Subcutaneous transplantation of human thyroid tissue into a pre-vascularized Cell Pouch™ device in a Mus musculus model: Evidence of viability and function for thyroid transplantation.

This study aimed to investigate the survival and efficacy indicators of human thyroid tissue transplantation into a retrievable, prevascularized implanted Sernova Corp Cell Pouch™ (CP) device. Thyroid tissue from human donors was transplanted subcutaneously into the pre-implanted CP device or into the subcutaneous (SC) space alone as a control in a nude Mus musculus model. Transplanted M. musculus were monitored for human serum thyroglobulin (TG) levels for 3 months until the transplants were removed for histological assessment. Human thyroid tissue survived and continued to produce TG in transplanted nude M. musculus in the CP, with no adverse events. CP transplants exhibited more persistent and robust production of human TG than tissue placed in the SC space alone from 3 to 13 weeks post transplantation. Fresh thyroid transplants had better survival and function compared to cryopreserved transplants. Thyroid transplant viability correlated with TG levels at 3 months post-transplant (p = 0.03). Immunofluorescence staining of transplants for TG and TPO localized in thyroid follicles. Human thyroid tissue transplanted into the subcutaneously implanted pre-vascularized CP in nude M. musculus survived and continued to produce robust and persistent human TG and warrants further investigation as a treatment for postoperative hypothyroidism.

Cryopreserved Rat Thyroid Autotransplantation in the Treatment of Postoperative Hypothyroidism.

To verify the viability and functionality of cryopreserved thyroid autotransplantation in rats who underwent total thyroidectomy in the treatment of postoperative hypothyroidism. Thirty-two Wistar rats were randomly assigned into groups (G) with eight animals each: control (CG); simulation (SG); hypothyroidism (HTG) and transplanted (TG). At the beginning and in the 13th week of the experiment, serum levels of total T3, free T4, TSH and calcium were determined. In both the first and 14th weeks, scintigraphic examinations, 99m-Tc pertechnetate radioisotope biodistribution and histopathology were performed. In the 14th week, the expression of proliferating cell nuclear antigen (PCNA) and cellular apoptosis (caspase-3) were also evaluated. In the 13th week, the transplanted animals had normal serum levels of total T3 and free T4. TSH levels showed a tendency towards normality. In the 14th week, scintigraphic exams displayed graft isotopic uptake in all animals in the TG group. Histological examinations 13 weeks after transplantation showed the viability and functionality of thyroid follicles. PCNA revealed significant immunoreactivity of the graft (p < 0.001) when the TG was compared to the CG. There was no difference between CG and TG considering the expression of activated caspase-3. The experimental study confirmed the viability and functionality of thyroid autotransplantation implanted in skeletal muscle with evidence of cell proliferation without cellular apoptosis. This surgical strategy was effective in the treatment of postoperative hypothyroidism.

Delayed Postnatal Growth and Anterior Pituitary Development in Growth-Retarded (grt) Female Mice.

Growth-retarded (grt) mice display primary congenital hypothyroidism due to the hyporesponsiveness of their thyroid glands to thyroid-stimulating hormone (TSH). We examined somatic growth, anterior pituitary development, and hormonal profiles in female grt mice and normal ones. Although growth in grt females was suppressed 2 weeks after birth, the measured growth parameters and organ weights gradually increased and finally reached close to the normal levels. Grt mice exhibited delayed eye and vaginal openings and remained in a state of persistent diestrus thereafter, plasma estrogen levels being lower than those in normal mice. Grt mice that received normal-donor thyroids showed accelerated growth and their body weights increased up to the sham-normal levels, indicating the importance of early thyroid hormone supplementation. In the anterior pituitary, there were fewer growth hormone (GH) and prolactin (PRL) cells in grt mice than in normal mice as examined at 12 weeks after birth, but the numbers of these cells did not differ from those in normal mice after 24 weeks. Grt mice had more TSH cells than normal mice until 48 weeks. Plasma GH levels in grt mice were lower than those in normal mice at 2 weeks, but did not differ substantially after 5 weeks. Compared with normal mice, grt mice had significantly lower plasma PRL and thyroxine levels, but notably higher TSH levels until 48 weeks. These findings indicate that thyroid hormone deficiency in grt mice causes delayed development and growth, and inappropriate development of GH, PRL and TSH cells, followed by the abnormal secretion of hormones by these pituitary cells.

Thyroid gland flap minimizes mucosal defects at supracricoid partial laryngectomy with cricohyoidoepiglottopexy.

Wound infection is a major complication after supracricoid partial laryngectomy with cricohyoidoepiglottopexy (CHEP) for radiation therapy failure. A 60-year-old man received chemoradiotherapy for a glottic carcinoma. CHEP, reusing the thyroid gland flap (TF), was performed because the cancer recurred after a salvage vertical partial laryngectomy following radiation therapy failure. The TF was sutured to the supraglottis and cricoid cartilage mucosa to minimize mucosal defects before the hyoid bone and cricoid cartilage were sutured. Wound healing after CHEP was good without infection. After decannulation, oral food intake was possible without aspiration, and speech function was comparable to that of other patients who had supracricoid partial laryngectomies. Histopathological examination revealed a close connection between the TF and its surrounding tissues without fibrous scarring. TF may improve wound healing after CHEP for radiation failure by minimizing mucosal defects.

Free thyroid transfer to anterolateral thigh for prevention of radiation induced hypothyroidism: An initial experience.

AIM: Radiation induced hypothyroidism (RIHT) is one of the commonest late side effects of radiation therapy and is seen in more than half of patients and affects quality of life significantly. We report our initial experience on feasibility of free microvascular transfer of thyroid gland out of radiation field to prevent development of RIHT. MATERIAL AND METHODS: A prospective pilot study was undertaken during August 2017 to May 2018. Six Patients with stage III/IV patients of oral cavity cancers who required wide excision/composite resections with microvascular free flap (ALT) reconstruction and adjuvant radiation therapy were enrolled. A written informed consent was obtained from all patients prior to the procedure. RESULTS: The mean age of cohort was 51 years with tongue most common site of primary cancer. The free transfer of thyroid gland to anterolateral thigh was done using microvascular technique. The mean additional time for procedure was 51 min. All patients had successful transfer with no associated immediate complications. Patients were followed up with Tc99 scan, USG Doppler and biochemical assay at routine intervals in peri and postoperative period to assess the anatomical and physiological function of the transferred gland. At median follow up of 8 months, 5 patients were euthyroid and remaining one had biochemical hypothyroidism. All patients had functional thyroid gland in anetrolateral thigh. Five patient were alive, one patient died due to disease. CONCLUSION: This is a small and early feasibility study for free thyroid gland transfer and validates the previously published data. The selected group of patients who have high chances of developing RIHT may benefit from this strategy. Further validation of the technique may be explored in a larger cohort.

[Long-term oucomes of tracheal transplantation: success and unsolved problems]. / Otdalennyi rezul'tat transplantatsii trakhei: uspekh i nereshennye problemy.

AIM: To analyze long-term outcomes of tracheal transplantation. MATERIAL AND METHODS: There were 1128 patients with cicatricial tracheal stenosis who have been operated at the Petrovsky Russian Research Center for Surgery and the Sechenov First Moscow State Medical University for the period 1963-2015. RESULTS: Operations have become safer. Postoperative morbidity and mortality reduced from 41.4% (1963-1980) to 5.6% (2001-2015) and from 21.9% (1963-1980) to 0.5% (2001-2015), respectively. Tracheal transplantation was performed in 2 cases and fundamentally different tracheal structures were applied. Donor thyreotracheal complex with restored blood supply through thyroid vessels was used in the first case (2006). Perennial experimental trials preceded clinical application of this technique. In the second case (2010) we applied scientific results of foreign colleagues (cellular technologies and methods of regenerative medicine to create artificial trachea). Patients are still alive after 12 and 8 years, respectively. Restoration of blood supply of donor trachea is possible through thyroid collaterals. This technique is successful in long-term period. Tissue-engineered trachea cannot be considered true trachea due to no all tracheal components. However, such trachea provides air-conducting, evacuation and protective functions. Tracheomalacia requires further researches as one of the main problems of tracheal transplantation.

Metastatic squamous cell carcinoma in autotransplanted thyroid: A diagnostic dilemma.

Metastasis to the thyroid is uncommon. Mostly, they are tumors that originate in the lung or head or neck. Metastases from breast or kidney carcinomas and metastatic melanoma have also been reported. Autotransplantation of benign thyroid tissue is a surgical procedure designed to achieve normal thyroid hormonal status following surgery. Metastasis into autotransplanted thyroid tissue has not been reported earlier. We report a case of squamous cell carcinoma (SCC) metastatic to autotrasplanted thyroid diagnosed on fine-needle aspiration. Further workup revealed a primary oral cavity SCC.

Heterotopic thyroid autotransplantation: A preliminary clinical study.

BACKGROUND: Thyroid autotransplantation offers an attractive alternative to subtotal thyroidectomy and replacement therapy. However, it has not been sufficiently clinically investigated. METHODS: Total thyroidectomy was performed for 20 patients with benign thyroid disorders, and at least 10 g of thyroid tissue were implanted intramuscularly. Graft monitoring was achieved through 99m Tc scan at 2 months, free triiodothyronine (FT3), FT4, and thyroid-stimulating hormone (TSH) measurements at 1, 2, 4, 6, 8, 10, and 12 months postoperatively, and clinical examination. RESULTS: Grafts survived and gradually functioned in all patients to a variable extent after a latent period (mean 99m Tc uptake = 1.28 ± 0.37%). Mean values for FT3, FT4, TSH at 12 months were 1.75 ± 0.48 pg/mL, 1.06 ± 0.26 ng/dL, and 28.08 ± 34.01 µIU/mL respectively. CONCLUSION: Thyroid autotransplantation restored euthyroid status in 33.3% of patients after 12 months. A role of age, operative time, and 99m Tc-uptake in determining the final graft outcome is possible.

First Complex Allotransplantation of Neck Organs: Larynx, Trachea, Pharynx, Esophagus, Thyroid, Parathyroid Glands, and Anterior Cervical Wall: A Case Report.

OBJECTIVE: Evaluate the possibility of performing a complex vascular allotransplant of all neck organs including skin. SUMMARY BACKGROUND DATA: There are 2 previous attempts described in the literature, none of them being that complex. The first one is nonfunctional due to chronic rejection, the second one is viable yet considerably limited in complexity (no parathyroids, no skin). METHODS: The allotransplantation was performed simultaneously on 2 adjacent operating rooms, using microsurgical techniques. RESULTS: The patient's voice, breathing through mouth, swallowing, and endocrinal functions have been fully restored. CONCLUSIONS: Achieved results show clearly that such operations performed in selected patients can nearly fully restore functional and aesthetic effects in 1 single procedure.

Technique and outcome of autotransplanting thyroid tissue after total thyroidectomy for simple multinodular goiters.

BACKGROUND/OBJECTIVE: Limited animal and human studies have shown function, albeit inadequate, of implanted thyroid tissue in muscles. This work aimed to ascertain results in a larger number of patients, finding practical method for implantation, studying the effect of changing weight of implant and effect of passage of time on its function. METHODS: Forty patients had total thyroidectomy for simple multinodular goiters. A piece of the excised gland was finely minced, mixed with saline as emulsion, and injected in thigh muscles. Twelve patients had 5-g implants, while 28 patients had 10-g implants. Four parameters were studied at 2 months, 6 months, and 12 months: technetium isotope uptake by the implant; thyroid stimulating hormone (TSH); free T3 (FT3); and free T4 (FT4). RESULTS: All autotransplanted thyroid tissue survived and functioned. After 12 months, mean values (± standard deviation) of isotope uptake, TSH, FT3, and FT4 of the 5-g implants were 0.44 ± 0.16%, 27.74 ± 30.4 UI/mL, 3.07 ± 1.10 pg/mL, and 1.01 ± 0.3 ng/dL, repectively. Those for the 10 g implants were 0.71 ± 0.20%, 22.78 ± 19.7 UI/mL, 3.92 ± 1.2 pg/mL, and 1.05 ± 0.3 ng/dL, repectively. Ten-gram implants showed significantly higher isotope uptake than 5-g. TSH, FT3, and FT4 significantly improved over the period of 1 year. CONCLUSION: Injection of thyroid tissue suspension is a simple method for thyroid autotransplantation. TSH was elevated in the majority to maintain normal or near normal thyroid hormones. Ten-gram implants showed higher isotope uptake than 5-g, although this difference was not reflected by thyroid hormone profile. The implant seemed to function better with the passage of time from 2 months to 12 months.

Transposition of lingual thyroid gland to the submandibular region by transoral approach.

The purpose of this case report is to demonstrate surgical technique of only functional but symptomatic lingual thyroid gland transposition to submandibular region by transoral approach without mandibulotomy and tongue-splitting. A 37-year-old female patient was admitted to our hospital with dysphagia and apnea symptoms. Physical examination revealed 3cm×3cm lingual thyroid gland was detected at the tongue base. The patient was euthyroid and thyroid gland was not detected in the neck. Under general anesthesia, right submandibular gland excision and transposition of lingual thyroid tissue to submandibular region with dorsal lingual artery axis flap were performed by transoral approach. Thyroid hormones remained normal in the postoperative period. In conclusion transoral transposition of lingual thyroid to submandibular region as a flap without mandibulotomy is a minimally invasive and function preserving alternative approach. Besides preserving thyroid functions, this transoral surgical technique can be preferred by patients who avoid skin incision for esthetic concerns.

Free thyroid transfer: Short-term results of a novel procedure to prevent post-radiation hypothyroidism.

BACKGROUND: The incidence of radiation-induced hypothyroidism (RIH) in patients with head and neck cancer is >50%. The purpose of this study was to assess the long-term efficacy of free thyroid transfer (FTT) for prevention of RIH in patients with head and neck cancer. METHODS: Hemithyroid dissection was completed in 10 patients with advanced head and neck cancer undergoing ablation, radial forearm free flap (RFFF) reconstruction, and postoperative radiotherapy (RT). The hemithyroid was anastomosed to the donor site vessels in the forearm. Thyroid laboratory testing and technetium (Tc) scans were performed 6 weeks and 12 months postoperatively to establish functional integrity. RESULTS: FTT was successfully performed in 9 of 10 recruited patients. Postoperative Tc scans demonstrated strong Tc uptake in the forearm donor site at 6 weeks and 12 months in all patients who underwent transplantations. CONCLUSION: FTT is feasible with maintenance of function, and may represent a novel strategy for prevention of RIH. © 2016 Elsevier Head & Neck Published by Wiley Periodicals, Inc. Head Neck 39: 1234-1238, 2017.

Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism.

PURPOSE: The incidence of hypothyroidism after radiation therapy for head and neck cancer (HNC) has been found to be ≤53%. Medical treatment of hypothyroidism can be costly and difficult to titrate. The aim of the present study was to assess the feasibility of free thyroid transfer as a strategy for the prevention of radiation-induced damage to the thyroid gland during radiation therapy for HNC. METHODS AND MATERIALS: A prospective feasibility study was performed involving 10 patients with a new diagnosis of advanced HNC undergoing ablative surgery, radial forearm free-tissue transfer reconstruction, and postoperative adjuvant radiation therapy. During the neck dissection, hemithyroid dissection was completed with preservation of the thyroid arterial and venous supply for implantation into the donor forearm site. All patients underwent a diagnostic thyroid technetium scan 6 weeks and 12 months postoperatively to examine the functional integrity of the transferred thyroid tissue. RESULTS: Free thyroid transfer was executed in 9 of the 10 recruited patients with advanced HNC. The postoperative technetium scans demonstrated strong uptake of technetium at the forearm donor site at 6 weeks and 12 months for all 9 of the transplanted patients. CONCLUSIONS: The thyroid gland can be transferred as a microvascular free transfer with maintenance of function. This technique could represent a novel strategy for maintenance of thyroid function after head and neck irradiation.

Validation of intra-operative parathyroid hormone and its decline as early predictors of hypoparathyroidism after total thyroidectomy: A prospective cohort study.

INTRODUCTION: Total thyroidectomy is a preferred surgical technique for benign as well as malignant thyroid pathologies, but many a times can cause hypoparathyroidism. The aim of this study is to evaluate the intra-operative parathyroid hormone (ioPTH) level and its decline as predictors for post-operative hypoparathyroidism after total thyroidectomy. METHODS: In this single-centre prospective cohort study, 90 patients who underwent total thyroidectomy for benign as well as malignant pathologies of thyroid gland were studied. Intra-operative parathyroid levels and at different time intervals parathyroid hormone and serum calcium levels were measured to predict hypoparathyroidism. The data was analysed using independent sample t test and p value < .05 was considered to be significant. RESULTS: There were 14 male and 76 female patients with a mean age of 41 years. Most common thyroid pathology for which total thyroidectomy was done was colloid goitre (62). Twenty four patients (26.66%) developed hypoparathyroidism. Intra-operative PTH was found to be most accurate predictor for diagnosing post-operative hypoparathyroidism (cut off was (11.3 pg/ml, calculated using ROC curves) and has maximum sum of sensitivity (91.7%) and specificity (97%). On taking cut off values of intra-operative PTH and PTH decline together, they were found to be most accurate predictor for permanent hypoparathyroidism. DISCUSSION: Early and accurate predictor of hypoparathyroidism is very important and always sought. Very early prediction during intra-operative periods can be used for auto transplantation of parathyroid gland. CONCLUSION: Intra-operative parathyroid hormone and its decline are accurate, reliable, and early predictor of hypoparathyroidism after total thyroidectomy.

Experimental autotransplantation and cryopreservation of the thyroid gland.

BACKGROUND: The purpose of this study was to investigate the functionality of autotransplanted thyroid tissues immediately or after cryopreservation in rabbits. METHODS: The study was completed with 12 rabbits randomized in 2 groups. Preoperative scintigraphies were performed for all subjects. The rabbits underwent total thyroidectomy. The first group underwent immediate thyroid autotransplantation. Thyroid tissues of the second group were cryopreserved and autoimplanted at the eighth postoperative week. The free triiodothyronine (fT3) and thyroxine (fT4) levels were monitored for 8 weeks. Postoperative scintigraphies were performed at the eigth week after autoimplantation. RESULTS: The subjects in the first group reached euthyroid levels at the eighth week while none of the second group reached that level, but all showed continuous increase. Although implanted thyroid tissues of 5 of the 6 rabbits in the first group were demonstrated during the first scintigraphy, the number was only 1 in the second group. CONCLUSION: Thyroid autografts were found to be functional and thought to have a potential preventing postoperative hypothyroidism.

[Proteasomes on thyroid tissue allotransplantation under induction of donor specific tolerance in rats].

The proteasomes in the liver of August rats (RT1C) were investigated 30 days after the allotransplantation of Wistar rat (RT1u) thyroid tissue under renal capsule with/without induction of donor specific tolerance by donor splenocyte intraportal administration. The level of the total proteasome pool, immune proteasomes containing the LMP2 and/or LMP7 subunits, proteasome 19S- and 11S-regulators was defined. The intact and sham-operated August rats were used as control groups. The level of all immune proteasome forms and 11S regulator increased while the level of the total proteasome pool and 19S regulator decreased in the liver of experimental animals compared to the control groups that indicated changes of liver functional state after transplantation. The 19S/11S ratio increased in the liver of non-tolerated rats compared to tolerated animals. In the liver of tolerated rats with survived transplants, the quantity of mononuclear cells, expressing the immune subunit LMP2, greatly increased in comparison with control and non-tolerated animals. Study of the survived transplants showed the increase of the ratio of LMP2/LMP7 immune subunits and 19S/11S regulators in them compared to the tissue replacing the rejected transplants. In the control intact thyroid tissue, the immune proteasomes were almost not revealed, while 19S/11S ratio was maximal. Thus, the development of the immune reaction or its suppression is accompanied by change of the balance between different proteasome forms. The immune subunit LMP7 and 11S regulator are connected with the response against donor tissue. On the contrary, the immune subunit LMP2 and 19S regulator are likely to be important for the immune tolerance development and survived tissue functioning. The low content of the immune proteasomes in the follicle cells was found by immunofluorescence assay. The formation of antigens for major histocompatibility complex class I molecules was impaired by low immune proteasome content that led to immunological tolerance to hormone-producing follicle cells.

Transposition of a lingual thyroid to the submandibular space using a modified technique.

OBJECTIVE: We report a modified surgical technique for transplanting an ectopic, lingual thyroid to the submandibular space, in order to maintain thyroid function while relieving obstructive symptoms. CASE REPORT: A 52-year-old woman complained of progressive dysphagia and dyspnoea. Ectopic lingual thyroid tissue was diagnosed. The ectopic thyroid gland was transplanted into the submandibular region via a lateral pharyngeal approach. A random muscle pedicle was prepared to provide a vascular supply to the transposed gland. RESULTS: Twelve-month follow up confirmed the survival of the transplanted thyroid gland, with preserved thyroid function. CONCLUSION: Surgical transplantation of a lingual thyroid to the submandibular region offers an alternative treatment method for this anomaly, which avoids the need for resection and lifelong thyroxine replacement.

Generation of functional thyroid from embryonic stem cells.

The primary function of the thyroid gland is to metabolize iodide by synthesizing thyroid hormones, which are critical regulators of growth, development and metabolism in almost all tissues. So far, research on thyroid morphogenesis has been missing an efficient stem-cell model system that allows for the in vitro recapitulation of the molecular and morphogenic events regulating thyroid follicular-cell differentiation and subsequent assembly into functional thyroid follicles. Here we report that a transient overexpression of the transcription factors NKX2-1 and PAX8 is sufficient to direct mouse embryonic stem-cell differentiation into thyroid follicular cells that organize into three-dimensional follicular structures when treated with thyrotropin. These in vitro-derived follicles showed appreciable iodide organification activity. Importantly, when grafted in vivo into athyroid mice, these follicles rescued thyroid hormone plasma levels and promoted subsequent symptomatic recovery. Thus, mouse embryonic stem cells can be induced to differentiate into thyroid follicular cells in vitro and generate functional thyroid tissue.

[The transplantation of revascularized thyroid-trachea-lung complex: the experimental study].

The osteoplastic tracheobronchopathy affects the trachea, main, lobar and smaller bronchi, causing their stenosis. Nowadays the mainstay of the treatment of such patients is the cryodestruction, laser destruction and the endoscopic buginage of the trachea and bronchi. The palliative nature and low efficacy of these procedures forces to search new ways of treatment. The traditional lung transplantation or separate trachea and lung transplantation is inappropriate because of the complex affection of both trachea and bronchi. The experimental study aimed the possibility of thyreotracheolung revascularized donor complex transplantation.