The role of miR-139-5p in radioiodine-resistant thyroid cancer.

PURPOSE: Radioiodine I-131 (RAI) is the therapy of choice for differentiated thyroid cancer (DTC). Between 5% and 15% of DTC patients become RAI refractory, due to the loss of expression/function of iodide metabolism components, especially the Na/I symporter (NIS). We searched for a miRNA profile associated with RAI-refractory DTC to identify novel biomarkers that could be potential targets for redifferentiation therapy. METHODS: We analyzed the expression of 754 miRNAs in 26 DTC tissues: 12 responsive (R) and 14 non-responsive (NR) to RAI therapy. We identified 15 dysregulated miRNAs: 14 were upregulated, while only one (miR-139-5p) was downregulated in NR vs. R tumors. We investigated the role of miR-139-5p in iodine uptake metabolism. We overexpressed miR-139-5p in two primary and five immortalized thyroid cancer cell lines, and we analyzed the transcript and protein levels of NIS and its activation through iodine uptake assay and subcellular protein localization. RESULTS: The finding of higher intracellular iodine levels and increased cell membrane protein localization in miR-139-5p overexpressing cells supports the role of this miRNA in the regulation of NIS function. CONCLUSIONS: Our study provides evidence of miR-139-5p involvement in iodine uptake metabolism and suggests its possible role as a therapeutic target in restoring iodine uptake in RAI-refractory DTC.

Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies.

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. METHODS: Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. OBJECTIVE: The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

Thyroid scintigraphy: an old tool is still the gold standard for an effective diagnosis of autonomously functioning thyroid nodules.

BACKGROUND: Patients with autonomously functioning thyroid nodules (AFTN) may not have an abnormal TSH value, particularly in iodine-deficient areas. AIM: To verify the accuracy of TSH as screening test in detecting AFTN and to evaluate ultrasonographic features of thyroid nodules which have resulted autonomously functioning at thyroid scintigraphy (TS). METHODS: Seventy-eight patients with nodular goiter, no marker of autoimmunity and at least one AFTN at TS were selected and divided in: Group 1 (no.=25) with TSH>0.35 IU/l, and Group 2 (no.=53) with TSH≤0.35 IU/l. RESULTS: In Group1 the mean nodule diameter was 19.8±9.4 mm; 12 nodules were isoechoic, 2 hyperechoic, and 11 hypoechoic. Vascular pattern was type I in 4, type II in 6 and type III in 15 nodules. In Group 2 the mean nodule diameter was 28.6±14.2 mm; 27 nodules were isoechoic, 9 hyperechoic and 17 hypoechoic. Vascular pattern was type I in 14, type II in 15 and type III in 24 nodules. CONCLUSION: In our study TSH alone was not able to identify AFTN in 32% of the patients. All hot nodules predominantly showed an isoechoic pattern with peri-intranodular vascularization; however, the presence of this pattern was not statistically significant. Moreover, we noticed a weak inverse correlation between the diameter of AFTN and TSH level. In conclusion, TS is the most sensitive tool to detect AFTN, allowing a precocious diagnosis even in the presence of a normal TSH value.

Application of Monte Carlo Algorithms to Cardiac Imaging Reconstruction.

Monte Carlo algorithms have a growing impact on nuclear medicine reconstruction processes. One of the main limitations of myocardial perfusion imaging (MPI) is the effective mitigation of the scattering component, which is particularly challenging in Single Photon Emission Computed Tomography (SPECT). In SPECT, no timing information can be retrieved to locate the primary source photons. Monte Carlo methods allow an event-by-event simulation of the scattering kinematics, which can be incorporated into a model of the imaging system response. This approach was adopted in the late Nineties by several authors, and recently took advantage of the increased computational power made available by high-performance CPUs and GPUs. These recent developments enable a fast image reconstruction with improved image quality, compared to deterministic approaches. Deterministic approaches are based on energy-windowing of the detector response, and on the cumulative estimate and subtraction of the scattering component. In this paper, we review the main strategies and algorithms to correct the scattering effect in SPECT and focus on Monte Carlo developments, which nowadays allow the threedimensional reconstruction of SPECT cardiac images in a few seconds.

Real-life management and outcome of thyroid carcinoma-related bone metastases: results from a nationwide multicenter experience.

PURPOSE AND PATIENTS: The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11-87) with differentiated thyroid carcinoma (DTC). RESULTS: Radio-active iodine (RAI) treatment was performed in 131 patients (91.6%), surgical approach and/or external radiotherapy in 68 patients (47.6%), and anti-resorptive bone-active drugs in 32 patients (22.4%; in 31 zoledronate and in one denosumab). At the start of treatment, 24 patients (75.0%) receiving anti-resorptive bone-active drugs had at least one clinical skeletal-related event (SRE) (p < 0.001). One or more clinical SREs (pathological fractures and/or malignant hypercalcemia and/or spinal cord compression) developed in 53 patients (37.1%). Development of SREs was significantly associated with metachronous BM (hazard ratio (HR) 2.04; p = 0.04), localization of BM to cervical spine (HR 3.89; p = 0.01), and lack of avid RAI uptake (HR 2.66; p = 0.02). Thirty-nine patients (27.3%) died in correlation with development of SREs (HR 6.97; p = 0.006) and localization of BM to the hip (HR 3.86; p = 0.02). Moreover, overall mortality was significantly decreased by RAI therapy (HR 0.10; p = 0.02), whereas no significant effects were induced by bone-active drugs (p = 0.36), external radiotherapy (p = 0.54), and surgery (p = 0.43) of BM. CONCLUSIONS: SREs are very frequent in BM from DTC and they impact patient survival. In the real life, the use of bone-active drugs is currently limited to zoledronate in patients with pre-existing SREs. In this clinical setting, RAI therapy, but not zoledronate, decreased mortality.

99mTc-sestamibi radio-guided surgery of loco-regional 131Iodine-negative recurrent thyroid cancer.

AIM: We report here our experience in a larger series of differentiated thyroid cancer (DTC) patients who had been treated by (99m)Tc-sestamibi radio-guided surgery (RGS) for (131)Iodine ((131)I)-negative loco-regional recurrent disease. METHODS: Fifty-eight patients with loco-regional (131)I-negative recurrent disease from DTC were studied with (99m)Tc-sestamibi directed RGS using a hand-held 11-mm gamma probe as an intra-operative detector. Patients were selected for RGS on the basis of (a) progressive increase of serum thyroglobulin (Tg) levels after first treatment during follow-up, (b) negative high dose (100 mCi, 3.7 GBq) (131)I whole-body scan, and (c) positive pre-operative (99m)Tc-sestamibi scintigraphy for the presence of loco-regional recurrent disease. There were 41 papillary (1 "tall" cell variant), 13 follicular and 4 Hürthle cells tumours. In 14 patients thyroid cancer recurred in the thyroid bed while cervical lymph node metastases were found in 37 patients, and 7 patients had recurrent disease both in the thyroid bed and in cervical lymph nodes. RESULTS: At bilateral neck exploration, 147 metastatic foci ranging from 4 mm to 51 mm in largest diameter (mean tumour diameter=17.3+/-9.5mm) were removed. Eighty-five of them (58%) had been pre-operatively identified at (99m)Tc-sestamibi scintigraphy. After RGS, serum Tg levels normalised in 43 of 58 patients (serum Tg<2 ng/ml--they were considered disease-free), serum Tg remained slightly increased in 12 patients without evidence of metastatic disease at scintigraphic and radiologic imaging (serum Tg<10 ng/mg--they were considered living with microscopic disease), while serum Tg significantly increased up to values>900 ng/ml in 3 patients who developed lung metastases. The mean lesion to background (99m)Tc-sestamibi uptake ratios decreased in all 58 patients (p<0.0001). Post-surgical follow-up ranged 6-72 months (mean+/-SD=29.6+/-13.5 months). The operating surgeon assessed RGS as very useful in 14 patients in whom metastatic foci were embedded in fibrotic tissues or located behind blood vessels, useful in 22 patients, moderately useful 17 patients and not useful in 5 patients. CONCLUSION: Our data suggest that a (99m)Tc-sestamibi intra-operative gamma probe can be used to identify and guide resection of recurrent loco-regional tumour in DTC patients with (131)I-negative loco-regional metastatic foci.

Evaluation of the surgical completeness after total thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND: To quantify the rate of patients without thyroid remnants, to identify predictive factors for the absence of residual thyroid tissue and to evaluate number, site, size and function of thyroid remnants after total thyroidectomy for differentiated thyroid carcinoma (DTC). METHODS: Thousand one hundred and seventy-eight patients who underwent total thyroidectomy for DTC were evaluated; 343 patients with lymph node or distant metastases and 115 patients with detectable thyroglobulin autoantibodies (TgAb) were excluded. (131)I ablative treatment (RAI) without preliminary diagnostic (131)I whole body scans (DxWBS), and 24-h (131)I quantitative neck uptake (RAIU test) and thyroglobulin (Tg) off L-T4 evaluation were performed in the remaining 720 pts. In 252 patients a 99mTc-pertechnetate pre-operative thyroid scan (99mTc-scan) was used for comparison with (131)I neck scans after RAI to evaluate site of thyroid remnants. Only patients with thyroid remnants were evaluated for successful ablation 6-10 months after RAI. RESULTS: Post-treatment whole body scan (TxWBS) demonstrated lack of thyroid remnants in 50/720 patients and the best predictive factors for the absence of residual thyroid tissue were RAIU <1% and undetectable Tg off L-T4. Thyroid remnants were present in 670/720 patients. In 252 patients with (99m)Tc-scan, 617 sites of functioning thyroid tissue were found: 381 within and 236 outside the thyroid bed. Complete successful ablation was achieved in 610/670 patients with thyroid remnants. CONCLUSIONS: This study confirms that most patients (93.1%) have thyroid remnant after total thyroidectomy for DTC. Most thyroid remnants were contralateral to tumour site and were even observed outside thyroid bed. However, a real total thyroidectomy, demonstrated by negative TxWBS, RAIU <1% and undetectable Tg off L-T4, was achieved in 6.9% of patients.

Clinical significance of focal and diffuse thyroid diseases identified by (18)F-fluorodeoxyglucose positron emission tomography.

(18)F-Fluorodeoxyglucose positron emission tomography (FDG-PET) thyroid incidentalomas are defined abnormal FDG uptake in the thyroid gland found at PET scan performed as part of a staging protocol and follow-up of patients with various kinds of malignancies. In the present study we report two cases of FDG PET thyroid incidentalomas, and review the literature with regard to the meaning of this new category of thyroid "disease". Since the advent of whole body FDG PET scan, a relatively high incidence of cases of thyroid FDG uptake has been reported as an incidental finding as in one of our patient. Focal uptake was found to be more likely associated to a malignant lesion, while a diffuse thyroid uptake to a benign thyroid disease. However, differential diagnosis is difficult, and reported data in literature are somewhat discordant. A focal thyroid uptake of FDG incidentally discovered at PET scan cannot be invariably considered a malignant thyroid nodule, however a prompt and complete work-up including laboratory examinations, ultrasonography and fine needle aspiration cytology, should be obtained to exclude a thyroid carcinoma. On the other hand, patients with a PET finding of diffuse FDG uptake can be considered at low risk of malignancy, being more likely associated to chronic thyroiditis or diffuse thyroid autonomy.

Iodine-131 radio-guided surgery in differentiated thyroid cancer: outcome on 31 patients and review of the literature.

In the present study we investigated the role of radio-guided surgery with Iodine-131 (I-131) in a group of 31 patients with differentiated thyroid cancer (DTC) and loco-regional recurrent disease. The principal inclusion criterion for I-131 radio-guided surgery in our protocol was the presence of an I-131 positive loco-regional disease relapse after previous total thyroidectomy and at least 2 ineffective conventional I-131 treatments. The protocol we used consisted of the following steps. Day 0: all patients were hospitalized and received a therapeutic 3.7 GBq (100 mCi) dose of I-131 after thyroid hormone therapy withdrawal in condition of overt hypothyroidism (serum TSH levels>30 microUI/ml). Day 3: a whole body scan following the therapeutic I-131 dose (TxWBS) administration was acquired. Day 5: neck surgery was performed through a wide bilateral neck exploration using a 15-mm collimated gamma probe, measuring the absolute intra-operative counts and calculating the lesion to background (L/B) ratio. Day 7: post-surgery TxWBS was performed using the remaining radioactivity to evaluate the completeness of tumoral lesions extirpation. The final histologic examination showed the presence of 184 metastatic foci; among them, 98 (53.2%) were evident by both TxWBS and gamma probe evaluation, 76 (41.3%) were demonstrated only by gamma probe, and 10 (5.4%) were negative by both TxWBS and gamma probe evaluation. During follow-up (8 months to 4.9 years, mean 2.8 years), DxWBS, serum Tg levels off l-T4, and US showed absence of loco-regional disease in 25 patients (80.6%) while 6 patients had persistent disease. In conclusion, this protocol allowed us to identify neoplastic foci with high sensitivity and specificity, enabling us to remove loco-regional I-131 disease recurrences resistant to previous conventional I-131 therapies. Furthermore, the gamma probe allowed detection of some additional tumoral foci in sclerotic areas or located behind vascular structures that were not visualized at the pre-surgery TxWBS evaluation.

The role of sentinel lymph node biopsy in patients with differentiated thyroid carcinoma.

AIM: To evaluate the "state of art" of clinical role of sentinel lymph node (SLN) biopsy procedure in patients affected by differentiated thyroid carcinoma. METHODS: All papers cited on PubMed/MEDLINE until June 2005, published in English, and referred to the key words "sentinel lymph node biopsy" AND "thyroid carcinoma" OR "thyroid cancer" were reviewed for the purpose of the present study. RESULTS: The first method used for SLN biopsy in thyroid carcinoma patients was the vital blue dye technique. This technique had some disadvantages as: (a) risk of disruption of the lymphatic channels deriving from the thyroid cancer; (b) difficulty in disclosing SLN lying outside the central compartment; (c) parathyroid glands can take up blue dye and, thus, can be misinterpreted as lymph nodes. Some of the above cited disadvantages were overcome by using the lymphoscintigraphy and intraoperative gamma probe technique. A combination of the blue dye and gamma probe technique has also been proposed with synergic results. CONCLUSION: The reported advantages of the SLN biopsy in small differentiated thyroid carcinoma patients can be resumed as follows: (a) better selection of patients who would benefit from compartment oriented nodal dissection; (b) more accurate lymph node staging; (c) better selection of patients who can require (131)I treatment after surgery (SLN positive for metastasis); (d) better identification of SLN located out of the central compartment.

Interaction between isoniazid and diverse vasodilators: role of decreased cerebral GABA.

OBJECTIVE: To determine if the interaction between isoniazid and hydralazine, consisting of increased hypotension accompanied by bradycardia, occurs with other vasodilators. METHODS: Blood pressure and heart rate responses to a number of vasodilators were determined in rats under chloralose-urethane, pretreated or not with 250 mg/kg of isoniazid. The influence of this dose of isoniazid on GABA levels in the hypothalamus and pons-medulla was assessed in other groups of rats. RESULTS: Increased hypotension and bradycardia following i.p. isoniazid were observed with dipyridamole, prazosin, pinacidil and hydralazine given i.v. Bradycardia without increased hypotension appeared with papaverine and verapamil, while increased hypotension with unchanged heart rate was observed with minoxidil and captopril. Isoniazid decreased GABA in the hypothalamus and pons-medulla. CONCLUSIONS: At the high dose used, isoniazid interacts with various vasodilators, irrespective of their mechanism of action. The interaction could be due to the influence of the drug on GABA levels at cardiovascular regulatory sites.

Disseminated bone marrow metastases of insular thyroid carcinoma detected by radioiodine whole-body scintigraphy.

We present 131I scintigraphic findings in a patient with insular carcinoma of the thyroid showing diffuse abnormal uptake throughout the skeleton. The scintigraphy closely resembled the pattern of [131I]MIBG distribution in children with bone marrow metastases of neuroblastoma. The extent of involvement was underestimated by bone scintigraphy and radiography. Insular carcinoma of the thyroid in the bone marrow was subsequently demonstrated by biopsy. The patient was treated with 242 mCi 131I given in two courses, which led to severe myelosuppression and died as a result of progressive disease and severe pancytopenia 10 mo after initial therapy.

Severe thyrotoxicosis due to functioning pulmonary metastases of well-differentiated thyroid cancer.

We report two cases of thyrotoxicosis resulting from hyperfunctioning lung metastases from differentiated thyroid cancer. In both patients, a simultaneous diagnosis of thyrotoxicosis and metastatic thyroid cancer was made, based on thyroid function tests as well as 131I whole-body scans showing low thyroid uptake of radioiodine and multiple foci of intense 131I uptake in the lungs. After total thyroidectomy (performed in Patient 2 only) and 131I therapy (cumulative dose of 12.3 GBq in Patient 1 and 9.6 GBq in Patient 2), there was a rapid clinical improvement with significant reduction of the pulmonary metastatic disease in both patients: Patient 1 became euthyroid, while Patient 2 became hypothyroid. Analysis of the 54 cases reported in the literature, including the 2 cases described here, shows this to be a very rare cause of thyrotoxicosis and one that can pose serious problems for both the diagnostic evaluation and choice of therapeutic strategy when compared with the much more common nonhyperfunctioning metastases from thyroid cancer. Lesser degrees of thyroid hormone secretion by differentiated thyroid cancer may be detected and exploited diagnostically by the chromatographic analysis of serum for endogenously labeled thyroid hormones after 131I administration.

Assessment of tricuspid regurgitation by pulsed Doppler ultrasonography of the hepatic veins.

Pulsed Doppler echocardiography was tested to assess the degree of tricuspid regurgitation (TR), classified by right ventriculography, in 47 patients. Forty-eight subjects without TR served as controls (39 with sinus rhythm and 9 with atrial fibrillation). Two Doppler methods were used: the distance of systolic turbulence within right atrium from the tricuspid plane and the quantitative analysis of the flow-velocity traces from the hepatic veins (HVs). Right atrial systolic turbulence was found in 41 of 47 patients with TR and in none of the control subjects, and moderately correlated with the angiographic grading (r = 0.57). In control subjects, TR flow-velocity traces from the HVs showed 2 anterograde flow waves, systolic and diastolic. The ratio of anterograde systolic/anterograde diastolic velocity was more than 0.6 in 38 subjects with sinus rhythm and in 8 with atrial fibrillation. Twenty-two control subjects had a positive wave (designated as "v") coincident with the end of T wave. In 30 patients with TR, a retrograde holosystolic wave was present. Of the remaining patients, 12 had a ratio of anterograde systolic/anterograde diastolic velocity less than 0.6. Fifteen had an end-systolic "v-like" wave, which occurred earlier than the v wave in control subjects (p less than 0.001). In patients with TR, maximal velocities of the anterograde diastolic and retrograde systolic flow correlated with angiographic grading (r = 0.74 and 0.73, respectively). An anterograde diastolic flow velocity more than 26 cm/s and a retrograde systolic flow velocity more than 16 cm/s excluded mild TR. Analysis of Doppler recordings of the HVs is valuable to semiquantitatively assess TR, complementing the right atrial Doppler findings.

Comparison of steerable continuous-wave versus pulsed-wave Doppler ultrasonography to renal artery angiography in diagnosing renal artery stenosis.

Pulsed-wave Doppler ultrasonography is widely used to noninvasively diagnose renal artery stenosis. The use of steerable continuous-wave Doppler has never been tested. We compared pulsed and steerable continuous-wave Doppler ultrasonography, demonstrating that although both methods are highly sensitive for severe stenoses, continuous-wave Doppler shows a better sensitivity for mild to moderate stenoses.

Steroid-protein interaction in human placenta.

Human placenta produces a large variety of bioactive substances with endocrine and neural competence: pituitary and gonadal hormones, hypothalamic-like releasing or inhibiting hormones, growth factors, cytokines and neuropeptides. The most recent findings indicate that locally produced hormones regulate the secretion of other placental hormones supporting a paracrine/autocrine regulation. In placental endocrinology, a particular relevance is played by steroid hormones. In fact, a specific gonadotropin-releasing hormone (GnRH)-human chorionic gonadotropin (hCG) regulation of placental steroidogenesis has been proposed as a placental internal regulatory system acting on steroids production from human placenta. In addition, activin and inhibin have been proposed as further regulatory substances of the synthesis and secretion of steroids; the addition of activin A to placental culture augments GnRH, hCG and progesterone, and this effect can be significantly reduced by the addition of inhibins. Finally, a steroid-steroid interaction is suggested by the evidence that placental estrogen has a positive role in the regulation of progesterone biosynthesis. Other steroid-protein interactions have been observed in human placenta. In fact, recent data indicate that progesterone inhibits placental corticotropin-releasing factor (CRF) and estrogens act on placental conversion of cortisol to cortisone, activating cortisol secretion by the fetal adrenal and enhancing fetal adrenal function with advancing gestation.

Successful induction of ovulation using highly purified follicle-stimulating hormone in a woman with Kallmann's syndrome.

OBJECTIVE: To describe a woman with Kallmann's syndrome who was treated successfully with highly purified FSH to achieve ovulation induction and pregnancy. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 32-year-old woman with Kallmann's syndrome who had been treated with oral contraceptives to prime secondary sex characteristics and genital organs since the age of 16 years. INTERVENTION(S): Highly purified FSH was administered intramuscularly for a total dose of 3,825 IU. MAIN OUTCOME MEASURE(S): Follicle number and diameter. RESULT(S): Three follicles with a diameter of > 1.7 cm and an endometrial thickness of 8 mm were observed. A clinical pregnancy, which subsequently was spontaneously aborted, was obtained. CONCLUSION(S): In primed patients with Kallmann's syndrome, highly purified FSH may be a useful alternative to pulsatile GnRH or menopausal gonadotropins to achieve ovulation induction and pregnancy.

Video-assisted thyroidectomy for papillary thyroid carcinoma.

BACKGROUND: In patients with small papillary thyroid carcinomas (PTC), we evaluated the operative feasibility and safety of video-assisted thyroidectomy (VAT) and the completeness of the surgical resection. METHODS: Video-assisted thyroidectomy was attempted in 24 patients with thyroid malignancy. Total thyroid resection for PTC was achieved completely by VAT in 20 of them, who were included in this study. RESULTS: In this study, 12 total thyroidectomies and 8 lobectomies followed by completion thyroidectomies were performed. Eight patients also underwent central neck lymph node dissection. Mean postoperative serum thyroglobulin was 0.2 ng/ml for patients receiving LT4 suppressive treatment and 4.2 ng/ml for patients after LT4 withdrawal. Postoperative ultrasonography showed no residual thyroid tissue. The mean radioiodine uptake at postoperative scintiscan was 2.2%. CONCLUSIONS: In the case of PTC, VAT is feasible and safe. The completeness of the surgical resection seems comparable with that reported for conventional surgery. Nevertheless, larger series and longer follow-up evaluation are necessary for definitive conclusions to be drawn about its oncologic validity.

The diagnostic application of radiocolloid liver scintigraphy in breast carcinoma.

The authors have reviewed their experiences in determining the presence of liver metastases in 103 patients by radiocolloid scanning. The sensitivity of liver scanning proved to be quite low if the presence of focal defects in the distribution of the tracer was chosen as the diagnostic criterion. The inclusion of less restrictive criteria such as liver enlargement or irregular distribution of the tracer, resulted in a higher sensitivity without lowering the predictive value of a negative scan. Using the latter diagnostic criterion, sensitivity, specificity and accuracy were in the range of 90%. Abnormal liver scans are common in patients classified at T3-T4 or N+ and their chances of being "true positive" are high. Conversely, abnormal scans are seldom found in patients classified at T1-T2 or N0 and probabilities of "false positive" results are high.