The expression of stromal biomarkers in small papillary thyroid carcinomas

Background The importance of stroma for tumor progression is recognized for many cancer types. In this study, we aim to evaluate the expression of types I (Col1) and IV (Col4) collagens, alpha-smooth muscle actin (a-SMA), and matrix metallopeptidase 9 (MMP-9) in the tumor stroma of small papillary thyroid carcinoma (PTC). Material and methods Twenty-five non-metastatic small PTCs (pT1N0) and nineteen metastatic small PTCs (pT1N1b) including corresponding metastatic lateral lymph nodes were selected and paraffinized tissue blocks retrieved. The samples were stained for Col1, COL4, a-SMA, and MMP-9 antibodies using immunohistochemistry. The expression of the stromal proteins was scored and analyzed based on the location, intensity, and distribution. Results Col1 and Col4 expression were significantly higher in normal thyroid tissue compared to PTC tissue. On the contrary, expression of a-SMA and MMP-9 was higher in PTC tissue compared to normal thyroid tissue. Both Col1 and Col4 were significantly more highly expressed in the non-metastatic tumors compared with metastatic tumors. The expression of a-SMA and MMP9 was slightly, but not significantly, higher in the metastasized tumors and their respective lymph nodes. There was a significant correlation between the metastasized tumors and their respective lymph nodes in Col1 and MMP-9 expression. Conclusions Col1, Col4, a-SMA, and MMP-9 expression in PTCs differs significantly from that of normal thyroid tissue. The higher expression of Col1 and Col4 in normal thyroid tissue and in the non-metastasized tumors indicates that Col1 and 4 might have a potential protective role in tumor progression. The higher expression of a-SMA and MMP9 in PTCs indicates that these proteins might have a role in promoting PTC progression and aggressiveness.Peer reviewe

Masked volume wise principal component analysis of small adrenocortical tumours in dynamic [11C]-metomidate positron emission tomography

<p>Abstract</p> <p>Background</p> <p>In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality.</p> <p>Methods</p> <p>In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0–45 minutes after the tracer injection, was used to study the tracer pharmacokinetics.</p> <p>Results</p> <p>Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15–45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining "hot spot" regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from "50% cut-off" ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment.</p> <p>Conclusion</p> <p>In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET measurements, for instance in therapy monitoring as well as for delineation of the tumour in radiation therapy planning.</p

Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases. CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)

Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow-up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country-specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68-1.15; p-trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend = 0.56), or fruit (HR: 1.00; 95% CI: 0.79-1.26; p-trend = 0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p-trend = 0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content

Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study

Background: Results from several cohort and case–control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. Methods: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results: Compared with participants consuming 0.1–4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1–1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR=0.77; 95% CI=0.60–0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes. Conclusions: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas

Clinical Studies on Adrenocortical Tumours using [11C]-metomidate Positron Emission Tomography

Adrenal tumours, discovered en passant in patients undergoing radiological examinations for non-adrenal disease, so-called adrenal incidentalomas, have increased dramatically in the recent era of more sophisticated diagnostic modalities such as high resolution multidetector computed tomography (CT) and magnetic resonance imaging (MRI). Furthermore, primary aldosteronism (PA) has been documented in several screening studies as being far more common than previously believed among hypertensive patients. In this thesis, a long-term follow-up cohort of patients who had undergone surgery for PA revealed that there was an excellent effect on blood-pressure, reduction of anti-hypertensive medication and hypokalaemia after surgery, even though the majority of these patients still required some anti-hypertensive medication. This was also true, in the higher than expected number of dominant nodular hyperplasia (nIHA) found in the study, but was slightly less pronounced than in aldosterone producing adenomas (APA).  Surgery was thus effective in lateralized PA. Metomidate positron emission tomography (MTO-PET) was explored in relation to histopathology in post-operative patients and found to be highly specific and sensitive in categorizing adrenocortical disease. Also, a higher standardized uptake value (SUV) ratio between tumours and normal adrenal cortex was found in hormonally hypersecreting adenomas as well as in adrenocortical cancer (ACC). The resolution limited the diagnosis of small tumours (&lt;1-1.5 cm). MTO-PET was compared to standard radiological modalities (CT and MRI) in the diagnostic work-up of adrenal incidentalomas. All three modalities categorized and characterized the lesions well, with MTO-PET showing the highest sensitivity and specificity.  However this method is currently recommended to be used as complementary to the others in unclear cases, due to high costs and less availability. The resolution of MTO-PET was improved with respect to less noise and better delineation of small tumours when applying masked volume-wise principal component analysis (MVW-PCA), which will possibly enable future detection of small tumours in PA patients. Dexamethasone suppression treatment prior to MTO-PET examinations in PA patients decreased SUV in normal adrenal cortex but could not be shown to increase the SUV ratio between adenoma and normal cortex enabling better detection of small tumours, even though all the tumours were readily categorized in the study. Heterogenic SUV reactions to dexamethasone treatment indicate a need for further studies and refinement of the suppression method. In conclusion, long-term results of surgery for lateralized PA are good. MTO-PET is a highly sensitive and specific method for categorizing adrenocortical disease. Modulation of the method, e.g. by using MVW-PCA and refined dexamethasone suppression treatment, may improve the resolution of the method in delineating small tumours in PA, thus making MTO-PET a non-invasive and non-operator dependent future alternative to the currently recommended adrenal venous sampling (AVS) for lateralization diagnosis prior to surgery for PA

Invasiveness and Metastatic Aggressiveness in Small Differentiated Thyroid Cancers : Demography of Small Papillary Thyroid Carcinomas in the Swedish Population

Background: The western world is seeing a rising incidence of thyroid cancer. Improved diagnostic methods do not entirely explain this increase. Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. Small PTC (&lt;= 20 mm) and especially papillary thyroid microcarcinomas (PTMC &lt;= 10 mm) are considered to be low-risk tumors but some cases are considerably more aggressive. Sufficient understanding of these mechanisms is a long-term goal for more efficient and safer treatment of these tumors. Methods: We identified 959 cases of small PTCs in the validated Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery, grouped according to lymph node metastasis. These were analyzed according to age, gender, tumor size and geographic region. Results: Patients with N1b disease (lateral lymph nodes metastases) had a smaller tumor size compared to patients with N1a disease (8.6 mm vs 10.1 mm respectively, p &lt; 0.05). Patients and specifically females with N1b disease were younger than those with N0 or N1a disease. Patients with N1b disease had a lower proportion of females (60%) compared to N0 and N1a groups (81% and 78%, respectively). The incidence of operated small PTCs and of lymph node engagement differs between geographic regions in Sweden. Conclusions: Small PTC and especially PTMC seem to show different patterns of aggressiveness and demography regarding lateral lymph node metastases and 7% had N1b disease and tumor &lt;1 cm, underscoring the importance of lymph node evaluation in PTMC patients. More understanding of predictive factors, mechanisms for metastatic disease and causes of regional differences, is needed

The Impact of a Surgical Unit's Structure and Operative Technique on Quality in Two Swedish Rural Hospitals

Introduction: Laparoscopic cholecystectomy (LC) is a commonly performed surgical procedure with a low complication rate. It is performed either as an acute or as an elective procedure. Most elective LCs are performed on nonlethal diseases and this is why good quality is important. Our study compared the quality of LC in two surgical units in northern Sweden (Sundsvall and ostersund) which use different clinical structures (subspecialised vs. general surgery) and surgical techniques (ultrasound fundus first vs. conventional diathermy). The study aimed to investigate whether these differences affected the quality of outcomes after LC. Materials and methods: This is a registry-based study which included 607 elective LCs from January 2014 to May 2016. There were 286 from Sundsvall and 321 from ostersund. Primary outcomes were operative time and the percentage of day surgeries. The secondary outcome was the presence of postoperative complications within the first 30 days in terms of bile duct injury, bleeding that necessitated reoperation, bile leakage and abscesses treated with drainage and mortality. Results: The time length of surgery was shorter in Sundsvall (mean 48.3 min) compared to ostersund (mean 108.6 min, p &lt; 0.001. The percentage of day care surgeries was 94% in Sundsvall and 23% in ostersund, p &lt; 0.001. Six patients (2.1%) had a complication in Sundsvall compared to seven patients (2.2%) in ostersund, p = 1.00. Conclusion: There is a significant difference between the two hospitals regarding operative time and the percentage of day surgeries. Complication rates in both units were equal and low

Primary Hyperparathyroidism is Underdiagnosed and Suboptimally Treated in the Clinical Setting

To evaluate whether patients presenting with laboratory results consistent with primary hyperparathyroidism (pHPT) are managed in accordance with guidelines. The laboratory database at a hospital in Sweden, serving 127,000 inhabitants, was searched for patients with biochemically determined pHPT. During 2014, a total of 365 patients with biochemical laboratory tests consistent with pHPT were identified. Patients with possible differential diagnoses or other reasons for not being investigated according to international guidelines were excluded after scrutinizing records, after new blood tests, and clinical assessments by endocrine surgeons. Altogether, 92 patients had been referred to specialists and 82 had not. The latter group had lower serum calcium (median 2.54 mmol/L) and PTH (5.7 pmol/L). Out of these 82 cases, 9 patients were diagnosed with pHPT or had some sort of long-term follow-up planned as outpatients. Primary hyperparathyroidism is overlooked and underdiagnosed in a number of patients in the clinical setting. It is important to provide local guidelines for the management of patients presenting with mild pHPT to ensure that these patients receive proper evaluation and follow-up according to current research

Risk factors for recurrent disease in small papillary thyroid cancers - a Swedish register-based study

Peer reviewe