Cancer recurrence in papillary thyroid microcarcinoma: a multivariate analysis on 231 patients with a 12-year follow-up.

AIM: Papillary thyroid microcarcinoma (PMC) is considered a common disease with a good prognosis and low rate of recurrence but the extension of initial surgical treatment and the need of completion thyroidectomy are still controversial. Aim of this study is the assessment of the prognostic factors that are predictive of cancer recurrence on a large controlled series of patients with a prolonged follow-up. METHODS: A total of 231 patients with PMC were followed up for a median period of 12 years (range 5-35 years). The patients included 54 males and 177 females, with a mean age at the time of first diagnosis of 45.7±12.7 years. RESULTS: At presentation 158 patients had no metastases, whereas 73 had lymph node metastases and 1 had bone metastases. Surgery included 177 total thyroidectomies and 54 lobectomies. Eighty-four patients underwent lymph node dissection, and 131 patients were treated with radioiodine therapy. The disease recurred in 15 patients (6.5%): 5 cases of local recurrence, all of which in the contralateral lobe after lobectomy, 13 cases of lymph-node metastases, and 2 cases of lung metastases. Multivariate analysis showed that two parameters were predictive for local recurrence: age <45 years (P=0.05; RR: 6.9; 95% CI: 1.59-29.9) and evidence of lymph-node metastases at presentation (P=0.03; RR: 3.24; 95% CI: 1.17-8.55) CONCLUSION: Total or near-total thyroidectomy seems to reduce the risk of local recurrences in non-incidental PMC. Prophylactic dissection of central compartment nodes in the absence of clinically evident metastases seems not to change the risk of recurrence. In incidental PTMC without multifocality, extracapsular extension or histologically-proven lymph node metastases, lobectomy is associated with a very low risk of recurrence. Follow-up with neck ultrasonography seems advisable at yearly intervals, as recurrences may present from less than one year until several years after thyroidectomy. Radioiodine ablation of thyroid remnants should be considered only in young patients in presence of multifocal tumors, histologically-proven metastatic lymph nodes to the significantly higher risk of recurrence.

Percutaneous laser ablation of metastatic lymph nodes in the neck from papillary thyroid carcinoma: preliminary results.

CONTEXT: Percutaneous laser ablation (PLA) may be useful in treating patients with metachronous metastatic lymph nodes in the neck. OBJECTIVE: Our objective was to assess PLA as a treatment of difficult-to-treat metachronous cervical lymph node metastases from papillary thyroid carcinoma. DESIGN AND SETTING: We conducted a retrospective analysis of prospectively collected data at a public hospital. PATIENTS: Fifteen patients with previous resection of papillary thyroid carcinoma with elevated serum levels of thyroglobulin (Tg) or anti-Tg antibodies (TgAbs) and 24 metachronous nodal metastases treated between September 2010 and April 2012 were followed with [¹8F]fluorodeoxyglucose (¹8FDG) positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced ultrasound (CEUS). INTERVENTION: Intervention was PLA. OUTCOME MEASURES: Technique feasibility and technical success were evaluated. Tg/TgAb serum levels and ¹8FDG-PET/CT, and CEUS appearance were assessed at 6 and 12 months and compared with baseline. Complications were recorded. RESULTS: PLA was always feasible, and technical success was achieved in all patients. At 6 months, local control was achieved in 11 of 15 patients (73%), with 6 (40%) having serum Tg/TgAb normalized (P = .017 vs baseline). Whereas 20 of 24 (83%) nodes were negative at ¹8FDG-PET/CT and CEUS (P < .001 vs baseline), 4 were ¹8FDG-PET/CT-positive (3 also CEUS-positive). At the 12-month follow-up, local control was achieved in 10 of 14 patients (71.4%). Sixteen of 20 nodes (80%) were negative at ¹8FDG-PET/CT and CEUS (P < .001 vs baseline), 4 were ¹8FDG-PET/CT-positive (2 also CEUS-positive). Four of 10 (40%) patients had normalization of serum Tg/TgAb (P = .098 vs baseline). No major complications occurred. CONCLUSIONS: PLA is potentially feasible, safe, and effective for the treatment of metachronous cervical nodal metastases from papillary thyroid carcinoma. This procedure may reduce or delay a large number of highly invasive repeat neck dissections.

Dosimetry in the therapy of metastatic differentiated thyroid cancer administering high 131I activity: the experience of Busto Arsizio Hospital (Italy).

AIM: The purpose of the present work was to evaluate the impact of 131I high activity therapy treatments of metastatic differentiated thyroid cancer (MDTC) in terms of feasibility, tolerance, efficacy, and the impact of dosimetry in order to optimize the process. METHODS: Seventeen MDTC patients underwent 27 treatments with 131I, with activity ranging from 6.2 GBq to 24.1 GBq. Red marrow (RM) peritherapy dosimetry was based on the Standard Operating Procedure of European Association of Nuclear Medicine (EANM SOP), while metastases dosimetry on the guidelines of Italian Association of Physicists in Medicine and Italian Association of Nuclear Medicine. In 12 cases prospective dosimetry was performed too, with the purpose of evaluating the possibility of maximizing the therapeutic activity, complying the 2 Gy red marrow (RM) dose constraint. The absorbed dose to 45 lesions was evaluated. The severity of myelotoxic effects was monitored during the follow-up. RESULTS: Treatments were generally well tolerated, also at the highest RM absorbed doses. RM absorbed doses ranged from 0.49 to 6.67 Gy, lesion doses from 1.1 Gy to 778 Gy. In case of repeated treatments on the same site, in 13 cases on a total of 15, an absorbed dose reduction was observed. RM prospective and peritherapeutic dosimetry differed somewhat: absorbed doses measured during therapy ranged from -7% to +40% with respect to provisional absorbed doses. CONCLUSION: In our experience high activity treatments were well-tolerated. Prospective dosimetry needs further investigation to become sufficiently reliable in order to comply the 2 Gy constraint. Lesions became progressively less iodine-avid in case of repeated treatments, so the "first big-shoot" treatment with the highest safe activity seems to be desirable to obtain the maximum efficacy.

Anaplastic thyroid carcinoma. Practical aspects of multimodal therapy and data emerging from a 40-year experience at a single Italian institution.

Anaplastic thyroid carcinoma is a rare malignant neoplasia with high biological aggressiveness and rapid and lethal clinical course. In selected patients, an aggressive multimodal therapy could decrease illness progression both in the neck e in other sites. However, it is not clear if these combined treatments improve survival. In our institution, the Department of Nuclear Medicine has a 40-year experience in monitor and treatment of a group of 48 patient with ATC confirmation that clinical presentation could overlap pre-existent nodular goitre or rapid enlarging mass of recent onset. At onset, age do not change final poor prognosis and the survival seems most favorable in patients with a primary tumor size <6 cm. A better mean survival was noticed in those patients who respond to the multimodal therapy (8 months vs 4.6 months). Radioiodine (131 I) therapy is unnecessary due to the loss of NIS expression of the ATC cells. Therefore, after quick clinical and instrumental work up, our experience and the literature data suggest that the first line therapy is represented from external radiotherapy combined also with cisplatin or doxorubicin, followed by "curative" surgical procedure of the primary lesion in the neck and subsequent chemotherapy. For those patients who show distant metastasis at onset chemotherapy is the first line therapy followed by external radiotherapy and when possible subsequent surgical procedure.

Prevalence, clinical significance and prognostic value of anti-thyroglobulin antibodies in the follow-up of patients with differentiated thyroid carcinoma: a retrospective study.

AIM: Elevated persistent value of antithyroglobulin antibodies (Ab-Tg) in differentiated thyroid carcinoma (DTC) patients may interfere with Tg determination. The aim of the study was to evaluate the use of Ab-Tg as tumor marker as a replacement for thyroglobulin (Tg). METHODS: From 1990 al 2004 767 patients have been treated and followed, mean follow-up years 6.9+/-2.4. Thirty-two patients Ab-Tg positive after radioiodine ablation, who had showed during the follow-up stable indosable value di Tg, have undergone analysis. RESULTS: The recurrences were statistically more significant when Ab-Tg were increased, than when Ab-Tg were stable or diminished during the time (P<0.0001). Lymphocytic thyroditis was found in thirteen patients (40.6%) at histological specimen after thyroidectomy. The persistence of lymphocytic thyroditis has not modified the value of Ab-Tg as tumor marker (P<0.001). The 10/32 (31.2%) patients Tg negative have been compared to the 61/712 patients Ab-Tg positive (8.6%) who relapse. The recurrence rate was significantly higher for the first group of patients than that for the second (P<0.0001). Multivariate analisys showed N1 (P<0.001; OR 2.51) and Ab-Tg positive (P<0.001; OR: 6.15) associated with recurrences. CONCLUSIONS: Ab-Tg must be determined, in concomitance with Tg, during the follow-up of DTC, to establish the accuracy of Tg, in order to use it as tumour marker. It must be kept in mind that the strongest indication for relapse due to Ab-Tg is an increasing of level in the same patient measured in the long time. Persistent elevated Ab-Tg levels are prognostic of future recurrences.

Prospective dosimetry with 99mTc-MDP in metabolic radiotherapy of bone metastases with 153Sm-EDTMP.

PURPOSE: On the basis of the encouraging results achieved in several clinical trials and its proven therapeutic efficacy, (153)Sm-ethylene diamine tetramethylene phosphonic acid (EDTMP) has become widely used to palliate pain from bone metastases. The results reported in the literature have led the product suppliers (QUADRAMET, Schering) to suggest administering a fixed activity per kilogram (37 MBq/kg). However, considering the observed extreme inter-patient variability of skeletal uptake of (153)Sm-EDTMP, a real therapy optimization would require the individualization of the activity to be administered on a dosimetric basis. This should be planned taking into account the generally accepted 2-Gy dose constraint to the haematopoietic red marrow, the critical organ in palliative treatments with beta-emitting, bone-seeking radiopharmaceuticals. METHODS: Seven to 14 days before treatment with (153)Sm-EDTMP, 44 patients underwent (99m)Tc-methylene diphosphonate (MDP) total-body bone scan with two scans (the first within 10 min of injection, the second after 6 h). The percentage bone uptake (Tc(%)) was evaluated as the ratio between total counts at 6 h, adjusted for decay, and total counts at the first scan. Tc(%) was then compared to Sm(%) similarly derived from 10-min and 24-h whole-body scans. Tc(%) and Sm(%) were compared both with and without Brenner's method for soft tissue uptake. RESULTS: The correlation between Tc(%) and Sm(%) was R (2) = 0.81 and R (2) = 0.88 with and without soft tissue correction, respectively. The difference between their average values was statistically significant (Sm(%) = 64.3 +/- 15.2, Tc(%) = 56.2 +/- 16.0; p = 0.017) with soft tissue correction, while was not statistically significant (Sm(%) = 68.2 +/- 15.5, Tc(%) = 66.9 +/- 14.0; p = 0.670) without soft tissue correction. CONCLUSIONS: The rate of retention of (99m)Tc-MDP in bone provides a reliable estimate of the (153)Sm-EDTMP rate of retention. The proposed method can be usefully adopted for prospective dosimetry seeing its extreme simplicity, and it requires no special investment in terms of human or instrumental resources. This allows an optimization of administered (153)Sm-EDTMP activity.

Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis?

Eighty nephrotic adults with focal segmental glomerulosclerosis (FSGS) and plasma creatinine lower than 3 mg/dL were given corticosteroids (53 patients) or immunosuppressive agents (27 patients) for a median of 16 and 75 weeks, respectively. Forty-two patients responded with complete remission (29 patients, 36%) or partial remission (13 patients, 16%). Twenty-six patients who did not respond were treated again. Two patients obtained complete remission and 13 partial remission. The probability of remission was associated with treatment with corticosteroids (P = 0.0001; RR, 3. 93; 95% CI, 2.00 to 7.72), absence of arterial hypertension (P = 0. 0023; RR, 2.59; 95% CI, 1.41 to 4.79), and a percentage of hyaline glomeruli lower than 5% (P = 0.0152; RR, 2.04; 95% CI, 1.15 to 3.64). The probability of being alive at 110 months without doubling of plasma creatinine was 69%. The risk of renal insufficiency was correlated with mesangial proliferation (P = 0.0025; RR, 5.50; 95% CI, 1.82 to 16.60) and with interstitial fibrosis (P = 0.0231; RR, 4. 44; 95% CI, 1.23 to 16.08) at initial biopsy. Considering partial or complete remission as a time-dependent variable, only the lack of remission (P = 0.0027; RR, 7.23; 95% CI, 1.98 to 26.33) and mesangial proliferation (P = 0.0069; RR, 4.59; 95% CI, 1.52 to 13. 88) were correlated with renal failure. Major side effects were observed in 11 patients (5 infections, 1 peptic ulcer, 2 diabetes, 3 neoplasias). This study shows that 70% of nephrotic adults with FSGS may obtain complete or partial remission and maintain stable renal function for about 10 years when given a prolonged therapy with corticosteroids or immunosuppressive drugs.

Detection of moderate and severe coronary artery stenosis with technetium-99m tetrofosmin myocardial single-photon emission tomography.

The aim of this study was to determine the diagnostic accuracy of technetium-99m tetrofosmin myocardial imaging for the localization of coronary artery stenoses of different degrees of severity. Stress-rest single-photon emission tomography (SPET) was performed on separate days in 80 patients (64 males, 16 females; mean age 61 years; 43 patients with previous myocardial infarction; 18 patients with pharmacological stress), within 6 months of coronary angiography. Scintigraphic images were blindly and independently evaluated by three observers. Coronary stenosis was defined as a >50% narrowing in luminal diameter; severe stenosis was defined as a proximal stenosis of >75% or a peripheral stenosis of >90%. Coronary angiography revealed normal coronary arteries or insignificant coronary stenosis in 13 patients and significant coronary stenoses in 67 patients. The sensitivity and specificity of 99mTc-tetrofosmin SPET in respect of severely stenosed vessels were, respectively, 80% and 65% for the left anterior descending artery (LAD), 100% and 46% for the right coronary artery (RCA) and 58 and 78% for the left circumflex artery (LCx) territories. Considering all the significantly stenosed vessels, a significant decrease in sensitivity was observed for LAD territories (to 59%, P=0.05), and a nonsignificant decrease for RCA (88%) and LCx (47%) territories while specificity values remained essentially unchanged. No significant changes in sensitivity or specificity were observed when regions with previous myocardial infarction were excluded. In conclusion, the sensitivity of 99mTc-tetrofosmin SPET for the localization of individual stenosed vessels is only moderate when all significant stenoses are considered, but the ability of this technique to predict the location of severe coronary artery stenoses seems satisfactory, with the exception of the low specificity in respect of RCA territories.

Feasibility of a rapid method to evaluate platelet survival time.

UNLABELLED: The purpose of this study was to evaluate the feasibility of a shorter method of performing platelet kinetic studies with respect to the conventional 8-9-day approach. METHODS: We studied 41 patients (28 women, 13 men; mean age 52 yr) with primary idiopathic thombocytopenic purpura (ITP) (n = 20), secondary ITP (n = 9), HCV associated thrombocytopenia (n = 9), splenectomy (n = 1) and hairy-cell leukemia (n = 1). The patients were in a steady-state of platelet turnover. Initial platelet counts ranged from 19 to 302 x 10(9)/liter (mean value = 83). Platelet survival times (PST) were measured from the blood radioactivity disappearance curve of 111In-oxine-labeled autologus platelets following the recommendations of the International Committee for Standardization in Haematology: blood samples were taken at 30 min and 2 and 4 hr and thereafter daily for 7 days. PST was calculated by the weighted mean method and ranged from 18 to 219 hr (mean value = 98). PST was also calculated using only the data collected at 2, 48 and 96 hr. If the radioactivity in the blood at 96 hr exceeded 10% of the 2-hr value, the additional point at 168 hr was used. RESULTS: By using this reduced dataset, we obtained a correlation of r = 0.97 with the PST obtained from the whole dataset. In 24 patients, the difference was between +/- 10 hr and exceeded 1 day in only 4. CONCLUSION: About 94% of the data may be recovered with only three or four blood samples and the duration may be shortened to 4 days in a significant proportion of patients (48% of ITP patients). This approach offers the advantages of increased patient throughput, compliance and reduced examination costs.

Postoperative infections after neurosurgery and cardiosurgery: the value of labelled white blood cells.

Post surgical-infections in neurosurgery and cardiosurgery are infrequent, but potentially fatal complications. The aim of this study was to compare the utility of 99mTc-HMPAO white blood cells scintigraphy (WBCS) with traditional diagnostic approaches in post-surgical complications, in order to obtain timely demonstration of a current infection. We studied 23 patients with a suspicion of infection after major cardiosurgery or neurosurgery. Planar imaging was performed at 4 and 20 hours after injection of autologous white blood cells labelled with 99mTc-HMPAO. Eight patients underwent CT scan, but only in one case did CT findings lead to a clear definition of a bulky inflammation process of the chest. WBCS identified one or more sites of focal increased uptake of the radiopharmaceutical in 6 patients: five of these patients were scheduled for a "second look" surgical operation that confirmed the sites and extention of the primary infection, thus confirming the presence of an abscess. In 3 cases WBCS showed only a weak increase of focal uptake and in 14 cases there was no evidence of abnormal uptake. The absence of deep infections was confirmed at surgery or at clinical follow-up. Thus WBCS seems to be useful in evaluating patients with the clinical suspicion of infective complications after surgery.

A laboratory and thrombokinetic study of HCV-associated thrombocytopenia: a direct role of HCV in bone marrow exhaustion?

OBJECTIVE: In order to investigate HCV associated thrombocytopenia, 6 patients suffering from this disease, in the absence of splenomegaly and other common causes of peripheral platelet destruction, underwent laboratory and scintigraphic tests. RESULTS: Thrombokinetic studies revealed a significant, nearly linear, delayed splenic accumulation with normal or low-normal values for the average platelet life span, low-normal recovery, and depressed platelet production. Megakariopoiesis was normal or slightly increased. HCV infection of the megakariocytes was found in two patients. Autoantibodies and liver disease were also investigated. CONCLUSIONS: A role of immunological mechanisms in HCV associated thrombocytopenia appears to be ruled out. The authors conclude that tests for HCV infection should be included in the evaluation of thrombocytopenia in adults and a possible direct involvement of HCV cannot be excluded.

The clinical value of prostate-specific antigen and bone scintigraphy in the staging of patients with newly diagnosed, pathologically proven prostate cancer.

Recent reports suggest that radionuclide bone scan (BS) may not be necessary in the standard staging evaluation of patients with prostate cancer when serum prostate-specific antigen (PSA) levels are normal. To evaluate the ability of PSA to predict BS findings, we retrospectively reviewed the case records of 118 consecutive patients (median age 73 years, range 50-90 years) with newly diagnosed, untreated, pathologically proven prostate cancer who underwent BS and serum PSA sampling within a period of no more than 3 months. Fifty-four out of 118 BSs demonstrated metastatic bone disease. A PSA value of less than 10 ng/ml excluded bone metastasis; of 35 patients with a serum PSA level of 20 ng/ml or less, seven had a positive BS (negative predictive value of 80%). These findings provide additional confirmation of the value of low serum PSA concentrations in excluding the need for a staging BS, although the threshold for a high value of negative predictive accuracy is lower than previously reported.

Mescaline action on "memory decay" and "problem solving" behavior in the rat.

The modifications of behavior caused in the rat by a chronic oral administration of mescaline have been studied in three experimental situations. In the staircase maze mescaline accelerated the spontaneous decay on the conditioned reflex (memory decay) during the period without daily training. Only the results observed at 30 mg/kg/day of mescaline were statistically significant. In a T maze two lateral alleys closed by two swinging doors, 30 mg/kg/day of mescaline increased the time spent in opening the first door. When the two doors of the lateral alleys were closed with a latch, mescaline 30 mg/kg/day, caused an increase in the time spent by the rat in opening the doors. Mescaline caused an increase in food consumption. The increase at 30 mg/kg/day is statistically significant.