Abstract
Macrophages can either promote or resolve inflammatory responses, and their polarization state is modulated by peripheral serotonin (5-hydroxytryptamine 5-HT). In fact, pro- and ...anti-inflammatory macrophages differ in the expression of serotonin receptors, with 5-HT2B and 5-HT7 expression restricted to M-CSF–primed monocyte-derived macrophages (M-MØ). 5-HT7 drives the acquisition of profibrotic and anti-inflammatory functions in M-MØ, whereas 5-HT2B prevents the degeneration of spinal cord mononuclear phagocytes and modulates motility of murine microglial processes. Because 5-HT2B mediates clinically relevant 5-HT–related pathologies (valvular heart disease, pulmonary arterial hypertension) and is an off target of anesthetics, antiparkinsonian drugs, and selective serotonin reuptake inhibitors, we sought to determine the transcriptional consequences of 5-HT2B engagement in human macrophages, for which 5-HT2B signaling remains unknown. Assessment of the effects of specific agonists and antagonist revealed that 5-HT2B engagement modifies the cytokine and gene signature of anti-inflammatory M-MØ, upregulates the expression of aryl hydrocarbon receptor (AhR) target genes, and stimulates the transcriptional activation of AhR. Moreover, we found that 5-HT dose dependently upregulates the expression of AhR target genes in M-MØ and that the 5-HT–mediated activation of AhR is 5-HT2B dependent because it is abrogated by the 5-HT2B–specific antagonist SB204741. Altogether, our results demonstrate the existence of a functional 5-HT/5-HT2B/AhR axis in human macrophages and indicate that 5-HT potentiates the activity of a transcription factor (AhR) that regulates immune responses and the biological responses to xenobiotics.
To assess the clinical utility of PERCIST and Hopkins criteria and changes in 18FFDG PET/CT quantitative parameters as prognostic factors for progression-free survival (PFS) and cancer-specific ...survival (CSS) in patients with head and neck squamous cell carcinoma treated by chemoradiotherapy.
Forty patients (34 men) diagnosed with head and neck squamous cell carcinoma were retrospectively assessed over an interval of 8 years. PERCIST and Hopkins criteria were used to assess response to treatment. Variations in the metabolic parameters maximum SUV (ΔSUVmax), metabolic tumor volume (ΔMTV) and total lesion glycolysis (ΔTLG) between pre- and post-treatment PET/CT studies were also determined. The Cox regression model, ROC curves and the Kaplan–Meier method were used for the analysis of prognostic factors and survival curves.
The mean follow-up was 39.4 months, with 24 progressions and 22 deaths. Both PERCIST and Hopkins criteria and the three metabolic parameters were predictive factors in the univariate analysis and only ΔSUVmax was in the multivariate analysis. Survival analysis showed statistically significant differences in PFS and CSS curves for the five parameters considered.
Application of PERCIST and Hopkins criteria as well as ΔSUVmax, ΔMTV and ΔTLG from PET/CT studies proved to be prognostic factors for survival in patients in our setting for treating head and neck cancer. The results may help to personalize treatment.
Valorar la utilidad clínica de los criterios PERCIST, Hopkins y de los cambios en los parámetros cuantitativos de la PET/TC con 18FFDG como factores pronósticos para la supervivencia libre de progresión (SLP) y la supervivencia cáncer específica (SCE) en pacientes con cáncer escamoso de cabeza y cuello tratados mediante quimiorradioterapia.
Se valoraron retrospectivamente 40 pacientes (34 hombres) diagnosticados de cáncer escamoso de cabeza y cuello durante un intervalo de 8 años. Se utilizaron los criterios PERCIST y Hopkins para determinar la respuesta al tratamiento. Asimismo, se cuantificaron las variaciones de los parámetros metabólicos SUV máximo (ΔSUVmax), volumen metabólico tumoral (ΔMTV) y glicólisis tumoral total (ΔTLG) entre los estudios PET/TC pre y postratamiento. El modelo de regresión de Cox, las curvas ROC y el método de Kaplan–Meier y se aplicaron para el análisis de factores pronósticos y curvas de supervivencia.
El seguimiento medio fue de 39,4 meses produciéndose 24 recidivas-progresiones y 22 muertes. Tanto los criterios PERCIST y Hopkins como los tres parámetros metabólicos fueron factores predictivos en análisis univariante y solo el ΔSUVmax en el multivariante. El análisis de supervivencia mostró curvas de SLP y SCE significativamente diferentes para los cinco parámetros considerados.
La aplicación de los criterios PERCIST y Hopkins, así como los ΔSUVmax, ΔMTV y ΔTLG de los estudios PET/TC demostraron ser factores pronósticos para la supervivencia en pacientes de nuestro entorno tratados por cáncer de cabeza y cuello. Los resultados podrían ayudar a personalizar el tratamiento.
Syringomyelia is a rare degenerative disease affecting the spinal cord and brain stem causing progressive neurological dysfunction. The presence of gastrointestinal symptoms in these patients is ...common, although references related to nuclear medicine imaging procedures in this pathology are limited, focusing on the study of gastric emptying. We present a 47-year-old male patient diagnosed with syringomyelia and persistent digestive symptoms who underwent gastrointestinal transit scintigraphy to assess the extent of dysmotility. Liquid gastric emptying and small-bowel transit were normal. Large bowel showed poor activity in descending and rectosigmoid colon, being compatible with generalized slow colon transit.
The POEMS syndrome is a rare and multisystemic disease characterized by the presence of polyneuropathy, organomegaly, endocrinopathy, presence of M protein, and alterations in the skin. The existence ...of bone lesions is frequent, being generally blastic or mixed and rarely lytic. We present the case of a 54-year-old male patient diagnosed with POEMS syndrome, with atypical presence of lytic lesions, who was referred for an 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) study for initial staging of the process. There were several hypermetabolic foci coinciding with bone lesions, reaching a maximum standardized uptake value of 15 at the level of the right iliac bone with associated soft-tissue mass. PET-CT is an adequate tool for evaluation, diagnosis, and monitoring of the pathology. The scan allows the detection and selection for its biopsy of bone lesions and lymphadenopathies.
The osteoid osteoma (OO) is the third most frequent benign bone tumor, whose location is more frequent in long bones of lower limbs. Its presence in the distal lower limb is uncommon, with the talus ...the most common reported location. Surgical treatments with radioguided surgery of OO of foot and ankle in our hospital were reviewed. We present a retrospective cohort study of 4 patients with clinical and radiologic findings suspicious OO with at least 1 year of follow-up. We used radioguided surgery for surgical resection after the injection of a dose of 99mTc-hydroxydiphosphonate. The nidus was located with the help of a portable gamma camera and gamma detection probe, concluding the surgical resection when its activity decreased to the levels present in healthy tissues. Samples were sent for pathologic anatomy for further examination. Lesions were localized in all patients. The cure rate, based on the absence of relapse of symptoms, was 100%. On the basis of our experience and on the available literature, we suggest that radioguided surgery is an effective and safe method for the treatment of OO in the foot and ankle. Although radiofrequency ablation is the first choice treatment for OO, radioguided surgery offers a number of advantagesan accurate delimitation of the nidus, allowing a more precise excision of the lesion; a decrease in postoperative complications; and the possibility of confirmation in histopathologic studies. Because of the small number of cases, a multicenter study could be useful to increase the number of cases and therefore provide more evidence to this type of treatment.Level of EvidenceLevel V. See Instructions for Authors for a complete description of levels of evidence.
Lymphatic drainage outside the ipsilateral axilla in breast cancer is discovered in as many as 25% of all sentinel lymph node procedures and it is evidenced by lymphoscintigraphy. Contralateral ...axillary drainage is a rare clinical situation, mostly if there is not prior breast surgery, but this situation is extremely exceptional if we also found internal mammary chain drainage. We have not found such a case published in literature. This atypical finding is source of doubts because it could have clinical implications in the management of patients. We present a woman just diagnosed of breast carcinoma with hot nodes in bilateral axillary and ipsilateral internal mammary chain lymph nodes, shown by preoperative lymphoscintigraphy. We review published cases with contralateral axillary drainage, which enhance the role of scintigraphic procedure in such cases and show induced controversies in selecting the most adequate management.
Gout is a common metabolic disorder, typically diagnosed in peripheral joints. Tophaceous deposits in lumbar spine are a very rare condition with very few cases reported in literature. The following ...is a case report of a 52-year-old patient with low back pain, left leg pain, and numbness. Serum uric acid level was in normal range. magnetic resonance imaging, bone scan, and gallium-67 images suggested an inflammatory-infectious process focus at L4. After a decompressive laminectomy at L4-L5 level, histological examination showed a chalky material with extensive deposition of amorphous gouty material surrounded by macrophages and foreign-body giant cells (tophaceous deposits).
Leptomeningeal carcinomatosis is an infrequent disease and although its treatment is palliative, earlier diagnosis will lead to prolonged survival and improve functional outcome. Whole-body FDG-PET ...allows the entire spinal cord to be examined noninvasively, so close attention should be paid to the spinal canal, since these lesions can easily be mistaken for physiologic uptake, sometimes there is no clinical suspicion and may occur without concurrent active cancer. We present a female patient with a history of carcinoma of the breast, who presented an elevation of serum tumor marker CA 15-3. An FDG-PET/CT study only revealed multiple abnormal uptake at the vertebral foramen at thoracic and lumbosacral regions suggesting leptomeningeal metastases that were confirmed by MRI and cerebrospinal fluid cytology.
FDG PET/CT studies allow evaluation of many areas not imaged with routine cancer staging. Although hypermetabolic lesions are detected, abnormalities of significance may be present that are not ...metabolically active, and such findings may have potential relevance for future patient care. In brain cortex, decreased FDG uptake is often associated with dementia, epilepsy, infarction, previous surgery, brain metastases, or radiation. We present a woman who underwent an FDG PET/CT study to evaluate response to chemotherapy for lymphoma. Several ametabolic areas were shown at both frontal and cerebellar cortex, and MRI confirmed the presence of multiple cavernous angiomas.
We present a 17-year-old female, previously diagnosed of autoimmune hyperthyroidism who had an acute neurological episode and presented high antithyroid antibodies titers, cerebral spinal fluid and ...electroencephalogram changes. Tc-99m ethylene dicysteine diethyl ester brain single-photon emission computed tomography (SPECT) showed global and patchy hypoperfusion. With glucocorticoid therapy, clinical symptoms disappeared; there was a decrease in antithyroid antibody levels and repeat brain SPECT revealed improvement of perfusion.