Thyroid and Parathyroid Functions After Pharyngo-Laryngo-Esophagectomy for Cervical Esophageal Cancer.

BACKGROUND: Cervical esophageal cancer (CEC) patients whose larynx function cannot be preserved often undergo chemoradiotherapy, whereas those with residual or recurrent lesions undergo a pharyngo-laryngo-esophagectomy (PLE); however, some need to undergo a pharyngolaryngectomy with total esophagectomy (PLTE) for synchronous or metachronous esophageal cancer. We retrospectively evaluated the relationship between preoperative irradiation (or the extent of esophageal resection) and postoperative endocrine complications in CEC, including hypothyroidism and hypoparathyroidism. METHODS: The cancers of 35 (5.4%) of 678 esophageal cancer patients with esophagectomy treated in 2000-2017 were CECs. We also analyzed the 17 cases of CEC patients who underwent PLE with thyroid lobectomy-11 with irradiation before PLE and 6 without irradiation. Seven patients underwent a PLTE. RESULTS: Hypothyroidism and hypoparathyroidism occurred in 14 and 12 patients, respectively. The hypothyroidism rate was significantly higher in patients with irradiation versus those without irradiation (100% vs. 50%; p = 0.010), and the hypoparathyroidism rate was significantly higher in the PLTE versus non-PLTE patients (100% vs. 50%; p = 0.026). The mean levothyroxine dosage was 1.60 µg/kg/day in the PLE patients post-irradiation. CONCLUSIONS: Irradiation appears to be a risk factor for hypothyroidism after PLE with thyroid lobectomy, while PLTE might have some effect on hypoparathyroidism. Due to vocal function loss, PLE patients may experience symptoms from endocrine complications. Levothyroxine treatment soon after PLE for post-irradiation patients and patients requiring as-needed calcium or vitamin D supplementation based on biochemical hypocalcemia for PLE (especially PLTE), may be effective in preventing symptomatic endocrine complications.

Development of molecular targeted drugs for advanced thyroid cancer in Japan.

Up until now there have been no promising drugs for the treatment of advanced thyroid cancer, but the development of novel therapeutic agents is now anticipated as a result of the advent of molecular targeted drugs that inhibit tumor growth signals or angiogenesis. Against a background in which the development of numerous molecular targeted drugs for advanced thyroid cancer is being pursued worldwide, the development of sorafenib, vandetanib, and lenvatinib is currently also under way in Japan. All three of these compounds are undergoing phase 3 trials or have been approved abroad, and because they are in the final stage of development in Japan, they are expected to be introduced in clinical settings in the near future. After they have been introduced, it will be necessary to understand the differences between these compounds and to administer them to patients appropriately.

Current status of molecularly targeted drugs for the treatment of advanced thyroid cancer.

The prognosis of almost all thyroid cancers is good, but some patients have indications for these molecularly targeted drugs. Some of these drugs, i.e., vandetanib, XL-184, sorafenib, motesanib, axitinib, and pazopanib, are clearly useful clinically.

[Unique treatment policy for thyoid cancer in Japan and other countries].

The treatment policy for patients with well-differentiated thyroid cancer varies among institutions. Although surgery has been the mainstay of treatment for this cancer, there is no consensus concerning the optimal extent of thyroid resection or the extent of lymph node dissection. Furthermore, controversy remains with regard to the indications for radiation therapy and hormonal therapy in surgical or nonsurgical cases. Thyroid resection is more extensive in other countries than in Japan, although the extent of lymph node dissection is limited in the former. For papillary carcinoma, total thyroidectomy is the treatment of first choice for all overseas respondents, but of only 20% in Japan, despite lymph node dissection being more extensive in Japan than in other countries. In Japan, high-dose 131I therapy is available only in a few institutions. Such limited indications reflect a discrepancy in the frequency of total thyroidectomy, a prerequisite for postoperative high-dose 131I therapy, between Japan and other countries.

Glucocorticoid-induced osteoporosis.

Glucocorticoids are important drugs in the treatment of variety diseases, but long-term period use can lead to various adverse effects, including osteoporosis. Glucocorticoid-induced osteoporosis is mainly caused by inhibition of osteoblastic bone formation, which results not only in decreased bone mineral density, but reduction of bone strength by trabecular thinning in bone microstructures. The evidence suggests that daily oral glucocorticoid doses higher than 5 mg prednisolone or equivalent increase the risk of fracture within 3-6 months after the start of therapy. High-dose inhaled glucocorticoids may also increase fracture risk. The diagnostic procedures are similar to those for primary osteoporosis, but the diagnostic threshold for bone mineral density needs to be higher than that for primary osteoporosis. Treatment with vitamin D, calcitonin, sex hormone replacement, and bisphosphonates has been shown to be effective, and bisphosphonates have been demonstrated to be the most valuable drugs for glucocorticoid-induced osteoporosis. There are several lines of evidence indicating that they are effective in preventing and treating low bone mineral density and in reducing fracture risk.