterations of red blood cells (RBCs) in IDA, such as variable degrees of microcytosis and decreased deformability may directly induce endothelial dysfunction via mechanobiological mechanisms. Using a combination of atomic force microscopy and microfluidics, we observed that subpopulations of IDA RBCs (idRBCs) are significantly stiffer and smaller than both healthy RBCs and the remaining idRBC population. Furthermore, computational simulations demonstrated that the smaller and stiffer idRBC subpopulations marginate toward the vessel wall causing aberrant shear stresses. This leads to increased vascular inflammation as confirmed with perfusion of idRBCs into our "endothelialized" microfluidic systems. Overall, our multifaceted approach demonstrates that the altered biophysical properties of idRBCs directly lead to vasculopathy, suggesting that the IDA and cardiovascular disease association extends beyond correlation and into causation.

Quantification of uptake in pelvis F-18 FLT PET-CT images using a 3D localization and segmentation CNN.

PURPOSE: The purpose of this work was to develop and validate a deep convolutional neural network (CNN) approach for the automated pelvis segmentation in computed tomography (CT) scans to enable the quantification of active pelvic bone marrow by means of Fluorothymidine F-18 (FLT) tracer uptake measurement in positron emission tomography (PET) scans. This quantification is a critical step in calculating bone marrow dose for radiopharmaceutical therapy clinical applications as well as external beam radiation doses. METHODS: An approach for the combined localization and segmentation of the pelvis in CT volumes of varying sizes, ranging from full-body to pelvis CT scans, was developed that utilizes a novel CNN architecture in combination with a random sampling strategy. The method was validated on 34 planning CT scans and 106 full-body FLT PET-CT scans using a cross-validation strategy. Specifically, two different training and CNN application options were studied, quantitatively assessed, and statistically compared. RESULTS: The proposed method was able to successfully locate and segment the pelvis in all test cases. On all data sets, an average Dice coefficient of 0.9396 ± $\pm$ 0.0182 or better was achieved. The relative tracer uptake measurement error ranged between 0.065% and 0.204%. The proposed approach is time-efficient and shows a reduction in runtime of up to 95% compared to a standard U-Net-based approach without a localization component. CONCLUSIONS: The proposed method enables the efficient calculation of FLT uptake in the pelvis. Thus, it represents a valuable tool to facilitate bone marrow preserving adaptive radiation therapy and radiopharmaceutical dose calculation. Furthermore, the method can be adapted to process other bone structures as well as organs.

Multimodality imaging in a case of multiple pulmonary hyalinizing granulomas - A decade follow-up.

A 44-year-old male was referred to our clinic (2015) to evaluate multiple lung nodules with increasing fatigue, dyspnea, and weight loss. He was being assessed to an outside hospital for the same since 2010. The X-ray and computed-tomography (CT)-chest showed numerous pulmonary nodules and bilateral hilar adenopathy. Imaging workup at our institute (2015) redemonstrated extensive calcified pulmonary nodules. 18fluoro-2-deoxy-d-glucose positron emission tomographyCT showed widespread pulmonary nodules with low-grade uptake. Video-assisted thoracic surgery lung biopsy revealed pulmonary hyalinizing granuloma (PHG). Recently because of increasing symptoms, he is being evaluated for a lung transplant. This case represents a rare diagnosis of PHG with a decade follow-up.

Role of FDG PET/CT for detection of primary tumor in patients with extracervical metastases from carcinoma of unknown primary.

AIM: To explore the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP). We evaluated patient outcomes as overall survival (OS). MATERIALS AND METHODS: In a single-center, retrospective study (2005-2019), patients with extracervical metastases from CUP underwent FDG PET/CT to detect primary tumor sites. The final diagnosis was based on histopathology/or clinical follow-up of at least 12 months. RESULTS: A total of 83 patients [Male 41 (49%), mean age 59 ± 14 years, range: 32-83 years] fulfilled the inclusion/exclusion criteria and were enrolled for analysis. The primary tumor was detected in 36 out of 83 (43%) patients based on histopathology/or clinical follow-up. PET/CT suggested the primary tumor site in 39 (47%) patients with diagnostic accuracy of 87%, sensitivity 89%, specificity 85%, PPV 82%, NPV 91% and detection rate 39%. Patients with oligometastases (<3) (2.16 years, 1.04-2.54) and primary unidentified (1 year, 0.34-2.14) had longer median survival time compared to the patients with multiple metastases (0.67 years, 0.17-1.58, p = 0.009) and primary identified (0.67 years,0.16-1.33, p = 0.002). The SUVmax of the primary or metastatic lesions with maximum uptake was not significantly related to survival. CONCLUSIONS: PET/CT could reveal the primary tumor site in 39% of the patients. It demonstrated the metastatic disease burden and distribution in patients with 'primary obscured', which directs management. Patients with multiple metastases and primary identified had a poorer prognosis. In patients with primary unidentified after PET/CT, a further search was futile.

Asymptomatic COVID-19 Infection Detected on 18F-FDG PET/CT Scan Done for Multiple Myeloma.

A 69-year-old woman with multiple myeloma came to our department for F-FDG PET/CT scan for routine surveillance. The patient denied any history of fever, cough, shortness of breath, or body aches. F-FDG PET/CT scan from vertex to knees was performed. PET/CT images revealed extensive peripheral ground-glass opacities showing intense FDG uptake (SUVmax 12) involving bilateral lower lobes. Possibility of an infective etiology including novel coronavirus (COVID-19) infection was raised. The patient's oropharyngeal swab for COVID-19 by polymerase chain reaction amplification test came back positive for COVID-19 infection. The patient and her husband were advised home quarantine for 14 days.

Theranostics: The Role of Quantitative Nuclear Medicine Imaging.

Theranostics is a precision medicine discipline that integrates diagnostic nuclear medicine imaging with radionuclide therapy in a manner that provides both a tumor phenotype and personalized therapy to patients with cancer using radiopharmaceuticals aimed at the same target-specific biological pathway or receptor. The aim of quantitative nuclear medicine imaging is to plan the alpha or beta-emitting therapy based on an accurate 3-dimensional representation of the in-vivo distribution of radioactivity concentration within the tumor and normal organs/tissues in a noninvasive manner. In general, imaging may be either based on positron emission tomography (PET) or single photon emission computed tomography (SPECT) invariably in combination with X-ray CT (PET/CT; SPECT/CT) or, to a much lesser extent, MRI. PET and SPECT differ in terms of the radionuclides and physical processes that give rise to the emission of high energy photons, as well as the sets of technologies involved in their detection. Using a variety of standardized quantitative parameters, system calibration, patient preparation, imaging acquisition and reconstruction protocols, and image analysis protocols, an accurate quantification of the tracer distribution can be obtained, which helps prescribe the therapeutic dose for each patient.

Identifying a Minor Histocompatibility Antigen in Mauritian Cynomolgus Macaques Encoded by APOBEC3C.

Allogeneic hematopoietic stem cell transplants can lead to dramatic reductions in human immunodeficiency virus (HIV) reservoirs. This effect is partially mediated by donor T cells recognizing lymphocyte-expressed minor histocompatibility antigens (mHAgs). The potential to mark malignant and latently infected cells for destruction makes mHAgs attractive targets for cellular immunotherapies. However, testing such HIV reservoir reduction strategies will likely require preclinical studies in non-human primates (NHPs). In this study, we used a combination of alloimmunization, whole exome sequencing, and bioinformatics to identify an mHAg in Mauritian cynomolgus macaques (MCMs). We mapped the minimal optimal epitope to a 10-mer peptide (SW10) in apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) and determined the major histocompatibility complex class I restriction element as Mafa-A1∗063, which is expressed in almost 90% of MCMs. APOBEC3C SW10-specific CD8+ T cells recognized immortalized B cells but not fibroblasts from an mHAg-positive MCM. These results provide a framework for identifying mHAgs in a non-transplant setting and suggest that APOBEC3C SW10 could be used as a model antigen to test mHAg-targeted therapies in NHPs.

Prospective Analysis of the Impact of 68Ga-DOTATOC Positron Emission Tomography-Computerized Axial Tomography on Management of Pancreatic and Small Bowel Neuroendocrine Tumors.

OBJECTIVES: A prospective clinical trial evaluated the effect of Ga-DOTATOC positron emission tomography-computerized axial tomography (PET-CT) on change in management of patients with lung, pancreatic, and small bowel neuroendocrine tumors. The primary eligibility criterion was a histologically proven tumor with positive somatostatin receptor subtype 2A immunohistochemistry. The primary and secondary end points were change in patient management and safety. METHODS: Referring physicians completed questionnaires pre- and post-Ga-DOTATOC PET-CT, stating current and planned patient management, respectively, with tumor board adjudication of final management decisions. Change in management was categorized as follows: no change; minor change (additional imaging, supportive care); or major change (octreotide/lanreotide therapy, tumor biopsy, surgery, peptide receptor radiotherapy, chemotherapy, biological therapy, liver embolization). RESULTS: A major change in management was recommended for 54 (47.37%) of 114 subjects and a minor change for 6 (5.26%) of 114 subjects, with no change for 54 (47.37%) of 114 subjects. Grade 1 adverse events were observed in 26 of 114 subjects (nausea, headache, back pain, diarrhea); one grade 2 (petechiae) and one grade 3 (abdominal pain) adverse event were observed. No grade 2 or 3 adverse events were related to study drug and none required intervention. CONCLUSIONS: Imaging with Ga-DOTATOC PET-CT has a significant impact on management of patients with neuroendocrine tumors.

Association of gallbladder hyperkinesia with acalculous chronic cholecystitis: A case-control study.

BACKGROUND: This is the first case-control study investigating an association between gallbladder hyperkinesia and symptomatic acalculous chronic cholecystitis. METHODS: This retrospective study in a single academic center compared resolution of biliary pain in adults with gallbladder hyperkinesia, defined as a hepatobiliary iminodiacetic acid scan ejection fraction ≥80%, undergoing cholecystectomy (study group) with those treated medically without cholecystectomy (control group). Of 1,477 hepatobiliary iminodiacetic acid scans done between 2013 and 2018, a total of 296 adults without gallstones had an ejection fraction ≥80%, of whom 46 patients met predetermined eligibility criteria. Demographic data, hepatobiliary iminodiacetic acid scan ejection fraction, chronicity of pain, and resolution of pain were compared between groups. RESULTS: Demographics (mean ± standard deviation) in the control group (n = 25) and in the study group (n = 21) were, respectively, age 40 y ± 16 y and 39 y ± 14 y, body mass index 28.9 ± 5.2 and 29.1 ± 7.1 kg/m2, with 15 (60%) and 18 (86%) females in each. Resolution of pain after cholecystectomy occurred in 18 of 21 patients (86%); however, pain persisted in 20 of 25 patients (80%) treated medically after mean follow-up of 36 ± 28 months (range 10-120 months) (P < .01). Pain resolution with cholecystectomy was independent of demographic variables, hepatobiliary iminodiacetic acid scan ejection fraction, and chronicity of pain. The odds of pain resolution was 19.7 times greater with cholecystectomy than without (odds ratio, 19.7; 95% confidence interval, 4.34, 89.43; P < .01), and remained robust even with the odds adjusted for each covariate. Gallbladder histopathology confirmed chronic cholecystitis in all 21 cholecystectomy specimens. CONCLUSION: Symptomatic gallbladder hyperkinesia could be a new indication for cholecystectomy in adults.

"Eye-Black" Sign Secondary to Nivolumab Immunotherapy.

A 54-year-old woman with known chest wall melanoma (post-wide local excision) presented for imaging after a yearlong therapy with nivolumab. F-FDG PET/CT was performed 1 day after she completed the immunotherapy. Maximum intensity projection images showed bilateral relatively symmetrical uptake in the facial region. On fused PET/CT images, the uptake was seen corresponding to subcutaneous malar prominence underneath the orbits (like eye-black stripe used in sports) with subcutaneous malar calcification. Repeat PET/CT performed after 3 months revealed significant decrease in the malar uptake. Interval resolution of the uptake likely suggested this being inflammatory and secondary to immunotherapy.

Discordant findings on preoperative imaging for primary hyperparathyroidism and thyroid disease: Choosing the path to follow.

BACKGROUND: Preoperative localization of abnormal parathyroid glands in primary hyperparathyroidism is often obtained by sestamibi, and ultrasonography. We aimed to identify which modality is most accurate when laterality of abnormal glands on preoperative imaging is discordant. METHODS: A single institution retrospective review identified 112 consecutive patients with primary hyperparathyroidism who underwent successful parathyroidectomy and sestamibi with pertechnetate. RESULTS: Sestamibi with pertechnetate had a sensitivity of 72% and positive predictive value of 90%; ultrasonography had sensitivity of 50% and positive predictive value 80%. Patients with thyroiditis had lesser sensitivity and positive predictive value on sestamibi with pertechnetate (53% and 77%, respectively), in contrast to ultrasonography (54%, 88%, respectively). The sensitivity and positive predictive value of sestamibi with pertechnetate and ultrasonography did not differ in patients with thyroid nodules. Seventeen patients (15%) had discordant laterality on preoperative imaging. In discordant cases, sestamibi with pertechnetate was correct in 53% overall but in only 17% of those with thyroiditis (P = .01), whereas ultrasonography was correct in 26% overall but in 50% of those with thyroiditis (P = .01). CONCLUSION: Thyroiditis decreased the sensitivity and positive predictive value of sestamibi with pertechnetate in primary hyperparathyroidism. In patients with discordant laterality on preoperative imaging, sestamibi with pertechnetate is the more accurate choice to guide operative planning, although ultrasonography may be a better guide in those with thyroiditis.

FDG PET based prediction of response in head and neck cancer treatment: Assessment of new quantitative imaging features.

INTRODUCTION: 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is now a standard diagnostic imaging test performed in patients with head and neck cancer for staging, re-staging, radiotherapy planning, and outcome assessment. Currently, quantitative analysis of FDG PET scans is limited to simple metrics like maximum standardized uptake value, metabolic tumor volume, or total lesion glycolysis, which have limited predictive value. The goal of this work was to assess the predictive potential of new (i.e., nonstandard) quantitative imaging features on head and neck cancer outcome. METHODS: This retrospective study analyzed fifty-eight pre- and post-treatment FDG PET scans of patients with head and neck squamous cell cancer to calculate five standard and seventeen new features at baseline and post-treatment. Cox survival regression was used to assess the predictive potential of each quantitative imaging feature on disease-free survival. RESULTS: Analysis showed that the post-treatment change of the average tracer uptake in the rim background region immediately adjacent to the tumor normalized by uptake in the liver represents a novel PET feature that is associated with disease-free survival (HR 1.95; 95% CI 1.27, 2.99) and has good discriminative performance (c index 0.791). CONCLUSION: The reported findings define a promising new direction for quantitative imaging biomarker research in head and neck squamous cell cancer and highlight the potential role of new radiomics features in oncology decision making as part of precision medicine.

FLT PET Radiomics for Response Prediction to Chemoradiation Therapy in Head and Neck Squamous Cell Cancer.

Radiomics is an image analysis approach for extracting large amounts of quantitative information from medical images using a variety of computational methods. Our goal was to evaluate the utility of radiomic feature analysis from 18F-fluorothymidine positron emission tomography (FLT PET) obtained at baseline in prediction of treatment response in patients with head and neck cancer. Thirty patients with advanced-stage oropharyngeal or laryngeal cancer, treated with definitive chemoradiation therapy, underwent FLT PET imaging before treatment. In total, 377 radiomic features of FLT uptake and feature variants were extracted from volumes of interest; these features variants were defined by either the primary tumor or the total lesion burden, which consisted of the primary tumor and all FLT-avid nodes. Feature variants included normalized measurements of uptake, which were calculated by dividing lesion uptake values by the mean uptake value in the bone marrow. Feature reduction was performed using clustering to remove redundancy, leaving 172 representative features. Effects of these features on progression-free survival were modeled with Cox regression and P-values corrected for multiple comparisons. In total, 9 features were considered significant. Our results suggest that smaller, more homogenous lesions at baseline were associated with better prognosis. In addition, features extracted from total lesion burden had a higher concordance index than primary tumor features for 8 of the 9 significant features. Furthermore, total lesion burden features showed lower interobserver variability.

Clinical Utility of Pretreatment and 3-Month 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Standardized Uptake Value in Predicting and Assessing Recurrence in T3-T4 Laryngeal Carcinoma Treated With Definitive Radiation.

OBJECTIVES: The aim of this study was to investigate the utility of pretreatment and 3-month 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) standardized uptake value (SUV) in predicting and assessing recurrence in T3-T4 laryngeal carcinoma treated with definitive radiation therapy (RT). METHODS: Patients with newly diagnosed T3-T4 laryngeal squamous cell carcinoma treated with definitive RT from 2004 to 2014 were reviewed. Patients who underwent pretreatment or 3-month PET/CT 2 to 4 months after treatment were included. Those with prior systemic, surgical, or RT treatment were excluded. The primary objective was to assess whether pretreatment or posttreatment maximum SUV of the primary site (pSUV) of disease was associated with local recurrence-free survival. Overall survival was a secondary end point. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the accuracy of 3-month PET/CT at the larynx primary. RESULTS: Twenty-eight patients were eligible for analysis. Median follow-up time was 34.7 months (range, 5.3-138.7 months), and median age was 57 years. Most patients had supraglottic (71.4%), T3 (89.3%), N2 (50.0%) disease, received chemotherapy (96.4%), and had histories of tobacco use (96.4%). On univariate analysis, 3-month posttreatment pSUV was associated with local recurrence-free survival ( P < .01), while pretreatment pSUV was not ( P = .41). No other associations were found with local recurrence-free survival. Neither pretreatment nor 3-month pSUV was significantly associated with overall survival. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of 3-month PET/CT at the primary site were 33%, 85%, 40%, and 81%, respectively. CONCLUSIONS: High initial fluorodeoxyglucose uptake in T3-T4 laryngeal primaries did not show an association with the risk for postradiation local relapse or overall survival, while increased fluorodeoxyglucose uptake at 3 months was associated with increased local recurrence. At 3 months, the relatively low sensitivity and positive predictive value may limit the utility of PET/CT in the assessment of persistent advanced laryngeal cancer after definitive radiation.