Imaging Gallbladder Lesions: What Can Positron Emission Tomography/Computed Tomography Add to the Conventional Imaging Approach?

OBJECTIVE: Incidental gallbladder lesions are common in imaging studies, although it is not always easy to discriminate benign lesions from gallbladder cancer with conventional imaging procedures. The present study aims to assess the capacity of positron emission tomography/computed tomography (PET/CT) with 2-[ 18 F]FDG to distinguish between benign and malignant pathology of the gallbladder, compared with conventional imaging techniques (contrast-enhanced CT or magnetic resonance imaging). METHODS: Positron emission tomography/CT and conventional imaging studies of 53 patients with gallbladder lesions were evaluated and visually classified as benign, malignant, or inconclusive. Agreement between PET/CT and conventional imaging was determined, and imaging findings were correlated with histology or follow-up. Positron emission tomography/CT images were also analyzed semiquantitatively (SUV max and maximum tumor-to-liver ratio [TLR max ]). The presence of adenopathies and distant metastases was assessed and compared between both imaging procedures. RESULTS: According to histology or follow-up, 33 patients (62%) had a malignant process and 20 (38%) had benign lesions. Positron emission tomography/CT and conventional imaging showed a moderate agreement ( κ = 0.59). Conventional imaging classified more studies as inconclusive compared with PET/CT (17.0% and 7.5%, respectively), although both procedures showed a similar accuracy. Malignant lesions had significantly higher SUV max and, especially, TLR max (0.89 and 2.38 [ P = 0.00028] for benign and malignant lesions, respectively). Positron emission tomography/CT identified more pathologic adenopathies and distant metastases, and patients with regional or distant spread had higher SUV max and TLR max in the gallbladder. CONCLUSIONS: Positron emission tomography/CT is accurate to distinguish between benign and malignant pathology of the gallbladder, with a similar performance to conventional imaging procedures but with less inconclusive results. Malignant lesions present higher SUV max and TLR max values.

Pembrolizumab for refractory primary mediastinal B-cell lymphoma with central nervous system involvement.

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive B-cell lymphoma characterized by the frequent presence of amplification and translocation events at 9p24.1, resulting in the expression of the programmed cell death-1 (PD-1) ligands PD-L1 and PD-L2. Pembrolizumab, a humanized anti-PD-1 monoclonal antibody, binds PD-1 and blocks this interaction, enhancing the activity of the immune system against tumor cells, and has shown activity in PMBCL and in some cases of primary and secondary central nervous system (CNS) lymphoma. We report the case of a 40-year-old woman diagnosed with relapsed PMBCL and secondary CNS involvement who responded to pembrolizumab monotherapy, allowing for a later allogeneic stem cell transplant.

Usefulness of 18F-FDG PET-CT for assessing large-vessel involvement in patients with suspected giant cell arteritis and negative temporal artery biopsy.

OBJECTIVE: To investigate the usefulness of 18F-FDG PET-CT for assessing large-vessel (LV) involvement in patients with suspected giant cell arteritis (GCA) and a negative temporal artery biopsy (TAB). METHODS: A retrospective review of our hospital databases was conducted to identify patients with suspected GCA and negative TAB who underwent an 18F-FDG PET-CT in an attempt to confirm the diagnosis. The gold standard for GCA diagnosis was clinical confirmation after a follow-up period of at least 12 months. RESULTS: Out of the 127 patients included in the study, 73 were diagnosed with GCA after a detailed review of their medical records. Of the 73 patients finally diagnosed with GCA, 18F-FDG PET-CT was considered positive in 61 cases (83.5%). Among the 54 patients without GCA, 18F-FDG PET-CT was considered positive in only eight cases (14.8%), which included 1 case of Erdheim-Chester disease, 3 cases of IgG4-related disease, 1 case of sarcoidosis, and 3 cases of isolated aortitis. Overall, the diagnostic performance of 18F-FDG PET-CT for assessing LV involvement in patients finally diagnosed with GCA and negative TAB yielded a sensitivity of 83.5%, specificity of 85.1%, and a diagnostic accuracy of 84% with an area under the ROC curve of 0.844 (95% CI: 0.752 to 0.936). The sensitivity was 89% in occult systemic GCA and 100% in extracranial LV-GCA. CONCLUSION: Our study confirms the utility of 18F-FDG PET-CT in patients presenting with suspected GCA and a negative TAB by demonstrating the presence of LV involvement across different subsets of the disease.

Differences in glucose metabolic activity in liver metastasis separates two groups of metastatic uveal melanoma patients with different prognosis.

BACKGROUND: Uveal melanoma metastasizes to the liver. We aimed to explore the metabolic activity of liver metastases (LM) as a biomarker for survival. METHODS: We analyzed newly diagnosed patients with metastatic UM (MUM) with LM detected by liver-directed imaging and had undergone a PET/CT at diagnosis. FINDINGS: 51 patients were identified between 2004 and 2019. Median age was 62 years, 41% male and 22% ECOG ≥1. LDH, ALP, and GGT were elevated in 49%, 37%, and 57% of patients. Median LM SUVmax was 8.5 (3-42.2). Same size lesions presented a wide range of metabolic activity. Median OS was 17.3 m (95% CI:10.6-23.9). Patients with SUVmax ≥8.5 had an OS of 9.4 m (95% CI:6.4-12.3), whereas patients with SUVmax <8.5 had an OS of 38.4 m (95% CI:21.4-55.5; p < 0.0001, HR = 2.9). We observed similar results when studying M1a disease separately. Multivariate analysis showed SUVmax as an independent prognostic factor for the whole population and those with M1a disease. INTERPRETATION: Increased metabolic activity of LM seems to be an independent predictor of survival. MUM is a heterogeneous disease and metabolic activity probably reflects a different intrinsic behavior.

Multiple Drug Regimen-Refractory Rosai-Dorfman-Destombes Disease Mimicking Relapsing Polychondritis Successfully Treated with Cobimetinib.

Rosai-Dorfman-Destombes disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans cell histiocytosis of unknown cause. The disease often manifests as painless bilateral cervical lymphadenopathy associated with systemic symptoms such as fever and weight loss. Extranodal disease is also frequent and can involve any organ, mostly the skin, nasal cavity, bone, and retro-orbital tissue. Swelling of cartilaginous tissues, such as the helix of the ear or laryngeal structures, may mimic the entity known as relapsing polychondritis. Although spontaneous remission is the most expected evolution, some cases require systemic treatment with prednisone, methotrexate or cytotoxic agents, with variable rates of success. In this respect, since somatic variants in the genes involved in the mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK) pathway have been observed to play a pathogenic role in RDD. Therefore, the use of therapies targeting these pathogenic variants appears to be a reasonable strategy. Here we present the case of a 37-year-old woman with RDD and extensive extranodal involvement that showed a rapid and complete response to the MEK inhibitor cobimetinib. LEARNING POINTS: Rosai-Dorfman-Destombes disease (RDD) may mimic the entity known as relapsing polychondritis but should be treated with drug therapy for the underlying disease.Mutations in MAPK/ERK pathway components should be determined in RDD with systemic involvement, although testing to determine every somatic mutation responsible for the disease is not available in all healthcare centres.MEK inhibitors like cobimetinib could be effective in RDD cases with severe and refractory systemic disease, even if molecular analysis has not been possible.

Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial.

PURPOSE: The need for an individualized management of indolent clinical forms in mantle cell lymphoma (MCL) is increasingly recognized. We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients. METHODS: This is a multicenter single-arm, open-label, phase II study with a two-stage design conducted in 12 Spanish GELTAMO sites (ClinicalTrials.gov identifier: NCT02682641). Previously untreated MCL patients with indolent clinical forms defined by the following criteria were eligible: no disease-related symptoms, nonblastoid variants, Ki-67 < 30%, and largest tumor diameter ≤ 3 cm. Both leukemic non-nodal and nodal subtypes were recruited. Patients received ibrutinib 560 mg once daily and a total of eight doses of rituximab 375 mg/m2. Ibrutinib could be discontinued after 2 years in the case of sustained undetectable minimal residual disease (MRD). The primary end point was the complete response (CR) rate achieved after 12 cycles according to Lugano criteria. RESULTS: Fifty patients with MCL (male 66%; median age 65 years) were enrolled. After 12 cycles of treatment, 42 (84%; 95% CI, 74 to 94) patients had an overall response, including 40 (80%; 95% CI, 69 to 91) with CR. Moreover, undetectable MRD in peripheral blood was achieved in 87% (95% CI, 77 to 97) of cases. At 2 years, 24 of 35 evaluable patients (69%) could discontinue ibrutinib because of undetectable MRD. Four patients had disease progression; three were non-nodal MCL and carried high genomic complexity and TP53 mutations at enrollment. No unexpected toxicity was seen except one patient with severe aplastic anemia. CONCLUSION: Frontline IR combination achieves a high rate of CRs and undetectable MRD in indolent clinical forms of MCL. Discontinuation seems appropriate in cases with undetectable MRD, except for TP53-mutated cases.

Efficacy and safety clinical trial with efavirenz in patients diagnosed with adult Niemann-pick type C with cognitive impairment.

BACKGROUND: Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca®) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. METHODS: This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. DISCUSSION: NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz's capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression.

SPECT-CT metabolic and morphological study of 2 types of cemented hip stem prostheses in primary total hip arthroplasty patients: A protocol for a randomized controlled clinical trial (SPECT-PROTMA).

BACKGROUND: Cemented hip arthroplasty requires applying a layer of polymethylmethacrylate (cement) in the space between the bone and the prosthetic stem. This can be achieved using 2 techniques: the thick-layer technique (requires a layer of at least 2 mm to surround an undersized prosthetic stem), and the thin-layer technique (requires a thin layer of cement, so that the prosthetic stem fills the femoral medullary canal). Both approaches have excellent long-term clinical and radiological outcomes, although an implant's insertion into the bone generates inevitable bone mass and bone metabolic changes around it. Combination of single photon emission computed tomography and computed tomography scan (SPECT-CT) imaging combines the single photon emission computed tomography's ability to provide detailed bone metabolism assessment with the computed tomography scan's capacity to provide a meticulous anatomical study. METHODS: This is a single center, open label, randomized clinical trial, performed in the premises of the Bellvitge University Hospital. Participants will be randomly assigned to the Thick-layer technique group (Exeter V40 Cemented Femoral Stem) or to the French paradox technique group (Müller Straight Stem). All participants will have a SPECT-CT scan study at 3, 6, 12, and 24 months after the surgery. DISCUSSION: Surgical distress itself and the implant's insertion into the bone may cause microvascular changes that alter periprosthetic bone mass and bone metabolism. To the best of our knowledge, there are no studies using SPECT-CT to compare bone metabolism evolution in the postoperative period between these 2 surgical cementation techniques. We aim to provide information in this regard that could help decision making in complicated implant cases and, maybe, pave the way for larger, and methodologically improved studies. TRIAL REGISTRATION: NCT05010733 (August 18, 2021).

Mediastinal Recurrence of Uterine Cervix Cancer on 18F-FDG PET/CT.

ABSTRACT: We report the case of a 64-year-old woman with a mediastinal relapse of a uterine cervix cancer with positive human papillomavirus, an unusual site of recurrence. She consulted because of solid and liquid dysphagia of sudden appearance. Endoscopic study and non-contrast-enhanced CT showed intraluminal esophageal stenosis with a retrograde esophageal distension. 18F-FDG PET/CT demonstrated an infiltrating hypermetabolic lesion in posterior mediastinum, middle and lower esophagus, and stomach, with no signs of local or regional relapse of the uterine neoplasm.

2-[18F]FDG PET/CT as a Predictor of Microvascular Invasion and High Histological Grade in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) generally presents a low avidity for 2-deoxy-2-[18F]fluoro-d-glucose (FDG) in PET/CT although an increased FDG uptake seems to relate to more aggressive biological factors. To define the prognostic value of PET/CT with FDG in patients with an HCC scheduled for a tumor resection, forty-one patients were prospectively studied. The histological factors of a poor prognosis were determined and FDG uptake in the HCC lesions was analyzed semi-quantitatively (lean body mass-corrected standardized uptake value (SUL) and tumor-to-liver ratio (TLR) at different time points). The PET metabolic parameters were related to the histological characteristics of the resected tumors and to the evolution of patients. Microvascular invasion (MVI) and a poor grade of differentiation were significantly related to a worse prognosis. The SULpeak of the lesion 60 min post-FDG injection was the best parameter to predict MVI while the SULpeak of the TLR at 60 min was better for a poor differentiation. Moreover, the latter parameter was also the best preoperative variable available to predict any of these two histological factors. Patients with an increased TLRpeak60 presented a significantly higher incidence of poor prognostic factors than the rest (75% vs. 28.6%, p = 0.005) and a significantly higher incidence of recurrence at 12 months (38% vs. 0%, p = 0.014). Therefore, a semi-quantitative analysis of certain metabolic parameters on PET/CT can help identify, preoperatively, patients with histological factors of a poor prognosis, allowing an adjustment of the therapeutic strategy for those patients with a higher risk of an early recurrence.

Diagnostic Accuracy of 18F-FDG PET/CT in Patients With Biochemical Evidence of Recurrent, Residual, or Metastatic Medullary Thyroid Carcinoma.

OBJECTIVE: Medullary thyroid carcinoma (MTC) is a rare malignancy. Location of residual, recurrent, or metastatic disease is crucial to treatment management and outcome. We aimed to evaluate the use of F-FDG PET/CT in localizing MTC foci in patients with biochemical relapse. METHODS: This is a retrospective cohort study. Review of 51 FDG PET/CT studies of 45 patients referred to restage MTC due to increased calcitonin (Ctn) and carcinoembryonic antigen (CEA) values at follow-up. FDG PET/CT diagnostic accuracy was determined through a patient-based analysis, using histology as criterion standard when available, or other imaging studies and clinical follow-up otherwise (mean, 4 years). RESULTS: There were 25 positive scans. Sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and positive likelihood ratio were 66.7%, 83.3%, 88.0%, 57.7%, 72.5%, and 4.0, respectively. Using a Ctn cutoff of 1000 pg/mL, sensitivity increased to 76.9%. There were significant differences of Ctn and CEA values between positive and negative FDG PET/CT (P < 0.05). Regarding true-positive studies, average SUVmax comparing locoregional and metastatic disease was at the limit of significance (P = 0.046). CONCLUSIONS: PET/CT can be useful to restage patients with biochemical relapse of MTC, with a better performance in higher Ctn levels. Its high positive predictive value (88%) may impact in the therapeutic management, although its low negative predictive value (57.7%) makes strict follow-up mandatory in examinations without pathologic findings.

Low-Dose PET/CT and Full-Dose Contrast-Enhanced CT at the Initial Staging of Localized Diffuse Large B-Cell Lymphomas.

Computed tomography (CT) has been used as the reference imaging technique for the initial staging of diffuse large B-cell lymphoma until recent days, when the introduction of positron emission tomography (PET)/CT imaging as a hybrid technique has become of routine use. However, the performance of both examinations is still common. The aim of this work was to compare the findings between low-dose 2-deoxy-2-((18)F)fluoro-d-glucose ((18)F-FDG) PET/CT and full-dose contrast-enhanced CT (ceCT) in 28 patients with localized diffuse large B-cell lymphoma according to PET/CT findings, in order to avoid the performance of ceCT. For each technique, a comparison in the number of nodal and extranodal involved regions was performed. PET/CT showed more lesions than ceCT in both nodal (41 vs. 36) and extranodal localizations (16 vs. 15). Disease staging according to both techniques was concordant in 22 patients (79%) and discordant in 6 patients (21%), changing treatment management in 3 patients (11%). PET/CT determined a better staging and therapeutic approach, making the performance of an additional ceCT unnecessary.

[Positron emission tomography combined with computed tomography in the initial evaluation and response assessment in primary central nervous system lymphoma]. / Tomografía por emisión de positrones combinada con tomografía computarizada en la evaluación inicial y valoración de la respuesta en el linfoma cerebral primario.

OBJECTIVE: To evaluate the role of positron emission tomography combined with computed tomography (PET-CT) in the initial evaluation and response assessment in primary central nervous system lymphoma (PCNSL). MATERIAL AND METHOD: Fourteen patients (8 males) with a median age 59.5 years diagnosed of PCNSL. A brain PET-CT and magnetic resonance imaging (MRI) were performed in the initial evaluation. In 7 patients a PET-CT after treatment was performed. RESULTS: PET-CT showed at diagnosis 31 hypermetabolic focuses and MRI showed 47 lesions, with a good grade of concordance between both (k = 0.61; P = .005). In the response assessment, correlation between both techniques was good, and PET-CT was helpful in the appreciation of residual MRI lesions. Overall survival at 2 years of negative vs. positive PET-CT at the end of treatment was 100 vs. 37.5%, respectively (P = .045). CONCLUSIONS: PET-CT can be useful in the initial evaluation of PCNSL, and especially in the assessment of response. Despite the fact that PET-CT detects less small lesions than MRI, a good correlation between MRI and PET-CT was observed. It is effective in the evaluation of residual lesions. Prospective studies are needed to confirm their possible prognostic value.

Bone marrow evaluation in initial staging of lymphoma: 18F-FDG PET/CT versus bone marrow biopsy.

PURPOSE: The evaluation of bone marrow infiltration (BMI) is of crucial importance in the staging of lymphoma. Although bone marrow biopsy (BMB) is the reference standard for the evaluation of BMI, it has limitations. PET/CT has become an excellent tool in staging of lymphoma, and bone marrow uptake is correlated with the involvement of lymphoma. The aim of this study was to assess the utility of PET/CT and its concordance with BMB in the detection of BMI in patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). PATIENTS AND METHODS: One hundred forty-seven patients with DLBCL (84) and HL (63) were referred for a PET/CT and a BMB (unilateral) at the initial staging. The reference standard was BMB. RESULTS: Bone marrow infiltration was detected by PET/CT in 39 (26%) and by BMB in 21 (14%) cases. There was concordance between PET/CT and BMB in 128 patients (87%) (74 DLBCL, 54 HL), 21 with positive PET/CT and BMB results and 107 with negative PET/CT and BMB results. Discordant results were observed in 19 patients (14%); 18 of them with positive PET/CT and negative standard BMB results (not performed in active sites). The sensitivity, specificity, accuracy, as well as positive and negative predictive values of FDG-PET/CT for the detection of BMI were 95%, 86%, 87%, 54%, and 99%, respectively. CONCLUSIONS: PET/CT detects more bone marrow involvement in DLBCL and HL compared with BMB. Its good concordance with BMB makes it a complementary technique, as it helps select the biopsy site in cases with negative results.

Impact of radioguided occult lesion localization on the correct excision of malignant breast lesions: effect of histology and tumor size.

AIM: To evaluate the impact of radioguided occult lesion localization (ROLL) in the correct location and excision of malignant breast lesions, and analyze if these results are affected by the histology and tumor size. MATERIALS AND METHODS: A total of 105 patients with occult breast lesions were studied. The mean age was 55 years. An intralesional dose of 18.5 MBq of 99mTc-labeled macroaggregated human albumin (AMA) was administered using stereotaxic mammography or ultrasound. Surgical resection was carried out with the help of a gammadetector probe. In the histological study, disease-free margin was defined by a distance between the tumor lesion and the surgical margin of more than 1 mm. The possible influence of tumor histology and lesion diameter with respect to free/affected margins was analyzed. RESULTS: Correct radiotracer placement was achieved in 100/105 of the cases (95.2%). In the remaining 5 cases (4.8%), radiotracer placement was incorrect, with 2 of them being malignant lesions that were found by macroscopic inspection, and the other 3 having benign pathology. Among the malignant lesions (44 cases), correct placement of the radiotracer was achieved in 42 cases (95.5%). Of these 42 malignant lesions, in which the ROLL was correctly performed, free surgical margins were obtained in 24 cases (57.1%), while the other 18 (42.9%) had infiltrated surgical margins. The most common histological type among the malignant lesions was invasive ductal carcinoma (71.4%). The histological types with an increased frequency of infiltration of surgical margins were invasive and microinvasive cancer (94.4%). All the affected margins were in lesions greater than 10 mm, and the highest incidence was in those between 20 and 30 mm (55.5%). CONCLUSION: In our experience, the advantages of the ROLL technique are a precise localization of malignant breast lesions (95.5%) and an increased probability of a complete excision with free margins in more than one half of them. Nevertheless, special consideration should be taken when dealing with invasive and microinvasive cancers and in those exceeding 10 mm because of their higher incidence of infiltrated margins.

123-I ioflupane (Datscan®) presynaptic nigrostriatal imaging in patients with movement disorders

123-I Ioflupane (Datscan®) presynaptic imaging has been shown to have a significant utility in the assessment of patients with movement disorders 123-I Ioflupane SPECT is able to distinguish between ParkinsonÆs disease (PD) and other forms of parkinsonism without degeneration of the nigrostriatal pathway, including a common movement disorder such as essential tremor, and to assess disease progression in PD and other neurodegenerative disorders involving the substantia nigra.

A imagem pré-sináptica através de 123-I Ioflupane (Datscan®) tem mostrado um papel significante na avaliação de pacientes com distúrbios do movimento. 123-I Ioflupane SPECT é capaz de distinguir entre Mal de Parkinson (MP) e outras formas de parkinsonismo sem degenerações da via nigroestriatal incluindo um distúrbio comum de movimento parecido com o tremor essencial e para medir a evolução da doença no Mal de Parkinson e outros distúrbios neurodegenerativos envolvendo a substantia nigra.