Association of BRAF V600E Mutant Allele Proportion with the Dissemination Stage of Papillary Thyroid Cancer.

The early identification of aggressive forms of cancer is of high importance in treating papillary thyroid cancer (PTC). Disease dissemination is a major factor influencing patient survival. Mutation status of BRAF oncogene, BRAF V600E, is proposed to be an indicator of disease recurrence; however, its influence on PTC dissemination has not been deciphered. This study aimed to explore the association of the frequency of BRAF V600E alleles in PTC with disease dissemination. In this study, 173 PTC samples were analyzed, measuring the proportion of BRAF V600E alleles by qPCR, which was then normalized against the proportion of tumor cells. Semiquantitative analysis of BRAF V600E mutant protein was performed by immunohistochemistry. The BRAF V600E mutation was present in 60% of samples, while the normalized frequency of mutated BRAF alleles ranged from 1.55% to 92.06%. There was no significant association between the presence and/or proportion of the BRAF V600E mutation with the degree of PTC dissemination. However, the presence of the BRAF mutation was significantly linked with angioinvasion. This study's results suggest that there is a heterogeneous distribution of the BRAF mutation and the presence of oligoclonal forms of PTC. It is likely that the BRAF mutation alone does not significantly contribute to PTC aggressiveness.

SIMULTANEOUS METASTASES OF PAPILLARY THYROID CARCINOMA AND NEUROENDOCRINE TUMOR OF THE CECUM TO CERVICAL LYMPH NODES: A CASE REPORT.

We present a case of a patient with simultaneous cervical lymph node metastasis of papillary thyroid cancer (PTC) and cecum neuroendocrine tumor (NET). A 45-year-old male patient with the diagnosis of metastatic NET of the cecum underwent fine needle aspiration (FNA) of a positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET) positive nodule in the left thyroid lobe. Due to FNA finding suspect of PTC, the patient underwent total thyroidectomy with central neck dissection. Histopathologic finding revealed PTC of the left thyroid lobe and small solitary lymph node PTC metastasis in the central neck region. Postoperative evaluation with neck ultrasound (US) revealed two enlarged suspected lymph nodes in cervical regions III and IV on the left side of the neck and the patient underwent FNA with measurement of thyroglobulin (Tg) in the aspirates. The FNA finding of the cervical lymph node in the region III revealed PTC metastasis with high Tg value in the aspirate, while FNA finding of the cervical lymph node in the region IV revealed NET metastasis with low Tg value in the aspirate. Postoperative serum Tg value was 17.75 µg/L and the patient underwent 5550 MBq iodine-131 (I-131) therapy. A year after I-131 therapy, follow-up neck US demonstrated complete cure of PTC cervical lymph node metastasis in the region III and stable in size NET cervical lymph node metastasis in the region IV. To our knowledge, this is the first report of simultaneous occurrence of cervical lymph node metastases of PTC and NET of the cecum.

Long-Term Outcome of Differentiated Thyroid Cancer Patients-Fifty Years of Croatian Thyroid Disease Referral Centre Experience.

Background: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

Malignancy risk with atypia of undetermined significance finding on thyroid nodule FNA: clinical experience from a tertiary institution.

The Bethesda System for Reporting Thyroid Cytopathology from 2009 introduced a new category in thyroid nodule fine-needle aspiration (FNA) findings named atypia of undetermined significance (AUS), which usually appears in around 5% of FNA findings. Our study aimed to assess the utility of AUS finding in determining the risk of malignancy in thyroid nodules. In our study, 160 patients with AUS finding on initial FNA were regularly followed-up. Total and specific malignancy rates were calculated after receiving histopathologic confirmation or histopathologic/cytologic exclusion of malignancy. Eventually 80 (50%) patients were referred to surgery, with malignancy rate of 37.5% on histopathology. Another 52 (32.5%) patients were confirmed to have benign nodules on repeat FNA. After combining results obtained from histopathologic reports with those obtained from cytologic follow-up, total malignancy rate was 22.72%. However, malignancy was confirmed in only one (5.26%) of 19 patients with AUS finding on repeat FNA with surgical and histopathologic follow-up. In conclusion, FNA is an extremely useful tool for clinicians to discriminate patients to be referred to surgery and those that can be followed-up safely without the need for further invasive procedures.

DIFFERENTIATED THYROID CANCER IN PEDIATRIC POPULATION (≤18 YEARS): POSTOPERATIVE TREATMENT WITH RADIOACTIVE IODINE (I-131).

The aim is to present data on the treatment and follow-up in a cohort of patients with pediatric thyroid cancer who underwent total thyroidectomy and received postoperative radioactive iodine (I-131) therapy. The study was conducted in a tertiary high-volume thyroid center, in pediatric patients with differentiated thyroid cancer who were consecutively treated during the 1965-2015 period. A total of 45 patients aged ≤18 years having undergone total thyroidectomy with or without selective neck dissection were included in the study. Decision on postoperative I-131 ablation was based on tumor characteristics, postoperative thyroglobulin level, preablative whole body scintigraphy, and/or neck ultrasound. Median age at diagnosis was 15 years. The presence of cervical lymph node metastases was significantly associated with papillary thyroid cancer, larger tumor size, involvement of two thyroid lobes, and multifocal disease. The presence of distant metastases was significantly associated with larger tumor size. None of the patients died during follow-up period, and the 5-year and 10-year overall survival rates were 100%. The 5-year and 10-year progression-free survival (PFS) rates were 87% and 73%, respectively. Male gender (p=0.046), age ≤15 years (p=0.029) and tumor size >15 mm (p=0.042) were significantly associated with inferior PFS. A significant positive trend of increase in the number of newly diagnosed patients was observed over time (p=0.011). Clinical management of pediatric thyroid cancer is challenging, especially in the light of increasing incidence in this population. Male patients younger than 15 years and with tumors of more than 15 mm in size require additional caution due to lower PFS observed.

HMGA2 Gene Expression in Fine-needle Aspiration Samples of Thyroid Nodules as a Marker for Preoperative Diagnosis of Thyroid Cancer.

There is a great interest in molecular markers that would help in the preoperative diagnosis of malignant thyroid nodules in cases of indeterminate fine-needle aspiration cytology. The aim of this study was to determine the diagnostic accuracy of HMGA2 gene expression in discriminating benign from malignant thyroid nodules. In this study, 237 preoperative thyroid fine-needle aspiration samples were analyzed prospectively for the expression of the HMGA2 gene by real-time reverse transcription polymerase chain reaction. The results were evaluated against the postoperative histopathologic diagnosis or definitive cytologic diagnosis in cases of nodular goiter and Hashimoto thyroiditis. Among 237 samples from patients with thyroid nodules that were analyzed, 231 were adequate for real-time reverse transcription polymerase chain reaction analysis. With a cutoff value of 8.71 for relative gene expression, HMGA2 was positive in 19 (16.4%) of 116 nodular goiter, 1 (2.6%) of 39 Hashimoto thyroiditis, 9 (28.1%) of 32 follicular adenoma, 0 (0%) of 5 Hurthle cell adenoma, 32 (88.9%) of 36 papillary carcinoma, and 3 (100%) of 3 follicular carcinoma samples. In discriminating between malignant and benign thyroid nodules, HMGA2 has shown specificity of 84.5%, sensitivity of 91.9%, positive predictive value of 53.1%, and negative predictive value of 98.2%. High sensitivity and negative predictive value of HMGA2 for preoperative detection of malignant thyroid nodules shown in this study indicate that it may have a role as an ancillary marker in cytology in the management of patients with thyroid nodules.

THYROGLOBULIN AS A TUMOR MARKER IN DIFFERENTIATED THYROID CANCER - CLINICAL CONSIDERATIONS.

- Initial treatment of the majority of patients with differentiated thyroid cancer (DTC) includes total thyroidectomy. Postoperative ablation therapy with radioactive iodine (I-131) is indicated in all high-risk patients, however, there is disagreement regarding its use in low- and intermediate-risk patients. Over the last few decades, thyroglobulin (Tg) has been established as the primary biochemical tumor marker for patients with DTC. Thyroglobulin can be measured during thyroid hormone therapy or after thyroid-stimulating hormone (TSH) stimulation, through thyroid hormone withdrawal or the use of human recombinant TSH. In many studies, the cut-off value for adequate Tg stimulation is a TSH value ≥30 mIU/L. However, there is an emerging body of evidence suggesting that this long-established standard should be re-evaluated, bringing this threshold into question. Recently, a risk stratification system of response to initial therapy (with four categories) has been introduced and Tg measurement is one of the main components. The relationship between the Tg/TSH ratio and the outcome of radioiodine ablation has also been studied, as well as clinical significance of serum thyroglobulin doubling-time. The postoperative serum Tg value is an important prognostic factor that is used to guide clinical management, and it is the most valuable tool in long term follow-up of patients with DTC.

Prediction of radioactive iodine remnant ablation failure in patients with differentiated thyroid cancer: A cohort study of 740 patients.

BACKGROUND: The purpose of this study was to detect parameters that could serve as predictors of radioactive iodine (I-131) ablation failure in patients with low-risk and intermediate-risk differentiated thyroid carcinoma (DTC). METHODS: Our cohort study included 740 patients with DTC who received postoperative I-131 remnant ablation. Anthropometric, biochemical, and pathohistological parameters were analyzed and correlated with ablation outcome using multivariable logistic regression models. RESULTS: Treatment failure rates were higher in patients <53 years, with N1a classification, and lymph node capsular invasion. In patients with N1a disease, thyroglobulin (Tg) > 2.4 ng/mL predicted treatment failure with 93.8% sensitivity and 52.5% specificity, and in patients with N1b disease, Tg > 14.9 ng/mL with 77.8% sensitivity and 92.9% specificity. I-131 activity was not associated with treatment outcome. CONCLUSION: Patients < 53 years old, with higher Tg levels, N1a classification, and lymph node capsular invasion have a higher risk of ablation failure. Stimulated Tg is an excellent predictor of treatment failure in patients with N1 disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 109-115, 2017.

A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer.

BACKGROUND: We assessed the treatment effect of panitumumab plus best supportive care (BSC) vs BSC on overall survival (OS) in patients with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC) and report the first prospective extended RAS analysis in a phase 3 trial. METHODS: Patients with wild-type KRAS exon 2 mCRC were randomised 1 : 1 to panitumumab (6 mg kg-1 Q2W) plus BSC or BSC. On-study crossover was prohibited. RAS mutation status was determined by central laboratory testing. The primary endpoint was OS in wild-type KRAS exon 2 mCRC; OS in wild-type RAS mCRC (KRAS and NRAS exons 2, 3, and 4) was a secondary endpoint. RESULTS: Three hundred seventy seven patients with wild-type KRAS exon 2 mCRC were randomised. Median OS was 10.0 months with panitumumab plus BSC vs 7.4 months with BSC (HR=0.73; 95% CI=0.57-0.93; P=0.0096). RAS ascertainment was 86%. In wild-type RAS mCRC, median OS for panitumumab plus BSC was 10.0 vs 6.9 months for BSC (HR=0.70; 95% CI=0.53-0.93; P=0.0135). Patients with RAS mutations did not benefit from panitumumab (OS HR=0.99; 95% CI=0.49-2.00). No new safety signals were observed. CONCLUSIONS: Panitumumab significantly improved OS in wild-type KRAS exon 2 mCRC. The effect was more pronounced in wild-type RAS mCRC, validating previous retrospective analyses.

PRIMARY FIBROSARCOMA OF THE THYROID GLAND: CASE REPORT.

Due to progressive dyspnea, a male patient aged 59 underwent medical examination in 2003 in a local hospital. Neck ultrasound and fine-needle aspiration biopsy (FNAB) of a suspect lesion in the thyroid gland revealed the presence of a malignant neoplasm, i.e. mesenchymal tumor. Immunocytochemistry for epithelial membrane antigen, chromogranin A and leukocyte common antigen (CD45) was negative, while vimentin and S-100 were positive. The patient was referred to a university hospital center, where further oncologic work-up was done. Neck ultrasound revealed a tumor in the left lobe of the thyroid, with extension to the aortic arch. After repeated FNAB, cytologic diagnosis of primary thyroid fibrosarcoma was established. Due to the locally advanced and consequently inoperable disease, primary radiotherapy to the neck region (64 Gy in 32 fractions) was applied, followed by 6 cycles of chemotherapy with doxorubicin. After completion of therapy, computed tomography scan demonstrated significant regression of primary disease, but it was still not amenable to surgical treatment. Thus, the decision of the oncology board was active surveillance of the patient. During 9-year follow up, no signs of progression or activity of the disease were found.

Cytokeratin 20 positive cells in blood of colorectal cancer patients as an unfavorable prognostic marker.

OBJECTIVES: Cytokeratin 20 (CK20) is one of the most investigated markers for the detection of circulating colorectal cancer (CRC) cells by reverse transcription polymerase chain reaction (RT-PCR). The aim of this study was to evaluate prognostic value of RT-PCR detection of circulating CRC cells using CK20 as a marker, and to compare the value of preoperative and postoperative blood sample analysis for that purpose. METHODS: Ribonucleic acid (RNA) was isolated from mononuclear cell fraction of blood samples taken from 95 CRC patients before and after tumor resection and from 23 healthy volunteers and assayed by real-time RT-PCR for CK20 expression. RESULTS: In patients positive for CK20 postoperatively both progression-free survival (PFS) and overall survival were significantly shorter than in patients negative for CK20 postoperatively, while the difference between patients positive and negative for CK20 preoperatively was not statistically significant in terms of neither PFS nor overall survival. CONCLUSION: Our results have shown prognostic value of circulating cancer cells detected in postoperative blood samples from CRC patients using CK20 as marker for RT-PCR, which has potential implications for treatment of these patients. In clinical practice, CK20 expression profile could be a factor in weighting treatment options in CRC patients. In cases where multiple treatment options are possible, patients with positive postoperative CK20 expression could be candidates to receive more aggressive treatment.

Connexin 43 Expression in Primary Colorectal Carcinomas in Patients with Stage III and IV Disease.

BACKGROUND/AIM: Protein connexin 43 (Cx43), a part of intercellular gap junctions, is frequently down-regulated in tumors. The aim of the study was to compare Cx43 expression in primary colorectal tumors of patients with stage III and IV disease. PATIENTS AND METHODS: Immunohistochemical expression of Cx43 was analyzed in 50 colorectal adenocarcinomas from surgically-treated patients of stage pT3N1-2 without metastases (M0) and 50 specimens of the same pTN stage from patients with synchronous liver metastases (M1). Association of Cx43 expression with clinicopathological factors and tumor site was also analyzed. RESULTS: There was no significant difference in Cx43 expression between M0 and M1 tumor specimens (p=0.817), as well as in Cx43 expression between colonic and rectal tumors (p=0.116), respectively. Stromal expression of Cx43 was higher in M1 than in M0 tumors (p=0.004). CONCLUSION: Stromal Cx43 expression is possible indicator of metastatic potential of colorectal adenocarcinoma.

Re-ablation I-131 activity does not predict treatment success in low- and intermediate-risk patients with differentiated thyroid carcinoma.

The aim of this study was to evaluate the efficacy of different radioactive iodine (I-131) activities used for re-ablation, to compare various combinations of treatment activities, and to identify predictors of re-ablation failure in low- and intermediate-risk differentiated thyroid carcinoma (DTC) patients. The study included 128 consecutive low- and intermediate-risk patients with DTC with ablation failure after total thyroidectomy. Patient characteristics, T status, tumor size, lymph node involvement, postoperative remnant size on whole-body scintigraphy, serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), anti-Tg antibody (TgAb), and Tg/TSH ratio were analyzed as potential predictors of the re-ablation success. Re-ablation was successful in 113 out of 128 patients (88.3 %). Mean first I-131 activity was 2868 ± 914 MBq (77.5 ± 24.7 mCi) and mean second I-131 activity 3004 ± 699 MBq (81.2 ± 18.9 mCi). There was no association between the first, second, and cumulative activity with re-ablation treatment outcome. Treatment failure was associated with higher Tg levels prior to re-ablation (Tg2) (OR 1.16, 95 % CI 1.05-1.29, P = 0.003) and N1a status (OR 3.89, 95 % CI 1.13-13.41, P = 0.032). After excluding patients with positive-to-negative TgAb conversion, Tg2 level of 3.7 ng/mL predicted treatment failure with a sensitivity of 75.0 %, specificity of 80.5 %, and a negative predictive value of 97.1 %. Patients with positive-to-negative TgAb conversion had higher failure rates (OR 2.96, 95 % CI 0.94-9.29). Re-ablation success was high in all subgroups of patients and I-131 activity did not influence treatment outcome. Tg may serve as a good predictor of re-ablation failure. Patients with positive-to-negative TgAb conversion represent a specific group, in whom Tg level should not be used as a predictive marker of treatment outcome.

Use of Alternative and Complementary Medicine in Patients with Malignant Diseases in High-Volume Cancer Center and Future Aspects

Usage of complementary and alternative medicine (CAM) is steadily increasing over the last decades, gaining medical, economic and sociological importance. The aim of the present study was to assess the use of complementary and alternative therapies in cancer patients. A cross-sectional, descriptive survey design was used to collect data through an anonymous questionnaire. A total of 267 patients were included in the study. The prevalence of CAM use among cancer patients in this study was 60.3%. It was found that 61 heterogeneous CAM therapies were used, the most popular among patients being naturopathy/folk medicine. In multivariate logistic regression analysis, independent predictors of CAM use were high income, divorced status, female sex and younger age. In conclusion, considering the fact that a large proportion of patients used at least one CAM approach, we need to continue our efforts to improve the patient-oncologist communication in order to deliver most reliable information to patients and to better understand the possible standard medicine-CAM interactions. According to results of the latest studies, CAM therapies that help manage pain, nausea, fatigue, anxiety, and other symptoms should be integrated into the patient overall care.

DEMOGRAPHIC AND CLINICOPATHOLOGIC FEATURES OF PATIENTS WITH PRIMARY BREAST CANCER TREATED BETWEEN 1997 AND 2010: A SINGLE INSTITUTION EXPERIENCE.

Breast cancer accounted for 28% of all new cancers and 18% of female cancer deaths in Europe in 2010. It is the most common type of cancer in women in Croatia, with an incidence rate of 56.9/100 000 in the year 2010, and the highest number of newly diagnosed women aged between 60 and 64. Multiple factors are associated with an increased risk of breast cancer: advancing age, family history, exposure to endogenous and exogenous reproductive hormones, dietary factors, benign breast disease, and environmental factors. To assess demographic and clinicopathologic features of primary breast cancer, we retrospectively analyzed 870 patients treated in our institution between 1997 and 2010. Data were obtained from medical documentation and a printed questionnaire regarding life habits. Most of our patients presented with a breast lump and were self-diagnosed by breast examination. This fact highlights the need of regular breast self-examination, although it should also be taken into account that most of our patients did not attend regular mammography screening (only 31%). One of the most concerning facts is that the mean time from observing the first symptom to visiting a physician was 4 months. Previous studies have identified ignorance, fear and fatalistic attitudes, poor socioeconomic conditions, and illiteracy as important factors resulting in delay. Considering these facts, education and raising awareness about the disease in the general population is one of the key weapons for lowering breast cancer mortality.

Clinical Significance of Multinodularity in Patients with Papillary Thyroid Carcinoma.

UNLABELLED: Backgroud/Aim: To assess the clinical significance of nodules in multinodular thyroid if one nodule is diagnosed as papillary carcinoma (PC), we investigated 97 patients with a multinodular thyroid and histopathological diagnosis of PC. PATIENTS AND METHODS: We assessed the following variables: age and gender, fine-needle aspiration diagnosis, PC nodule size and dominance, intraglandular dissemination (ID), regional lymph node (RLN) status, and distribution of diagnoses of the other nodules. RESULTS: Among 97 patients with PC, additional diagnoses were: nodular goiter (NG) in 64 patients, ID in 28, Hashimoto's thyroiditis (HT) in 26, and follicular or Hürthle cell adenoma in seven. CONCLUSION: Patients with ID, and without NG or HT more often had RLN metastases. Lower rates of RLN metastases in patients with NG and HT are probably due to smaller PC nodule sizes found during routine follow-up of these benign diseases.

INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.

Metastases to pituitary gland are unusual and mostly asymptomatic, presenting with local symptoms in one of ten patients, and only 3%-5% of them are of prostate origin. Here we report and evaluate the effectiveness and safety of multimodal treatment in a patient with pituitary metastasis of a prostate foamy gland carcinoma. A 78-year-old male patient presented with blurred vision and headache without a previous history of malignancy. Magnetic resonance imaging scans revealed a large sellar mass, with infiltration of the surrounding structures. Maximal transsphenoidal reduction of pituitary metastasis was performed, with a histologic finding of metastatic prostate foamy gland adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy. The patient received 3D conformal external beam radiotherapy with 6 MV photons to the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy showed shrinkage of the tumor process, with rapid prostate specific antigen decline to 0.3 ng/mL. The visual function was fully established and headache resolved. On the last follow up 14 months after the diagnosis, the patient was alive and free from clinical signs of disease. Tailored treatment, including limited radiotherapy in a higher palliative dose, in a patient with foamy gland symptomatic pituitary metastatic disease resulted in good local and systemic control of the disease. In older male patients with clinical and/or radiologic characteristics suggestive of metastatic pituitary disease, the prostate specific antigen test should be included as part of the work-up.

Sunitinib-induced thyrotoxicosis - a not so rare entity.

BACKGROUND/AIM: The tyrosine kinase inhibitor (TKI) sunitinib malate is nowadays a standard first-line treatment option for patients with metastatic clear-cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the incidence and clinical course of thyrotoxicosis in our cohort of patients treated with sunitinib. PATIENTS AND METHODS: Medical records of all patients treated with first-line sunitinib for mRCC at our Institution between November 2008 and March 2014 were retrospectively reviewed. Thyroid function was assessed after every 2 cycles of therapy, during the 2 weeks off period. RESULTS: Out of the 62 included patients, hypothyroidism has developed during therapy in 12 patients (19%) and it was preceded by thyrotoxicosis in 2 (3.2%). CONCLUSION: Sunitinib-induced thyrotoxicosis (SIT), a not so rare entity, was followed by hypothyroidism. The patterns of occurrence and possible significance of SIT, as predictive marker of better treatment response to sunitinib, need to be validated in further studies.

Familial adenomatous polyposis in three generations of a single family: a case study.

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited syndrome characterized by the development of numerous polyps in the colon and rectum. If left untreated, the affected patients inevitably develop colon cancer by the age of 40 years. A resection of the colon (colectomy) or of the colon and rectum (proctocolectomy) is needed to minimize the risk of cancer. CASE PRESENTATION: We report a case of FAP through three generations of a single family, in which the grandmother and granddaughter underwent total colectomy with ileoanal anastomosis and did not develop colon cancer, while the son underwent subtotal colectomy with ileorectal anastomosis and developed recurrent rectal cancer. Data regarding timely surgery, surveillance, and chemoprevention are discussed. CONCLUSION: The FAP phenotype determines the type of treatment. In severe polyposis, proctocolectomy with ileoanal anastomosis seems to be the optimal method for minimizing the risk of cancer development. This case report advocates complete rectal removal, especially in cases of poor patient compliance with colonoscopic surveillance.