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1.
  • Bayadsi, Haytham, et al. (author)
  • Invasiveness and Metastatic Aggressiveness in Small Differentiated Thyroid Cancers : Demography of Small Papillary Thyroid Carcinomas in the Swedish Population
  • 2020
  • In: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 44:2, s. 461-468
  • Journal article (peer-reviewed)abstract
    • 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 (<= 20 mm) and especially papillary thyroid microcarcinomas (PTMC <= 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 < 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 <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.
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2.
  • Bayadsi, Haytham, et al. (author)
  • Risk factors for recurrent disease in small papillary thyroid cancers : a Swedish register-based study
  • 2023
  • In: Langenbeck's archives of surgery (Print). - : Springer. - 1435-2443 .- 1435-2451. ; 408:1
  • Journal article (peer-reviewed)abstract
    • AIMS: To study the correlation between clinicopathological risk factors and the risk for intervention-requiring cancer recurrence in patients with small papillary thyroid cancers (sPTCs). MATERIALS AND METHODS: Records for 397 patients with sPTC (T1 ≤ 20mm) were obtained from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) between 2010 and 2016. Follow-up time was at least 5 years. Data regarding intervention-requiring cancer recurrence were obtained from patient medical records and analysed regarding lymph node (LN) status (N0, N1a and N1b) and recurrence. RESULTS: Age was significantly lower in the N1a and N1b groups compared to N0 (45 vs. 40.5 vs. 49 years, respectively; p = 0.002). Tumour size was smaller in the N1a group compared to N1b group (9 vs. 11.8 mm; p <0.01). The mean number of metastatic LNs at initial surgery was higher in the N1b compared to N1a group (6.6 vs. 3; p = 0.001), and in the recurrent compared to the non-recurrent group (7 versus 3.9; p <0.01). The recurrence rate was higher in the N1b group than the N1a and N0 groups (25% vs. 2.4% vs. 1.4%, respectively; p = 0.001). CONCLUSIONS: Lymph node stage N1b at diagnosis, and having five or more metastatic nodes, are strong risk factors for cancer recurrence and decreased disease-free survival in sPTC. The management of patients with sPTC should include thorough lymph node mapping for optimal treatment and individual risk stratification.
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3.
  • Bayadsi, Haytham, 1987-, et al. (author)
  • The correlation between small papillary thyroid cancers and gamma radionuclides Cs-137, Th-232, U-238 and K-40 using spatially-explicit, register-based methods
  • 2023
  • In: Spatial and Spatio-Temporal Epidemiology. - : Elsevier. - 1877-5845 .- 1877-5853. ; 47
  • Journal article (peer-reviewed)abstract
    • A steep increase of small papillary thyroid cancers (sPTCs) has been observed globally. A major risk factor for developing PTC is ionizing radiation. The aim of this study is to investigate the spatial distribution of sPTC in Sweden and the extent to which prevalence is correlated to gamma radiation levels (Caesium-137 (Cs-137), Thorium-232 (Th-232), Uranium-238 (U-238) and Potassium-40 (K-40)) using multiple geospatial and geo-statistical methods. The prevalence of metastatic sPTC was associated with significantly higher levels of Gamma radiation from Th-232, U-238 and K-40. The association is, however, inconsistent and the prevalence is higher in densely populated areas. The results clearly indicate that sPTC has causative factors that are neither evenly distributed among the population, nor geographically, calling for further studies with bigger cohorts. Environ-mental factors are believed to play a major role in the pathogenesis of the disease.
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4.
  • Bayadsi, Haytham, et al. (author)
  • The expression of stromal biomarkers in small papillary thyroid carcinomas
  • 2022
  • In: World Journal of Surgical Oncology. - : BioMed Central (BMC). - 1477-7819. ; 20:1
  • Journal article (peer-reviewed)abstract
    • 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.
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5.
  • Bayadsi, Haytham, 1987- (author)
  • Tumour stromal and demographical factors affecting the metastatic aggressiveness of small differentiated papillary thyroid cancers in Sweden
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • Background: The incidence of papillary thyroid cancer (PTC) has been increasing over the recent decades, especially that of small papillary thyroid cancers (sPTCs) (≤ 20mm in size). sPTCs are generally classified as low risk cancers with a very favourable diagnosis, yet some of these cancers still cause locoregional and distant metastasis, recurrence and even death.Aims: To investigate the role of tumour stromal, environmental and demographical factors affecting the metastatic aggressiveness of sPTCs in Sweden.Material & Methods: Selected tumour stromal proteins (Types I (Col1) and IV (Col4) collagens, alpha smooth muscle actin (a-SMA) and matrix metallopeptidase 9 (MMP-9)) were analysed for their role in metastatic disease (Paper I). Demographic and clinicopathological differences regarding recurrence between metastasized vs. non-metastasized sPTCs in Sweden were studied in 2 registry-based retrospective observational cohort studies (Papers II & III). The geographic distribution of patients with sPTC in Sweden was pinpointed and layered with maps of gamma radiation deposits of radionuclides Caesium-137 (Cs-137), Thorium-232 (Th-232), Uranium-238 (U-238) and Potassium-40 (K-40) using different spatial analysis methods (Paper IV).Results: Col1 and Col4 were significantly more expressed in the non-metastatic tumours compared with metastatic ones. Patients with N1b disease were younger, had a smaller tumour size and higher recurrence rates compared to patients with N0 and N1a disease. The mean number of metastatic LNs at initial surgery was higher in the N1b group than the N1a group and correlated with more recurrent disease. The prevalence of metastatic sPTC was associated with significantly higher levels of gamma radiation from Th-232, U-238 and K-40.Conclusions: The higher expression of Col1 and Col4 in the non-metastasized tumours indicates a potential protective role in tumour progression. LN stage N1b at diagnosis, and having five or more metastatic nodes, are strong risk factors for cancer recurrence and decreased disease-free survival in sPTC. Environmental factors such as gamma radiation are believed to play a major role in the pathogenesis of the PTC. These findings altogether underscore the importance of LN evaluation, tumour biological as well as environmental factors in sPTC patients, suggesting that the management of these patients should be based on an individual risk stratification instead of a “one size fits all” approach.
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6.
  • Blohm, My, et al. (author)
  • Learning by doing : an observational study of the learning curve for ultrasonic fundus-first dissection in elective cholecystectomy
  • 2022
  • In: Surgical Endoscopy. - : Springer. - 0930-2794 .- 1432-2218. ; 36, s. 4602-4613
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Surgical safety and patient-related outcomes are important considerations when introducing new surgical techniques. Studies about the learning curves for different surgical procedures are sparse. The aim of this observational study was to evaluate the learning curve for ultrasonic fundus-first (FF) dissection in elective laparoscopic cholecystectomy (LC).METHODS: The study was conducted at eight hospitals in Sweden between 2017 and 2019. The primary endpoint was dissection time, with secondary endpoints being intra- and postoperative complication rates and the surgeon's self-assessed performance level. Participating surgeons (n = 16) were residents or specialists who performed LC individually but who had no previous experience in ultrasonic FF dissection. Each surgeon performed fifteen procedures. Video recordings from five of the procedures were analysed by two external surgeons. Patient characteristics and data on complications were retrieved from the Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks).RESULTS: Dissection time decreased as experience increased (p = 0.001). Surgeons with limited experience showed more rapid progress. The overall complication rate was 14 (5.8%), including 3 (1.3%) potentially technique-related complications. Video assessment scores showed no correlation with the number of procedures performed. The self-assessed performance level was rated lower when the operation was more complicated (p < 0.001).CONCLUSIONS: Our results show that dissection time decreased with increasing experience. Most surgeons identified both favourable and unfavourable aspects of the ultrasonic FF technique. The ultrasonic device is considered well suited for gallbladder surgery, but most participating surgeons preferred to dissect the gallbladder the traditional way, beginning in the triangle of Calot. Nevertheless, LC with ultrasonic FF dissection can be considered easy to learn with a low complication rate during the initial learning curve, for both residents and specialists.
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7.
  • Enberg, U., et al. (author)
  • Increased ratio of mRNA expression of the genes CYP17 and CYP11B1 indicates autonomous cortisol production in adrenocortical tumors
  • 2009
  • In: Journal of Endocrinological Investigation. - 0391-4097 .- 1720-8386. ; 32:10, s. 810-815
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Due to increased use of imaging techniques, adrenal incidentalomas are frequently detected. The majority are non-hyperfunctioning adrenocortical tumors. We have previously shown that expression of the gene CYP17, coding for the enzyme in the cortisol pathway, correlates with cortisol release from adrenocortical tumors in vitro. The aim of this study was to compare clinical data with mRNA expression of CYP17 and CYP11B1 in adrenocortical tumors from patients with and without Cushing's syndrome and to identify adrenal tumors that may cause subclinical Cushing's syndrome. DESIGN: A retrospective study of 34 patients undergoing adrenalectomy due to an adrenal tumor. METHODS: Clinical data were collected. In the adrenal gland the mRNA expression of the genes CYP17 and CYP11B1 was studied with in situ hybridisation technique. RESULTS: The median ratio of CYP17/CYP11B1 expression in tumors from patients with Cushing's syndrome was significantly higher than the median ratio in the non-hyperfunctioning tumors. Tumors from 2 patients with subclinical Cushing's syndrome had ratios within the upper range for non-hyperfunctioning tumors. CONCLUSIONS: The ratio between the expression of the genes CYP17 and CYP11B1 in tumors from patients with Cushing's syndrome is significantly higher than in the non-hyperfunctioning tumors. This indicates that 17alpha-hydroxylase is a major determinant of cortisol overproduction. The patients with subclinical Cushing's syndrome in this study are too few to draw any firm conclusions although the results suggest that subclinical Cushing's syndrome may be identified post-operatively with this method.
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8.
  • Enell, Jacob, et al. (author)
  • Primary Hyperparathyroidism is Underdiagnosed and Suboptimally Treated in the Clinical Setting
  • 2018
  • In: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 42:9, s. 2825-2834
  • Journal article (peer-reviewed)abstract
    • 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.
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10.
  • Hellman, Per, et al. (author)
  • Stenting of the superior mesenteric vein in midgut carcinoid disease with large mesenteric masses
  • 2010
  • In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 34:6, s. 1373-1379
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Midgut carcinoid (MGC) tumors generally develop in the small intestine and in >50% of cases also present with lymph node metastases in the mesentery. The majority of these tumors are surgically resectable, but a fraction are inoperable and may cause obstruction of the superior mesenteric vein (SMV), often associated with stasis of the intestinal wall and severe symptoms. These symptoms include severe abdominal pain, attacks of diarrhea, and malnutrition. METHODS: Seven patients with severe MGC including a large fibrotic inoperable mesenteric mass and severe symptoms were studied. After an obstructed SMV and signs of venous stasis in the small intestine were demonstrated, an expandable stent was inserted after puncturing an intrahepatic portal venous branch. The associated venography, patient symptoms, and radiological signs on computed tomography (CT) scans were evaluated. RESULTS: Four patients demonstrated resolution of their symptoms. In one patient who had intra-abdominal lymph leakage/chyloperitoneum, a complete normalization of the circulation followed and the intra-abdominal lymph leakage stalled. The venographies demonstrated normalization of the venous blood flow through the SMV, and CT scans demonstrated reduction in the thickness of the intestinal wall. In two cases there were no changes in the symptoms, and in one case a slight worsening of the symptoms ensued. In general, reductions of symptoms were associated with the degree of normalization of venous blood flow. CONCLUSIONS: We conclude that in selected patients with MGC stenting of the SMV may improve symptoms.
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11.
  • Hennings, Joakim, 1969-, et al. (author)
  • 11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism
  • 2010
  • In: Langenbeck's archives of surgery (Print). - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 395:7, s. 963-967
  • Journal article (peer-reviewed)abstract
    • Purpose: To evaluate whether dexamethasone suppression treatment can improve 11 C-metomidate positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism (PA). Materials and Methods: Eleven patients with proven PA and two patients with non-hyperfunctioning adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before and 3 days after administration of oral dexamethasone suppression treatment. Small “hot-spot” regions of interest (ROIs) comprising 4-pixels (SUVhs) and 1-pixel  (SUVmax) were placed in the tumour area with the highest radioactivity concentration and their respective standardised uptake values (SUV) were recorded. Results: All tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher in PA compared to non-functional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p<0.05) but tumour SUV was not significantly decreased after suppression in either PA or non-functional tumours (p>0.05).  However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p>0.05). Conclusion: MTO-PET is a highly sensitive method for detecting and categorising even small adrenocortical tumours in PA. In this series dexamethasone-suppressed MTO-PET was ubable to increase the tumour-to-normal-adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal venous sampling.
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12.
  • Hennings, Joakim, et al. (author)
  • [11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings
  • 2006
  • In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:4, s. 1410-4
  • Journal article (peer-reviewed)abstract
    • CONTEXT: Adrenal incidentalomas are common findings necessitating extensive laboratory work-up and repetitive radiological examinations. Positron emission tomography (PET) using (11)C-labeled metomidate (MTO) has previously been described as a tool for specific adrenocortical imaging. OBJECTIVE: We evaluated 212 MTO-PET examinations in 173 patients to identify its role in the management of adrenal tumors. DESIGN: Seventy-five histopathological examinations from 73 patients were retrospectively analyzed. SETTING: All examinations were performed at a referral center. PATIENTS: Patients who were operated or biopsied due to adrenal tumors had histopathological diagnoses of adrenocortical adenoma (n = 26), adrenocortical cancer (ACC; n = 13), adrenocortical hyperplasia (n = 8), pheochromocytoma (n = 6), metastasis (n = 3), and tumors of nonadrenal origin (n = 19). MAIN OUTCOME MEASURES: The main outcome measures were statistical analyses and findings while scrutinizing images. The hypothesis that MTO-PET is of value in the management of adrenal tumors, especially incidentaloma, was stated before data collection. RESULTS: Sensitivity was 0.89 and specificity was 0.96 for MTO-PET in proving adrenocortical origin of the lesions. Pheochromocytomas, metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET measurements using standardized uptake values (SUV) in pathological adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from normal adrenocortical tissue. SUV was higher in aldosterone-hypersecreting adenomas, and the SUV ratio between the tumor and the contralateral gland was significantly higher in all hormonally hypersecreting adenomas as well as in ACC. CONCLUSION: MTO-PET is a specific and sensitive method for diagnosing adrenocortical tumors. MTO-PET is useful in the imaging work-up of adrenal incidentalomas and may be beneficial for the examination of patients with primary aldosteronism or ACC.
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  • Hennings, Joakim, 1969- (author)
  • Clinical Studies on Adrenocortical Tumours using  [11C]-metomidate Positron Emission Tomography
  • 2009
  • Doctoral thesis (other academic/artistic)abstract
    • 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 (<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.
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14.
  • Hennings, Joakim, et al. (author)
  • Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas
  • 2009
  • In: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 69:2, s. 314-23
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Given the higher sensitivity of modern computed tomography (CT) scanners, adrenal incidentalomas are being discovered increasingly often. This implies a growing quantitative diagnostic and clinical problem. CT and/or magnetic resonance imaging (MRI) and usually thorough hormonal testing are routinely used to determine the origin of these lesions. Recently, positron emission tomography (PET) using the tracer (11)C-metomidate (MTO) has been established as an alternative diagnostic method with high sensitivity for identifying adrenocortical lesions. The aim of this study was to evaluate the clinical use and value of MTO-PET compared to CT and MRI in the characterisation and work-up of adrenal incidentalomas. METHODS: Initially, we retrospectively evaluated 20 adrenal incidentalomas in patients who had undergone CT, MRI and MTO-PET and from whom we had either histopathological diagnosis or clinical follow-up data. After this analysis we conducted a prospective study in order to compare the imaging modalities. In the latter study, 24 incidentalomas were imaged by CT, MRI and MTO-PET and the results were correlated to those from histopathology (n=8) and clinical diagnosis after follow-up (n=16). RESULTS: In the retrospective analysis, MRI and especially MTO-PET, correlated well to histopathology and clinical diagnosis after follow-up, whereas specificity with CT was low. This was possibly due to the presence of several haematomas/fibrosis which were misdiagnosed as adrenocortical adenomas. In the prospective cohort, sensitivity and specificity with CT were 0.71 and 1.0, respectively, and further characterisation by MRI increased these values to 0.86 and 1.0, whereas maximum sensitivity and specificity were reached when MTO-PET was added. CONCLUSION: The diagnosis of an adrenocortical adenoma may be established by CT in most patients and by MRI in an additional number. For the few remaining patients needing further characterisation, MTO-PET is advantageous as an additional imaging modality.
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16.
  • Hennings, Joakim, et al. (author)
  • Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism
  • 2010
  • In: Langenbeck's archives of surgery (Print). - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 395:2, s. 133-137
  • Journal article (peer-reviewed)abstract
    • PURPOSE: The purpose of this is to study long-time results of surgery for primary aldosteronism. MATERIALS AND METHODS: Thirty patients operated on for primary aldosteronism were followed for an average of 7 years. All but five required potassium substitution. Systolic as well as diastolic hypertension (mean 157/93 mmHg) was present necessitating one to five antihypertensive drugs daily (mean 2.33). Preoperative indications for surgery included presumed adenoma (aldosterone-producing adenoma (APA)) or in one case unilateral dominance of hyperplasia. RESULTS: Histopathology was classified into adenoma (n = 9), dominant nodule (n = 16), and general hyperplasia without dominating nodules (n = 5), demonstrating a higher frequency of hyperplasia than anticipated. Long-term results revealed well-controlled blood pressure (BP; mean 134/80 mmHg). Antihypertensive medication was reduced (average of 1.78 per day), but only 36% of the patients were taken off these drugs completely. S-Aldosterone was normalized. All but one (a recurrence) were normokalemic without potassium substitution at follow-up. The APA group needed less medication (median 0.5 vs. 1.5 and 2 per day) and more patients in this group were totally medication free (50%). Two recurrences occurred in the group with general hyperplasia without dominating nodules. CONCLUSION: Nodular hyperplasia is more common than anticipated. Hypersecretion of aldosterone may be released from a large nodule identified as an adenoma, as well as from a generally hyperplastic gland that has not been identified as such. Nevertheless, surgery for lateralized disease results in good long-term control of BP with less antihypertensive medication. However, patients with dominant nodule or general hyperplasia without dominating nodules need more postoperative treatment than patients with APA. The majority of patients do not achieve normotension without medications, but they do become normokalemic.
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18.
  • Kaçmaz, Enes, et al. (author)
  • International survey on opinions and use of minimally invasive surgery in small bowel neuroendocrine neoplasms
  • 2022
  • In: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 48:6, s. 1251-1257
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Although minimally invasive surgery is becoming the standard technique in gastrointestinal surgery, implementation for small bowel neuroendocrine neoplasms (SB-NEN) is lagging behind. The aim of this international survey was to gain insights into attitudes towards minimally invasive surgery for resection of SB-NEN and current practices.METHODS: An anonymous survey was sent to surgeons between February and May 2021 via (neuro)endocrine and colorectal societies worldwide. The survey consisted of questions regarding experience of the surgeon with minimally invasive SB-NEN resection and training.RESULTS: A total of 58 responses from five societies across 20 countries were included. Forty-one (71%) respondents worked at academic centers. Thirty-seven (64%) practiced colorectal surgery, 24 (41%) endocrine surgery and 45 (78%) had experience in advanced minimally invasive surgery. An open, laparoscopic or robotic approach was preferred by 23 (42%), 24 (44%), and 8 (15%) respondents, respectively. Reasons to opt for a minimally invasive approach were mainly related to peri-operative benefits, while an open approach was preferred for optimal mesenteric lymphadenectomy and tactile feedback. Additional training in minimally invasive SB-NEN resection was welcomed by 29 (52%) respondents. Forty-three (74%) respondents were interested in collaborating in future studies, with a cumulative median (IQR) annual case load of 172 (86-258).CONCLUSIONS: Among respondents, 69% applies minimally invasive surgery for resection of SB-NEN. Arguments for specific operative approaches differ, and insufficient training in advanced laparoscopic techniques seems to be a barrier. Future collaborative studies can provide better insight in selection criteria and optimal technique.
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19.
  • Llaha, Fjorida, et al. (author)
  • Adherence to mediterranean diet and the risk of differentiated thyroid cancer in a European cohort : the EPIC study
  • 2022
  • In: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
  • Journal article (peer-reviewed)abstract
    • Background: The Mediterranean diet (MD) has been proposed as a healthy diet with a potential to lower the incidence of several types of cancer, but there is no data regarding thyroid cancer (TC). We investigated the association between MD adherence, and its components, and the differentiated TC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Methods: Over 450,000 men and women from nine European countries were followed up for a mean of 14.1 years, during which 712 differentiated TC cases were identified. Adherence to MD was estimated using the relative MD (rMED) score, an 18-point scale including alcohol, and the adapted rMED (arMED) score, a 16-point scale excluding alcohol. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors.Results: Adherence to the arMED score was not associated with the risk of differentiated TC (HRhigh vs. low adherence = 0.94, 95% CI: 0.70–1.25; p-trend 0.27), while a suggestive, but non-statistically significant inverse relationship was observed with rMED (HRhigh vs. low adherence = 0.88, 95% CI: 0.68–1.14; p-trend 0.17). Low meat (HRlow vs. high meat intake = 0.81, 95% CI: 0.67–0.99; p-trend = 0.04) and moderate alcohol (HRmoderate vs. non−moderate intake = 0.88, 95% CI: 0.75–1.03) intake were related with lower differentiated TC risk.Conclusions: Our study shows that a high adherence to MD is not strongly related to differentiated TC risk, although further research is required to confirm the impact of MD and, especially, meat intake in TC risk.
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20.
  • Odelberg, Nina, et al. (author)
  • The Impact of a Surgical Unit's Structure and Operative Technique on Quality in Two Swedish Rural Hospitals
  • 2020
  • In: Journal of investigative surgery. - : Taylor & Francis Group. - 0894-1939 .- 1521-0553. ; 33, s. 924-929
  • Journal article (peer-reviewed)abstract
    • 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 < 0.001. The percentage of day care surgeries was 94% in Sundsvall and 23% in ostersund, p < 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.
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21.
  • Rask, Eva, 1958-, et al. (author)
  • Adrenocorticotropin-independent Cushing's syndrome in pregnancy related to overexpression of adrenal luteinizing hormone/human chorionic gonadotropin receptors
  • 2009
  • In: Journal of Endocrinological Investigation. - : Editrice kurtis. - 0391-4097 .- 1720-8386. ; 32:4, s. 313-316
  • Journal article (peer-reviewed)abstract
    • Cushing's syndrome during pregnancy is rare, and rather than being of pituitary origin most patients exhibit ACTH-independent adrenal hypercortisolism. In some cases the syndrome has spontaneously resolved post partum, suggesting the presence of a pregnancy-associated stimulatory factor(s). We describe a case with aberrant adrenal LH/hCG receptors in a large adrenal tumor as a possible explanation for cortisol hypersecretion and tumor growth in Cushing s syndrome during pregnancy. A 27-yr-old woman presented with hypertension and diabetes mellitus in early pregnancy. Investigations revealed hypercortisolemia, suppressed ACTH-levels, and a 6.4- cm right adrenal tumor. The tumor was successfully removed by laparoscopy at 26th week of pregnancy. Hypercortisolism and hypertension resolved post-operatively. The tumor displayed higher LH/hCG receptor mRNA and protein positivity than adjacent normal adrenal tissue as examined by in situ hybridization and immunocytochemistry. High physiological levels of hCG, in conjunction with aberrant adrenal LH/hCG receptor overexpression, may have contributed to the development of Cushing's syndrome in pregnancy.
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22.
  • Razifar, Pasha, et al. (author)
  • Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography
  • 2009
  • In: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 9:6
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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23.
  • Rinaldi, Sabina, et al. (author)
  • Circulating endogenous sex steroids and risk of differentiated thyroid carcinoma in men and women
  • 2024
  • In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 154:12, s. 2064-2074
  • Journal article (peer-reviewed)abstract
    • Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96–2.92, ptrend =.06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96–3.30, ptrend =.06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28–1.05, ptrend =.07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women.
  •  
24.
  • Rinaldi, Sabina, et al. (author)
  • Thyroid-Stimulating Hormone, Thyroglobulin, and Thyroid Hormones and Risk of Differentiated Thyroid Carcinoma: The EPIC Study
  • 2014
  • In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 106:6, s. 097-097
  • Journal article (peer-reviewed)abstract
    • Background Increased levels of thyroglobulin (Tg) and thyroid-stimulating hormone (TSH) are associated with differentiated thyroid carcinoma (TC) risk, but strong epidemiological evidence is lacking. Methods Three hundred fifty-seven incident TC case patients (n = 300 women and 57 men; mean age at blood collection = 51.5 years) were identified in the EPIC cohort study and matched with 2 (women) or 3 (men) control subjects using incidence density sampling. Matching included study center, sex, age, date, time, and fasting status at blood collection. Levels of total and free (f) thyroxine (T4) and triiodo-thyronine (T3), TSH, Tg, and anti-Tg antibodies (TgAb) were measured by commercially available immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression. All statistical tests were two-sided. Results TC risk was positively associated with Tg (OR for the highest vs lowest quartile = 9.15; 95% CI = 5.28 to 15.90; P < .001) and negatively associated with TSH level (OR = 0.56; 95% CI = 0.38 to 0.81; P = .001). Odds ratios were not modified by adjustment for weight and height and were consistent across sexes, age groups, and countries. The association with Tg was stronger in follicular than papillary TC. The odds ratio for TgAb-positivity was 1.50 (95% CI = 1.05 to 2.15; P = .03). Among case patients, TSH level was stable over time, whereas Tg level was higher in proximity to TC diagnosis. Areas under the receiver operating characteristic curve were 57% and 74% for TSH and Tg level, respectively. Conclusions High Tg levels precede by up to 8 years the detection of TC, pointing to a long sojourn time of the disease. Low TSH levels may predispose to TC onset. Neither marker has sufficient accuracy to be a screening test.
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25.
  • Schmidt, Julie A, et al. (author)
  • Insulin-like growth factor-I and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition
  • 2014
  • In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:6, s. 976-985
  • Journal article (peer-reviewed)abstract
    • Background: Little is known about the causes of thyroid cancer, but insulin-like growth factor-I (IGF-I) might play an important role in its development due to its mitogenic and anti-apoptotic properties. Methods: This study prospectively investigated the association between serum IGF-I concentrations and risk of differentiated thyroid carcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. 345 incident cases of differentiated thyroid carcinoma were individually matched to 735 controls by study centre, sex, and age, date, time, and fasting status at blood collection, follow-up duration, and for women menopausal status, use of exogenous hormones, and phase of menstrual cycle at blood collection. Serum IGF-I concentrations were measured by immunoassay, and risk of differentiated thyroid cancer in relation to IGF-I concentration was estimated using conditional logistic regression. Results: There was a positive association between IGF-I concentrations and risk of differentiated thyroid carcinoma: the odds ratio for a doubling in IGF-I concentration was 1.48 (95% confidence interval: 1.06 - 2.08; ptrend = 0.02). The positive association with IGF-I was stable over time between blood collection and cancer diagnosis. Conclusion: These findings suggest that IGF-I concentrations may be positively associated with risk of differentiated thyroid carcinoma. Impact: This study provides the first prospective evidence of a potential association between circulating IGF-I concentrations and risk of differentiated thyroid carcinoma and may prompt the further investigations needed to confirm the association.
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26.
  • Sellgren, Fredrik, et al. (author)
  • Outcomes After Surgery for Unilateral Dominant Primary Aldosteronism in Sweden
  • 2020
  • In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 44, s. 561-569
  • Journal article (peer-reviewed)abstract
    • Background Primary aldosteronism (PA) is the most common cause of secondary hypertension. Surgery is the mainstay of treatment for unilateral dominant PA, but reported cure rates varies. The aim of the present study was to investigate contemporary follow-up practices and cure rates after surgery for PA in Sweden. Methods Patients operated for PA and registered in the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) 2009-2015 were identified. Patient data were extracted, and follow-up data (1-24 months) was recorded. Doses of antihypertensive medication and potassium supplementation were calculated using defined daily doses (DDD), and the Primary Aldosteronism Surgical Outcome (PASO) criteria were used to evaluate outcomes. Results Of 190 registered patients, 171 (47% female, mean age 53 years, median follow-up 3.7 months) were available for analysis. In 75 patients (44%), missing data precluded evaluation of biochemical cure according to the PASO criteria. Minimal invasive approach was used in 168/171 patients (98%). Complication rate (Clavien-Dindo >3a) was 3%. No mortality was registered. Pre/postoperatively 98/66% used antihypertensives (mean DDD 3.7/1.5). 89/2% had potassium supplementation (mean DDD 2.0/0) before/after surgery. Complete/partial biochemical and clinical success according to the PASO criteria were achieved in 92/7% and 34/60%, respectively. Conclusion In this study, reflecting contemporary clinical practice in Sweden complete/partial biochemical and clinical success after surgery for PA was 92/7% and 34/60%. Evaluation of biochemical cure was hampered by lack of uniform reporting of relevant outcome measures. We suggest mandatory reporting of surgical outcomes using the PASO criteria for all units performing surgery for PA.
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27.
  • Sen, Abhijit, et al. (author)
  • Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study
  • 2015
  • In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 113:5, s. 840-847
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
28.
  • Zamora-Ros, Raul, et al. (author)
  • Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study
  • 2021
  • In: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 113:1, s. 162-171
  • Journal article (peer-reviewed)abstract
    • Background: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. Objectives: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). Methods: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. Results: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. Conclusions: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.
  •  
29.
  • Zamora-Ros, Raul, et al. (author)
  • 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
  • 2019
  • In: European Journal of Nutrition. - : Springer Berlin/Heidelberg. - 1436-6207 .- 1436-6215. ; 58:8, s. 3303-3312
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
30.
  • Zamora-Ros, Raul, et al. (author)
  • Consumption of fish is not associated with risk of differentiated thyroid carcinoma in the European prospective investigation into cancer and nutrition (EPIC) study
  • 2017
  • In: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 147:7, s. 1366-1373
  • Journal article (peer-reviewed)abstract
    • Background: Differentiated thyroid cancer (TC) is the most common endocrine cancer. Fish can be an important source of iodine and other micronutrients and contaminants that may affect the thyroid gland and TC risk. Objective: We prospectively evaluated the relations between the consumption of total fish and different fish types and shellfish and TC risk in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: EPIC is a cohort of > 500,000 men and women, mostly aged 35-70 y, who were recruited in 10 European countries. After a mean follow-up of 14 y, 748 primary differentiated TC cases were diagnosed; 666 were in women and 601 were papillary TC. Data on intakes of lean fish, fatty fish, fish products, and shellfish were collected by using countryspecific validated dietary questionnaires at recruitment. Multivariable Cox regression was used to calculate HRs and 95% CIs adjusted for many potential confounders, including dietary and nondietary factors. Results: No significant association was observed between total fish consumption and differentiated TC risk for the highest compared with the lowest quartile (HR: 1.03; 95% CI: 0.81, 1.32; P-trend = 0.67). Likewise, no significant association was observed with the intake of any specific type of fish, fish product, or shellfish. No significant heterogeneity was found by TC subtype (papillary or follicular tumors), by sex, or between countries with low and high TC incidence. Conclusion: This large study shows that the intake of fish and shellfish was not associated with differentiated TC risk in Europe, a region in which iodine deficiency or excess is rare.
  •  
31.
  • Zamora-Ros, Raul, et al. (author)
  • Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
  • 2018
  • In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:3, s. 449-459
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
32.
  • Zamora-Ros, Raul, et al. (author)
  • Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study
  • 2016
  • In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 138:1, s. 65-73
  • Journal article (peer-reviewed)abstract
    • Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4vs.Q1, 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4vs.Q1, 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI25 and with sugar intake in those with BMI<25. Moreover, inverse associations with starch and GI were observed in subjects with BMI<25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people. What's New? The role of lifestyle factors in the growing numbers of thyroid cancer remains unclear. Here, the authors uncover associations with high total energy intake and low consumption of polyunsaturated fatty acids in a large European cohort (EPIC). They further find positive associations with starch intake and glycemic index only in people with a body mass index equal or larger than 25, possibly implicating an altered insulin response in the etiology of this cancer.
  •  
33.
  • Zamora-Ros, Raul, et al. (author)
  • Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
  • 2020
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:7, s. 1841-1850
  • Journal article (peer-reviewed)abstract
    • Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77–1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80–1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
  •  
34.
  • Zamora-Ros, Raul, et al. (author)
  • Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study
  • 2015
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 1218-1227
  • Journal article (peer-reviewed)abstract
    • Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for 5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for 9 vs. 1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR=1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR=1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause.
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