Alessandro Sindoni

Thyroid Metastases from Renal Cell Carcinoma: Review of the Literature

The thyroid gland is a rare site of clinically detectable tumor metastasis and kidneys are frequently the site of the parent malignancy. In the present review on thyroid metastases from renal cell carcinoma, cases were searched on PubMed by entering the strings: “renal carcinoma [or“hypernephroma”] AND thyroid metastasis/metastases”. Thus, we retrieved a total of 111 cases that were published between 1964 and 2007, a total that became 113 by adding two patients observed by us. The female to male ratio was 1.35:1. The primary renal cancer was almost always unilateral (90%) (with no significant side preference) and only rarely bilateral (9% in men, 4% in women), whereas bilaterality of thyroid metastases was relatively more frequent (28%). Thyroid metastasis from renal cancer was commonly single with a unique node that appears solid and hypoechoic at ultrasonography, approximately 9 years after nephrectomy. Concordance of lateralization was insignificantly greater for the right kidney/right thyroid lobe pattern (54%) than for the left kidney/left thyroid lobe pattern (40%), regardless of gender. Finally, survival was longer for women. Thyroid metastases, even if rare in the clinical practice, must be considered in the differential diagnosis of a thyroid nodule, particularly in patients who have a history of malignancies.

Increased annual frequency of Hashimoto’s thyroiditis between years 1988 and 2007 at a cytological unit of Sicily

Like other auto-immune diseases, Hashimotos thyroiditis (HT) results from the interaction of genetic with environmental factors. Only few studies have evaluated the year-to-year change in frequency of HT over a wide period of time. The endocrine division of our Hospital has reported a great increase in the annual frequency of HT between 1975 and 2005, and a progressive decrease in both age at presentation and female to male (F/M) ratio starting in the mid-1990s. Between years 1988 and 2007, we have collected 8397 adequate examinations by fine needle aspiration cytology (FNAC) on 8397 persons referred for the evaluation of a solitary or dominant thyroid nodule (total FNAC and persons=8520) with a 14-fold increase in 2007 over 1988. In this 20-year period, cases of HT, De Quervains thyroiditis (DQT) and Riedels thyroiditis (RT) were 490, 36 and two, respectively. HT cases were one in 1988 but 90 in 2007, with a significant upward temporal trend (r=0.919, P<0.001) and significant downward trend for age at FNAC (r=-0.466, P<0.05). In contrast, DQT cases were zero and one, respectively, with no significant temporal trend (r=0.29, P=0.21). The HT increase in frequency started in 1996 (+350% over 1995). Until 1995 there was only one man, but there were 22 men in 2005-2007. These FNAC data provide independent confirmation to the data from the endocrine division of the same hospital, further supporting the conclusion that only environmental modifications can explain these marked changes that have occurred in such a relatively short period of time.

Thyroid metastasis of clear cell renal carcinoma: Report of a case

Renal cell carcinoma can recur many years after diagnosis and nephrectomy metastasizing even in uncommon sites, including thyroid gland. Thyroid metastases are extremely rare, the most frequent site of origin are renal tumors. Metastases in thyroid gland appear as painless nodules or masses, “cold” at scintiscan. We report the case of a 67‐year‐old male patient affected by clear cell renal carcinoma, diagnosed by fine‐needle aspiration cytology procedures, and treated with anticancer medical therapy, who noticed after some months a mass in the neck‐thyroid region requiring deeper medical investigations. By this way, thyroid fine‐needle aspiration cytology reported a lesion made of malignant epithelial cells compatible with metastases of renal carcinoma (clear cell). Clinical and pathological data, together with immunostaining, supported the diagnosis of metastatic clear cell renal carcinoma. The diagnosis of metastatic disease, although difficult clinically and pathologically, should be suspected in patients with a clinical history of cancer, particularly in case of renal cell carcinoma, but fine‐needle aspiration cytology can provide the clue for diagnosis. Diagn. Cytopathol. 2009.

Clinical usefulness of 99mtc-mibi scintigraphy in the postsurgical evaluation of patients with differentiated thyroid cancer

Objective99mTc-methoxyisobutyl isonitrile (MIBI) has been reported to show considerable clinical utility in the study of many neoplastic diseases. The aim of our study was to investigate the possible role of 99mTc-MIBI in the initial follow-up of patients with differentiated thyroid cancer (DTC) for detecting residual thyroid uptake and/or loco-regional/distant metastases. MethodsEighty-two patients with DTC (61 women, 21 men; mean age: 49 years) were studied after total or near-total thyroidectomy (not earlier than 3 months after thyroidectomy but before they underwent radioiodine therapy). About 20 min after the intravenous administration of 370 MBq of 99mTc-MIBI, planar images (and, if necessary, tomographic images, single photon emission tomography) of the cervical and thoracic regions were recorded and compared with posttherapy radioiodine scanning and thyreoglobulin serum levels. ResultsMIBI scans detected thyroid remnants in 53 of 82 patients (65%) and metastatic foci in 10 of 11 (91%) patients, in whom a standard activity of 1110 MBq of 131I administered following MIBI scan had shown the presence of thyroid remnants or metastatic foci, respectively. One metastatic patient was false negative for both MIBI scan and post-131I dose whole body scan. ConclusionOur data indicate that an MIBI scan has a high sensitivity in detecting metastatic lesions from DTC. Therefore, an MIBI scan after thyroidectomy and immediately before radioiodine treatment may be clinically useful for choosing the best therapeutic approach in terms of either ablative or therapeutic 131I activity for both thyroid remnants and/or DTC metastases and for evaluating surgical reappraisal of metastatic lymph nodes.

Combination of immune checkpoint inhibitors and radiotherapy: Review of the literature

Literature experiences in cancer treatment usually deal with either targeting the tumour cell or the immune system, which often fail to reach the curative purposes in many solid tumours. On the other hand, one mechanism of radiation-induced tumour control is the activation of the adaptive immune system by tumour antigen release following radiotherapy. So, combining radiation therapy with immune checkpoint blockade treatment at the same time may represent a way to stimulate the adaptive immune system, with further amplification of immune responses reached through systemic immune checkpoint blockade. Until now, only few studies deal with the association of immune checkpoint blockade treatment and radiotherapy. In this review, we evaluate this association, highlighting this possibility as a new strategy to improve outcome in cancer patients.

Usefulness of four dimensional (4D) PET/CT imaging in the evaluation of thoracic lesions and in radiotherapy planning: Review of the literature

In the past decade, Positron Emission Tomography (PET) has become a routinely used methodology for the assessment of solid tumors, which can detect functional abnormalities even before they become morphologically evident on conventional imaging. PET imaging has been reported to be useful in characterizing solitary pulmonary nodules, guiding biopsy, improving lung cancer staging, guiding therapy, monitoring treatment response and predicting outcome. This review focuses on the most relevant and recent literature findings, highlighting the current role of PET/CT and the evaluation of 4D-PET/CT modality for radiation therapy planning applications. Current evidence suggests that gross tumor volume delineation based on 4D-PET/CT information may be the best approach currently available for its delineation in thoracic cancers (lung and non-lung lesions). In our opinion, its use in this clinical setting is strongly encouraged, as it may improve patient treatment outcome in the setting of radiation therapy for cancers of the thoracic region, not only involving lung, but also lymph nodes and esophageal tissue. Literature results warrants further investigation in future prospective studies, especially in the setting of dose escalation.

Annual increase in the frequency of papillary thyroid carcinoma as diagnosed by fine-needle aspiration at a cytology unit in Sicily.

OBJECTIVEAn increased frequency of papillary thyroid carcinoma (PTC) has been reported in the literature, including studies based on fine-needle aspiration cytology (FNAC).DESIGNTo substantiate our own ascertainment of such an increase, we retrieved all the diagnoses of ultrasound-guided FNAC which was performed on 11,389 patients referred for cytological evaluation of a single or dominant thyroid nodule from 1988 to 2010. FNAC yielded 11,258 adequate specimens.RESULTSThe number of patients with PTC was 200 (age 10–83 yrs) and increased significantly from 1988 to 2010 (r= 0.916, P<0.001). Expressing data as percent of FNAC in any given year, PTC and colloid goiter increased, while adenomatous goiter, follicular lesions and anaplastic or medullary thyroid cancer decreased. PTC accounted for 0% of all FNAC diagnoses in 1988 but for 2% in 2010, with a peak of 2.6% in 2006. Of interest, chronic lymphocytic thyroiditis (CLT) also increased, preceding the increase of PTC by 5–6 years.CONCLUSIONWe conclude that in the regions on either side of the Strait of Messina (Italy), PTC has become progressively more frequent during the 23-year period between 1988 and 2010 and that this increase lagged behind the increase of CLT.

Prognostic value of HMGB1 and oxidative stress markers in multiple trauma patients: A single-centre prospective study

Serious multiple traumatic injuries may rapidly become fatal or be complicated by a life-threatening sequelae leading to a significant increase of the mortality rate. Trauma scoring systems are used to evaluate the critical status of the patient and recently many different biomarkers have been taken into account to better estimate the potential clinical outcome. The aim of the present study is to analyse the expression pattern of high-mobility group box-1 (HMGB1), oxidative stress markers and nuclear factor erythroid 2-related (Nrf2) in critically ill traumatic patients (at hospital admittance and after 6 and 24 h), in order to find out their potential role as early post-traumatic predictors markers. Forty-seven patients admitted for multiple trauma and 15 healthy participants were prospectively recruited. Eight patients (17%) died within 92 h of admission; this subgroup of patients presented the highest severity scores and their HMGB1 expression levels were significantly correlated with ISS, whereas patients with higher ISS exhibited higher levels of HMGB1 (P <0.001). Our study suggests the role of HMGB1 as a predictive biomarker of outcome in injured patients and hypothesizes the protective role of Nrf2 in bringing down the oxidative stress and HMGB1 release; measuring HMGB1 in combination with Nrf2 might represent a potentially useful tool in the early detection of post-trauma complications.

The role of PET/CT in the management of patients affected by head and neck tumors: a review of the literature

The management of head and neck tumor (HNSCC) has been changing over the years, especially due to the aid of imaging techniques that help physicians to attain a correct diagnosis. These techniques represent a valuable tool to help tailor treatment and during follow-up of patients affected by malignancies. The aim of this review is to summarize the results of the most recent and relevant studies about the use of PET imaging in HNSCCs. This review is divided into six chapters: (1) The role of PET/CT in the pre-treatment phase; (2) PET/CT and radiotherapy planning; (3) PET/CT in the post-treatment setting; (4) PET/CT and SUVmax for prediction of prognosis; (5) miscellanea on the utility of PET in specific HNSCCs; (6) non-FDG PET tracers used in HNSCC. Promising results have been obtained so far. Despite the encouraging outcomes, more investigations are needed to warrant the value of this technique, especially in the pre-treatment setting.

Cell proliferation parameters and apoptosis indices in pituitary macroadenomas

Background: Pituitary adenomas are usually well-differentiated tumors but may show locally aggressive behavior. Aim: To investigate the relationship between proliferation and apoptosis parameters and tumor recurrence in a series of 20 radically resected pituitary macroadenomas (11 functioning, 9 non-functioning). Materials and methods: Proliferative activity and DNA ploidy were analyzed by flow cytometry (FCM) on fresh surgical specimens. Immunohisto-chemistry for Ki-67/MIB-1 and for the anti-apoptotic protein Bcl-2 was performed on paraffin-embedded specimens from the same tumors. Tumor regrowth was evaluated by magnetic resonance imaging (MRI). Results: Six adenomas recurred after surgery, regardless of hormonal hypersecretion. Pre-surgical tumor size was significantly higher in recurrent than in non-recurrent adenomas (p=0.003). Pre-surgical MRI demonstrated cavernous sinus (CS) invasiveness in all recurrent tumors, while none of the non-invasive adenomas recurred (p=0.042, Fisher’s exact test). The DNA content was aneuploid in 5/20 adenomas, one of which recurred. Cell percentages in the S (%SPF) and G2+M (%G2-M) phases and proliferative index (PI) (PI= %SPF + %G2-M) were significantly higher in aneuploid than in diploid adenomas (p<0.05), but no significant differences concerning all FCM parameters were observed between recurrent and non-recurrent adenomas. Similarly, MIB-1 did not show a significant difference of expression between recurrent and non-recurrent adenomas (p=0.33). Bcl-2 immunoreactivity was detected in 12/15 pituitary adenomas, involving 63±35% of tumor cells, regardless of tumor recurrence. Conclusions: In this group of radically resected pituitary macroadenomas, neuroradiological finding of CS invasiveness — but not FCM parameters nor MIB-1 and Bcl-2 expression — is useful for predicting tumor recurrence.