Early prediction of response by ¹8F-FDG PET/CT during preoperative therapy in locally advanced rectal cancer: a systematic review.

AIM: To assess the predictive value of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in early assessing response during neo-adjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: A systematic review was performed by search of MEDLINE Library for the following terms: "rectal carcinoma OR rectal cancer", "predictive OR prediction OR response assessment OR response OR assessment", "early OR ad interim", "therapy", "FDG OR (18)F-FDG", "PET OR PET/CT". Articles performed by the use of stand-alone PET scanners were excluded. RESULTS: 10 studies met the inclusion criteria, including 302 patients. PET/CT demonstrated a good early predictive value in the global cohort (mean sensitivity = 79%; mean specificity = 78%). SUV and its percentage decrease (response index = RI) were calculated in all studies. A higher accuracy was demonstrated for RI (mean sensitivity = 82%; pooled specificity = 85%) with a mean cut-off of 42%. The mean time point to perform PET scan during CRT resulted to be at 1.85 weeks. Some PET parameters resulted to be both predictive and not statistical predictive of response, maybe due to the small population and few studies bias. CONCLUSION: PET showed high accuracy in early prediction response during preoperative CRT, increased with the use of RI as parameter. In the era of tailored treatment, the precocious assessment of non-responder patients allows modification of the subsequent strategy especially the timing and the type of surgical approach.

Complications in thyroid resurgery: a single institutional experience on 233 patients from a whole series of 4,752 homogeneously treated patients.

The aim of this study was to examine a homogeneous, consecutive recent series of patients who underwent reoperation on the thyroid bed to assess the incidence of the complications commonly correlated with resurgery. We reviewed clinical charts of 233 patients who underwent resurgery taken from a total of 4,752 patients previously operated on for benign and malignant thyroid diseases from 2006 to 2010 by the same surgical team. We evaluated the incidence of postoperative hemorrhage, hypoparathyroidism, and recurrent laryngeal nerve (RLN) palsy. Analyses were done separately in relation to the type of the type of resurgery adopted: (A) monolateral completion; (B) bilateral completion, after monolateral (B1) or bilateral prior surgery (B2); and (C) lymph node dissection. We also separately analyzed patients according to their final histological diagnosis of benign or malignant disease. Regarding hemorrhage, 6/233 patients (2.5 %) underwent surgical revision of the thyroid within 12 h for postoperative hemorrhage. They included 2 (1.5 %) of the 129 monolateral reoperations (A), 3 (4 %) of the 74 bilateral reoperations (B), and 1 (3.3 %) of the 30 central dissections for nodal relapse (C). Transient and definitive postoperative hypoparathyroidism was recorded in 78 (36.4 %) and 7 (3.3 %) of the 214 eligible patients. Transient RLN palsy occurred in 21 RLNs at risk (7 %) and definitive RLN palsy in 5 (1.7 %). Elective total thyroidectomy cannot always be supported as an effective policy for preventing recurrences in patients with a single, benign node: lobectomy, preferably with extemporaneous histological examination, unquestionably represents the best minimal approach to thyroid resection.

Role of FDG PET/CT in investigating the mechanisms underlying atherosclerotic plaque formation and evolution

Este artículo se centra en el papel de la FDG PET/TC en la identificación de la aterosclerosis y en la relevancia de las células inflamatorias como los macrófagos y los linfocitos T en la formación de la placa aterosclerótica. Se discute también sobre la vulnerabilidad de la placa inflamatoria y el riesgo asociado a determinar incidentes cardio y cerebro-vasculares independientemente de la presencia de vasos estenóticos, así como sobre la evolución hacia la placa calcificada. El importante papel de la FDG PET/TC en el diagnóstico precoz de la placa inflamatoria se discute tanto en estudios con animales como a nivel clínico. Se discute, finalmente, la posibilidad de curar la placa inflamatoria, el tipo de fármacos utilizados y la posibilidad de controlar el tratamiento anti-inflamatorio a través de FDG PET/TC(AU)

This review article is focused on the role of FDG-PET/CT in visualizing atherosclerosis and on the relevance of inflammatory cells such as macrophages and T-lymphocytes in the formation of the atherosclerotic plaque. The vulnerability of the inflammatory plaque and the risk derived from the provocation of cardio- and cerebrovascular incidents independently from the presence of stenotic vessels are discussed as well as the evolution toward calcified plaque. The important role of FDG-PET/CT in early diagnosis of inflammatory plaque is discussed in both animal studies and in clinical setting. The possibility of curing inflammatory plaques, type of drugs, and the possibility of monitoring the anti-inflammatory treatment by FDG-PET/CT are also discussed(AU)

Role of FDG PET/CT in investigating the mechanisms underlying atherosclerotic plaque formation and evolution.

This review article is focused on the role of FDG-PET/CT in visualizing atherosclerosis and on the relevance of inflammatory cells such as macrophages and T-lymphocytes in the formation of the atherosclerotic plaque. The vulnerability of the inflammatory plaque and the risk derived from the provocation of cardio- and cerebrovascular incidents independently from the presence of stenotic vessels are discussed as well as the evolution toward calcified plaque. The important role of FDG-PET/CT in early diagnosis of inflammatory plaque is discussed in both animal studies and in clinical setting. The possibility of curing inflammatory plaques, type of drugs, and the possibility of monitoring the anti-inflammatory treatment by FDG-PET/CT are also discussed.

Diagnóstico de sarcoidosis desconocida asociada a eritema nodoso, mediante 18F-FDG PET/TAC / Diagnosis of unknown sarcoidosis associated to erythema nodosum with 18F-FDG PET/CT

Una mujer de 76 años fue remitida a nuestro Centro de Medicina Nuclear para someterse a 18F-FDG PET/TAC con sospecha clínica de vasculitis. La PET de cuerpo entero resultó negativa para vasculitis pero mostró hipermetabolismo moderado en varios ganglios linfáticos del mediastino y una captación intensa en las glándulas parótidas. Dado que la paciente refirió en anamnesis lesiones eritematosas de la piel en ambas piernas, realizamos una adquisición de PET de las extremidades inferiores que mostró una captación difusa en la región perimaleolar en ambas piernas. Sobre la base de los hallazgos de la PET/TAC que sugirieron sarcoidosis la paciente fue sometida a un lavado broncoalveolar (BAL) y a una biopsia de un ganglio linfático mediastínico que confirmó la sospecha de sarcoidosis(AU)

A 76-year-old woman was referred to our centre to perform 18F-FDG PET/CT with the clinical suspicion of vasculitis. Whole body PET was negative for vasculitis but it depicted moderate hypermetabolism in several lymph nodes of the mediastinum and intense uptake of the tracer in the parotid glands. Since the patient referred skin lesion on both legs a particular acquisition of the lower extremities was performed which showed diffuse uptake on the perimalleolar region of both legs. On the basis of the PET/CT findings that were suggestive for sarcoidosis the patient performed bronchoalveolar lavage (BAL) and biopsy of a mediastinal lymph node which confirmed the suspicion of sarcoidosis(AU)

Diagnosis of unknown sarcoidosis associated to erythema nodosum with 18F-FDG PET/CT.

A 76-year-old woman was referred to our centre to perform (18)F-FDG PET/CT with the clinical suspicion of vasculitis. Whole body PET was negative for vasculitis but it depicted moderate hypermetabolism in several lymph nodes of the mediastinum and intense uptake of the tracer in the parotid glands. Since the patient referred skin lesion on both legs a particular acquisition of the lower extremities was performed which showed diffuse uptake on the perimalleolar region of both legs. On the basis of the PET/CT findings that were suggestive for sarcoidosis the patient performed bronchoalveolar lavage (BAL) and biopsy of a mediastinal lymph node which confirmed the suspicion of sarcoidosis.

Molecular imaging in the management of thyroid cancer.

Thyroid cancer is the most common endocrine malignancy in adults. The disease is classified into papillary, follicular, medullary and anaplastic types, each with characteristic histology and patterns of biological behavior. Diagnosis of thyroid cancer is usually made by needle aspiration of suspicious thyroid nodules. Disease management of well-differentiated thyroid cancer relies upon characteristic accumulation of radioisotopes of iodine that continues to play a central role in detection and treatment of disease. Recombinant human thyrotropin (rhTSH) is used as an alternative to thyroid hormone withdrawal to provide TSH stimulation necessary for diagnostic radioiodine scintigraphy and preparation for thyroid remnant ablation and cancer therapy. Hybrid SPECT/CT cameras combining functional scintigraphic information with CT anatomy are replacing stand-alone gamma cameras and these devices have been shown to outperform traditional planar and SPECT imaging techniques. Similarly, clinical application of novel radioisotopes like [124I]iodine with PET/CT for thyroid cancer imaging provides improved lesion resolution and direct tumor dosimetry. Alternative tracers such as [18F]fluorodeoxyglucose (FDG) can be used to evaluate well-differentiated thyroid cancers that no longer express the Na+/I- symporter, with a role in staging Hürthle cell, poorly differentiated, and anaplastic thyroid cancers. Medullary thyroid cancer recurrences are often difficult to detect using conventional imaging and traditional radionuclide studies, whereas [18F]FDG and [18F]fluorodihydroxyphenylalanine (DOPA) PET and PET/CT show promise for localizing the often elusive source (s) of elevated calcitonin in these patients.

Arterial hypertension and thyroid disorders: what is important to know in clinical practice?

This review describes the pathogenic mechanisms of blood pressure (BP) regulation and long-term control in thyroid disorders. Variations from the euthyroid status affect virtually all physiological systems but the effects on the cardiovascular system are particularly pronounced. Thyroid disorders induce several hemodynamic changes leading to elevated BP as a consequence of their interaction with endothelial function, vascular reactivity, renal hemodynamic and renin-angiotensin system. However, in thyroid disorders, the regulation of BP and the development and maintenance of variable forms of arterial hypertension (HT) are different. Hyperthyroidism results in an increased endothelium-dependent responsiveness secondary to the shear stress induced by the hyperdynamic circulation, and contributes to reduce vascular resistance. Conversely, hypothyroidism is accompanied by a marked decrease in sensitivity to sympathetic agonists with an increase of peripheral vascular resistance and arterial stiffness. Furthermore in animal models, hypothyroidism reduces the endothelium-dependent and nitric oxide-dependent vasodilatation. HT due to thyroid disorders is usually reversible with achievement of euthyroidism, but in some cases pharmacological treatment for BP control is required. In hyperthyroidism, ß-blockers are the first-choice treatment to control BP but when they are contraindicated or not tolerated, ACE-inhibitors or calcium-channel blockers (CCB) are recommended. Hypothyroidism is a typical low rennin HT form showing a better antihypertensive response to CCB and diuretics; indeed in hypothyroidism a low-sodium diet seems further to improve BP control. Randomized clinical trials to compare the efficacy on BP control of the antihypertensive treatment in thyroid disorders are needed.

Minimally invasive radio-guided surgery for primary hyperparathyroidism: From preoperative to intraoperative localization imaging.

The introduction and successful implementation of minimally invasive radio-guided parathyroidectomy (MIRP) has revolutionized the surgical approach to remove parathyroid adenomas. A prerequisite for such success is an accurate localization of the offending adenoma. To achieve this goal, a multimodality approach is commonly employed using a combination of anatomical and functional imaging. Of the anatomical cross-sectional techniques, ultrasonography is the most widely available but is operator-dependent and has reduced sensitivity, specially in the presence of thyroid nodules. Similarly, computed tomography and magnetic resonance imaging have low sensitivities but provide value in detecting retrotracheal, retro-oesophageal and mediastinal adenomas. Functional imaging with 99(m)Tc-Sestamibi is currently the most vital imaging procedure in this respect with variable protocols including dual-phase and dual isotope imaging. The sensitivity and specificity can improve by acquiring in single photon emission tomography (SPECT) mode and using co-registration with low dose CT to provide anatomical data (SPECT/CT). The current recommended approach is the combination of functional imaging with 99(m)Tc-Sestamibi and high-resolution ultrasound (US), supplemented with intraoperative gamma probe in certain cases and quick persurgical measurement of parathyroid hormone. This review aims to explore the utility of various imaging modalities, alone and in combination, in detecting parathyroid adenoma and facilitating the current approach of MIRP.

The additional diagnostic value of a single-session combined scintigraphic and ultrasonographic examination in patients with thyroid and parathyroid diseases.

AIM: The aim of this study was to investigate the diagnostic efficacy and the clinical impact of scintigraphy combined with ultrasonography (USG) in the management of thyroid and parathyroid disorders in a large series of patients. METHODS: A total of 387 consecutive patients referred to the Nuclear Medicine Department of Hacettepe University in the period from January to September 2007 for investigating a thyroid (N. 339 patients: 232 females and 107 males, mean age+/-SD=48.9+/-13.6 years) or a parathyroid disease (N. 48 patients: 34 females and 14 males, mean age+/-SD=47.4+/-9.6 years) were prospectively evaluated, systematically performing both scintigraphy and USG in a single-day session. All the examinations were independently reviewed by two nuclear medicine physicians; in cases of discrepancy (3%) a final diagnosis was reached by consensus. For thyroid pathologies, USG results were considered to provide additional diagnostic information over scintigraphy: 1) if more nodules were identified; 2) if an irregular hyperactive area at scintigraphy suspicious for the presence of a nodule was clearly characterized at USG; 3) if a nodule missed at scintigraphy because of small size (<1 cm) was well depicted at USG, thus allowing an USG-guided fine needle aspiration cytology (FNAC) to reach a final diagnosis. For parathyroid pathologies, USG was considered to provide additional diagnostic information over scintigraphy if a low intensity radiotracer retention from the parathyroid suspected of being a parathyroid enlargement was clearly depicted at USG. In thyroid diseases, scintigraphy was considered to provide additional diagnostic information over USG, if the functional status of a diffuse or uni- or multi-nodular goiter were clearly defined at scintigraphy. In parathyroid diseases, scintigraphy was considered to provide additional diagnostic information over USG, if the differential diagnosis between a lymph node or a muscle or a vessel depicted at USG was clearly defined as a parathyroid enlargement at scintigraphy. Lastly, the clinical impact of the single-day combined scintigraphic/USG protocol was evaluated. RESULTS: USG. In the thyroid diseases group, USG was particularly useful: 1) to detect additional nodules in glands with suppressed thyroid tissue; 2) to disclose small thyroid nodules (<1 cm) in which it was possible to perform a USG-FNAC. In the parathyroid diseases group, USG was particularly useful for the detection of parathyroid enlargements not visualized at scintigraphy because characterized by a rapid wash-out of the radiotracer and thus by a low radioactivity intensity in the delayed scintigraphic images. Scintigraphy. In the thyroid diseases group, scintigraphy was particularly useful: 1) to diagnose a diffuse hyperfunctioning thyroid gland, and to differentiate in multinodular goiters the hyper- from the hypo-functioning nodules. In the hyperparathyroid diseases group, scintigraphy was particular useful in making a differential diagnosis between a true parathyroid enlargement vs. a lymph node or a muscle or a vessel as depicted at USG, and in cases with deeply or ectopically-positioned parathyroid glands. Combined imaging approach. Combined interpretation provided additional benefit in 225 of 339 patients (64.4%). Overall, using the combined scintigraphic/USG single-day protocol, in the thyroid diseases group the therapeutic strategy (drug therapy vs radioiodine therapy vs surgery) was changed in 176/225 patients (78.2%, P<0.001 by chi(2) of Pearson), and in the parathyroid disease group the therapeutic strategy (medical therapy vs surgery) was changed in 18/48 patients (37.5%, P<0.01 by chi2 test of Pearson). CONCLUSION: In agreement with some previous published experiences, the combined single-day scintigraphic/USG protocol systematically adopted in a large series of consecutive patients with thyroid and parathyroid diseases, enrolled in a limited period of time, proved to significantly increase the global diagnostic accuracy and to change the therapeutic strategy in more than two third of patients with a thyroid disease and in more than one third of patients with a parathyroid disease.

18F-FDG small animal PET for early detection of human anaplastic large cells lymphoma xenograft in immunocompromised mice.

The purpose of the present study was to assess if small animal PET is useful for serially monitoring the development of a human anaplastic large cell lymphoma (ALCL) murine xenograft and for the early selection of tumour bearing animals. The human ALCL Karpas 299 cell line was subcutaneously injected in 6-week-old NOD/SCID (non-obese diabetic/NCrCrl- Prkdc) mice (10(7) cells/mouce in 150 pil FBS) at the right flank level. Small animal 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was serially performed (intravenous injected dose: 20 MBq in < 0.15 ml, uptake time: 60 min, image acquisition: 1 bed position of 15 min): early PET at 2 days after cell inoculation in 4/8 mice and at 4 days in the remainig 4/8, later PET scans were performed in all the animals at 7, 14, 21 and 28 days after inoculation. The images were evaluated visually and the tumour to background ratio (TBR) was used for semiquantitative analysis. Pathology sections were obtained in all cases. PET detected the presence of the tumour as early as seven days after inoculation in 4/8 mice and at 14 days in 2/8. Of the two remaining mice, one died after the first PET scan (thus preventing any evaluation of detection time) while the other showed a microscopic neoplastic infiltration at tracheal level at autopsy. Mean TBR progressively increased in all positive cases, particularly in the first 3 weeks, reaching a plateau afterwards. PET was positive in 6/8 (75%) animals, detecting the presence of viable tumour cells earlier than macroscopic evaluation, thus may be used for the early identification of tumour bearing animals.

Thyroid disorders and diabetes mellitus.

Diabetes mellitus and thyroid diseases are quite frequently associated. This is true especially when they share the same cause: autoimmune etiology. The hormones involved in this disorders are: insulin, glucagon, thyroxine (T4) and triiodothyronine (T3). All of these affect the carbohydrate metabolism, so that the coexistence of thyroid dysfunction and diabetes may render the glycemic control more difficult to be preserved.

Surgical treatment of primary hyperparathyroidism: from bilateral neck exploration to minimally invasive surgery.

The human parathyroid glands, first described by Sandström in 1880, attracted interest because they were subject to inadvertent removal or ischemic injury during radical thyroid surgery. That this caused metabolic derangements was not known until many years later. Following on Kocher's studies, research continued to improve techniques sparing the parathyroids during thyroid surgery but without developing parathyroid surgery as such. For over a century, the lack of suitable surgical instruments, accurate preoperative localizing imaging techniques, and reliable laboratory tests hindered the evolution of parathyroid surgery, relegating it a marginal existence. Only after 1930, when it became clear that hyperparathyroidism is caused by an increased production of parathyroid hormone (PTH) by overactive parathyroid glands in the neck and/or the mediastinum, could parathyroid surgery, which shares a similar approach with thyroid surgery, be developed for treating hyperparathyroidism. The aim of parathyroid surgery is to cure hyperparathyroidism. Until advanced surgical and laboratory diagnostic technologies became available, concern about the risk of failure led surgeons to search all four glands by bilateral neck exploration, which proved unnecessary in 80% of cases. Recent years have seen parathyroid surgery evolve with the introduction of more efficacious preoperative localization imaging techniques and the use of rapid intraoperative parathormone assay, so that parathyroid surgery is now more selective and can be performed as a minimally invasive procedure in some cases.