Systemic and Neurosarcoidosis With Rare Involvement of the Extremities' Peripheral Nerves.

ABSTRACT: We present a case of sarcoidosis with a rare presentation of involvement of peripheral nerves of the lower limbs and subcutaneous nodules detected on 18F-FDG PET/CT. The patient also had involvement of the spinal nerves and dura, histologically proven to be sarcoidosis. There were other manifestations of systemic sarcoidosis like metabolically active cervical and mediastinal lymphadenopathy. This case highlights the role of 18F-FDG PET/CT in evaluating the uncommon sites of sarcoid involvement. Although many cases of sarcoid involvement of central nervous system have been reported, peripheral nerves involvement in the extremities was not found on a literature search.

Prostate-Specific Membrane Antigen PET/CT Detection of Prostate Cancer Metastasis to Thyroid and Cricoid Cartilages.

ABSTRACT: Prostate-specific membrane antigen (PSMA) PET/CT has revolutionized the imaging of prostate cancer. Historically, prostate cancer metastasis to thyroid and cricoid cartilages was thought to be exceedingly rare, with only a few reported cases in the literature. Prostate cancer metastasis to the laryngeal cartilages was detected in 4 of 221 patients who underwent imaging with 18 F-PSMA (Pylarify) or 68 Ga-PSMA (Illuccix) PET/CT for initial staging of high-risk prostate cancer or restaging evaluation in the setting of biochemical recurrence from April 2022 through October 2023. The increased sensitivity and specificity of PSMA PET/CT allow for the detection of previously occult metastatic disease.

10-year update to the combined 16-month nuclear medicine and diagnostic radiology residency: The NuRad pathway.

BACKGROUND: The decline in nuclear medicine (NM) residencies in the United States has led to a shortage of NM physicians. To help address this, a 16-month NM pathway for diagnostic radiology (DR) residents was developed in 2010. At the University of Arkansas for Medical Sciences, we matched our first resident into the NuRad (NM + DR) pathway in 2013. Despite our success, we remain one of only five programs in the United States that offers a combined training pathway through the National Resident Matching Program. OBJECTIVES: Review our 10-year experience with the NuRad pathway at UAMS and highlight the key components and significance of the 16-month NM pathway. METHODS: Retrospective review of NRMP applicants to the DR and NuRad pathway from 2013 and 2023 at UAMS. Literature and website review of the educational structure of the 16-month NM pathway. RESULTS: We have seen significant increase in the number of applicants to the NuRad pathway at UAMS over the last 10 years with 184 applicants for 1 position in 2023, up from 18 applicants in 2013. Furthermore, we have seen an increase in the USMLE step scores for applicants during this time. CONCLUSIONS: There is a growing need for NM trained physicians in the United States. Over the last 10 years, we have seen increasing interest in the NM 16-month pathway as a part of DR residency. A wider implementation of this combined training pathway is needed, if we are to realize its full potential.

Scintigraphic Detection of Abdominal Pseudocyst: A Complication of Ventriculoperitoneal Shunt.

We report a case of a large abdominal pseudocyst detected on scintigraphy in a patient with a history of ventriculoperitoneal shunt placement who presented with headache and suspected shunt malfunction.

Giant left pheochromocytoma with vascular anomalies and pelvic horseshoe kidney: a case report.

BACKGROUND: Pheochromocytoma is a neuroendocrine tumor, and its treatment is dependent on surgical resection. Due to the wide availability of cross-sectional imaging, pheochromocytomas are commonly seen as small tumors less than 10 cm in size and are mostly treated with minimally invasive surgery. Their concomitant presence with horseshoe kidney or other anatomical and vascular anomalies is rare. Herein, we present a surgically complex giant pheochromocytoma case who underwent an open left radical adrenalectomy. CASE PRESENTATION: A 41-year-old Hispanic female presented with a 12 × 8 cm left hypervascular adrenal mass, pelvic horseshoe kidney, and severely dilated large left retro-aortic renal vein which branched into a left adrenal vein, congested left ovarian vein, and left uterine plexus. She was managed with insulin and metformin for uncontrolled diabetes with an A1c level of 9% and doxazosin for persistent hypertension. Clinical diagnosis of pheochromocytoma was confirmed with elevated urine and serum metanephrine and normetanephrine. The pre-operative ACTH was within normal range with a normal dexamethasone suppression test and 24-hour urine free cortisol. The adrenalectomy of the highly aggressive adrenal mass was performed via open approach to obtain adequate surgical exposure. Due to the large size of the tumor and its significant involvement with multiple adjacent structures, coordination with multiple surgical teams and close hemodynamic monitoring by anesthesiology was required for successful patient outcomes including preservation of blood supply to the pelvic horseshoe kidney. The histopathological diagnosis was pheochromocytoma with negative surgical margins. The patient was followed at 1, 4, 12, and 24 weeks postoperatively. She had a normal postoperative eGFR and was able to discontinue antihypertensive and antidiabetic medications at four weeks. She had transient adrenal insufficiency, which resolved at five months. The horseshoe kidney was intact except for a minimal area of hypo-enhancement in the left superior renal moiety due to infarction, which was significantly improved at six months. CONCLUSION: Our patient had a giant pheochromocytoma with anatomical variations complicating an already surgically challenging procedure. Nonetheless, with multiple provider collaboration, detailed pre-operative surgical planning, and meticulous perioperative monitoring, radical resection of the giant pheochromocytoma was safe and feasible with successful postoperative outcomes.

Synchronous Ectopic Thyroid Gland and Ectopic Parathyroid Adenoma on 99mTc-Sestamibi Scintigraphy and Correlative Imaging.

99mTc-sestamibi scintigraphy localizes parathyroid adenoma as a persistent focus of uptake on delayed images, whereas thyroid glands in normal or ectopic locations are seen on only early images and wash out on delayed images. We report a case of absence of eutopic neck thyroid activity and synchronous ectopic lingual thyroid and mediastinal parathyroid adenoma on scintigraphy confirmed with CT.

Resting-state brain metabolic fingerprinting clusters (biomarkers) and predictive models for major depression in multiple myeloma patients.

BACKGROUND: Major depression is a common comorbidity in cancer patients. Oncology clinics lack practical, objective tools for simultaneous evaluation of cancer and major depression. Fludeoxyglucose F-18 positron emission tomography-computed tomography (FDG PET/CT) is universally applied in modern medicine. METHODS: We used a retrospective analysis of whole-body FDG PET/CT images to identify brain regional metabolic patterns of major depression in multiple myeloma patients. The study included 134 multiple myeloma (MM) patients, 38 with major depression (group 1) and 96 without major depression (group 2). RESULTS: In the current study, Statistic Parameter Mapping (SPM) demonstrated that the major depression patient group (n = 38) had significant regional metabolic differences (clusters of continuous voxels) as compared to the non-major depression group (n = 96) with the criteria of height threshold T = 4.38 and extent threshold > 100 voxels. The five significant hypo- and three hyper-metabolic clusters from the computed T contrast maps were localized on the glass-brain view, consistent with published brain metabolic changes in major depression patients. Subsequently, using these clusters as features for classification learner, the fine tree and medium tree algorithms from 25 classification algorithms best fitted our data (accuracy 0.85%; AUC 0.88; sensitivity 79%; and specificity 88%). CONCLUSION: This study demonstrated that whole-body FDG PET/CT scans could provide added value for screening for major depression in cancer patients in addition to staging and evaluating response to chemoradiation therapies.

BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells.

BH3 mimetic drugs may be useful to treat acute lymphoblastic leukemia (ALL) but the sensitivity of primary tumor cells has not been fully evaluated. Here, B-lineage ALL cell cultures derived from a set of primary tumors were studied with respect to sensitivity to the BH3 mimetics ABT-263 and ABT-199 and to Bcl-2 dependence and function. These ALL cells each expressed high levels of Bcl-2 and exhibited great sensitivity to ABT-263 and ABT-199, which induced rapid apoptotic cell death. BH3 profiling indicated that the ALL cultures were Bcl-2 dependent. Coimmunoprecipitation studies revealed a multifaceted role for Bcl-2 in binding proapoptotic partners including Bax, Bak, Bik, and Bim. ABT-263 disrupted Bcl-2:Bim interaction in cells. Mcl-1 overexpression rendered ALL cells resistant to ABT-263 and ABT-199, with Mcl-1 assuming the role of Bcl-2 in binding Bim. Freshly isolated pediatric ALL blasts also expressed high levels of Bcl-2 and exhibited high sensitivity to Bcl-2 inhibition by the BH3 mimetic compounds. Overall, our results showed that primary ALL cultures were both more sensitive to BH3 mimetics and more uniform in their response than established ALL cell lines that have been evaluated previously. Furthermore, the primary cell model characterized here offers a powerful system for preclinical testing of novel drugs and drug combinations to treat ALL.

Cyclin B1 overexpression induces cell death independent of mitotic arrest.

Microtubule inhibitors are widely used in cancer chemotherapy. These drugs characteristically induce mitotic arrest and cell death but the mechanisms linking the two are not firmly established. One of the problems is that cancer cells vary widely in their sensitivity to these agents, and thus comparison of data from different systems is difficult. To alleviate this problem we sought to molecularly induce mitotic death and study its mechanisms, by expressing non-degradable cyclin B (R42A) in HeLa cells. However, this approach failed to induce significant mitotic arrest, Cdk1 activation, or phosphorylation of anti-apoptotic Bcl-2 proteins, all characteristics of cells treated with microtubule inhibitors. Furthermore, cyclin B1-R42A induced rapid cell death, and when expressed in synchronized cells, cell death occurred in G1 phase. Decreasing the plasmid concentration reduced transfection efficiency but restored mitotic arrest and eliminated non-specific death. These results show that inappropriate overexpression of cyclin B1 causes non-specific cell death and suggest caution in its use for the study of mitotic events.

Molecular analysis of functional redundancy among anti-apoptotic Bcl-2 proteins and its role in cancer cell survival.

Bcl-2 family proteins act as essential regulators and mediators of intrinsic apoptosis. Several lines of evidence suggest that the anti-apoptotic members of the family, including Bcl-2, Bcl-xL and Mcl-1, exhibit functional redundancy. However, the current evidence is largely indirect, and based mainly on pharmacological data using small-molecule inhibitors. In order to study compensation and redundancy of anti-apoptotic Bcl-2 proteins at the molecular level, we used a combined knockdown/overexpression strategy to essentially replace the function of one member with another. The results show that HeLa cells are strictly dependent on Mcl-1 for survival and correspondingly refractory to the Bcl-2/Bcl-xL inhibitor ABT-263, and remain resistant to ABT-263 in the context of Bcl-xL overexpression because endogenous Mcl-1 continues to provide the primary guardian role. However, if Mcl-1 is knocked down in the context of Bcl-xL overexpression, the cells become Bcl-xL-dependent and sensitive to ABT-263. We also show that Bcl-xL compensates for loss of Mcl-1 by sequestration of two key pro-apoptotic Bcl-2 family members, Bak and Bim, normally bound to Mcl-1, and that Bim is essential for cell death induced by Mcl-1 knockdown. To our knowledge, this is the first example where cell death induced by loss of Mcl-1 was rescued by the silencing of a single BH3-only Bcl-2 family member. In colon carcinoma cell lines, Bcl-xL and Mcl-1 also play compensatory roles, and Mcl-1 knockdown sensitizes cells to ABT-263. The results, obtained employing a novel strategy of combining knockdown and overexpression, provide unique molecular insight into the mechanisms of compensation by pro-survival Bcl-2 family proteins.

Identification of a mitotic death signature in cancer cell lines.

This study examined the molecular mechanism of action of anti-mitotic drugs. The hypothesis was tested that death in mitosis occurs through sustained mitotic arrest with robust Cdk1 signaling causing complete phosphorylation of Mcl-1 and Bcl-xL, and conversely, that mitotic slippage is associated with incomplete phosphorylation of Mcl-1/Bcl-xL. The results, obtained from studying six different cancer cell lines, strongly support the hypothesis and identify for the first time a unique molecular signature for mitotic death. The findings represent an important advance in understanding anti-mitotic drug action and provide insight into cancer cell susceptibility to such drugs which has important clinical implications.

Cyclin-dependent kinase-1 (Cdk1)/cyclin B1 dictates cell fate after mitotic arrest via phosphoregulation of antiapoptotic Bcl-2 proteins.

The prevailing model suggests that cell fate after mitotic arrest depends on two independent and competing networks that control cyclin B1 degradation and the generation of death signals. However, recent evidence for Cdk1/cyclin B1-mediated phosphorylation and inactivation of antiapoptotic Bcl-2 proteins suggests the existence of significant cross-talk and interdependence between these pathways. Further, the nature of the mitotic death signals has remained elusive. In this study, we sought to test the hypothesis that fate after mitotic arrest is dictated by the robustness of Cdk1/cyclin B1 signaling to Bcl-2 proteins and to identify signals that may represent a mitotic death signature. We show that when treated with Taxol, slippage-resistant HT29 colon carcinoma cells display robust Cdk1 activity and extensive Mcl-1/Bcl-x(L) phosphorylation and die in mitosis, whereas slippage-prone DLD-1 colon carcinoma cells display weak Cdk1 activity and partial and transient Mcl-1/Bcl-x(L) phosphorylation and die in subsequent interphase or survive. Furthermore, modulation of this signaling axis, either by inhibition of Cdk1 in slippage-resistant HT29 or by enforcing mitotic arrest in slippage-prone DLD-1 cells, evokes a switch in fate, indicating that the strength of Cdk1 signaling to Bcl-2 proteins is a key determinant of outcome. These findings provide novel insight into the pathways that regulate mitotic death, suggest that the robustness of these signaling events may be useful as a marker to define susceptibility to antimitotic drugs, and encourage a revision in the current model describing fate after mitotic arrest.