Useful assessment of myocardial viability and dyssynchrony from gated perfusion scintigraphy for better qualification for resynchronization therapy. Part 3.

The first part of the review concerning myocardial imaging by single photon emission computed tomography (SPECT) discussed the basic aspects of interpretation of left ventricular perfusion disorders in stress and rest examination. The second part presented the interpretation of gated SPECT imaging in relation to the assessment of systolic and diastolic left ventricular functions. The third part concerns the assessment of myocardial viability and phase analysis from gated SPECT in the qualification of patients with left ventricular systolic dysfunction for cardiac resynchronization therapy.

Postoperative Radioiodine Treatment within 9 Months from Diagnosis Significantly Reduces the Risk of Relapse in Low-Risk Differentiated Thyroid Carcinoma.

PURPOSE: Although postoperative radioiodine (RAI) therapy has been used in patients with differentiated thyroid carcinoma (DTC) for many years, there is still lack of data defining the timing of RAI administration. A retrospective analysis was carried out to answer the question whether the time of postoperative RAI treatment demonstrated any impact on long-term outcomes, particularly in low-risk DTC. MATERIAL: The analyzed group involved 701 DTC patients staged pT1b-T4N0-N1M0, who underwent total thyroidectomy and postoperative RAI therapy. According to the time interval between DTC diagnosis and RAI administration, patients were allocated to one of three groups: up to 9 months (N = 150), between 9 and 24 months (N = 323), and > 24 months (N = 228). Median follow-up was 12.1 years (1.5-15.2). RESULTS: Based on an initial DTC advancement and postoperative stimulated thyroglobulin concentration patients were stratified as a low-, intermediate-, and high-risk group. Low-risk patients, who received RAI therapy up to 9 months, demonstrated significantly lower risk of relapse comparing to those, in whom RAI was administered between 9 and 24 months and after 24 months since DTC diagnosis: 0%, 5.5%, and 7.1%, respectively. Regarding intermediate- and high-risk groups, the differences in the timing of postoperative RAI treatment were not significant. CONCLUSION: If postoperative RAI treatment is considered in low-risk DTC, any delay in RAI administration above 9 months since diagnosis may be related to poorer long-term outcomes.

The role of postoperative adjuvant radiotherapy in the local control in medullary thyroid carcinoma.

BACKGROUND: The value of postoperative radiotherapy in the treatment of medullary thyroid carcinoma (MTC) has not been unequivocally demonstrated. Therefore our study aimed to answer the question of whether adjuvant radiotherapy showed any impact on the risk of local recurrence and whether there were any differences in response to radiotherapy between hereditary and sporadic MTC. METHODS: A retrospective analysis involved 254 MTC patients, among them 73 patients with a hereditary disease. Two hundred and twenty-four patients, including 43 persons at high risk of local relapse, underwent only initial surgery, 18 other patients were operated due to MTC recurrences, whereas the remaining 12 patients had cytoreductive procedure or were not amenable for surgery. Radiotherapy was carried out in 132 patients. One hundred and twenty patients underwent adjuvant radiotherapy, among them 102 patients after initial surgery. The median follow up was 10 years (range 0.5-29 years). RESULTS: Local recurrence occurred in 107/254 patients, among them in 63 subjects after prior radiotherapy. The frequency of relapse showed significant, increasing trend toward higher MTC stages (p<0.001). More relapses were noticed in patients with lymph node metastases at diagnosis. Adjuvant radiotherapy was associated with a lower risk of nodal recurrence only in high-risk patients, particularly if lymph node metastases were present at MTC diagnosis. The differences between hereditary and sporadic subgroups were not significant. CONCLUSIONS: Adjuvant radiotherapy has a limited importance in MTC treatment. It should be considered in high-risk MTC patients. The presence of RET mutation does not influence the response to radiation.

Myocardial perfusion scintigraphy - interpretation of gated imaging. Part 2.

The first part of the review describes the basic aspects of interpreting myocardial perfusion defects in single photon emission computed tomography (SPECT) scintigraphy. It also presents indications for invasive diagnostics based on stress perfusion defects. This article provides basic information concerning the interpretation of gated SPECT imaging, including such parameters as left ventricular wall motion and thickening as well as left ventricular wall systolic and diastolic function. Gated examination combined with the assessment of myocardial perfusion reduces the rate of false positives results of myocardial perfusion scintigraphy in perfusion tests, additionally providing data on left ventricular systolic and diastolic function.

Interpreting myocardial perfusion scintigraphy using single-photon emission computed tomography. Part 1.

This article discusses the protocol for myocardial perfusion scintigraphy performed with single-photon emission computed tomography (SPECT). Indications for SPECT are listed with consideration given to the results of the increasingly more common angio-CT examinations of the coronary arteries (multislice computed tomography). The paper also presents basic information about interpreting the results, including the scores of left ventricle myocardial perfusion using the 17-segment polar map, and explains the concept of total perfusion deficit.

Ongoing risk stratification for differentiated thyroid cancer (DTC) - stimulated serum thyroglobulin (Tg) before radioiodine (RAI) ablation, the most potent risk factor of cancer recurrence in M0 patients.

INTRODUCTION: Adequate postoperative risk assessment currently constitutes the principle of DTC treatment and further management. The aim of the study - a retrospective assessment of risk factors influencing DTC relapse. MATERIAL AND METHODS: The study group consisted of 510 DTC staged pT1b-T4N0-N1M0, in whom total thyroidectomy and complementary radioiodine (RAI) treatment were carried out. In 71% papillary thyroid cancer was diagnosed, whereas in the remaining 29% - follicular thyroid carcinoma. Based on TNM classification from 1997, T1 feature was diagnosed in 11.6%, T2 in 35.1%, T3 in 8.4%, T4 in 9,4%, while in 35.5% - Tx. Lymph node metastases were present in 24.7% of cases. Median follow-up was 12.1 years (1.5-15.2). RESULTS: Age at DTC diagnosis, tumour diameter (T), lymph node metastases (N1), stimulated thyroglobulin, and RAI uptake in thyroid bed at qualification for RAI ablation significantly influenced freedom from progression time (FFP) in a multivariate analysis. When postoperative stimulated Tg was > 30 ng/mL the risk of relapse increased nearly six-fold, whereas the presence of N1 feature - four-fold. The total risk of relapse in the whole group was 12.55% while median FFP was 154.8 months. Five-year and 10-year FFP was 90.1% and 87.5%, respectively. CONCLUSIONS: Postoperative stimulated thyroglobulin level was the most potent, independent risk factor influencing FFP in DTC patients. Age above 60 years, an initial DTC stage (T and N features), and low RAI uptake in thyroid bed ( < 1%) were related to a higher risk of DTC relapse, whereas the investigated histopathological features were insignificant.

[Radiosynovectomy of the knee--experience thereof]. / Radiosynowektomia stawu kolanowego --doswiadczenia wlasne.

The aim of the study was the evaluation of 90Y radiosynovectomy performed in chronic exudative knee synovitis. The analyzed material comprised 81 90Y injections made between 2004 and 2008. The circumference of a knee, the volume of removed exudate, the knee mobility, the presence of pain, the temperature of a knee and the presence of floating patella (exudate) were evaluated. The percentage of pain-free patients increased from 12% to 50% after 1 year; an additional 10% of patients reported pain relief. The patient percentage with an increased knee temperature fell from 42% to 31% and the patients percentage with exudates decreased from 76% to 27. No improvement was found with respect to knee circumference. The knee mobility improvement (the patients percentage with full mobility) increased from 25% to 59% one month after the treatment) and exudate volume reduction was found only in the subgroup of patients suffering from pigmented villonodular synovitis. The obtained results permit the conclusion that 90Y radiosynovectomy for chronic exudative knee synovitis is an effective treatment modality; it relieves pain and reduces the patients percentage with exudate and increased knee temperature, and in the subgroup of patients suffering from the pigmented villonodular synovitis improves the knee mobility and reduces the volume of evacuated exudate.

Metal-proteinase ADAM12, kinesin 14 and checkpoint suppressor 1 as new molecular markers of laryngeal carcinoma.

The assessment of gene expression profile in laryngeal cancer allows implementation of molecular biology methods in diagnostics, as well as in prognosticating the course of disease, thus allowing taking most optimal decisions as regards the method of treatment, scope of surgical procedure, or the necessity of adding complementary radiotherapy. The aim of the project was to analyze the gene expression profile in laryngeal cancer using oligonucleotide microarrays, having in mind searching new molecular markers for that carcinoma. The study comprised a group of 43 patients (38 males and 5 females) suffering from squamous cell laryngeal carcinoma, diagnosed and surgically treated in the years 2005-2007 in the ENT Department of the Silesian Medical University in Katowice, Poland. RNA was isolated from frozen tissue fragments, with the use of columns RNeasy Midi and Mini Kit (Qiagen). For the examination of gene expression profile, oligonucleotide microarrays of high density were used, provided by Affymetrix (U 133 2.0 PLUS) containing over 54,000 probes for over 47,000 transcripts. Four genes previously not examined in that respect in laryngeal carcinoma, occurred to be good markers of the neoplasm. They are: metal-proteinase ADAM12, cyclin-dependent kinase 2-CDK2, kinesin 14-KIF14, suppressor 1 of checkpoint-CHES1. The analysis of gene expression profile allows, in laryngeal carcinoma, to point out to new genes, which in future may become molecular markers of the carcinoma.

Total thyroidectomy and adjuvant radioiodine treatment independently decrease locoregional recurrence risk in childhood and adolescent differentiated thyroid cancer.

UNLABELLED: We sought to assess whether extensive surgical treatment, postsurgical radioiodine therapy, or both decrease the risk of locoregional recurrence (LR) after curative primary treatment in children and adolescents diagnosed with differentiated thyroid cancer (DTC) at age

[Effectiveness evaluation of knee joint 90Y radiosynovectomy]. / Ocena skutecznosci radiosynowektomii stawu kolanowego przy uzyciu 90Y.

INTRODUCTION: Chronic knee synovitis with effusion, because of the special role of knee joint is an important therapeutic problem. This leads to searching for new treatment modalities. One of them is radiosynovectomy based on anti-proliferative and anti-inflammatory activity of ionizing radiation. It is made using 90Y mainly (high energy of beta [electrons] radiation [2.2 MeV], large average penetration in soft tissues [3.6 mm] and long physical half-life [2.7 days]). MATERIAL AND METHOD: Analyzed material is comprised of 30 patients (33 treatments) suffering from proliferative synovitis of knee joint treated by radiosynovectomy using intra-articular injection of 6 mCi 90Y. In 20 cases the reason of disease was non-specific reactive arthritis, in 5 rheumatoid arthritis, in 3 villonodular synovitis, in 3 psoriasis and in 2 ulcerative colitis. Symptoms duration varied from 3 to 144 months (mean 43). A knee circumference at the treatment day varied from 33.5 cm to 49 cm (mean 41). The operation was based on knee biopsy, evacuation of exudate and delivery of 6 mCi of colloid 90Y. Follow up ranged up to 14 months (mean 4.4). Patients were examined 2 weeks, 1, 3, 6 and 12 months after treatment. During examination a knee circumference was measured, a knee mobility, temperature and patella floating symptom were examined. Pain in treated region was assessed and amount of exudate was measured. RESULTS: A knee circumference and exudate amount enlarged during following controls, and compared between the treatment day and the last control did not differ significantly (41 vs. 41.6 cm and 43 vs. 42.5 ml respectively) but number of biopsies decreased. A percentage of patients with impaired knee mobility also did not change (59% vs. 58%). Probably, it was caused by resignation from control examination when symptoms disappeared. A percentage of patients without pain relief decreased from 43.5% 2 weeks after treatment to 20% one year later and a patient percentage with complete pain relief increased from 8.5% to 60%. A patient percentage with increased knee temperature and with floating patella decreased significantly (54 vs. 25% and 83 vs. 48% respectively). CONCLUSIONS: Obtained results do not allow to form univocal conclusions regarding effectiveness of 90Y radiosynovectomy. The decreasing biopsies number, decreasing percentage of patient with increased knee temperature and with floating patella; increased percentage of patients with analgetic effect and with total pain relief show a necessity of renewed evaluation of this treatment modality on the base of bigger patients number and longer and more precise observation.

[Optimization of 131I ablation in patients with differentiated thyroid carcinoma: comparison of early outcomes of treatment with 100 mCi versus 60 mCi]. / Optymalizacja leczenia uzupelniajacego jodem promieniotwórczym u chorych na zróznicowanego raka tarczycy: porownanie wczesnych wynikow leczenia aktywnoscia 100 i mCi 60 mCi.

INTRODUCTION: The aim of this study was to compare the early outcomes between two groups of patients with differentiated thyroid carcinoma (DTC) who received 60 or 100 mCi of (131)I for remnant ablation. MATERIAL AND METHODS: 224 DTC patients with primary tumor > 1 cm of diameter or multifocal were randomised into prospective clinical trial. Patients with extrathyroideal extension of primary tumor and nodal metastases or M1 were not enrolled. 99 patients received 60 mCi, and 125--100 mCi of radioiodine as the first ablative dose. RESULTS: The effectiveness of thyroid ablation was evaluated after one year, during endogenous TSH (thyroid stimulating hormone) stimulation, and after two years during Lthyroxine therapy. Whole body scintigraphy (WBS) was performed under thyroxine withdrawal and thyroglobulin serum level was assessed. Distant micrometastases were detected in 9.8% of patients by post-therapy WBS, 11 patients in group A treated with 60 mCi and 11 in group B treated with 100 mCi. In other patients no symptoms of persistent disease were detected. At one year follow up full remission was diagnosed in 176 patients: 76 in group A and 100 in group B. The remaining ones, 13.3% and 11.2% respectively, received the second course of (131)I for remnant ablation. There were no statistically significant differences in Tg (thyroglobulin) serum level either 12 or 24 months after 131I treatment. CONCLUSIONS: Our evaluation of early efficacy of adjuvant radioiodine treatment in low risk DTC patients shows no differences between two radioiodine activities - 60 and 100 mCi in relation to thyroid ablation. Thus, the activity of 60 mCi is recommended.

[Medullary thyroid carcinoma: the comparison of the hereditary and sporadic types of cancer]. / Rak rdzeniasty tarczycy: porównanie postaci dziedzicznej i sporadycznej.

INTRODUCTION: The assessment of frequency and type of mutation and differences in prognosis between sporadic and hereditary type of medullary thyroid carcinoma (MTC), based on own DNA analysis, was performed. MATERIAL AND METHODS: The group of 190 persons with hereditary MTC or asymptomatic mutation carriers was analyzed. Patients with sporadic MTC without RET gene mutation were included into control group (708 persons). The recognition of MTC type was based on assessment of family history, physical examination and genetic analysis. The family history consisted of information about MTC, pheochromocytoma and other neoplasms and hyperparathyroidism in relatives. RESULTS: The mutations located in codon 634 of exon 11 were the most often (43% of all mutations and 49% of mutations in syndrome MEN 2A/FMTC). The age of diagnosis was ranged between 7 and 71 years (mean age: 39 +/- 15.2 years, median age: 41 years). In hereditary MTC the mean age of diagnosis was 27 +/- 13.9 years and was significantly lower than in sporadic one, where it was 45.7 +/- 14.3 years. The relationship between diagnosis, age and subtypes of hereditary MTC was assessed--no significant differences in examined subgroups were observed. The mean age of diagnosis in MEN 2A/FMTC and MEN 2A syndrome was 28-29 years, in MEN 2B - 21 years. The overall survival in sporadic MTC after 5 years was 97%, in hereditary MTC - 79%. Analysis performed after excluding suprarenal causes of death revealed no statistically significant differences in overall survival between both subtypes of MTC. CONCLUSIONS: 1. Hereditary MTC is still diagnosed too late, besides of DNA analysis. 2. In hereditary and sporadic MTC the prognosis is comparable.

Use of monoclonal anti-EGFR antibody in the radioimmunotherapy of malignant gliomas in the context of EGFR expression in grade III and IV tumors.

We investigated the putative benefits of simultaneous teleradiotherapy and anti-epidermal growth factor receptor (EGFR) 125I monoclonal antibody (MAb) 425 radioimmunotherapy, when applied after neurosurgery in high-grade gliomas, over teleradiotherapy alone. In comparison to previous studies which have reported good results with this type of radioimmunotherapy, we advanced the adjuvant radioimmunotherapy step, that is, gave it during, not after, teleradiotherapy. The randomized prospective study examined two groups: simultaneous postoperative teleradiotherapy and radioimmunotherapy (TRT + RIT; eight patients) versus teleradiotherapy alone (TRT; 10 patients). Patients who after primary operation of grade III (6 cases) or IV glioma (12 cases), showed no or less than 2 mL of remnant tumor on post-operative magnetic resonance (MR) study and were not treated postoperatively by chemotherapy were enrolled and randomized. Anti-EGFR 125IMAb 425 RIT was started during week 4 of radiotherapy, not later than 8 weeks after neurosurgery, and was repeated three times at 1-week intervals. Total activity given was 5026 + 739 MBq/patient. The tolerance of TRT was good. No immediate side effects of concomitant anti-EGRF 125I RIT were observed. Observation showed a median total survival (as evaluated from the primary neurosurgical treatment) of 14 months (range 3.5-28 months). There was no improvement in disease-free or total survival in the group of patients treated by TRT + RIT after neurosurgery. In addition, an immunohistochemical analysis of EGFR expression in gliomas was performed in a group of 100 cases and was distinctly positive in 50% grade IV gliomas and 68% grade III gliomas. We conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR 125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of high-grade gliomas after neurosurgery. We also recommend individual confirmation of EGFR expression in further anti-EGFR radioimmunotherapy trials.

[Gene expression analysis by DNA microarray in papillary thyroid cancer]. / Analiza ekspresji wybranych genów w raku brodawkowatym tarczycy technika mikromacierzy DNA.

In our study we present chosen elements of microarray analysis of gene expression profile in papillary thyroid cancer. The study group included 16 papillary thyroid cancer tissues and 16 corresponding normal tissues. Samples were analyzed on high density oligonucleotide microarrays (GeneChip HG-U133A) which contain 22.000 genes. 110 genes, which had significant changed expression, were selected by MAS 5.0 program. 3 genes were chosen to the deeper analysis: dipeptidylpeptidase 4 (DPP4), fibronectin 1 (FN1), tissue inhibitor of metalloproteinase 1 (TIMP1). DPP4-RNA were absent in normal tissue while in cancer tissue it was detected in large amount. FN1 and TIMP1 expression were detected in normal tissue but markedly increased in papillary thyroid cancer. Among these 3 genes DPP4 seems to be the best molecular marker for papillary thyroid cancer.

RET polymorphisms in codons 769 and 836 are not associated with predisposition to medullary thyroid carcinoma.

The study was undertaken to verify whether the RET gene polymorphisms are associated with MTC in patients negative for germline mutations. Two hundred five patients with apparent sporadic MTC were subjected to genetic analysis of RET exons 10, 11, 13, 14, 16 and 22 RET germline mutation carriers were identified with 10.7% frequency. The frequency among 26 patients not older than 30 was 27%. In patients excluded for known mutations we analyzed two polymorphic sites: RET codon 769 and 836. As control group, 90 healthy subjects were investigated. In young patients the observed allelic frequencies were 32% for variant L769/CTG and 5% for variant S836/AGT. Although these values were higher than in older MTC patients (22 and 3%, respectively), as well as in the control group (27 and 2%) the difference was insignificant. We conclude that in Polish patients polymorphisms at RET codons 769 and 836 are not associated with medullary thyroid carcinoma.

Recombinant human TSH-aided radioiodine treatment of advanced differentiated thyroid carcinoma: a single-centre study of 54 patients.

We sought to evaluate the efficacy, biochemical effects, safety and outcome of recombinant human thyroid-stimulating hormone (rhTSH) as an adjunct to radioiodine treatment of advanced differentiated thyroid carcinoma (DTC). We also sought to determine whether rhTSH is useful as an adjunct to radioiodine treatment following isotretinoin re-differentiation therapy of DTC metastases that have lost function. Therefore, in 54 consecutive patients who had retained bulky metastatic and/or locoregional lesions of DTC despite the exhaustion of other therapeutic options, we gave one to four courses of two consecutive daily intramuscular injections of rhTSH, 0.9 mg, followed by a therapeutic activity of (131)I per os on day 3. Fifty patients had received prior radioiodine treatment aided by l-thyroxine (T(4)) withdrawal. We included in the study 23 patients who had received a trial of isotretinoin therapy for re-differentiation of confirmed de-differentiated metastases. In a blinded, within-patient comparison of post-therapy whole-body scans after the first rhTSH-aided and latest withdrawal-aided treatments in patients with functional metastases at baseline, 18 of 27 (67%) scan pairs were concordant, four (15%) were discordant in favour of the rhTSH-aided scan and five (19%) were discordant in favour of the withdrawal-aided scan. In total, 37 (74%) of 50 paired scans were concordant, eight (16%) favoured rhTSH and five (10%) favoured withdrawal. All differences appeared to be attributable to clinical causes, not to any difference between endogenous and exogenous TSH stimulation. Reflecting the biochemical activity of rhTSH and the release of thyroglobulin (Tg) due to tumour destruction, median serum Tg concentration rose approximately fourfold between baseline and day 6 of the rhTSH-aided treatment course. rhTSH was well tolerated, with mostly minor, transient toxicity, except for neck oedema in three patients with neck infiltrates and pathological spine fracture in one patient with a large vertebral metastasis. At 6 months, complete response occurred in one (2%), partial response in 12 (26%) and disease stabilisation in 19 (40%) of 47 evaluable patients. The rate of complete + partial response was 41% and that of disease stabilisation, 30%, in the 27 evaluable patients with functional metastases at baseline; the corresponding rates were 10% and 55% in the 20 evaluable patients with non-functional metastases at baseline. Although within-patient comparison of early outcome after both modalities is limited by a significantly greater median number of courses and a greater median cumulative activity of radioiodine given under withdrawal, response to rhTSH-aided and withdrawal-aided treatment was similar in 23 (52%) of 44 evaluable patients, superior with rhTSH in 12 (27%) and superior with withdrawal in seven (16%). In two patients, a superior response was obtained after isotretinoin pretreatment and rhTSH and attributed to re-differentiation therapy. In conclusion, our study provides preliminary evidence that rhTSH safely and effectively aids radioiodine treatment of advanced DTC, and does so to an at least equivalent degree as does T(4) withdrawal.

Simultaneous radiotherapy and radioimmunotherapy of malignant gliomas with anti-EGFR antibody labelled with iodine 125. Preliminary results.

BACKGROUND: In this paper we present the preliminary results of a prospective trial of the efficacy of simultaneous radiotherapy and anti-EGFR (125)I radioimmunotherapy of malignant gliomas with 2 years' total survival as the end-point, raising the question whether anti-EGFR (125)I radioimmunotherapy influences the disease-free survival in these patients. MATERIAL AND METHODS: Patients with anaplastic astrocytoma or primary glioblastoma were previously treated by a macroscopically radical neurosurgical approach and randomized either to radiotherapy + radioimmunotherapy arm or treated by radiotherapy alone. Seven patients were included in the group with radioimmunotherapy, among them five with GBM and two with AA, and five patients in the control arm. Patients were irradiated to 60 Gy using three-dimensional conformal noncoplanar techniques. Anti-EGFR (125)I monoclonal antibody 425 radioimmunotherapy (50 mCi/course) was started during 4th week of radiotherapy and was repeated three times in one week intervals. RESULTS: Time of follow-up ranges between 2 and 10 months in the anti-EGFR (125)I radioimmunotherapy arm and 4 and 9 months in the control arm. Recurrence was diagnosed in all patients in the EGFR (125)I group with a lethal outcome in two of them and in 4 patients in the control group. Median time to recurrence was 2 and 5 months respectively. CONCLUSIONS: Taking into account early recurrences observed, we propose to continue the studies on the efficacy of adjuvant anti-EGFR (125)I radioimmunotherapy in a selected group of patients in whom the greatest benefit may be expected on the basis of molecular studies, among them EGFR expression investigation.