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Clinical and Translational... Dec 2015Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This...
OBJECTIVES
Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This study aims to identify the best imaging modality for detecting malignant transformation in IPMN, the sensitivity and specificity of risk features on imaging, and the usefulness of tumor markers in serum and cyst fluid to predict malignancy in IPMN.
METHODS
Databases were searched from November 2006 to March 2014. Pooled sensitivity and specificity of diagnostic techniques/imaging features of suspected malignancy in IPMN using a hierarchical summary receiver operator characteristic (HSROC) approach were performed.
RESULTS
A total of 467 eligible studies were identified, of which 51 studies met the inclusion criteria and 37 of these were incorporated into meta-analyses. The pooled sensitivity and specificity for risk features predictive of malignancy on computed tomography/magnetic resonance imaging were 0.809 and 0.762 respectively, and on positron emission tomography were 0.968 and 0.911. Mural nodule, cyst size, and main pancreatic duct dilation found on imaging had pooled sensitivity for prediction of malignancy of 0.690, 0.682, and 0.614, respectively, and specificity of 0.798, 0.574, and 0.687. Raised serum carbohydrate antigen 19-9 (CA19-9) levels yielded sensitivity of 0.380 and specificity of 0903. Combining parameters yielded a sensitivity of 0.743 and specificity of 0.906.
CONCLUSIONS
PET holds the most promise in identifying malignant transformation within an IPMN. Combining parameters increases sensitivity and specificity; the presence of mural nodule on imaging was the most sensitive whereas raised serum CA19-9 (>37 KU/l) was the most specific feature predictive of malignancy in IPMNs.
PubMed: 26658837
DOI: 10.1038/ctg.2015.60 -
Diagnostic Pathology Oct 2015Nodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. "Follicular" refers to origin of cells and in...
BACKGROUND
Nodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. "Follicular" refers to origin of cells and in the same time to growth pattern - building follicles. Nodular follicular thyroid lesions have in common many morphological features, therefore attempts were made to define additional criteria for distinction between follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma. Increasing number of immunohistochemical markers is in the continual process of evaluation.
METHODS
Tissue microarrays incorporating, total 201 cases, out of which 122 malignant and 79 benign follicular lesions, including neoplastic and non-neoplastic, were constructed and immunostained with antibodies to CD56, CK19, Galectin-3, HBME-1. Tissue cores were exclusively being acquired from tumour/lesion on interface with normal thyroid tissue. A systematic review of literature was done for period from the year 2001 to present time.
RESULTS
All analysed markers may make a difference between benign lesions/tumours from differentiated thyroid carcinomas (p = <0.01, for all markers). Expression of all markers is significantly higher in papillary carcinoma than in follicular adenoma (p < 0.01). Statistically significant difference in expression of Galectin-3 and CD56 between follicular carcinoma and follicular adenoma was registered (p = 0.043; p = 0.028, respectively). The only marker which expression showed statistically significant difference between adenoma and carcinoma of Hurthle cells was Galectin 3 (p = 0.041). CK19 and HBME-1 were significantly expressed more in papillary carcinoma as compared to follicular carcinoma.
CONCLUSION
Galectin 3 is most sensitive marker for malignancy, while loss of expression of CD56 is very specific for malignancy. Expected co-expression for combination of markers in diagnosis of follicular lesions decreases sensitivity and increases specificity for malignancy.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Adenocarcinoma, Follicular; Biomarkers, Tumor; Carcinoma, Papillary; CD56 Antigen; Galectin 3; Keratin-19; Thyroid Neoplasms
PubMed: 26503236
DOI: 10.1186/s13000-015-0428-4 -
PloS One 2015Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) for patients with clinically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) for patients with clinically negative central compartment lymph nodes (CN0) remains controversial. The phrase "clinically negative" is used to indicate that patients exhibited no clinical evidence of CLNM by ultrasonography (US) or computerized tomography (CT) preoperatively. In this study, we analyze the risk factors for CLNM in CN0 patients.
METHODS
The PUBMED and SCIE databases were systematically searched for works published through January 31, 2015. All of the patients included in this study underwent thyroidectomy+PCLND. Revman 5.3 software was used to analyze the data.
RESULTS
Twenty studies and 9084 patients were included in this meta-analysis. The following variables were associated with an increased risk of CLNM in CN0 patients: age < 45 years (OR = 1.59, 95% CI = 1.42-1.78, p<0.00001), male sex (OR = 1.95, 95% CI = 1.63-2.32, p<0.00001), multifocality (OR = 1.43, 95% CI = 1.22-1.67, p<0.00001), tumor size > 2 cm for PTC patients (OR = 2.98, 95% CI 2.08-4.28, p<0.00001) or tumor size > 0.5 cm for papillary thyroid microcarcinoma (PTMC) patients (OR = 2.30, 95% CI = 1.71-3.09, p<0.00001), location of the primary tumor in the central area and low pole (OR = 1.86, 95% CI = 1.48-2.33, p<0.00001), lymphovascular invasion (OR = 4.35, 95% CI = 2.24-8.46, p<0.0001), extrathyroidal extension (OR = 2.27, 95% CI = 1.76-2.94, p<0.00001), and capsular invasion (OR = 1.72, 95% CI = 1.39-2.41, p<0.00001). PTC (tumor size > 1 cm) exhibited a higher risk factor associated with CLNM than PTMC (tumor size < 1 cm) (OR = 2.83, 95% CI = 2.15-3.72, p<0.00001). Bilateral tumors (OR = 1.21, 95% CI = 0.92-1.58, p = 0.17) and lymphocytic thyroiditis (OR = 0.88, 95% CI = 0.71-1.09, p = 0.25) had no association with CLNM in CN0 patients.
CONCLUSIONS
Our systematic review identified several clinical features associated with CLNM in CN0 patients, including age, sex, multifocality, size, location, lymphovascular invasion, capsular invasion, and extrathyroidal extension. These factors should guide the application of PCLND in CN0 patients.
Topics: Carcinoma; Carcinoma, Papillary; Humans; Lymphatic Metastasis; Risk Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 26431346
DOI: 10.1371/journal.pone.0139021 -
International Journal of Clinical and... 2015The hobnail variant of papillary thyroid carcinoma (PTC) is a rare, aggressive variant in which > 30% of the tumor cells have hobnail features. The clinical behavior and... (Review)
Review
The hobnail variant of papillary thyroid carcinoma (PTC) is a rare, aggressive variant in which > 30% of the tumor cells have hobnail features. The clinical behavior and pathologic characteristics of these tumors are still unclear due to the rarity of the entity. The present study aimed to investigate cytologic, clinical, pathological, and molecular features of the hobnail variant from our data and from the literature. We retrospectively retrieved 10 cases of hobnail variant from 2,904 consecutive PTC patients. Cytologic and histopathologic slides from those 10 patients were reviewed. We performed molecular analysis for BRAF, ALK, and TERT promoter mutations on paraffin blocks from surgical specimens, and further analyzed the clinicopathologic characteristics of all case reports published in the literature until now. Cytologically, all tumors were characterized by single cells with eccentric nuclei and tapering cytoplasm (comet-like cells), and syncytial or micropapillary clusters with apically placed nuclei resulting in a hobnail appearance in both conventional smears and liquid-based cytology. The BRAF V600E mutation was found in 8 cases (80%) whereas no cases had ALK fusion or TERT promoter mutations. In the literature review of 55 patients including our cases, most patients presented with advanced stage cancer, and disease-specific survival rates were 83%, 71%, and 54% at 5, 10, and 20 years after the initial surgery, respectively. Characteristic cytologic features can allow a preoperative diagnosis of the hobnail variant of PTC based on cytology specimens. Further studies should be performed to identify the molecular genetics of the variant.
Topics: Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Biomarkers, Tumor; Biopsy; Carcinoma; Carcinoma, Papillary; DNA Mutational Analysis; Disease-Free Survival; Female; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Male; Middle Aged; Mutation; Neoplasm Staging; Phenotype; Promoter Regions, Genetic; Proto-Oncogene Proteins B-raf; Receptor Protein-Tyrosine Kinases; Retrospective Studies; Survival Analysis; Telomerase; Thyroid Cancer, Papillary; Thyroid Neoplasms; Time Factors; Treatment Outcome; Young Adult
PubMed: 26339365
DOI: No ID Found -
World Journal of Gastroenterology Jun 2015To analyze the available evidence about the risk of extrapancreatic malignancies and pancreatic ductal adenocarcinoma associated to pancreatic intraductal papillary... (Review)
Review
AIM
To analyze the available evidence about the risk of extrapancreatic malignancies and pancreatic ductal adenocarcinoma associated to pancreatic intraductal papillary mucinous tumors (IPMNs).
METHODS
A systematic search of literature was undertaken using MEDLINE, EMBASE, Cochrane and Web-of-Science libraries. No limitations for year of publication were considered; preference was given to English papers. All references in selected articles were further screened for additional publications. Both clinical series and Literature reviews were selected. For all eligible studies, a standard data extraction form was filled in and the following data were extracted: study design, number of patients, prevalence of pancreatic cancer and extrapancreatic malignancies in IPMN patients and control groups, if available.
RESULTS
A total of 805 abstracts were selected and read; 25 articles were considered pertinent and 17 were chosen for the present systematic review. Eleven monocentric series, 1 multicentric series, 1 case-control study, 1 population-based study and 3 case report were included. A total of 2881 patients were globally analyzed as study group, and the incidence of pancreatic cancer and/or extrapancreatic malignancies ranged from 5% to 52%, with a mean of 28.71%. When a control group was analyzed (6 papers), the same incidence was as low as 9.4%.
CONCLUSION
The available Literature is unanimous in claiming IPMNs to be strongly associated with pancreatic and extrapancreatic malignancies. The consequences in IPMNs management are herein discussed.
Topics: Carcinoma, Pancreatic Ductal; Humans; Incidence; Neoplasms, Cystic, Mucinous, and Serous; Neoplasms, Second Primary; Pancreatic Neoplasms; Prevalence; Prognosis; Risk Assessment; Risk Factors
PubMed: 26109820
DOI: 10.3748/wjg.v21.i23.7313 -
International Journal of Clinical and... 2014To evaluate the risk factors influencing the recurrence of papillary thyroid carcinoma. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the risk factors influencing the recurrence of papillary thyroid carcinoma.
METHODS
This meta-analysis used MEDLINE (PubMed), EMBASE and CNKI including all cohort studies reporting the risk factors influencing the recurrence after the initial operation on PTC up to February 23, 2014. Software RevMan 5.2 was used for meta-analysis.
RESULTS
Thirteen studies with a total of 7048 patients were included in our meta-analysis. Of all variables, gender, extrathyroid extension, LNM, tumor size, distance metastasis, thyroid surgery types and 131-I given or not were significantly correlated with recurrence, While overall recurrence was similar between the group of ≤ 45 years and > 45 years, multifolicality and solitary. However, when stratified the participants by study location (ie, Asian including China, Korea, Japan, Western country including America, France, Italy, Australia), a statistically significant summary odds ratio for age were found in Western country but none in Asian.
CONCLUSION
The risk factors influencing recurrence includes male, extrathyroid extension, LNM, tumor size more than 2 cm, distance metastasis and subtotal thyroidectomy. However, selection of operation mode should be based on not only the recurrence but the comprehensive consideration of the clinical features.
Topics: Adult; Age Factors; Carcinoma; Carcinoma, Papillary; Chi-Square Distribution; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Odds Ratio; Risk Factors; Sex Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome; Tumor Burden
PubMed: 25337182
DOI: No ID Found -
Medicine Sep 2012Clinicians have long sought to characterize biological markers of neoplasia as objective indicators of tumor presence, pathogenicity, and prognosis. Armed with data that... (Meta-Analysis)
Meta-Analysis Review
Clinicians have long sought to characterize biological markers of neoplasia as objective indicators of tumor presence, pathogenicity, and prognosis. Armed with data that correlate biomarker activity with disease presence and progression, clinicians can develop treatment strategies that address risks of disease recurrence or persistence and progression. The B-type Raf kinase (BRAF V600E) mutation in exon 15 of the BRAF gene has been noted to be a putative prognostic marker of the most prevalent form of thyroid cancer, papillary thyroid cancer (PTC)--a tumor type with high proclivity for recurrence or persistence. There has been a remarkable interest in determining the association of BRAF mutation with PTC recurrence or persistence. Using many new studies that have been published recently, we performed a meta-analysis to investigate correlations of BRAF mutation status with PTC prognosis, focusing on the recurrence or persistence of the disease after initial treatment. The study was based on published studies included in the PubMed and Embase databases addressing the BRAF mutation and the frequency of recurrence of PTC. We selected studies with data that enabled measurement of the risk ratio for recurrent disease. We also analyzed the factors that are classically known to be associated with recurrence. These factors included lymph node metastasis, extrathyroidal extension, distant metastasis, and American Joint Committee on Cancer (AJCC) stages III/IV. We used 14 articles that included an analysis of these factors as well as PTC recurrence data, with a total of 2470 patients from 9 different countries. The overall prevalence of the BRAF mutation was 45%. The risk ratios in BRAF mutation-positive patients were 1.93 (95% confidence interval [CI], 1.61-2.32; Z = 7.01; p < 0.00001) for PTC recurrence, 1.32 (95% CI, 1.20-1.45; Z = 5.73; p < 0.00001) for lymph node metastasis, 1.71 (95% CI, 1.50-1.94; Z = 8.09; p < 0.00001) for extrathyroidal extension, 0.95 (95% CI, 0.63-1.44; Z = 0.23; p = 0.82) for distant metastasis, and 1.70 (95% CI, 1.45-1.99; Z = 6.46; p < 0.00001) for advanced stage AJCC III/IV. Thus, in this meta-analysis, the BRAF mutation in PTC was significantly associated with PTC recurrence, lymph node metastasis, extrathyroidal extension, and advanced stage AJCC III/IV. Patients with PTC harboring mutated BRAF are likely to demonstrate factors that are associated with an increased risk for recurrence of the disease, offering new prospects for optimizing and tailoring initial treatment strategies to prevent recurrence.
Topics: Carcinoma; Carcinoma, Papillary; Disease Progression; Humans; Mutation; Neoplasm Recurrence, Local; Prognosis; Proto-Oncogene Proteins B-raf; Risk; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 22932786
DOI: 10.1097/MD.0b013e31826a9c71 -
Cancer Control : Journal of the Moffitt... Apr 2011Central compartment lymph node dissection is a common adjunct to thyroidectomy in the treatment of papillary thyroid cancer. The indications, surgical technique,... (Review)
Review
BACKGROUND
Central compartment lymph node dissection is a common adjunct to thyroidectomy in the treatment of papillary thyroid cancer. The indications, surgical technique, potential benefits, and operative risks of this procedure should be clearly defined in order to provide optimal care to these patients.
METHODS
A systematic review of the literature and an analysis of evidence-based recommendations were performed regarding central neck node dissection for patients with papillary thyroid carcinoma.
RESULTS
Cervical nodal metastasis in papillary thyroid cancer is a common occurrence. The presence of metastasis is associated with increased recurrence rates and may decrease survival. Detection of central and lateral neck nodal metastasis preoperatively with clinical examination and cervical ultrasound is important in determining the appropriate initial surgical management. Level VI neck dissection and central neck dissection are terms often used interchangeably to describe surgical excision of all lymph nodes from the hyoid bone to the sternal notch between the carotid arteries, but the addition of the superior mediastinal lymph nodes in compartment VII should be included in the central neck dissection. Due to improved recurrence rates and survival, therapeutic central neck dissection is recommended for all patients with nodal involvement detected pre- or intraoperatively. Prophylactic central neck dissection in patients without detectable nodal disease remains a controversial topic due to a lack of definitive evidence of improved recurrence rates or survival and the possibility of higher complication rates compared to total thyroidectomy alone. Reoperative central nodal dissection can be a challenging procedure with increased complication rates but with good outcomes in experienced centers.
CONCLUSIONS
Central neck lymph node dissection plays an important role in the appropriate treatment of papillary thyroid cancer at initial presentation and in cases of recurrent disease. Surgeons caring for this group of patients should have familiarity and skill with this procedure.
Topics: Carcinoma; Carcinoma, Papillary; Humans; Lymphatic Metastasis; Neck Dissection; Reoperation; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 21451450
DOI: 10.1177/107327481101800202 -
Journal of Thoracic Oncology : Official... Feb 2011Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung... (Review)
Review
International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.
INTRODUCTION
Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies.
METHODS
An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach.
RESULTS
The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized.
CONCLUSIONS
This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.
Topics: Adenocarcinoma; Humans; Lung Neoplasms; Neoplasm Staging; Societies, Medical
PubMed: 21252716
DOI: 10.1097/JTO.0b013e318206a221 -
The Cochrane Database of Systematic... Oct 2009Radioactive iodine treatment for differentiated thyroid cancer possibly results in xerostomia. Amifostine has been used to prevent the effects of irradiation to salivary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Radioactive iodine treatment for differentiated thyroid cancer possibly results in xerostomia. Amifostine has been used to prevent the effects of irradiation to salivary glands. To date, the effects of amifostine on salivary glands in radioactive iodine treated differentiated thyroid cancer remain uncertain.
OBJECTIVES
To assess the effects of amifostine on salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer.
SEARCH STRATEGY
Studies were obtained from computerized searches of MEDLINE, EMBASE, The Cochrane Library and paper collections of conferences held in Chinese.
SELECTION CRITERIA
Randomised controlled clinical trials and quasi-randomised controlled clinical trials comparing the effects of amifostine on salivary glands after radioactive iodine treatment for differentiated thyroid cancer with placebo and a duration of follow up of at least three months.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed risk of bias and extracted data.
MAIN RESULTS
Two trials with 130 patients (67 and 63 patients randomised to intervention versus control) were included. Both studies had a low risk of bias. Amifostine versus placebo showed no statistically significant differences in the incidence of xerostomia (130 patients, two studies), the decrease of scintigraphically measured uptake of technetium-99m by salivary or submandibular glands at twelve months (80 patients, one study), and the reduction of blood pressure (130 patients, two studies). Two patients in one study collapsed after initiation of amifostine therapy and had to be treated by withdrawing the infusion and volume substitution. Both patients recovered without sequelae. Meta-analysis was not performed on the function of salivary glands measured by technetium-99m scintigraphy at three months after high dose radioactive iodine treatment due to the highly inconsistent findings across studies (I(2) statistic 99%). None of the included trials investigated death from any cause, morbidity, health-related quality of life or costs.
AUTHORS' CONCLUSIONS
Results from two randomised controlled clinical trials suggest that the amifostine has no significant radioprotective effects on salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer patients. Moreover, no health-related quality of life and other patient-oriented outcomes were evaluated in the two included trials. Randomised controlled clinical trials with low risk of bias investigating patient-oriented outcomes are needed to guide treatment choice.
Topics: Adenocarcinoma, Follicular; Amifostine; Carcinoma, Papillary; Humans; Iodine Radioisotopes; Radiation Injuries; Radiation-Protective Agents; Radionuclide Imaging; Randomized Controlled Trials as Topic; Salivary Glands; Thyroid Neoplasms; Xerostomia
PubMed: 19821441
DOI: 10.1002/14651858.CD007956.pub2