Long-Term Outcome of Differentiated Thyroid Cancer Patients-Fifty Years of Croatian Thyroid Disease Referral Centre Experience.

Background: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low.

99mTc-MIBI SPECT/CT SCINTIGRAPHY AND ULTRASOUND OF THE ANTERIOR NECK REGION IN DIAGNOSING PARATHYROID GLAND PATHOLOGY IN PATIENTS WITH THYROID NODULES.

Parathyroid scintigraphy with 99mTc-MIBI is an imaging technique used in nuclear medicine and performed in patients with suspected hyperparathyroidism (HPT). The objective of this study was to evaluate the role of this technique in patients who, along with suspected HPT, also have thyroid nodules. Retrospective analysis included a period of 8 years (2006-2013). The study included 91 patients with clinical or laboratory suspected HPT. Pathologic changes in parathyroid glands were demonstrated in 47 (70%) of 67 patients with positive scintigraphy. Pathologic changes in parathyroid glands were not evident in the remaining 20 (30%) patients. Out of nine patients with negative scintigraphy results but with suspected enlargement of the parathyroid gland examined by ultrasound, eight (89%) patients did not show pathologic changes in the parathyroid gland, whereas one (11%) patient had evident changes. Eight (54%) of 15 patients with suspected scintigraphy had positive ultrasound findings, as well as fine needle aspiration cytology (FNAC) findings with parathyroid hormone (PTH) determination in the aspirate. Seven (46%) patients had negative FNAC findings and PTH in the aspirate. The study showed scintigraphy to have high sensitivity (98%) in detecting patients with pathologic changes in the parathyroid glands. In patients with suspected HPT, scintigraphy needs to be combined with FNAC and PTH determination in the aspirate due to its low specificity of 28%.

PRIMARY HYPERPARATHYROIDISM AND SERUM CALCIUM IN BREAST CANCER PATIENTS EVALUATED FOR LOW BONE MASS - A SINGLE CENTER EXPERIENCE.

The bone health guidelines for breast cancer (BC) patients recommend bone mineral density (BMD) testing. Patients with low BMD and elevated serum calcium levels (SCLs) are further evaluated for primary hyperparathyroidism (PHPT). We aimed to determine the prevalence of PHPT in treated BC patients with low BMD and analyze the association of SCLs with histopathologic tumor features and cancer treatment. This retrospective study included postmenopausal BC patients examined at Osteoporosis Clinic between 2013 and 2020. Clinical and BMD data were collected from patient medical records. Patients with biochemical suspicion of PHPT underwent standard parathyroid imaging procedures. Nine out of 137 (6.6%) patients were diagnosed with PHPT; 8/9 patients underwent parathyroidectomy and one patient was advised to follow-up. Among the rest of 128 non-PHPT patients, higher SCLs showed a trend of positive association with higher tumor grade and axillary lymph node involvement, and received immunotherapy, although without statistical significance. We found a higher prevalence of PHPT in treated BC patients compared to the general population. Higher SCLs show a trend of positive correlation with some more aggressive histopathologic tumor features and with immunotherapy. The results of this study suggest that assessment of SCLs should be routinely performed to rule out PHPT in treated BC patients with low BMD.

Thyroglobulin Measurement in Needle Aspiration for Detection of Recurrences and Neck Metastases in Patients with Differentiated Thyroid Carcinoma: Significance of Anti-Tg Antibodies.

The worldwide incidence of differentiated thyroid cancer (DTC) has increased in recent decades, likely due to frequent use of cervical ultrasonography (US) and US-guided fine needle aspiration biopsy (FNA)., US is performed during follow-up after thyroidectomy, and US-guided FNA with cytology is used if suspicious cervical lymph nodes (LN) or thyroid bed masses are detected. Knowing that serum anti-Tg antibodies (sTgAb) affect the use of serum Tg (sTg) as a tumor marker, the aim of our study was to assess the usefulness of Tg determination in needle aspirates (FNA-Tg) in presence of sTgAb. This retrospective study included 149 patients with DTC and 159 aspirations of suspicious LN and thyroid bed masses. As expected, there was a negative correlation between sTg and sTgAb levels (p<0.05), while FNA-Tg levels had a positive correlation with FNA-TgAb levels (p<0.05). Furthermore, we found a positive correlation between sTg and FNA-Tg levels (p<0.05), but not between sTgAb and FNA-TgAb or sTgAb and FNA-Tg. In conclusion, these results show that FNA-Tg values were not affected by sTgAb and that FNA-Tg measurement were highly effective in detecting cervical DTC metastases. However, combined use with cytology is suggested for neck evaluation because cytology could reveal metastases from other tumor sites.

An Unusual Case of Papillary Thyroid Carcinoma Iodine-131 Avid Metastasis to the Adrenal Gland.

Papillary thyroid carcinoma (PTC) is considered one of the most favorable tumors, indolent, with rare distant dissemination. Lungs and bones are the most common metastatic sites. Unusual sites of PTC distant metastases are extremely rare. Brain, liver, skin, kidney, pancreas, and adrenal gland PTC metastases have been sporadically reported in the literature. An 86-year-old female patient underwent total thyroidectomy and neck dissection due to PTC. Postoperative whole body iodine-131 scintigraphy with I-131 SPECT/CT of the abdomen revealed radioiodne avid left adrenal gland metastasis together with high postoperative serum thyroglobulin (Tg) value of more than 5000 µg/L and high serum Tg antibodies. Considering the above-mentioned findings, patient's age and multiple comorbidities, radioiodine therapy was applied. PTC metastases to the adrenal gland are extremely rare, and to our knowledge, only nine cases have been reported in the literature. This case report complements rare examples of unusual PTC metastases.

Regional bone loss following femoral neck fracture: A comparison between cemented and cementless hemiarthroplasty.

The aim of this prospective, randomised study was to measure and evaluate regional bone mineral changes and clinical results following the use of cemented and cementless hemiarthroplasty (HA) for treatment of femoral neck fracture in elderly patients. The study comprised 60 patients, 30 with cemented HA (group A) and 30 with cementless HA (group B). All patients underwent osteodensitometry of the contralateral hip, lumbar spine and bilateral distal femur. Dual-energy x-ray absorptiometry (DEXA) was scheduled at 1 month, 6 months and 1 year after surgery. Harris Hip Score (HHS) was used for functional assessment. Overall mortality rate was 20.3% within 1 year after surgery. There were no significant differences in morbidity, mortality and hospital stay between the two groups of patients. The implantation of cemented prosthesis took statistically significantly longer than that of cementless prosthesis (79.03±3.59 vs 68.02±5.97min; p=0.00). Functional score in patients treated with cemented HA was significantly higher compared with those with cementless HA. There was a trend of less intensive reduction of bone mineral density (BMD) in regions of interest of the lumbar spine and ipsilateral distal femur in patients with cemented HA (group A), whereas bone loss was less pronounced for the contralateral hip and distal femur in patients treated with cementless HA (group B). Management of displaced femoral neck fractures in elderly patients with cemented and cementless HA provides a comparable outcome with regard to morbidity and mortality; however, functional outcome of patients treated with cementless HA tends to be lower. There is less intensive BMD reduction in lumbar spine and ipsilateral distal femur in patients treated with cemented HA, whereas BMD reduction in patients treated with cementless HA is more likely to be less intensive in contralateral hip and distal femur.

Periprosthetic bone loss following hemiarthroplasty: a comparison between cemented and cementless hip prosthesis.

The aim of this prospective randomized clinical study was to evaluate the magnitude of bone mineral changes as well as the clinical results after cemented and cementless haemiarthroplasty (HA) for femoral neck fracture. The study was comprised of 60 patients (mean age 85.2 years); 30 of them underwent cemented HA and 30 cementless HA. All patients underwent osteodensitometry for the purpose of Bone Mineral Density (BMD) evaluation. BMD was measured with dual-energy X-ray absorptiometry test (DEXA scans), which was scheduled at 1 month, 6 months and 1 year after surgery. BMD was evaluated at each of the seven Gruen zones. Harris Hip Score (HHS) at 3 months, 6 months and 12 months was used for evaluation of functional outcome. No difference was found between the two groups of patients in terms hospital stay, morbidity and mortality. The procedure took longer time in group A (cemented HA) compared to group B (cementless HA) (79.03 ± 3.59 vs 68.02 ± 5.97 minutes; p = 0.00). The Harris hip score averaged 76.97 ± 7.49 one year after surgery. At each follow - up examination the HHS was significantly higher in patients with cemented HA. We noted a trend of less intensive BMD reduction in all Gruen zones in group A compared to group B. However, the difference in BMD reduction between these two groups was significant only in zones 2, 3 and 4. Our results support the view that cemented hemiarthroplasty should be used for the management of displaced femoral neck fractures providing better functional outcomes and lower periprosthetic bone loss.

Internal fixation with locking plate of 3- and 4-part proximal humeral fractures in elderly patients: complications and functional outcome.

Despite recent advances in operative techniques, internal fixation of (3- and 4-part) displaced proximal humeral fractures in elderly patients with osteoporotic bone remains controversial, sometimes followed by poor results. The aim of the present study was to evaluate outcomes of internal fixation with locking plate of multi-fragment proximal humeral fractures in elderly patients. The study cohort comprised 59 consecutive patients (mean age 70.1) with 3- and 4-part fractures who had undergone open reduction and internal fixation with locked plate at Sestre milosrdnice University Hospital Center in Zagreb, Croatia. All patients were invited for follow-up examinations and underwent standard x-ray examination preoperatively to assess fracture pattern in the operating theatre as well as at 6 weeks, 3 and 6 months, 1 year, and then annually after surgery to assess fracture healing or complications. Clinical outcomes were measured by constant score. Patients were followed-up for 14 to 36 months. The overall complication rate was 27.1%. The mean constant score at 1-year follow-up was 70.2 points for 3-part fractures vs. 64.2 for 4-part fractures (p < 0.0001). In conclusion, despite a relatively high overall complication rate, internal fixation with locking plate provided moderate to good functional results in the treatment of osteoporotic complex proximal humeral fractures.

Differential expression of proteins with heparin affinity in patients with rheumatoid and psoriatic arthritis: a preliminary study.

OBJECTIVES: Using proteomic approach in this study, we sought to identify proteins with heparin affinity associated with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and non-inflammatory arthritis (NIA). METHODS: Plasma samples from adult RA, PsA and NIA patients, 20 of each, were collected. After enrichment of proteins with heparin affinity, SDS-PAGE and in-gel digestion with trypsin were performed. Peptides were concentrated, micro-purified, separated and measured by nano-scale HPLC system coupled to a mass spectrometer. Peak lists were generated from raw spectra and searched against human complete proteome set by MaxQuant software. Statistical analysis of protein relative expression levels was done in IPython interactive Python shell using NumPy and Matplotlib libraries. Individual protein impact on the whole dataset correlation was done by excluding one protein at a time and calculating the correlation coefficient of remaining data points. RESULTS: Three hundred and eighty-four different proteins were identified keeping false discovery rate to 1%, from which 163 were identified in all three conditions. The plasma proteome showed a good correlation between rheumatoid (RA) and psoriatic arthritis (PsA). Out of 10 proteins whose impact on the correlation coefficient fell outside of two standard deviations from the mean, four were up-regulated (complement factor I, complement component C8 beta, glyceraldehyde-3-phosphate dehydrogenase and inter-alpha-trypsin inhibitor heavy chain H1), and two were down-regulated (immunoglobulin heavy chain V-III region BRO, and immunoglobulin J chain), both in PsA and RA by a similar ratio when compared to NIA. The remaining four proteins (Serpin A11, complement factor H-related protein 5, cartilage acidic protein 1 and coagulation factor IX) were down-regulated in PsA and up-regulated in RA when compared to NIA. CONCLUSIONS: We found differently expressed proteins in patients with inflammatory and non-inflammatory rheumatic conditions. Out of 384 proteins with heparin affinity four proteins should be further validated as potential diagnostic biomarkers in patients with RA and PsA.