The diagnostic predictive value of neutrophil-to-lymphocyte ratio in thyroid cancer adjusted for tumor size.

The role of systemic inflammation has not been clearly defined in thyroid cancers. There have been conflicting reports on whether systemic inflammatory markers have predictive value for thyroid cancers. We aimed to evaluate the association between systemic inflammatory markers and clinicopathological factors in thyroid cancers and to assess their predictive value for thyroid cancers in detail. Five hundred thirty-one patients who underwent surgery for thyroid nodules were included. The patient population consisted of 99 individuals (18.6%) with benign thyroid nodules and 432 individuals (81.4%) with thyroid cancers. In 432 patients with thyroid cancers, neutrophil-to-lymphocyte ratio (NLR) was significantly higher in the cases with tumors greater than 2 cm than in those with tumors less than 2 cm. (p = 0.027). NLR and platelet-to-lymphocyte ratio (PLR) were significantly higher in cases with lateral lymph node metastasis (LNM) than in those without LNM (p = 0.007 and 0.090, respectively). The nodule size was significantly higher in benign thyroid nodules than in thyroid cancers (p < 0.001). When the cases were stratified by tumor size, NLR was a significant predictor of thyroid cancers in cases with nodules greater than 2 cm (Exp(B) = 1.85, 95% CI = 1.15-2.97, p = 0.011), but not in those with nodules less than 2 cm. In thyroid cancers, preoperative NLR was associated with pathological prognosticators such as tumor size and lateral lymph node metastasis. When the size difference between thyroid cancers and benign thyroid nodules was adjusted, NLR could be a significant predictor of thyroid cancers.

Metástasis raras de cáncer papilar de tiroides en músculo esquelético: serie de casos / Rare metastases of papillary thyroid cancer in skeletal muscle: case series

Las metástasis del carcinoma papilar de tiroides (CPT) generalmente son a nivel locorregional, la diseminación a distancia es poco habitual, sin embargo la invasión de tejidos blandos aunque inusual puede ocurrir, y afecta negativamente la supervivencia. El presente estudio describe una serie de casos de Metástasis Musculares de CPT. Se realizó un estudio transversal de un solo centro que evaluó diez pacientes con CPT con metástasis en músculo. La edad de los pacientes fue entre 46 a 77 años, siendo la edad promedio de 60 años, 7 de los cuales fueron de sexo masculino que corresponde al 70%, todos con antecedente de CPT con respuesta estructural incompleta, además de las metástasis en músculo presentaron afectación de tres o más órganos, con necesidad de varios tratamientos, cada paciente registró entre 1 a 8 cirugías, recibieron entre 100 a 780mCi de I131 (yodo radiactivo), ocho ameritaron radioterapia, todos tuvieron indicación de tratamiento con ITK, sin embargo solo cuatro pacientes tuvieron acceso a dicho medicamento. La mayoría de las metástasis del CPT en músculo fueron diagnosticadas en los estudios de imagen PET/ CT, después de la tiroidectomía el tiempo de su presentación fue muy variable entre 1 a 18 años, el número de músculos comprometidos se reporta entre uno a cuatro, siendo el glúteo (4 casos) el músculo metastásico más frecuente. La presencia de metástasis musculares empeora el pronóstico en nuestra serie de pacientes.

Metastases of thyroid papillary carcinoma (CPT) are generally at the locoregional level, the dissemination from a distance is unusual, however the invasion of soft tissues, although rare can occur, and it negatively affects survival. The present study describes several Muscular Metastases of CPT cases. A transversal study in one only center was performed and assessed ten patients CPT metastases in muscles.The patients age ranged from 46 to 77, being the average age of 60, and 7 of them were male, corresponding to the 70%, everyone with CPT records with an incomplete structural response. Besides muscular metastases they also presented issues with three or more organs, needing many treatments. Each patient registered between 1 to 8 surgeries, they received between 100 to 780mCi of I131. Eight required radiotherapies, everyone required treatment with ITK, however, just four patients had access to that medication. Most of the CPT metastases in muscles were diagnosed in PET/CT image studies, after the thyroidectomy, the time for its presentation was very variable between 1 to 18 years, the number of compromised muscles is reported between one to four, being the buttock (4 cases) the most frequently muscle with metastases. The presence of muscular metastases aggravates the prognosis in our series of patients.

Correlation between serum circRNA and thyroid micropapillary carcinoma with cervical lymph node metastasis.

The study aims to characterize the circular RNA (circRNA) expression profile that is functionally related with the invasiveness of papillary thyroid microcarcinoma (PTMC).A total of 13 pairs of female patients with non-invasive PTMC or lymph node metastasis PTMC (PTMC (L)) were included and the serum RNA was obtained. CircRNA microarray was performed to identify the circRNA expression profile. Real time-PCR was used to verify circRNA expression. Bioinformatic approaches were adopted to annotate the function of differentially expressed circRNAs and construct the circRNA-miRNA-mRNA network.In total, 400 significantly upregulated and 290 significantly downregulated circRNAs were identified in PTMC (L) compared with PTMC. Among them, 10 circRNAs were selected and validated by real time-PCR. Putative microRNAs (miRNAs) that could bind to the differentially expressed circRNAs were predicted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of target genes of the differentially expressed circRNAs revealed that these circRNAs may play an important role in lymph node metastasis. Finally, circRNA targeted miRNAs were predicted and a circRNA-miRNA-mRNA network was constructed for hsa_circRNA_404686.Our results showed that several circRNAs, such as hsa_circRNA_404686, may serve as promising diagnostic marker for PTMC (L) in female.

A Blood-based Gene-expression Scoring System for Cancer Screening in Patients With Branch-duct Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: In patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), we aimed to develop a novel blood-based biomarker utilizing a gene-expression profile for the detection of pancreatic malignancies, such as IPMN-derived carcinoma (IPMC) or pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We enrolled 40 patients with pancreatic tumors (24 BD-IPMNs, four IPMCs and 12 PDACs) and identified the characteristic gene-expression profiles in pancreatic malignancies. Subsequently, we constructed a gene-expression scoring system for the proper diagnosis of pancreatic malignancies. The result was validated in 14 patients (five IPMNs, three IPMCs and six PDACs). RESULTS: The scoring system utilizing the expression levels of 13 genes showed high diagnostic yield (sensitivity=94.0%, specificity=92.0% and area under the curve=0.94), which was confirmed in the validation set. Furthermore, its diagnostic yield was not reduced even in early-stage pancreatic malignancies (sensitivity=85.0%, specificity=93.0% and area under the curve=0.88). CONCLUSION: We developed a blood-based gene expression scoring system for cancer screening in patients with BD-IPMNs.

Plasma-Derived miRNA-222 as a Candidate Marker for Papillary Thyroid Cancer.

We analyzed five miRNA molecules (miR-221; miR-222; miR-146b; miR-21; miR-181b) in the plasma of patients with papillary thyroid cancer (PTC), nodular goiter (NG) and healthy controls (HC) and evaluated their diagnostic value for differentiation of PTC from NG and HC. Preoperative PTC plasma miRNA expression (n = 49) was compared with plasma miRNA in the HC group (n = 57) and patients with NG (n = 23). It was demonstrated that miR-221; miR-222; miR-146b; miR-21 and miR-181b were overexpressed in preoperative PTC plasma samples compared to HC (p < 0.0001; p < 0.0001; p < 0.0001; p < 0.0001; p < 0.002; respectively). The upregulation in tumor tissue of these miRNAs was consistent with The Cancer Genome Atlas Thyroid Carcinoma dataset. A significant decrease in miR-21; miR-221; miR-146b and miR-181b expression was observed in the plasma of PTC patients after total thyroidectomy (p = 0.004; p = 0.001; p = 0.03; p = 0.036; respectively). The levels of miR-222 were significantly higher in the preoperative PTC compared to the NG group (p = 0.004). ROC curve (receiver operating characteristic curve) analysis revealed miR-222 as a potential marker in distinguishing PTC from NG (AUC 0.711; p = 0.004). In conclusion; circulating miR-222 profiles might be useful in discriminating PTC from NG.

Clinical Analysis of Preoperative Anti-thyroglobulin Antibody in Papillary Thyroid Cancer Between 2011 and 2015 in Beijing, China: A Retrospective Study.

The anti-thyroglobulin antibody (TgAb) has been suggested to be more common in patients with papillary thyroid cancer (PTC). Here, we performed a retrospective study investigated the correlation between TgAb level and PTC in Chinese patients between 2011 and 2015. Patients with goiter who underwent thyroidectomy and received a confirmed pathological diagnosis were enrolled into the study. Clinical characteristics and preoperative thyroglobulin antibody (TgAb) level data were collected from all enrolled patients. Based on the preoperative TgAb test results, patients were divided into a TgAb negative (TgAb-) group (<60 IU/mL) and a TgAb positive (TgAb+) group (≧60 IU/mL). Of the 4,046 patients, 671 patients were TgAb+ while 3,375 patients were TgAb-. There were 535 (79.7%) patients with PTC in the TgAb+ group, and 2,154 (63.8%) patients with PTC in the TgAb- group. The prevalance of PTC was significantly higher in TgAb+ patients than in TgAb- patients. TgAb+ patients were stratified into four groups based on the TgAb titer. The prevalence of PTC did not increase with TgAb titer. No significant difference in TgAb level was noted in patients with different clinicopathologies, including TNM stage, lymph node metastasis, and multifocal carcinoma. Regression analysis suggested a higher risk of PTC malignancy among TgAb+ patients. Preoperative TgAb level ≥60 IU/mL might be associated with a higher risk of PTC. However, there was no titer-dependent association between elevated TgAb titer and PTC malignancy.

Serum antithyroglobulin antibody levels are not a good predictive factor on detection of disease activity in patients with papillary thyroid carcinoma.

OBJECTIVE: Thyroglobulin antibodies (TgAb) are detected in thyroid cancer patients up to 25%. We investigated the prognostic value of TgAb positivity in patients with papillary thyroid carcinoma (PTC) after initial therapy. PATIENTS AND METHODS: A database of 109 consecutive patients who underwent total thyroidectomy and therapeutic lateral neck dissection followed by remnant ablation for PTC between January 1989 and December 2014 was reviewed We recorded the patients' all serum Tg and TgAb levels over time to establish changing trends. Patients were classified as either positive or negative according to serum TgAb levels. The recurrence or persistence rates in both groups were compared. RESULTS: Of the 109 patients enrolled 14 patients had TgAb positivity. Thirty-two (29.3%) showed disease recurrence or persistent disease during 101 months of follow-up. Twenty-seven of 95 patients (28.4%) with negative TgAb had persistent or recurrent disease, whereas 5 of 14 patients (35.7%) with positive TgAb had persistence or recurrence (P = 0.57). No significant difference in disease-free survival (115.3 ± 10.8 vs. 224.1 ± 16.6 months, P = 0.78) and overall survival (P = 0.59) was observed between TgAb positive and TgAb negative patients. CONCLUSIONS: TgAb status is not useful as a prognostic and predictive factor for clinical outcomes in patients with PTC in our experience.

Serum Adiponectin and Progranulin Level in Patients with Benign Thyroid Nodule or Papillary Thyroid Cancer.

BACKGROUND: Obesity is associated with thyroid cancer risk. Adiponectin has insulin-sensitizing and anti-inflammatory effects, while progranulin is associated with inflammation and tumorigenesis. We investigated serum adiponectin and progranulin levels in patients with benign thyroid nodule (benign group) and papillary thyroid cancer (PTC; PTC group). The associations between these levels and the clinicopathological features of PTC were evaluated. METHODS: We included 157 patients who underwent thyroid surgery (17% of benign and 83% of PTC group). Clinicopathological features including size, lymph node metastasis, extrathyroidal extension (ETE), multifocality, American Thyroid Association risk stratification were evaluated. RESULTS: The age was 42.0 years, and 69% were female. Serum adiponectin and progranulin levels were 6.3 µg/mL and 101.5 ng/mL in the benign group and 5.4 µg/mL and 106.1 ng/mL in the PTC group, respectively (P=0.6 and P=0.4, respectively). Serum adiponectin levels showed no significant differences according to clinicopathological features of PTC. The proportions of patients with primary tumor size >1 cm were 3%, 5%, 8%, and 8% according to serum progranulin level quartiles, respectively (P=0.03). The proportions of patients with microscopic/gross ETE were 8%/0%, 9%/1%, 11%/1%, and 11%/2% according to serum progranulin level quartiles, respectively. Median serum progranulin level was significantly higher in patients with PTC >1 cm than in patients with papillary thyroid microcarcinoma (P=0.04, 115.3 ng/mL and 104.7 ng/mL, respectively). CONCLUSION: Serum adiponectin and progranulin levels showed no significant difference between benign and PTC groups. Increased serum progranulin levels were significantly associated with PTC >1 cm and microscopic and gross ETE.

Serum Anti-p53 Antibody Can Serve as a Predictive Marker for Histological Grade of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: The aim of the study was to clarify the diagnostic impact of measuring serum anti-p53 antibody (S-p53Ab) in predicting the histological grades of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: We compared the measured values and positive prevalence of S-p53Ab across the different histological grades of 111 resected IPMN cases. We also evaluated the TP53 alterations using immunohistochemistry and next-generation sequencing. RESULTS: Serum anti-p53 antibody were detected in 6 of 111 cases, all of their histological grades were high-grade dysplasia (HGD) and invasive carcinoma (INV). Positive prevalence of S-p53Ab was higher in cases with INV (4/35 cases, 11.4%) than those with HGD (2/38 cases, 5.3%), whereas S-p53Abs were undetectable in cases with low-grade dysplasia. Measured S-p53Ab values were not correlated with either carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA 19-9). In 4 of 6 S-p53Ab-positive cases, the TP53 alterations-somatic pathogenic mutations or aberrant immunoreactivity-were identified in their IPMN lesions. A combination assay of S-p53Ab, CEA, and CA 19-9 revealed a 38.4% sensitivity and 81.6% specificity for predicting HGD/INV. CONCLUSIONS: Serum anti-p53 antibody can serve as a surrogate marker for TP53 alterations and help predict the presence of HGD/INV in cases with IPMN, in combination with CEA and CA 19-9.

Unexpected metastasis of intraductal papillary neoplasm of the bile duct without an invasive component to the brain and lungs: A case report.

BACKGROUND: Despite an expanding number of studies on intraductal papillary neoplasm of the bile duct (IPNB), distant metastasis remains unexplained especially in cases of carcinoma in situ. In the present study, we report a rare and interesting case of IPNB without invasive components that later metastasized to lungs and brain. CASE SUMMARY: A 69-year-old male was referred to our hospital due to suspected cholangiocarcinoma. Laboratory tests on admission reported a mild elevation of alkaline phosphatase, γ-glutamyl transpeptidase, and total bilirubin in serum. Endoscopic retrograde cholangiography revealed a filling defect in the common bile duct (CBD) extending to the left hepatic duct. Peroral cholangioscopy delineated a tumor in the CBD that had a papillary pattern. Multidetector computed tomography and magnetic resonance cholangiopancreatography detected partial blockage ot interlude in the CBD leading to cholestasis without evidence of metastasis. Therefore, a diagnosis of IPNB cT1N0M0 was established. Left hepatectomy with bile duct reconstruction was performed. Pathological examination confirmed an intraepithelial neoplasia pattern without an invasive component and an R0 resection achievement. The patient was monitored carefully by regular examinations. However, at 32 mo after the operation, a 26 mm tumor in the lungs and a 12 mm lesion in the brain were detected following a suspicious elevated CA 19-9 level. Video-assisted thoracoscopic surgery of left upper lobectomy and stereotactic radiotherapy are indicated. In addition to histopathological results, a genomic profiling analysis using whole exome sequencing subsequently confirmed lung metastasis originating from bile duct cancer. CONCLUSION: This case highlights the important role of genomic profiling analysis using whole exome sequencing in identifying the origin of metastasis in patients with IPNB.

Definition of the Response to Initial Therapy with Radioiodine in Patients with Differentiated Thyroid Carcinoma: Basal or Stimulated Thyroglobulin?

Basal thyroglobulin (b-Tg) measured with second-generation assay or stimulated Tg (s-Tg) can be used to define the response to therapy of differentiated thyroid carcinoma. However, they do not always define the same category and guidelines do not establish "if" or "when" s-Tg needs to be obtained. We studied 304 patients without clinically apparent disease or disease detected by neck ultrasonography and without anti-Tg antibodies 9-12 months after therapy. Based on b-Tg, 196 patients had an excellent response and 108 had an indeterminate response. Based on s-Tg, a change in category occurred in 10.2% of the patients with an initial excellent response (all to indeterminate response) and in half the patients with an initial indeterminate response (44.4% to excellent response and 5.5% to biochemical incomplete response). One case of recurrence was observed among patients with an initial excellent response but whose response changed to indeterminate after s-Tg, while no disease was detected among those who remained in the initial category; however, this difference was not significant. In patients with an initial indeterminate response, no recurrence was detected among those whose response changed to excellent after s-Tg, while 11.1 and 33.3% of those who remained in the initial category or whose response changed to biochemical incomplete, respectively, had structural disease. This study suggest that, in low- or intermediate-risk patients, s-Tg better defines the response to therapy with 131I when it is classified as indeterminate based on b-Tg using second-generation assay. However, s-Tg is not necessary when b-Tg defines the response as excellent.

Altered Serum MicroRNA Profile May Serve as an Auxiliary Tool for Discriminating Aggressive Thyroid Carcinoma from Nonaggressive Thyroid Cancer and Benign Thyroid Nodules.

Thyroid cancers are the most common malignancy of the endocrine system; however, there is no reliable blood biomarkers for thyroid cancer diagnosis and even for aggressive and nonaggressive thyroid cancers as well as benign nodule discrimination. The present study is aimed at evaluating whether circulating microRNA (miRNA) can differentiate aggressive and nonaggressive thyroid cancer from benign thyroid nodules. In this study, we performed a multiphase, case-control study to screen serum miRNA expression profile in 100 patients with papillary thyroid cancer (PTC), 15 patients with aggressive medullary thyroid carcinoma (MTC), 91 patients with benign nodules, and 89 healthy controls using TaqMan low-density array followed by extensive reverse transcription quantitative real-time PCR validation. The results showed that the serum levels of miR-222-3p, miR-17-5p, and miR-451a were markedly increased, while miR-146a-5p, miR-132-3p, and miR-183-3p were significantly decreased in the PTC and benign nodule groups compared with the control group. There was no difference in the miRNA expression profile between the PTC group and the benign nodule group. Nevertheless, the serum levels of miR-222-3p and miR-17-5p were significantly increased in the MTC group than the benign nodule and control group. Moreover, receiver operating characteristic curve analyses demonstrated that the 2 miRNAs and their panel can accurately discriminate MTC from the benign nodule group and healthy controls. These findings indicated that the altered circulating miRNAs may discriminate PTC and benign thyroid nodules from controls, and serum miR-222-3p and miR-17-5p have the potential to serve as auxiliary tools for diagnosing more aggressive thyroid carcinomas, such as MTC.

Pancreatic Fluid Interleukin-1ß Complements Prostaglandin E2 and Serum Carbohydrate Antigen 19-9 in Prediction of Intraductal Papillary Mucinous Neoplasm Dysplasia.

OBJECTIVES: We sought to determine if interleukin (IL)-1ß and prostaglandin E2 (PGE2) (inflammatory mediators in pancreatic fluid) together with serum carbohydrate antigen (CA) 19-9 could better predict intraductal papillary mucinous neoplasm (IPMN) dysplasia than individual biomarkers alone. METHODS: Pancreatic cyst fluid (n = 92) collected via endoscopy or surgery (2003-2016) was analyzed for PGE2 and IL-1ß (enzyme-linked immunosorbent assay). Patients had surgical pathology-proven IPMN. Threshold values (PGE2 [>1100 pg/mL], IL-1ß [>20 pg/mL], and serum CA 19-9 [>36 U/mL]) were determined. RESULTS: Levels of IL-1ß were higher in high-grade dysplasia (HGD)/invasive-IPMN (n = 42) compared with low/moderate IPMN (n = 37) (median [range], 54.6 [0-2671] vs 5.9 [0-797] pg/mL; P < 0.001; area under curve [AUC], 0.766). Similarly, PGE2 was higher in HGD/invasive IPMN (n = 45) compared with low/moderate IPMN (n = 47) (median [range], 1790 [20-15,180] vs. 140 [10-14,630] pg/mL; P < 0.001; AUC, 0.748). Presence of elevated PGE2 and IL-1ß (AUC, 0.789) provided 89% specificity and 82% positive predictive value (PPV) for HGD/invasive IPMN. Elevated levels of all 3 provided 100% specificity and PPV for HGD/invasive IPMN. CONCLUSIONS: Cyst fluid PGE2, IL-1ß, and serum CA 19-9 in combination optimize specificity and PPV for HGD/invasive IPMN and may help build a panel of markers to predict IPMN dysplasia.

Thyroid Antibody Status is Associated with Central Lymph Node Metastases in Papillary Thyroid Carcinoma Patients with Hashimoto's Thyroiditis.

OBJECTIVE: The aim of this study was to explore the impact of thyroid antibody status on central lymph node metastases (CLNM) in papillary thyroid carcinoma (PTC) patients with Hashimoto's thyroiditis (HT). METHODS: A retrospective analysis was performed on 346 PTC patients with HT who underwent thyroidectomy and ipsilateral central lymph node dissection (CLND). Histopathological characteristics of the tumor and serum levels of thyroid hormone, as well as antibodies, were collected and analyzed. RESULTS: The multivariate logistic regression analysis showed that being male [odds ratio (OR) 3.269, 95% confidence interval (CI) 1.240-8.619], tumor size > 1 cm [1 cm < diameter (D) ≤ 2 cm: OR 6.947, 95% CI 2.886-16.722; 2 cm < D: OR 5.880, 1.937-17.846], and antibody status [thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) double negative: OR 3.791, 95% CI 1.391-10.331; TPOAb and TgAb double positive: OR 4.047, 95% CI 1.509-10.856; TgAb single positive: OR 6.024, 95% CI 2.019-17.970] were independent risk factors for CLNM. Additionally, a risk-score scale, including sex, antibody status, and tumor size, was established to predict CLNM. The sensitivity, specificity, positive predictive value, and negative predictive value were 55.7%, 84.4%, 74.4%, and 70%, respectively, when the cut-off point was chosen as 3. CONCLUSIONS: Antibody status is a critical independent risk factor for CLNM in PTC patients with HT. For the CLND strategy, a more conservative option could be considered in a low-risk cohort with the following characteristics: female sex, smaller tumor size, and TPOAb single positive.

Comparison of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with thyroiditis and papillary tumors.

OBJECTIVE: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been introduced as prognostic markers of thyroid cancer and strong inflammatory markers. The study was performed to investigate the association of the PLR and NLR with thyroid inflammation and papillary cancer. METHODS: Patients with thyroiditis and patients with papillary carcinomas were compared with sex-, age-, and body mass index-matched healthy controls. The NLR and PLR were calculated and compared among the three groups. RESULTS: The NLR was significantly higher in patients with thyroiditis and non-significantly higher in patients with papillary cancer than in healthy controls. The PLR was significantly higher in both patients with thyroiditis and papillary cancer than in healthy controls. Like the NLR, the PLR was not different between patients with thyroiditis and papillary cancer. The NLR was significantly and positively associated with the PLR and white blood cell count. CONCLUSION: The PLR and NLR showed similar results in both thyroid inflammation and cancer. It seems difficult to obtain clear results in separating cancer from inflammatory events using these parameters. We suggest using them as supportive parameters of thyroid papillary cancer or inflammation.

Neutrophil to Lymphocyte Ratio is Useful in Differentiation of Malign and Benign Thyroid Nodules.

OBJECTIVE: Significant amount of thyroid nodules are malignant. Inflammation plays crucial role in the pathogenesis of many disorders, including cancer. Neutrophil to lymphocyte ratio (NLR), has been suggested as an index of inflammatory response and association between increased NLR and cancer has also been reported. In this retrospective analysis, we aimed to study NLR levels in patients with malign and benign thyroid nodules and healthy control subjects. METHODS: The patients who underwent surgery for nodular goiter in general surgery clinics of our university hospital between June 2012 and June 2015 and 68 healthy volunteers were included. Patients with thyroid nodules divided into malign or benign nodule groups according to the pathology report. Thyroid carcinomas other than micropapillary tumor were excluded. Preoperative hemogram parameters of these groups were compared. RESULTS: Mean NLR of malign nodule group (2.1±0.9%) was significantly higher than both those in benign nodule (1.7±0.9%) and control groups (1.7±0.6%). CONCLUSION: We suggest that elevated NLR in patients with thyroid nodules in preoperative period may be an indicator of underlying malign nodular disease. Increased NLR in such patients should encourage physician to perform cancer screening in thyroid gland.

MMP-9-1562 C/T single nucleotide polymorphism associates with increased MMP-9 level and activity during papillary thyroid carcinoma progression.

Papillary thyroid carcinoma (PTC), a common form of thyroid malignancy, displays significant variations in clinical features and outcome. The malignant transformation of the thyroid is driven by altered expression of many matrix-modulating enzymes, including matrix metalloproteinase-9 (MMP-9). A single nucleotide polymorphism in its promotor (-1562 C/T) is suspected to cause overexpression of MMP-9, which in turn contributes to development of a tumour unfavourable phenotype. The aim of this study was to investigate the impact of MMP-9 promotor genotype on MMP-9 expression in PTC samples, and to assess its value as a possible risk factor for developing PTC or its aggressive phenotype. A total of 105 PTC patients and 43 healthy controls were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In order to estimate MMP-9 expression, PTC tissue sections were stained immunohistochemically. Statistical analysis showed that PTC cases and controls did not differ significantly in genotype frequencies (OR = 2.27, CI = 0.854-6.022). In PTC samples, the presence of the T allele was accompanied by elevated MMP-9 expression (p = 0.047) as well as a higher risk of developing extrathyroid extensions (p = 0.037) and high TNM stages (p = 0.009). Moreover, we observed overexpression of MMP-9 in cases presenting with extrathyroid invasion (p = 0.001), lymph node metastasis (p = 0.028), large tumour size (p = 0.031) and advanced stage (p = 0.005) compared to indolent tumours, along with enhanced enzymatic activity demonstrated by in situ zymography. Data suggests that MMP-9 (-1562 C/T) does not facilitate predisposition for PTC but affects the disease course by modulating MMP-9 expression. Genotyping MMP-9 provides important information which may prove beneficial in risk stratification of PTC patients.

Circulating Thrombospondin-2 enhances prediction of malignant intraductal papillary mucinous neoplasm.

BACKGROUND: IPMNs are cystic pancreatic lesions with variable malignant potential. Thrombospondin-2 (THBS2)-an endogenous, anti-angiogenic matrix glycoprotein-may modulate tumor progression. We hypothesized that circulating levels of THBS2 could aid in preoperative prediction of malignant IPMN. METHODS: Preoperative serum/plasma samples were procured from patients undergoing surgery. Circulating levels of THBS2 were measured (enzyme-linked immunosorbent assay) and compared to surgical pathology IPMN dysplastic grade. RESULTS: 164 patients underwent THBS2 testing (100 Low/Moderate-IPMN; 64 High-Grade/Invasive-IPMN). Circulating THBS2 (mean ±â€¯SD) was greater in High-Grade/Invasive-IPMN than Low/Moderate-grade IPMN (26.6 ±â€¯12.7 ng/mL vs. 20.4 ±â€¯8.2 ng/mL; P < 0.001). THBS2 (AUC = 0.65) out-performed CA19-9 (n = 144; AUC = 0.59) in predicting IPMN grade. The combination of THBS2, CA19-9, radiographic main-duct involvement, main-duct diameter, age, sex, and BMI (AUC 0.82; n = 137) provided a good prediction model for IPMN grade. CONCLUSION: Circulating THBS2 is correlated with IPMN dysplasia grade. THBS2 alone did not strongly predict IPMN grade but rather strengthened prediction models for High-Grade/Invasive IPMN when combined with other clinical/biomarker data.