Clinical and Paraclinical Considerations Regarding ki67's Role in the Management of Differentiated Thyroid Carcinoma-A Literature Review.

Background and Objectives: The ki67 nuclear protein is a tool for diagnosis and prognosis in oncology that is used to evaluate cell proliferation. Differentiated thyroid carcinoma is usually a slow-growing neoplasm, the most common type being the papillary form. Some clinical and pathological aspects may predict aggressive behaviour. There are reported cases of recurrence without clinico-pathological findings of aggressiveness. To obtain better predictions of the disease outcome in thyroid carcinoma, many immunohistochemical markers have been studied. The aim of this narrative literature review is to identify the benefits that ki67 may add to the management of patients with differentiated thyroid carcinoma, according to the latest evidence. Materials and Methods: We performed a search on the PubMed and Google Scholar databases using controlled vocabulary and keywords to find the most suitable published articles. A total number of sixty-eight items were identified, and five other articles were selected from other sources. After refining the selection, the inclusion criteria and exclusion criteria were applied, and a total number of twenty-nine articles were included in this literature review. Results and Discussion: The studies consist of retrospective studies (89.66%), case reports (6.9%) and literature reviews (3.45%), evaluating the role, implications and other parameters of ki67 as a diagnostic and/or prognostic tool. The statistical correlations between ki67 and other features were systematized as qualitative results of this review in order to improve the treatment strategies presented in the included articles. Conclusions: The included studies present converging data regarding most of the aspects concerning ki67. The ki67 proliferation index is a diagnostic/prognostic tool of interest in differentiated thyroid carcinoma and a good predictor of disease-free survival, disease recurrence and metastatic development. Prospective studies on large cohorts may add value for ki67 as a specific tool in the management strategy of differentiated thyroid carcinoma.

Metabolic Profiles and Blood Biomarkers to Discriminate between Benign Thyroid Nodules and Papillary Carcinoma, Based on UHPLC-QTOF-ESI+-MS Analysis.

In this study, serum metabolic profiling of patients diagnosed with papillary thyroid carcinoma (PTC) and benign thyroid pathologies (BT) aimed to identify specific biomarkers and altered pathways when compared with healthy controls (C). The blood was collected after a histological confirmation from PTC (n = 24) and BT patients (n = 31) in parallel with healthy controls (n = 81). The untargeted metabolomics protocol was applied by UHPLC-QTOF-ESI+-MS analysis and the statistical analysis was performed using the MetaboAnalyst 5.0 platform. The partial least squares-discrimination analysis, including VIP values, random forest graphs, and heatmaps (p < 0.05), was complemented with biomarker analysis (with AUROC ranking) and pathway analysis, suggesting a model for abnormal metabolic pathways in PTC and BT based on 166 identified metabolites. There were 11 classes of putative biomarkers selected that were involved in altered metabolic pathways, e.g., polar molecules (amino acids and glycolysis metabolites, purines and pyrimidines, and selenium complexes) and lipids including free fatty acids, bile acids, acylated carnitines, corticosteroids, prostaglandins, and phospholipids. Specific biomarkers of discrimination were identified in each class of metabolites and upregulated or downregulated comparative to controls, PTC group, and BT group. The lipidomic window was revealed to be more relevant for finding biomarkers related to thyroid carcinoma or benign thyroid nodules, since our study reflected a stronger involvement of lipids and selenium-related molecules in metabolic discrimination.

Therapeutic results in children with brain tumors - a single center experience over 18 years.

Background and aims: Tumors of the central nervous system represent the main cause of death by cancer in children. The diagnosis and molecular classification of these neoplasms have seen great improvement in the past years, due to ongoing genomic advances. In general, the treatment consists of surgery, radiation therapy and chemotherapy. However, the currently available pharmacological treatment options have limited effectiveness due to the particular characteristics of the blood-brain barrier. Methods: We decided to study the therapeutic results in children treated for brain tumors in the Cluj-Napoca "Prof. dr. Ion Chiricuta" Oncology Institute, between 2001 and 2018, in order to provide a more accurate understanding of the disease and the available therapeutic options in our center. Results: Out of the 207 cases included in this study, we recorded 98 deaths (47.3%). This is significantly less than the 5-year survival rate recorded in the US between 2012 and 2018 (74.9%). There are many factors that could explain the low survival rate, such as a very late diagnosis, the inability to implement innovative radiation therapy techniques until 2018, and the fact that between 2001 and 2010 the chemotherapy regimens in our center were not as effective as the more recent ones. Conclusions: The therapeutic results recorded in this study are similar to those in other middle-income countries, however, the available treatment options for pediatric brain tumors are not as effective as those currently in use for other pediatric and adult malignancies.

Impact of BRAFV600E Mutation on Event-Free Survival in Patients with Papillary Thyroid Carcinoma: A Retrospective Study in a Romanian Population.

We aimed to evaluate the prognostic value of BRAFV600E mutation in a series of 127 papillary thyroid carcinoma (PTC) cases as a single factor, and in synergic interaction with other standard risk factors. BRAFV600E mutation was assessed by real-time PCR. Event-free survival (EFS) was calculated between the date of the first evaluation and the date of occurrence of an adverse event or the date of the last known status. The prevalence of BRAFV600E mutation was 57.2%. The Kaplan-Meier analysis showed a significant reduction of EFS among cases harboring BRAFV600E mutation compared to non-mutated cases (p = 0.010). In addition, BRAFV600E mutation was found to better predict adverse outcomes when associated with the following risk factors: age ≥ 55 years old (p < 0.001), male gender (p < 0.001), conventional (p = 0.005) and tall cell (p = 0.014) histology, tumor size > 40 mm (p = 0.001), extrathyroidal extension (p = 0.001), multifocality (p = 0.001) and lymph node metastasis (p < 0.001). In univariate analysis, a 3.74-fold increased risk for a reduced EFS (p = 0.018) was found for BRAFV600E-mutated cases, but no increased risk was further confirmed by multivariate analysis. Our results highlight that BRAFV600E mutation cannot be used alone as an independent predictive factor in PTC patients, but is prognostically valuable if integrated in the context of other clinicopathological risk factors.

Radioiodine-131 Therapy Used for Differentiated Thyroid Cancer Can Impair Titanium Dental Implants: An In Vitro Analysis.

BACKGROUND: The aim was to assess, in vitro, the effects of radioiodine-131 (I-131) on the structure of titanium implants. MATERIAL AND METHODS: A total of 28 titanium implants were divided into 7 groups (n = 4) and irradiated at 0, 6, 12, 24, 48, 192 and 384 hours. At the end of the experiment, each sample was investigated via scanning electron microscopy (SEM) and electrochemical measures. RESULTS: The control sample revealed a smooth and compact surface. The small micro-sized porosity is slightly visible at the macroscopic level, but the precise details cannot be observed. A mild exposure to the radioactive solution for 6 to 24 h showed a good preservation of the macro-structural aspects such as thread details and surface quality. Significant changes occurred after 48 h of exposure. It was noticed that the open-circuit potential (OCP) value of the non-irradiated implants move toward more noble potentials during the first 40 min of exposure to the artificial saliva and then stabilizes at a constant value of -143 mV. A displacement of the OCP values toward more negative values was observed for all irradiated implants; these potential shifts are decreasing, as the irradiation period of the tested implants increased. CONCLUSION: After exposure to I-131, the structure of titanium implants is well preserved up to 12 h. The eroded particles start to appear in the microstructural details after 24 h of exposure and their numbers progressively increase up to 384 h after exposure.

Triple Primary Malignancies: Tumor Associations, Survival, and Clinicopathological Analysis: A 25-Year Single-Institution Experience.

The detection of multiple primary malignancies is on the rise despite their rare occurrence rate. This research aims to determine the prevalence, tumor association patterns, overall survival, and the correlation between survival time and independent factors in patients with triple primary malignancies. This single-center retrospective study included 117 patients with triple primary malignancies admitted to a tertiary cancer center between 1996 and 2021. The observed prevalence was 0.082%. The majority of patients (73%) were over the age of fifty at the first tumor diagnosis, and regardless of gender, the lowest median age occurred in the metachronous group. The most common tumor associations were found between genital-skin-breast, skin-skin-skin, digestive-genital-breast, and genital-breast-lung cancer. The male gender and being over the age of fifty at the first tumor diagnosis are associated with a higher risk of mortality. Compared with the metachronous group, patients with three synchronous tumors demonstrate a risk of mortality 6.5 times higher, whereas patients with one metachronous and two synchronous tumors demonstrate a risk of mortality three times higher. The likelihood of subsequent malignancies should always be considered throughout cancer patients' short- and long-term surveillance to ensure prompt tumor diagnosis and treatment.

Low-Molecular-Weight Heparins (LMWH) and Synthetic Factor X Inhibitors Can Impair the Osseointegration Process of a Titanium Implant in an Interventional Animal Study.

Background and objectives: Cementless total hip arthroplasty is a common surgical procedure and perioperative thromboprophylaxis is used to prevent deep vein thrombosis or pulmonary embolism. Osseointegration is important for long-term implant survival, and there is no research on the effect of different thromboprophylaxis agents on the process of osseointegration. Materials and Methods: Seventy rats were allocated as follows: Group I (control group), Group II (enoxaparin), Group III (nadroparin), and Group IV (fondaparinux). Ovariectomy was performed on all subjects, followed by the introduction of an intramedullary titanium implant into the femur. Thromboprophylaxis was administered accordingly to each treatment group for 35 days postoperatively. Results: Group I had statistically significantly lower anti-Xa levels compared to treatment groups. Micro-CT analysis showed that nadroparin had lower values compared to control in bone volume (0.12 vs. 0.21, p = 0.01) and percent bone volume (1.46 vs. 1.93, p = 0.047). The pull-out test showed statistically significant differences between the control group (8.81 N) compared to enoxaparin, nadroparin, and fondaparinux groups (4.53 N, 4 N and 4.07 N, respectively). Nadroparin had a lower histological cortical bone tissue and a higher width of fibrous tissue (27.49 µm and 86.9 µm) at the peri-implant area, compared to control (43.2 µm and 39.2 µm), enoxaparin (39.6 µm and 24 µm), and fondaparinux (36.2 µm and 32.7 µm). Conclusions: Short-term administration of enoxaparin, nadroparin, and fondaparinux can reduce the osseointegration of titanium implants, with nadroparin having the most negative effect. These results show that enoxaparin and fondaparinux are preferred to be administered due to a lesser negative impact on the initial implant fixation.

Association of Parathyroid and Differentiated Thyroid Carcinomas: A Narrative Up-To-Date Review of the Literature.

Aim: Parathyroid carcinoma (PC) is a rare endocrine malignancy that represents 0.005% of all malignant tumors. Associated PC and differentiated thyroid carcinoma (DTC) is an exceptionally rare condition, and the preoperative diagnostics and proper treatment are challenging. Almost all PCs and the majority of DTCs are diagnosed postoperatively, making correct surgical treatment questionable. Specific guidelines for parathyroid and thyroid carcinomas association treatment are lacking. The purposes of our study were to identify the association between parathyroid and thyroid carcinomas, to analyze the available published data, and to evaluate the possible relationship between preoperative diagnostic and surgical decision-making, and outcome-related issues. Material and methods: We performed a literature review of several databases from the earliest records to March 2022, using controlled vocabulary and keywords to search for records on the topic of PC and WDTC pathological association. The reference lists from the initially identified articles were analyzed to obtain more references. Results: We identified 25 cases of PC and DTC association, 14 more than the latest review from 2021. The mean age of patients was 55, with a female to male ratio of about 3:1. Exposure to external radiation was identified in only one patient, although it is considered a risk factor the development of both PC and DTC. The preoperative suspicion of PC was stated by the authors in only 25% of cases, but suspicion based on clinical, laboratory, ultrasound (US), and fine needle aspiration (FNA) criteria could have been justified in more than 50% of them. With neck ultrasound, 40% of patients presented suspicious features both for PC and thyroid carcinoma. Intra-operatory descriptions of the lesions revealed the highest suspicion (83.3%) of PC, but en bloc resection was recommended and probably performed in only about 50% of the cases. Histopathological examinations of the thyroid revealed different forms of papillary thyroid carcinoma (PTC) in most cases. Postoperative normocalcemia was achieved in 72% of patients, but follow-up data was missing in about 25% of cases. Conclusion: Associated PC and DTC is an exceptionally rare condition, and the preoperative diagnostic and treatment of the patients is a challenge. However, in most cases pre- and intraoperative suspicious features are present for identification by a highly specialized multidisciplinary endocrine team, who can thus perform the optimal treatment to achieve curability.

Thyroid carcinoma associated with other primary neoplasms, a single center study.

Background and aims: Thyroid carcinoma is the most frequent endocrine malignancy. It develops following a complex interaction of environmental and genetic factors. Its incidence is on the rise mostly due to the frequent diagnosis of microcarcinomas (tumor <1 cm). In most cases, it has very good prognosis and survival rates. The incidence of a second primary malignancy in thyroid cancer patients is higher than in the general population. In this article, we focus on the role of BRAF V600E mutation in the development of other primary neoplasms associated with thyroid carcinoma. Methods: This study was conducted in the department of Nuclear Medicine and Genetics of the "Prof. Dr. Ion Chiricuța" Institute of Oncology of Cluj-Napoca. We evaluated patients with thyroid carcinoma, who were diagnosed and treated for other malignancies such as breast, colorectal, lung cancer and malignant melanoma. In addition, we tested for the BRAF V600E mutation using paraffin samples of patients. Results: We identified 17 patients that had thyroid carcinoma associated with other primary malignancies. Two of the patients included in the study had three associated primary cancers. The time interval between the diagnoses of two primary neoplasms in the same patient was 6.15 years, with a standard deviation (SD) of 5.39 years. The most common primary tumor associated with thyroid carcinoma in this study was breast cancer. We applied genetic testing for the BRAF V600E mutation in 12 patients. The BRAF V600E mutation positivity rate was 26.9% and most of the cancer associations were metachronous (occurring at least 6 months after thyroid cancer). Conclusions: The BRAF V600E mutation is an important prognostic factor in the neoplasms included in this study, but its presence is not a predictive factor for the appearance of a metachronous or synchronous associated primary neoplasm to thyroid cancer.

Thyroid Cancer Diagnostics Related to Occupational and Environmental Risk Factors: An Integrated Risk Assessment Approach.

There are still many questions remaining about the etiopathogenesis of thyroid cancer, the most common type of endocrine neoplasia. Numerous occupational and environmental exposures have been shown to represent important risk factors that increase its incidence. Updated information about thyroid cancer diagnostics related to occupational and environmental risk factors is reviewed here, considering an integrated risk assessment approach; new data concerning thyroid cancer etiology and pathogenesis mechanisms, diagnostic biomarkers and methodologies, and risk factors involved in its pathogenesis are presented. A special emphasis is dedicated to specific occupational risk factors and to the association between environmental risk agents and thyroid cancer development. The occupational environment is taken into consideration, i.e., the current workplace and previous jobs, as well as data regarding risk factors, e.g., age, gender, family history, lifestyle, use of chemicals, or radiation exposure outside the workplace. Finally, an integrative approach is presented, underlying the need for an accurate Risk Assessment Matrix based on a systematic questionnaire. We propose a complex experimental design that contains different inclusion and exclusion criteria for patient groups, detailed working protocols for achieving coherent and sustainable, well-defined research stages from sample collection to the identification of biomarkers, with correlations between specific oncometabolites integrated into the Risk Assessment Matrix.

SERS-based DNA methylation profiling allows the differential diagnosis of malignant lymphadenopathy.

This study highlights the potential of surface-enhanced Raman scattering (SERS) to differentiate between B-cell lymphoma (BCL), T-cell lymphoma (TCL), lymph node metastasis of melanoma (Met) and control (Ctr) samples based on the specific SERS signal of DNA extracted from lymph node tissue biopsy. Differences in the methylation profiles as well as the specific interaction of malignant and non-malignant DNA with the metal nanostructure are captured in specific variations of the band at 1005 cm-1, attributed to 5-methylcytosine and the band at 730 cm-1, attributed to adenine. Thus, using the area ratio of these two SERS marker bands as input for univariate classification, an area under the curve (AUC) of 0.70 was achieved in differentiating between malignant and non-malignant DNA. In addition, DNA from the BCL and TCL groups exhibited differences in the area of the SERS band at 730 cm-1, yielding an AUC of 0.84 in differentiating between these two lymphadenopathies. Lastly, using multivariate data analysis techniques, an overall accuracy of 94.7% was achieved in the differential diagnosis between the BCL, TCL, Met and Ctr groups. These results pave the way towards the implementation of SERS as a novel tool in the clinical setting for improving the diagnosis of malignant lymphadenopathy.

Total Tumor Diameter and Unilateral Multifocality as Independent Predictor Factors for Metastatic Papillary Thyroid Microcarcinoma.

The purpose of this study was to assess whether total tumor diameter (TTD) and multifocality are predictors for metastatic disease in papillary thyroid microcarcinomas (PTMC). Eighty-two patients with histologically proven PTMC were retrospectively included. Patients were divided according to the presence of metastatic disease in the metastatic (n = 41) and non-metastatic (n = 41) demographic-matched group. The morphological features of PTMCs (primary tumor diameter, multifocality, TTD, number of foci, and tumor site) were compared between groups using univariate, multivariate, and receiver operating characteristic analyses. TTD (p = 0.026), TTD > 10 mm (p = 0.036), and Unilateral Multifocality (UM) (p = 0.019) statistically differed between the groups. The combination of the two independent predictors (TTD and UM) was able to assess metastatic risk with 60.98% sensitivity and 75.61% specificity. TTD and UM can be used to predict metastatic disease in PTMC, which may help to better adapt the RAI therapy decision. We believe that TTD and multifocality are tumor features that should be considered in future guidelines.

Updates on the 2016 World Health Organization Classification of Pediatric Tumors of the Central Nervous System - a systematic review.

Tumors of the central nervous system (CNS) represent the main cause of death through solid tumors in children and the second most frequent neoplasm in this patient group. The poor survival rate is due to many factors, such as the large diversity of morphological features, the particular micro-environmental characteristics of the nervous tissue, the relative rareness in relation to other childhood diseases, which leads to late diagnosis and the limited effectiveness of the available treatment options. Up until 2016, brain tumors were classified according to their histologic features. The new 2016 World Health Organization (WHO) Classification of CNS tumors incorporates molecular features, alongside the immunohistology, in order to provide a more accurate understanding of the disease. The treatment consists of surgery, radiation therapy and chemotherapy. We decided to review the literature on this pathology, in order to show the importance of the recent discoveries in this field.

A Comparative Study between 18F-FDG PET/CT and Conventional Imaging in the Evaluation of Progressive Disease and Recurrence in Ovarian Carcinoma.

The aim of this study is to compare the efficiency of conventional imaging and 18F-FDG PET-CT in detecting progressive disease and recurrences over a period of one year (2018), in the case of ovarian cancer, and also to assess the importance of 18F-FDG PET/CT in changing the course of the treatment for these patients. This study included 29 patients diagnosed in various stages with ovarian carcinoma, most of them of epithelial origin. All patients were evaluated throughout their treatment using 18F-FDG PET/CT and various conventional techniques (computed tomography (CT), magnetic resonance imaging (MRI), abdominal and intravaginal ultrasound, chest X-ray). PET/CT was more useful and effective in our group of patients in detecting progressive disease compared with conventional imaging (37.93% vs. 17.24%) and also in establishing the recurrences (24.14% vs. 6.90%). Moreover, F18-FDG PET-CT led to a therapeutic change in 55.17% of the patients of our group, compared with only 17.24% after conventional imaging. This underlines the crucial aspect of the metabolic changes of tumors that should be assessed alongside the morphological ones, with PET-CT imaging remaining the only viable tool for achieving that at present. PET/CT with 18F-FDG represents one of the most important imaging techniques used in the diagnosis and management of ovarian carcinoma. Our results seem to fall in line with what other authors reported, indicating that 18F-FDG PET-CT is potentially gaining more ground in the management of ovarian carcinoma, by influencing therapeutic strategies and by being able to detect relapse and progression accurately.

Continuous Intravenous Administration of Granulocyte-Colony-Stimulating Factors-A Breakthrough in the Treatment of Cancer Patients with Febrile Neutropenia.

(1) Background: Febrile neutropenia (FN) remains one of the most challenging problems in medical oncology and is a very severe side effect of chemotherapy. Its late consequences, when it is recurrent or of a severe grade, are dose reduction and therapy delays. Current guidelines allow the administration of granulocyte-colony-stimulating factors (G-CSF) for profound FN (except for the case when a pegylated form of G-CSF is administrated with prophylactic intention) in addition to antibiotics and supportive care. (2) Methods: This is a prospective study that included 96 patients with confirmed malignancy, treated with chemotherapy, who developed FN during their oncological therapy, and were hospitalized. They received standard treatment plus a dose of G-CSF of 16 µg/Kg/day IV continuous infusion. (3) Results: The gender distribution was almost symmetrical: Male patients made up 48.96% and 51.04% were female patients, with no significance on recovery from FN (p = 1.00). The patients who received prophylactic G-CSF made up 20.21%, but this was not a predictive or prognostic factor for the recovery time from aplasia (p = 0.34). The median chemotherapy line where patients with FN were included was two and the number of previous chemotherapy cycles before FN was three. The median serological number of neutrophils (PMN) was 450/mm3 and leucocytes (WBC) 1875/mm3 at the time of FN. Ten patients possess PMN less than 100/mm3. The median time to recovery was 25.5 h for 96 included patients, with one failure in which the patient possessed grade 5 FN. Predictive factors for shorter recovery time were lower levels of C reactive protein (p < 0.001) and procalcitonin (p = 0.002) upon hospital admission and higher WBC (p = 0.006) and PMN (p < 0.001) at the time of the provoking cycle of chemotherapy for FN. The best chance for a shorter duration of FN was a short history of chemotherapy regarding the number of cycles) (p < 0.0001). (4) Conclusions: Continuous IV administration of G-CSF could be an alternative salvage treatment for patients with profound febrile neutropenia, with a very fast recovery time for neutrophiles.

Thyroid Microcarcinoma in Pediatric Population in Romania.

Thyroid microcarcinoma in pediatric population in Romania Non-medullary thyroid cancer (TC) is the most common endocrine malignancy, with an increasing incidence in the recent years, due to the increase of the thyroid microcarcinoma. Thyroid microcarcinoma (mTC) is defined, according to WHO criteria, as ≤1 cm dimension thyroid carcinoma, being a rare disease in children population. In adults, the current guidelines recommend a limited surgical approach. In children, however, there are no specific guidelines for mTC. Due to the scarcity of these tumors, mTC in children have largely been understudied, to our knowledge with only one previous publication reporting on the outcomes of a large historic series of patients with mTC from the USA. In Romania, the incidence of TC is rising, one of the reason may be the effect of Chernobyl nuclear accident in the past and the iodine deficiency. The purpose of this study was to describe the characteristics and outcome of children diagnosed with mTC in Romania diagnosed from 1 January 2000 to 31 December 2018. During the study period we identified 77 cases of differentiated TC (papillary and follicular) and of these 20 cases (19.4%) were mTC. The mTC represented roughly one fifth of our nationwide pediatric population diagnosed in the last 20 years, the majority of cases being recorded in adolescents aged between 15-18 years. Although patients with apparently more unfavorable local phenotype were identified, this was not reflected in the outcome of the patients in terms of remission of the disease and survival. Our study illustrates the heterogeneity of the real-life practice with respect to the pediatric mTC, and underscores the need for carefully designed multicenter international studies, including larger cohorts of patients in order to provide the data required for establishing evidence based uniform protocols. The European Reference Networks (ERN), such as the ERN for Rare Endocrine Diseases (Endo-ERN) provides an ideal platform to initiate such collaborative studies.

The Side Effects of Therapeutic Radioiodine-131 on the Structure of Enamel and Dentin in Permanent Human Teeth.

Radioiodine-131 (I-131) is an essential therapy for patients with differentiated thyroid carcinomas (DTC). Generally, I-131 is safe and well tolerated, but patients may present early or late complications in the oral and maxillofacial areas. Thus, the aim of this study was to evaluate in-vitro, the alteration of enamel and dentin after I-131 exposure using histopathological assessment, scanning electron microscopy (SEM) and atomic force microscopy (AFM). For I-131 irradiation, an in-vitro protocol was used that simulates the procedure for irradiation therapy performed for patients with DTCs. A total of 42 teeth were divided into seven groups (n = 6) and irradiated as follows: control, irradiation groups (3, 6, 12, 36, 48 h, 8 days). Histological changes were observed at 48 h (enamel surface with multifocal and irregular areas) and at 8 days (enamel surface with multiple, very deep, delimited cavities). SEM imaging revealed the enamel destruction progresses along with the treatment time increasing. The alterations are extended into the enamel depth and the dislocated hydroxyapatite debris is overwhelming. The enamel-dentine interface shows small gaps after 6 h and a very well developed valley after 12 h; the interface microstructure resulted after 8 days is deeply altered. The AFM imaging shows that I-131 affects the protein bond between hydroxyapatite nano-crystals causing loss of cohesion, which leads to significant increasing of nano-particles diameter after 6 h. In conclusion, both enamel and dentin appear to be altered between 12 and 48 h and after 8 days of treatment are extended in depth.