Papillary (PTC) and follicular (FTC) thyroid cancer (TC) belong to
differentiated thyroid cancer (DTC). The initial treatment of DTC is surgery
followed by radioiodine remnant ablation. Although the ...prognosis of
DTC is generally good, approximately 10-15% of DTC patients will devolp
advanced disease and their disease will become radioiodine refractory. Even
in radioiodine refractory patients the natural history of disease can be slowly progressive or indolent.The expanded knowledge of the the biological basis of DTC has opened new opportunities in therapy – targeted therapy, aimed at inhibiting specific molecular targets and pathways in tumor proliferation, survival and progression. We rewieved different tageted therapies in DTC. Sorafenib was the first and only targeted drug approved by FDA for progressive and radiodine-refractory DTC. Also, lenvatinib had promising efficacy results in phase III trial, probably even better than sorafenib, but with more treatment-related deaths. The timing of targeted therapy for DTC is of decisive importance. The potential benefit should be balanced with potential toxicity of targeted
therapies.
To investigate the prognostic value of urokinase-type plasminogen activator (uPA) and its inhibitor, type-1 plasminogen activator inhibitor (PAI-1), in differentiated thyroid cancer.
Prospective ...cohort study.
University hospital.
Cytosolic concentrations of uPA and PAI-1 were determined in 105 patients with differentiated thyroid carcinoma and normal matched tissues using an enzyme-linked immunoassay (ELISA).
Both uPA and PAI-1 concentrations were significantly higher in differentiated thyroid tumors (uPA = 0.509 ± 0.767 and PAI-1 = 6.337 ± 6.415 ng/mg) compared to normal tissues (uPA = 0.237 ± 0.051, P < .001; PAI-1 = 2.368 ± 0.418 ng/mg, P < .001). uPA and PAI-1 were significantly higher if extrathyroidal invasion (uPA, P = .015; PAI-1, P < .001) or distant metastasis (PAI-1 P < .001) was present, as well as in tumors whose size exceeded 1 cm in diameter (uPA, P = .002; PAI-1, P = .001). Survival analysis revealed the significant impact of both uPA and PAI-1 on progression-free survival (PFS) (82.22 vs 49.478 months for patients with low and high uPA, respectively, P < .001; 87.068 vs 44.964 months for patients with low and high PAI-1, respectively, P < .001). Univariate analysis showed that gender, tumor size, tumor grade, extrathyroid invasion, local lymph node involvement, distant metastasis, uPA, and PAI-1 were significant predictors of PFS. However, multivariate analysis identified only distant metastasis and tumor tissue uPA and PAI-1 as independent prognostic factors.
These findings indicate that high uPA and PAI-1 levels represent independent unfavorable prognostic factors in patients with differentiated thyroid carcinoma.
Summary
HER-2/neu extracellular domain (ECD) can be detected in blood as a soluble circulating protein. The aim of this study was to analyze the relationship between HER-2/neu extracellular domain in ...the serum and the prognosis in breast cancer patients. We also correlated HER-2/neu ECD with various clinicopathological factors including steroid receptor, HER-2/neu receptor coexpression. The serum from seventy nine patients with invasive breast cancer and twenty individuals without malignancy was analyzed using the enzyme-linked immune adsorbent assay method. The cut-off value was estimated by the ROC curve analysis (15.86 μg/L). HER-2/neu ECD values in the serum of patients with breast cancer were significantly higher than in control subjects. Circulating HER-2/neu ECD was significantly associated with the histological grade of tumors and the status of axillary lymph nodes. Negative correlation was observed between HER-2/neu ECD in the serum and estrogen receptor positivity. When we analyzed HER-2/neu ECD in relation with coexpression of steroid receptor and HER-2/neu receptor in tissue, statistically higher values were found in the subgroup of patients with steroid receptor negative, HER-2/neu negative tumors than in the other subgroups. HER-2/neu ECD was not an independent factor in the univariate and multivariate analysis. However, elevated HER-2/neu ECD levels were found in patients with breast cancer possessing more aggressive phenotype.
Details of a case involving a 48-year-old female patient who was referred for bone scintigraphy because of severe osteoporosis (L1L4 T score was 3.5; serum calcium values and 24-h calciuria in normal ...range). Bone scintigraphy showed bilateral, intense pulmonary 99mTc-methylenediphosphonate uptake, which led to clinical suspicion of pulmonary alveolar microlithiasis.
Higher levels of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) are linked to the poor prognosis in a variety of malignances. uPA and PAI-1 were expressed in most thyroid ...carcinomas, as had been measured immunohistochemically. However, no relationship between their expression and clinicopathological parameters were found. Aim of the present study was to investigate the expression and clinical relevance of uPA and PAI-1 in thyroid cancer.
uPA and PAI-1 in paired cytosol samples of thyroid tumor and normal tissue were determined in 23 patients using enzyme-linked immunosorbent assay and correlated to the known prognostic features.
Both uPA and PAI-1 concentrations were significantly higher in malignant thyroid tumors (uPA=1.342 +/- 2.944 and PAI-1=17.615 +/- 31.933 ng/mg protein) than in normal tissue (uPA=0.002 +/- 0.009, P=0.011 and PAI-1=2.333 +/- 0.338 ng/mg protein, P=0.001) with positive correlation of the two proteins in the tumors. There were no differences in proteins' levels between benign tumors and normal tissue. Both proteins' concentrations were significantly different among various histological grades (uPA P=0.024 and PAI-1 P=0.017), showing higher values in higher tumor grades (grade I uPA=0.116 +/- 0.247 and PAI-1=4.802 +/- 4.151 ng/mg protein; grade III uPA=8.45 +/- 2.192 and PAI-1=94.65 +/- 59.468 ng/mg protein). The uPA and PAI-1 levels showed significant differences among different histological types of thyroid cancer (uPA P=0.049 and PAI-1=0.017). The lowest values were in adenomas (uPA=0.013 +/- 0.025 and PAI-1=2.785 +/- 1.069 ng/mg protein) and the highest in anaplastic carcinomas (uPA=8.45 +/- 2.192 and PAI-1=94.65 +/- 59.468 ng/mg protein). uPA and PAI-1 were significantly higher in anaplastic vs. well-differentiated cancers (uPA P=0.014 and PAI-1 P=0.026), if extrathyroidal invasion (uPA P=0.019 and PAI-1 P=0.009) or distant metastases (uPA P=0.006 and PAI-1 P=0.003) had been present, and in tumors whose size exceeded 1 cm in diameter (uPA P=0.009 and PAI-1 P=0.035). Only PAI-1, but not uPA was significantly higher in multicentric vs. solitary tumors (P=0.012) and lymph node positive compared to lymph node negative patients (P=0.042). The differences of uPA and PAI-1 did not reach the significant level when patients with well-differentiated tumors below and above 40 years of age had been compared. Survival analysis revealed the significant impact of both uPA and PAI-1 on the Progression-Free Survival (PFS) (38.84 vs. 3.67 months for patients with low and high uPA, respectively, P<0.001; 38.2 vs. 12 months for patients with low and high PAI-1, respectively, P=0.016).
The correlation of high uPA and PAI-1 with the known prognostic factors of poorer outcome and with lower PFS rate in patients with thyroid cancers proved that these proteins could be an additional prognostic parameter.
The aim of this study was to determine whether ultrasonography itself was able to distinguish benign from malignant lymphadenopathy in patients with thyroid cancer.
We evaluated lymph nodes in a ...group of patients with thyroid cancer. Nodes were detected and measured by ultrasonography, and their shape, echogenicity, size, and location were noted. Ultrasonographically guided fine-needle aspiration biopsy (FNAB) was performed, and smears were analyzed cytologically.
Ultrasonographically guided FNAB was performed in 578 neck nodes in a group of 631 patients with thyroid cancer. In most cases, metastases had a round shape and various echo structures, with a predomination of hypoechoic nodes without a hilum. There were statistical differences in size between metastatic and benign nodes in terms of maximum diameter, minimum diameter, and volume. Among these, minimum diameter and the shape of the nodes seemed to be the most reliable in suggesting malignancy. A round shape with a longitudinal/transverse ratio of less than 2 of hypoechoic nodes indicated the presence of metastases, and we then performed FNAB. The absence of an echogenic hilum and the presence of cystic portions and calcifications were significantly greater in malignancies than in benign lesions (P<.001). In most cases, metastatic nodules were situated in the lower third of the neck. Reactively enlarged nodes occurred more frequently in the upper part of the neck.
Ultrasonography itself cannot distinguish benign from malignant lesions, but an echographic appearance suggests malignancy and helps in the selection of the node to aspirate with ultrasonographically guided FNAB, which is crucial for a final diagnosis.
Rak je drugi najvažniji uzrok smrti u našoj zemlji, odmah nakon bolesti srca i krvnih žila. S pretpostavkom porasta incidencije i smrtnosti od raka u idućim godinama, projekcije su da će se znatno ...povisiti troškovi dija-gnostike i liječenja raka, i zbog uvođenja novih dijagnostičkih tehnika i zbog inovativnih lijekova te metoda liječenja. Posljedično se nameće imperativ što boljeg iskorištavanja financijskih sredstava, raspoloživog osob-lja i tehnike, a sve radi osiguranja kontinuiteta prikladne dijagnostike i liječenja. Optimalnim provođenjem dijagnostičkih metoda mogu se spriječiti nepotrebno odugovlačenje obrade, rasipanje financijskih sredstava i nepotrebno opterećenje zdravstvenih djelatnika te skratiti liste čekanja. HDIO je donio ove smjernice radi prevladavanja navedenih problema, vodeći brigu o najvećoj koristi za bolesnika, što bi na kraju trebalo dovesti do racionalizacije i standardizacije dijagnostičkih postupaka u svakodnevnoj kliničkoj praksi. Smjernice bi trebale pomoći da iz cijele palete dijagnostičkih postupaka koji su nam na raspolaganju odaberemo najrelevan-tnije za pojedino sijelo i kliničku proširenost bolesti.
Rak je drugi najvažniji uzrok smrti u našoj zemlji, odmah nakon bolesti srca i krvnih žila. S pretpostavkom porasta incidencije i smrtnosti od raka u idućim godinama, projekcije su da će se znatno ...povisiti i troškovi dijagnostike i liječenja raka, i zbog uvođenja novih dijagnostičkih tehnika i zbog inovativnih lijekova te meto-da liječenja. Posljedično se nameće imperativ što boljeg iskorištavanja financijskih sredstava, raspoloživog osoblja i tehnike, a sve radi osiguranja kontinuiteta prikladne dijagnostike i liječenja. Optimalnim provođenjem dijagnostičkih metoda mogu se spriječiti nepotrebno odugovlačenje obrade, rasipanje financijskih sredstava i nepotrebno opterećenje zdravstvenih djelatnika te skratiti liste čekanja. HDIO je donio ove smjernice radi prevladavanja navedenih problema, vodeći brigu o najvećoj koristi za bolesnika, što bi na kraju trebalo dovesti do racionalizacije i standardizacije dijagnostičkih postupaka u svakodnevnoj kliničkoj praksi. Smjernice bi trebale pomoći da iz cijele palete dijagnostičkih postupaka koji su nam na raspolaganju odaberemo najrelevan-tnije za pojedino sijelo i kliničku proširenost bolesti.
Melanoma in the Western world has an increasing incidence. One of the most important factor for the increase in incidence is sporadic, uncontrolled exposure to the sun. The basis for the treatment of ...primary melanoma is surgical treatment. Treatment of metastatic disease of melanoma in recent years experienced significant changes. BRAF and MEK inhibitors, immunotherapy with programmed cell-death immune checkpoint inhibitors (anti-PD-1-antibodies) are new options for the treatment of metastatic disease. A mulitidisiplinary team of Croatian Society for Medical Oncology provides recommendations for diagnosis, treatment and follow-up of melanoma primarily driven to the discovery of new drugs and therapeutic options, that change the prognosis of patients with metastatic melanoma.
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