On the role of autophagy in the progression of differentiated thyroid cancer (literature review)

The aim of the study was to analyze and summarize available literature data on the role of autophagy in thyroid cancer. Material and methods. We analyzed 34 publications available from pubmed and elibrary. Ru databases concerning thyroid cancer and autophagy. Results. The review discussed the role of autophagy in the progression of thyroid cancer. The development of autophagy-targeted therapy was shown can improve treatment for thyroid cancer. Differentiated thyroid cancer (dtc) is the most common endocrine malignancy. Treatment of dtc patients who are resistant to radioactive iodine therapy is a major challenge. Molecular targeted therapy using tyrosine kinase inhibitors significantly improves treatment outcomes. Conclusion. To enhance the therapeutic effect of treatment with multi-target tyrosine kinase inhibitors, as well as to overcome drug resistance, it is necessary to study the role of autophagy in the development and progression of thyroid cancer.

Morphological Characteristics of the Lacrimal Apparatus in its Obstruction of Various Genesis

Purpose: morphological assessment of the lacrimal ducts at various anatomical levels in patients with primary (PANDO) and secondary (SALDO) obstruction after radioactive iodine therapy.Methods. The material was obtained during endoscopic dacryocystorinostomy with revision of Hasner's valve in patients with PANDO (n=7) in the distal segments of the nasolacrimal duct and in patients with SALDO (n=7) after radioactive iodine therapy. During the surgery, a biopsy of Hasner's valve, as well as a biopsy of the lacrimal sac wall were performed. The resulting material was stained with hemotoxylin and eosin, alcyan blue and by Masson method. Morphological and morphometric analyses were performed in semi-automatic mode. The results of histochemical staining of sections were translated into points taking into account the area and optical density (chromogenicity) in relative units: 1 – weak (0 – 0.3); 2 – moderate (0.3 – 0.6); 3 – significant (>0.6). The nonparametric Mann-Whitney criterion was used for statistical analysis. The differences were considered significant at p<0.05.Results. The comparative morphological study both confirmed the available information concerning the radiation nature of the obstruction and allowed to quantify the fibrosis level of the stromal component and other lacrimal ducts structures.Conclusion. It was shown that the nasolacrimal duct sclerosis is significantly lower (p=0.029) in patients with SALDO than in patients with PANDO while fibrosis in the lacrimal sac is the same in patients of the compared groups.

Rationale for therapeutic decision-making in locally advanced and metastatic radioactive iodine (RAI)-refractory differentiated thyroid cancer, starting from a clinical case

Iodine uptake and organification are the hallmarks of thyroid cells differentiation. The loss of these characteristics in thyroid cancer leads to radioactive iodine refractoriness, a rare condition that bears a low survival rate and poor prognosis. We present a 52-year-old patient presenting dry cough and dyspnea in the supine position. Imaging examinations revealed a thyroid nodule with a high suspicion of malignancy in the right thyroid lobe, multiple laterocervical and mediastinal lymph nodes, lung, bone, and brain metastases. Fine needle aspiration cytologic features have advocated for papillary thyroid cancer (PTC). The patient underwent total thyroidectomy and selective lymphadenectomy. Subsequently, the patient received suppressive treatment with levothyroxine and four courses of radioactive iodine therapy. In addition, to treat bone and brain metastases, the patient experienced external radiotherapy and glucocorticoid therapy. Despite this rigorous therapeutic management, the patient obtained an incomplete structural and functional response. Although the last two posttherapeutic 131I whole-body scans were negative, the patient had elevated stimulated thyroglobulin levels and loco-regional recurrence by thyroid ultrasound. This aspect would suggest that thyroid cells become unable to uptake 131I, most likely through the emergence of new genetic mutations in the cancer cells. In conclusion, our patient's case suggests a 131I-refractory PTC, requiring the initiation of novel targeted systemic agents such as tyrosine kinase inhibitors, in order to improve structural and functional outcomes of radioactive iodine therapy and to afford prolonged progression-free survival advantage.

Pneumatosis intestinalis associated with lenvatinib during thyroid cancer treatment: a case report

Background Pneumatosis intestinalis is a rare disease characterized by gas-filled cysts within the submucosa or serosa of the intestinal tract. In recent years, pneumatosis intestinalis was reported in patients undergoing cancer treatment, and some case reports exist that report that pneumatosis intestinalis occurs during administration of vascular endothelial growth factor inhibitors, such as bevacizumab and sunitinib. Here, we report the first case of pneumatosis intestinalis during lenvatinib treatment. Case presentation A 77-year-old Japanese man presented to our hospital with a chief complaint of numbness in the right leg and weakness of the lower limbs 9 years after right thyroid lobectomy. Computed tomography showed a tumor 90 mm in size from the lumbar spine to the sacrum, causing spinal cord compression. Blood tests showed that the patient’s thyroglobulin level was increased to 11,600 ng/ml. We diagnosed him with thyroid cancer with bone metastases. External beam radiotherapy (39 Gy/13 Fr) was performed on the bone metastases, followed by total thyroidectomy and radioactive iodine therapy. Four months after radioactive iodine therapy, lenvatinib was introduced because the symptoms of numbness and weakness recurred. Lenvatinib was introduced at dose of 24 mg, and then it was reduced to 14 mg owing to Common Terminology Criteria for Adverse Event grade 3 paronychia of the right foot. Although no further significant adverse events occurred, a scheduled computed tomography image showed pneumatosis intestinalis of the ascending colon 14 weeks after the introduction of lenvatinib. No abdominal or digestive symptoms were observed; therefore, we selected conservative treatment. We discontinued lenvatinib for a week, but we were required to restart lenvatinib as the numbness in the right leg worsened after withdrawal. Since the introduction of lenvatinib, 3 years and 5 months passed; we continued lenvatinib treatment, and the therapeutic effect remains partial response. There has been no recurrence of pneumatosis intestinalis. Conclusions Although rare, it is important to recognize that pneumatosis intestinalis can occur in association with lenvatinib and should be differentiated from intestinal perforation. Pneumatosis intestinalis association with lenvatinib can be improved by withdrawal.