Bone metastases from differentiated thyroid carcinoma: current knowledge and open issues.

Bone represents the second most common site of distant metastases in differentiated thyroid cancer (DTC). The clinical course of DTC patients with bone metastases (BM) is quite heterogeneous, but generally associated with low survival rates. Skeletal-related events might be a serious complication of BM, resulting in high morbidity and impaired quality of life. To achieve disease control and symptoms relief, multimodal treatment is generally required: radioiodine therapy, local procedures-including surgery, radiotherapy and percutaneous techniques-and systemic therapies, such as kinase inhibitors and antiresorptive drugs. The management of DTC with BM is challenging: a careful evaluation and a personalized approach are essential to improve patients' outcomes. To date, prospective studies focusing on the main clinical aspects of DTC with BM are scarce; available analyses mainly include cohorts assembled over multiple decades, small samples sizes and data about BM not always separated from those regarding other distant metastases. The aim of this review is to summarize the most recent evidences and the unsolved questions regarding BM in DTC, analyzing several key issues: pathophysiology, prognostic factors, role of anatomic and functional imaging, and clinical management.

Imaging of neuroendocrine tumors of the pancreas.

Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan®) is still the most available technique. Gallium 68-SST analogue PET have been demonstrated to be more sensitive than SRS-SPEC and it will be the future of functional imaging for NET. Finally, 18FDG PET/CT is indicated for more aggressive PNET as defined either by negative SRS and huge tumor burden or ki67 above 10% or poorly differentiated PNEC tumors.

Antiangiogenic Tyrosine Kinase Inhibitors: Occurrence and Risk Factors of Hemoptysis in Refractory Thyroid Cancer.

BACKGROUND: Antiangiogenic tyrosine kinase inhibitors (TKIs) are the mainstay of advanced thyroid cancer (TC) treatment. Concern is rising about TKI-related toxicity. OBJECTIVE: To determine the incidence and to investigate the risk factors of hemoptysis in TC patients during TKI treatment. METHODS: We analyzed consecutive TC patients treated with TKI in our center between 2005 and 2013 and performed an independent review of computed tomography scan images for airway invasion assessment. Occurrence of grade 1-2 or grade 3-5 hemoptysis according to Common Terminology Criteria for Adverse Events version 4.03 and risk factors for hemoptysis were investigated. RESULTS: A total of 140 patients (89 males; median age, 52 y) with medullary (56%), differentiated (33%), and poorly differentiated (11%) TC were enrolled. Thyroidectomy±neck dissection was performed in 123 patients and neck/mediastinum external-beam radiotherapy in 41 (32% with therapeutic purpose and 68% with adjuvant purpose). Patients received from 1 to 4 lines of TKI (median 1). Median follow-up was 24 months. Airway invasion was found in 65 (46%) cases. Hemoptysis occurred in 9 patients: grade 1-2 in 7 cases (5%) and grade 3-5 in 2 (1.4%) cases (fatal in 1). Hemoptysis was associated with presence of airway invasion (P = .04), poorly differentiated pathology (P = .03), history of therapeutic external-beam radiotherapy (P = .003), and thyroidectomy without neck dissection (P = .02). CONCLUSION: Airway invasion, poorly differentiated pathology, therapeutic external-beam radiotherapy, and thyroidectomy without neck dissection are associated with and increased risk of hemoptysis in TC patients during antiangiogenic TKI treatment. Further research is needed to confirm this data and to sort out interactions between these risk factors. A careful assessment of airway invasion is mandatory before TKI introduction.

Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma.

There is no standard for second-line chemotherapy in poorly differentiated grade 3 neuroendocrine carcinoma (G3-NEC) patients. We analyzed the antitumor efficacy of 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy in this population. A single-center retrospective analysis of consecutive G3-NEC patients treated with FOLFOX chemotherapy after failure of a cisplatinum-based regimen between December 2003 and June 2012 was performed. Progression-free survival (PFS), overall survival (OS), response rate, and safety were assessed according to RECIST 1.1 and NCI.CTC v4 criteria. Twenty consecutive patients were included (seven males and 13 females; median age 55; range 23-87 years) with a performance status of 0-1 in 75% of them. Primary location was gastroenteropancreatic in 12, thoracic in four, other in two, and unknown in two patients. There were 12 (65%) large-cell and 7 (30%) small-cell G3-NEC tumors, and 1 (5%) unknown. All patients had distant metastases. Twelve (60%) patients received FOLFOX as second-line treatment and 8 (40%) as third-line treatment or later and the median number of administered cycles was 6 (range 3-14). The median follow-up was 19 months. Median PFS was 4.5 months. Among the 17 evaluable patients, five partial responses (29%), six stable diseases (35%), and six progressive diseases (35%) were observed. Median OS was 9.9 months. Main Grade 3-4 toxicities were neutropenia (35%), thrombopenia (20%), nausea/vomiting (10%), anemia (10%), and elevated liver transaminases (10%). Our results indicate that the FOLFOX regimen could be considered as a second-line option in poorly differentiated G3-NEC patients after cisplatinum-based first-line treatment but warrant further confirmation in future larger prospective studies.

Screening in asymptomatic SDHx mutation carriers: added value of ¹8F-FDG PET/CT at initial diagnosis and 1-year follow-up.

PURPOSE: Specific recommendations on screening modalities for paraganglioma (PGL) and phaeochromocytoma (PCC) in asymptomatic SDHx mutation carriers (relatives) are still lacking. We evaluated the added value of (18)F-FDG PET/CT in comparison with morphological imaging at initial diagnosis and 1 year of follow-up in this population. METHODS: The study included 30 consecutive relatives with a proven SDHx mutation who were investigated by (18)F-FDG PET/CT, gadolinium-enhanced magnetic resonance angiography of the head and neck, thoracic/abdominal/pelvic (TAP) contrast-enhanced CT and/or TAP MRI. (123)I-MIBG scintigraphy was performed in 20 subjects and somatostatin receptor scintigraphy (SRS) in 20 subjects. The gold standard was based on pathology or a composite endpoint as defined by any other positive imaging method and persistent tumour on follow-up. Images were considered as false-positive when the lesions were not detected by another imaging method or not confirmed at 1 year. RESULTS: At initial work-up, an imaging abnormality was found in eight subjects (27%). The final diagnosis was true-positive in five subjects (two with abdominal PGL, one with PCC and two with neck PGL) and false-positives in the other three subjects (detected with (18)F-FDG PET/CT in two and TAP MRI in one). At 1 year, an imaging abnormality was found in three subjects of which one was an 8-mm carotid body PGL in a patient with SDHD mutaion and two were considered false-positive. The tumour detection rate was 100% for (18)F-FDG PET/CT and conventional imaging, 80% for SRS and 60% for (123)I-MIBG scintigraphy. Overall, disease was detected in 4% of the subjects at the 1-year follow-up. CONCLUSION: (18)F-FDG PET/CT demonstrated excellent sensitivity but intermediate specificity justifying combined modality imaging in these patients. Given the slow progression of the disease, if (18)F-FDG PET/CT and MRI are normal at baseline, the second imaging work-up should be delayed and an examination that does not expose the patient to radiation should be used.

Phase I trial of everolimus in combination with thoracic radiotherapy in non-small-cell lung cancer.

BACKGROUND: This phase I study evaluated the safety and efficacy of the oral mTOR inhibitor everolimus in combination with thoracic radiotherapy followed by consolidation chemotherapy in locally advanced or oligometastatic untreated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Everolimus dose was escalated in incremental steps [sequential cohorts of three patients until the occurrence of dose-limiting toxicity (DLT)] and administered orally weekly (weekly group: dose of 10, 20 or 50 mg) or daily (daily group: 2.5, 5 or 10 mg), 1 week before, and during radiotherapy until 3.5 weeks after the end of radiotherapy. Two cycles of chemotherapy (cisplatin-navelbine) were administrated 4.5 weeks after the end of radiotherapy. RESULTS: Twenty-six patients were included in two centers, 56% had adenocarcinoma and 84% had stage III disease. In the weekly group (12 assessable patients), everolimus could be administered safely up to the maximum planned weekly dose of 50 mg; however, one patient experienced a DLT of interstitial pneumonitis at the weekly dose level of 20 mg. In the daily group (9 assessable patients): one DLT of interstitial pneumonitis with a fatal outcome was observed at the daily dose level of 2.5 mg; two other DLTs (one grade 3 esophagitis and one bilateral interstitial pneumonitis) were found at the daily dose level of 5 mg. Overall there were five patients with G3-4 interstitial pneumonitis related to treatment. Among 22 assessable patients for response, there were 9 (41%) partial response and 7 (32%) stable disease. At a median follow-up of 29 months, the 2-year overall survival and progression-free survival actuarial rates were 31% and 12%, respectively. CONCLUSION: In previously untreated and unselected NSCLC patients, the recommended phase II dose of everolimus in combination with thoracic radiotherapy is 50 mg/week. Pulmonary toxicity is of concern and should be carefully monitored to establish the potential role of mTOR inhibitor with concomitant radiotherapy. EUDRACT N: 2007-001698-27.

Ultrasensitive serum thyroglobulin measurement is useful for the follow-up of patients treated with total thyroidectomy without radioactive iodine ablation.

CONTEXT: Thyroglobulin (Tg) measurement is a major tool for the follow-up of differentiated thyroid cancer (DTC) patients; however, in patients who do not undergo radioactive iodine (RAI) ablation, normal ultrasensitive Tg levels measured under levothyroxine treatment (usTg/l-T4) are not well defined. OBJECTIVE AND DESIGN: This single-center retrospective study assessed usTg/l-T4 level in 86 consecutive patients treated with total thyroidectomy without RAI ablation for low-risk DTC (n=77) or for tumors of uncertain malignant potential (TUMP) (n=9). RESULTS: DTCS were classified as PT1, PT2, and PT3 in 75, 1, and 1 case respectively and PN0, PN1, and PNX in 40, 6, and 31 respectively. following surgery, ten patients had TG antibodieS (TGAB). Among those without TGAB, the first USTG/L-T4 determination obtained at a mean time of 9 months after surgery was 0.1NG/ML in 62% of cases, 0.3NG/ML in 82% of cases, 1NG/ML in 91%, and 2NG/ML in 96% of cases. after a median follow-up of 2.5 years (range: 0.6-7.2 years), one patient had persistent disease with an usTg/l-T4 at 11 ng/ml and an abnormal neck ultrasonography (US) and two patients had usTg/l-T4 level >2 ng/ml (3.9 and 4.9 ng/ml) with a normal neck US. Within the first 2 years following total thyroidectomy without RAI ablation, usTg/l-T4 level is ≤2 ng/ml in 96% of the cases. CONCLUSION: After total thyroidectomy, sensitive serum Tg/l-T4 level is ≤2 ng/ml in most patients and can be used for patient follow-up.

Therapeutic management of advanced adrenocortical carcinoma: what do we know in 2011?

The prognosis of advanced adrenocortical carcinoma (ACC) is dismal but heterogeneous. In 2011, mitotane is the only drug approved in Europe and US for the treatment of advanced ACC. Mitotane exerts both antisecretory and antiproliferative effects, which are delayed over time, and requires careful biological and morphological evaluations coupled with mitotane plasma measurement monitoring. In the absence of demonstration of any superior activity of combined polychemotherapy, the least toxic regimen should be considered in routine care. Locoregional therapies, including surgery of the primary tumor and metastases, should be considered part of the therapeutic arsenal. A prolonged survival can be observed in the case of tumor objective response and/or high plasma mitotane levels. New protocols are urgently needed, coupled with ancillary studies dedicated to progress in the findings of predictors or surrogates. International networks and comprehensive databases gathering clinical and biological data constitute the prerequisites for progress.

Persistent disease and recurrence in differentiated thyroid cancer patients with undetectable postoperative stimulated thyroglobulin level.

(131)I is given in differentiated thyroid cancer (DTC) without taking into account thyroglobulin (Tg) levels at the time of ablation, whereas 6-18 months later it is a major criterion for cure. This single-center retrospective study assessed the frequency and risk factors for persistent disease on postablation whole body scan (WBS) and postoperative neck ultrasonography (n-US) and for recurrent disease during the subsequent follow-up, in patients with DTC and undetectable TSH-stimulated Tg level (TSH-Tg) in the absence of Tg antibodies (TgAb) at the time of ablation. Among 1031 patients ablated, 242 (23%) consecutive patients were included. Persistent disease occurred in eight cases (3%) (seven abnormal WBS and one abnormal n-US), all with initial neck lymph node metastases (N1). N1 was a major risk factor for persistent disease. Among 203 patients with normal WBS and a follow-up over 6 months, TSH-Tg 6-18 months after ablation was undetectable in the absence of TgAb in 173 patients, undetectable with TgAb in 1 patient and equal to 1.2  ng/ml in 1 patient. n-US was normal in 152 patients and falsely positive in 3 patients. After a mean follow-up of 4 years, recurrence occurred in two cases (1%), both with aggressive histological variants. The only risk factor for recurrence was an aggressive histological variant (P = 0.03). In conclusion, undetectable postoperative TSH-Tg in the absence of TgAb at the time of ablation is frequent. In these patients, repeating TSH-Tg 6-18 months after ablation is not useful. (131)I ablation could be avoided in the absence of N1 and aggressive histological variant.

Do histological, immunohistochemical, and metabolic (radioiodine and fluorodeoxyglucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome?

The aim of this study is to search for relationships between histology, radioiodine ((131)I) uptake, fluorodeoxyglucose (FDG) uptake, and disease outcome in patients with metastatic thyroid cancer. Eighty patients with metastatic thyroid cancer (34 males, 46 females, mean age at the time of the diagnosis of metastases: 55 years) were retrospectively studied. All patients were treated with radioactive iodine and evaluated by FDG-positron emission tomography (PET). Primary tumor tissue sample was available in all cases. Forty-five patients (56%) had a papillary, 12 (15%) a follicular, and 23 (29%) a poorly differentiated thyroid cancer. Cellular atypias, necrosis, mitoses, thyroid capsule infiltration, and vascular invasion were frequently detected (70, 44, 52, 60, and 71% respectively). Metastases disclosed FDG uptake in 58 patients (72%) and (131)I uptake in 37 patients (45%). FDG uptake was the only significant prognostic factor for survival (P=0.02). The maximum standardized uptake value and the number of FDG avid lesions were also related to prognosis (P=0.03 and 0.009). Age at the time of the diagnosis of metastases (P=0.001) and the presence of necrosis (P=0.002) were independent predictive factors of FDG uptake. Radioiodine uptake was prognostic for stable disease (P=0.001) and necrosis for progressive disease at 1 year (P=0.001). Histological subtype was not correlated with in vivo tumor metabolism and prognosis. In conclusion, FDG uptake in metastatic thyroid cancer is highly prognostic for survival. Histological subtype alone does not correlate with (131)I/FDG uptake pattern and patient outcome. Well-differentiated thyroid cancer presenting histological features such as necrosis and FDG uptake on PET scan should be considered aggressive differentiated cancers.

Fluorodesoxyglucose uptake in the remaining adrenal glands during the follow-up of patients with adrenocortical carcinoma: do not consider it as malignancy.

OBJECTIVE: To make the specificity of fluorodesoxyglucose ((18)FDG) positron emission tomography (PET) precise, in the follow-up of patients with adrenal cancer. DESIGN: This single centre retrospective study assessed the frequency and outcome of (18)FDG uptake in the remaining adrenal glands after adrenalectomy for adrenocortical carcinoma (ACC) or malignant phaeochromocytoma (PH). RESULTS: Two hundred and ten (18)FDG PET scans in 62 ACC patients, all under 1,ortho-1,para'-dichloro-diphenyl-dichloro-ethane (o,p'-DDD) treatment, and 30 (18)FDG PET scans in 8 PH patients were reviewed. Abnormal (18)FDG uptake in the remaining adrenal glands was found in 19 (8%) (18)FDG PET scans, in 10 (16%) ACC patients and in none of the PH patients. (18)FDG uptake was found in 4% of the patients before the onset of o,p'-DDD, in 29% of the patients 0-6 months after the onset of o,p'-DDD (P=0.05), in 26% of the patients 6-12 months (P=0.072) after the onset of o,p'-DDD and in 14% of the patients 12-24 months after the onset of o,p'-DDD. It was never found later than 24 months after the onset of o,p'-DDD. Adrenal glands with (18)FDG uptake were normal on computed tomography scans with i.v. contrast agent in all cases. (18)FDG uptake in the remaining adrenal glands decreased and disappeared on subsequent FDG PET imaging in eight of the patients with follow-up available. CONCLUSIONS: (18)FDG uptake in the remaining adrenal glands occurred in 14-29% of the patients followed for ACC within 24 months after adrenalectomy and onset of o,p'-DDD. This uptake is transient and should not be considered as suspicious for malignancy.

Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis?

CONTEXT: Peritoneal carcinomatosis (PC) is a rare site of distant metastases in patients with adrenocortical cancer (ACC). One preliminary study suggests an increased risk of PC after laparoscopic adrenalectomy (LA) for ACC. OBJECTIVE: The objective of the study was to search for risk factors of PC including surgical approach. DESIGN: This was a retrospective cohort study conducted in an institutional practice. PATIENTS: Sixty-four consecutive patients with ACC seen at our institution between 2003 and 2009 were included. Mean tumor size was 132 mm. Patients had stage I disease in 2 cases, stage II disease in 32 cases, stage III disease in 7 cases, stage IV disease in 21 cases, and unknown stage disease in 2 cases. Surgery was open in 58 cases and laparoscopic in 6 cases. MAIN OUTCOME: The main outcome was the risk factors of PC. RESULTS: PC occurred in 18 (28%) patients. It was present at initial diagnosis in three cases and occurred during follow-up in 15 cases. The only risk factor of PC occurring during follow-up was the surgical approach with a 4-year rate of PC of 67% (95% confidence interval (CI), 30-90%) for LA and 27% (95% CI, 15-44%) for open adrenalectomy (P=0.016). Neither tumor size, stage, functional status, completeness of surgery, nor plasma level of op'DDD was associated with the occurrence of PC. CONCLUSION: We found an increased risk of PC after LA for ACC. Whether this is related to an inappropriate surgical approach or to insufficient experience in ACC surgery should be clarified by a prospective program.

Role of whole-body [18F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and conventional techniques in the staging of patients with Hodgkin and aggressive non Hodgkin lymphoma.

PURPOSE: The aim of this study was to evaluate the role of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the staging of Hodgkin's and aggressive non-Hodgkin's lymphoma (HL and NHL), comparing it with conventional diagnostic methods, i.e. contrast-enhanced CT and bone marrow biopsy. MATERIALS AND METHODS: Sixty-five consecutive patients (30 HL and 35 NHL) who underwent conventional disease staging and FDG-PET/CT were included. Concordance between conventional methods and PET was established when both procedures identified the same disease stage. Discordant findings were investigated further by using other diagnostic techniques (ultrasonography or magnetic resonance imaging) and/or clinical follow-up. RESULTS: PET correctly staged 93.8% of enrolled patients (61/65), whereas conventional techniques correctly staged 89.2% (58/65; p=NS, Chi(2) test). There was complete concordance in 54/65 patients (83.1%); among the remaining 11 cases, PET upstaged eight patients (seven true positive and one false positive), and downstaged three (all false negative). In 5/65 patients, chemotherapy treatment was modified on the basis of PET findings. CONCLUSIONS: Our data confirm the high accuracy of FDG-PET/CT in staging HL and NHL. FDG-PET/CT should therefore be used routinely in the initial evaluation of both patient subgroups.

FDG-PET in the detection of bone marrow disease in Hodgkin's disease and aggressive non-Hodgkin's lymphoma and its impact on clinical management.

AIM: Identification of bone marrow disease (BMD) is a crucial step in the diagnostic work-up of patients with lymphoma. In lymphoma staging, bone marrow biopsy (BMb) is considered as the gold standard, despite its limitations. The aim of this study was to compare the usefulness of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) vs BMb in the detection of BMD in patients with Hodgkin's disease (HL) or aggressive non-Hodgkin's lymphoma (NHL) and its impact on therapy. METHODS: A total of 194 consecutive patients with malignant lymphoma were referred for staging. The clinical stage was defined according to the Ann Arbor classification by means of contrast enhanced computed tomography (CT), BMb and whole body FDG-PET/CT scan. Sensitivity, specificity, accuracy in BMD evaluation were calculated for PET and BMb. RESULTS: FDG-PET vs BMb: sensitivity 65.3% vs 55.1%; specificity 98.6% vs 100%; accuracy 90.2% vs 88.7%; positive and negative predictive value 94.1% and 89.3% vs 100% and 86.8%, respectively. Although PET and BMb had similar sensitivity and accuracy, BMD was identified by both methods in only 10 out of 49 patients. There were no significant differences in PET and BMb accuracy between the HL and the NHL patients. Moreover, treatment regimen was changed in 12 patients on the basis of FDG-PET findings. CONCLUSION: Our study demonstrates that BMb and FDG-PET are complementary in the evaluation of BMD. FDG-PET improves the sensitivity of BMb, especially in the presence of focal BMD. Performing FDG-PET before BMb is advised for optimal biopsy site targeting.

The role of 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) in the management of patients with colorectal cancer.

AIM: In patients with colorectal cancer an accurate diagnostic work-up is mandatory in order to perform the most specific treatment. At this moment 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) is considered an accurate imaging technique in staging/restaging several malignancies. The aim of this paper is to review the scientific literature available about the role of FDG-PET in the management of patients with colorectal cancer. METHODS: An overview on Medline of scientific literature concerning FDG-PET and colorectal cancer was performed. The most relevant studies are reported. Advantages, limitations and new chances in using FDG-PET in these subsets of patients are summarized. RESULTS: FDG-PET is a useful tool in the evaluation of colorectal cancer. In comparison to conventional imaging technique, FDG-PET has an additional diagnostic value because it allows to metabolically characterize undetermined lesions suspected for recurrence of disease, to perform a complete pre-surgical staging and to identify occult metastatic disease. In clinical practice its use leads to a change in therapeutic choices in a high percentage of cases. CONCLUSIONS: FDG-PET should be considered an essential diagnostic tool in the management of patients with colorectal cancer, especially in recurrent disease evaluation.

Goiter prevalence and urinary iodine status in urban and rural/mountain areas of Piedmont region.

Piedmont region was reported in the 70s as a mild iodine-deficient area with a goiter prevalence > 10%. This study aimed at characterizing the current status of iodine deficiency in Piedmont, with special attention to putative differences between urban and rural/mountain areas. A cross-sectional, observational study was performed according to the surveillance methods for iodine deficiency disorders recommended by the World Health Organization (WHO). Ultrasound local thyroid volume reference values and median urinary iodine concentration were obtained in 2178 schoolchildren aged 11-15 yr, resident in Piedmont region for more than 5 yr to assess both goiter prevalence and iodine intake. Anamnestic and anthropometric data, thyroid volume by both bimanual palpation and ultrasound were assessed, and spot urinary iodine samples were collected. The median urinary iodine concentration was 115.8 microg/l and the prevalence of goiter 3.1%, indicating this area as iodine-sufficient. Nevertheless, 39% of the schoolchild population had urinary iodine levels < 100 microg/l and 6.8% < 50 microg/l. No differences in goiter prevalence and median urinary iodine excretion were observed between urban and rural/ mountain populations. In conclusion, Piedmont is now an iodine-sufficient region. As no programs of salt iodization have been carried out in the last 30 yr, a silent iodine replacement has occurred. Despite a sufficient median urinary iodine excretion, a program of iodine prophylaxis is strongly recommended due to a large part of iodine-deficient population.

Role of whole body positron emission tomography/computed tomography scan with 18F-fluorodeoxyglucose in patients with biopsy proven tumor metastases from unknown primary site.

AIM: The aim of this study was to evaluate the role of whole body PET/CT scan with (18)F-fluorodeoxyglucose (FDG) in the detection of the primary tumor in patients with metastatic cancer from unknown primary origin (CUP syndrome). METHODS: Sixty-eight consecutive patients, with CUP syndrome (39 lymph nodes, 29 visceral biopsy proven tumor metastases), underwent a whole-body FDG-PET/CT study. All enrolled patients were unsuccessfully studied, within the previous month, with physical examination, laboratory tests and conventional diagnostic procedures. All the pathological findings identified at PET/CT scan and suspected for primaries, were further investigated. After PET study, the minimum follow-up period for the inclusion in the studied population was 3 months. RESULTS: The primary tumor site was correctly identified by FDG-PET/CT in 24 patients (24/68, 35.3%): lung (n=9), rino/oro-pharynx (n=6), pancreas (n=5), colon (n=2), uterus (n=2). In 5 cases, FDG-PET scan did not identify a primary pathological focus, which was subsequently detected by other diagnostic methods within 3 months. In 39 patients (39/68, 57.4%), the primary tumor site was not localized. However, in 9 of them, FDG-PET/CT scan identified further unexpected metastases, modifying the stage of disease. Overall, the following oncological treatment was influenced by the PET scan, in a total of 33 patients (33/68, 48.5%). CONCLUSIONS: Our data strongly support the diagnostic contribution of whole body FDG-PET/CT scan in the evaluation of patients with CUP syndrome and suggest its use in an early phase of the diagnostic iter to optimize patient management.

Galectin-3: presurgical marker of thyroid follicular epithelial cell-derived carcinomas.

Preoperative follicular lesion characterisation represents an unsolved diagnostic problem in thyroid nodular disease. Although fine-needle aspiration biopsy is the most reliable preoperative diagnostic procedure, it shows inherent limitations in differentiating adenoma from follicular carcinoma and, sometimes, follicular variants of papillary carcinoma. Galectin-3 cytoplasmic neoexpression has been proposed as a peculiar feature of thyroid malignant cells, easily detectable in cytological and histological samples. The aim of this study was to re-evaluate the galectin-3 expression in a large sample of thyroid lesions using an immunohistocytochemical biotin-free detection system and a specific anti-human-galectin-3 monoclonal antibody in order to avoid the interference of technical factors, a cause of conflicting results recently reported by some authors. We analysed galectin-3 expression of 39 follicular carcinomas, 26 papillary carcinomas, and 105 adenomas in both cell-block samples and their histological counterparts. All cell-block and histological papillary carcinoma samples showed high levels of galectin-3 immunoreactivity. Thirty-four follicular carcinomas were positive, whereas 5 were negative in cell-blocks but positive in their histological counterparts. Twelve out of 105 adenomas expressed galectin-3 in cell-blocks and histological samples. The diagnostic accuracy of preoperative galectin-3 evaluation in adenomas vs follicular carcinomas was 90.0%. Galectin-3 expression was also investigated in 22 minimally-invasive follicular carcinomas. All of them showed galectin-3 immunoreactivity in both cytological and histological specimens with the exception of two cases, where galectin-3 positivity was observed only in the surgical material. The routine correct use of galectin-3, by increasing the diagnostic accuracy of conventional cytology, improves the management of thyroid nodules and can lead to a sensitive reduction of useless thyroid surgeries.

Thyroid volume and urinary iodine excretion in the schoolchild population of a Northwestern Italian sub-Alp metropolitan area.

Iodine deficiency is recognised as a major preventable public-health worldwide problem. The aim of this study is to assess local reference values for thyroid volume, and give a snapshot of the epidemiology of goiter and iodine nutritional status of the Turin schoolchild population. Sonographic thyroid volume and median urinary iodine excretion were obtained in 1067 schoolchildren aged 11-15 yr resident in Turin for more than 5 yr to assess both goiter prevalence and iodine intake. All the subjects were asked to fill in a questionnaire about their life habits. Anamnestic and anthropometric data, thyroid volume by both bimanual palpation and ultrasonography were assessed, and spot urinary iodine samples were collected. The results show that the median urinary iodine concentration is 113.1 microg/l and the prevalence of goiter <5%, indicating this area as iodine-sufficient. Nevertheless, 40.5% of the schoolchild population has urinary iodine levels lower than the cut-off level recommended as iodine-sufficiency. Interestingly, the high relative prevalence of ultrasound features of autoimmune thyroid disease suggests autoimmune-thyroiditis as a frequent thyroid disease in Turin schoolchildren. As no active programs of salt, milk or water iodisation have ever been carried out, a silent iodine prophylaxis has probably occurred in the city. Despite a sufficient median urinary iodine excretion, a focused program of iodine prophylaxis should be developed due to the presence of a large rate of iodine-deficient population.

Acromegaly due to ectopic secretion of GHRH by bronchial carcinoid in a patient with empty sella.

GH hyperproduction due to ectopic secretion of GHRH is a rare cause of acromegaly. Since 1959, approximately 50 cases of ectopic GHRH production from extrapituitary tumors have been described. Here we report the clinical and biochemical features of a 47-yr-old Caucasian woman with ectopic GHRH syndrome sustained by a bronchial carcinoid. The criteria for the diagnosis of acromegaly due to ectopic GHRH secretion were satisfied in our patient (i.e. confirmation of active GH hypersecretion, unequivocal demonstration of GHRH production and secretion from an extrapituitary tumor and cure of acromegaly after neoplasm removal). The tumor was an atypical carcinoid and there was a familial history of lung and colorectal cancer. Acromegaly was slightly active (mean GH value: 7.4 ng/ml, IGF-I: 436 ng/ml) and after tumor removal there was a progressive decline of GH levels, consistent with remission of pituitary somatotroph hyperplasia. Pituitary radiology showed an empty sella demonstrating for the first time its association with ectopic GHRH syndrome.