Prognosis After Brain Metastasis from Differentiated Thyroid Carcinoma

Background

In patients with differentiated thyroid carcinoma (DTC), lung and bone metastasis sometimes occur. However, brain metastasis (BM) is extremely rare. Because most previous reports about BM from DTC included a relatively small number of cases, the clinical characteristics and outcomes of BM are still unclear.

Patients and methods

Between 1965 and 2013, among 961 patients who had died because of DTC, 24 patients were diagnosed with BM from DTC. One patient with BM from DTC is still alive. To identify the prognostic factors for longer survival after BM, the medical records of these 25 patients were retrospectively reviewed.

Results

The median age at BM diagnosis was 66 years. Typical symptoms associated with BM had appeared in 20 patients (80 %). The Karnofsky Performance Status (KPS) was good (≥70) in 10 patients and poor (≤60) in 15 patients. Seven patients had a single intracranial lesion of BM, 6 patients had 2 or 3 lesions, and 9 patients had 4 or more. Eleven patients did not receive any treatment for BM, and 14 patients underwent surgical resection, radiation therapy, or both. One-year and 5-year disease-specific survival rates were 28 and 10.6 %, respectively. Good KPS (≥70), small number of intracranial lesions (≤3), and treatment for BM were prognostic factors for long survival on univariate analysis (p < 0.05). On multivariate analysis, only treatment for BM was significant.

Conclusion

Treatment of BM from DTC is indicated in patients who have a good KPS and fewer intracranial lesions, and some of them may achieve long survival.

     

Revisiting Low-Risk Thyroid Papillary Microcarcinomas Resected Without Observation: Was Immediate Surgery Necessary?

Introduction

Low-risk thyroid papillary microcarcinomas (PMCs) without evidence of metastasis grow slowly if at all. However, we recommended surgery for tumors touching the trachea (TR) or located in the course of the recurrent laryngeal nerve (RN). Here we compared the cases of low-risk PMC patients who underwent immediate surgery to cases of TR- and RN-involved PMCs.

Materials and methods

We enrolled 1143 low-risk PMC patients who underwent immediate surgery in the years 2006–2014. The PMCs of 437 patients touched the TR on imaging studies: 270, 104, and 63 were graded as low, intermediate, and high risk, respectively, for TR invasion based on the angles between the tumor and the TR surface. The tumor was in the course of the RN in 144 patients, with 35 graded low risk and 109 high risk for RN invasion based on the normal rim of the thyroid in the direction of the RN.

Results

Invasion of the TR cartilage was observed only in high-risk patients. Peritracheal connective tissue was resected in 21, 15, and 6 of the high-, intermediate- and low-risk patients, respectively. Significant invasion of the RN requiring complete resection was observed in only nine patients at high risk for RN invasion. The incidence of TR invasion in high- and intermediate patients and the incidence of RN invasion in the high-risk patients were significantly higher than those of the low-risk patients. Tumors <7 mm did not show TR or RN invasion.

Conclusion

Among PMCs that touched the TR or were located in the course of the RN, observation could be the first choice for tumors <?7 mm and those ≥?7 mm judged as low risk for TR or RN invasion. However, for PMCs with high-risk features, immediate surgery after cytological diagnosis by a needle aspiration biopsy is recommended.

     

Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength

The Bcl2 family proteins, Bcl2 and BclXL, suppress apoptosis by preventing the release of caspase activators from mitochondria through the inhibition of Bax subfamily proteins. We reported that BCL2 overexpression in osteoblasts using the 2.3 kb Col1a1 promoter increased osteoblast proliferation, failed to reduce osteoblast apoptosis, inhibited osteoblast maturation, and reduced the number of osteocyte processes, leading to massive osteocyte death. We generated BCLXL (BCL2L1) transgenic mice using the same promoter to investigate BCLXL functions in bone development and maintenance. Bone mineral density in the trabecular bone of femurs was increased, whereas that in the cortical bone was similar to that in wild‐type mice. Osteocyte process formation was unaffected and bone structures were similar to those in wild‐type mice. A micro‐CT analysis showed that trabecular bone volume in femurs and vertebrae and the cortical thickness of femurs were increased. A dynamic bone histomorphometric analysis revealed that the mineralizing surface was larger in trabecular bone, and the bone‐formation rate was increased in cortical bone. Serum osteocalcin but not TRAP5b was increased, BrdU‐positive osteoblastic cell numbers were increased, TUNEL‐positive osteoblastic cell numbers were reduced, and osteoblast marker gene expression was enhanced in BCLXL transgenic mice. The three‐point bending test indicated that femurs were stronger in BCLXL transgenic mice than in wild‐type mice. The frequency of TUNEL‐positive primary osteoblasts was lower in BCLXL transgenic mice than in wild‐type mice during cultivation, and osteoblast differentiation was enhanced but depended on cell density, indicating that enhanced differentiation was mainly owing to reduced apoptosis. Increased trabecular and cortical bone volumes were maintained during aging in male and female mice. These results indicate that BCLXL overexpression in osteoblasts increased the trabecular and cortical bone volumes with normal structures and maintained them majorly by preventing osteoblast apoptosis, implicating BCLXL as a therapeutic target of osteoporosis. © 2016 American Society for Bone and Mineral Research.     

Impact of immunohistological subtypes on the long-term prognosis of patients with metastatic breast cancer

Purpose

Although improved long-term prognoses for patients with metastatic breast cancer (MBC) have been demonstrated, few reports address overall survival (OS) with sufficient follow-up. Furthermore, the relevance of immunohistological subtypes to OS in MBC has not been clarified.

Methods

We evaluated, retrospectively, the OS of patients who had been initiated on systemic therapy for MBC between 2000 and 2008.

Results

The subjects of this study were 527 patients with MBC treated by systemic therapy. The median survival time (MST) was 55.5 months. The MST for each immunohistological subtype was as follows: luminal, 59.9 months; luminal-HER2, not reached; triple-negative, 18.6 months; and HER2-enriched, 49.9 months. According to multivariate analysis, metastasis-free intervals of ≥2 years and treatment with anthracycline for MBC were predictive of better OS. The predictors of shorter OS included disease progression after first-line treatment for MBC, triple-negative, and all histological factors, except papillotubular carcinoma, with liver metastasis, and having three or more initial metastatic sites.

Conclusions

The prognosis of the patients with MBC in this series was better than that reported before 2000, which is probably attributable to the use of novel, improved pharmacological agents. For example, luminal-HER2 tumors can be treated using both aromatase inhibitors and trastuzumab. Because of the lower toxicities, it is now possible to administer these agents for longer periods, resulting in better prognoses.

     

Successful living donor liver transplantation for classical maple syrup urine disease

MSUD is an autosomal recessive condition characterized by a deficiency in the enzyme, BCKDH, which catalyzes the breakdown of BCAAs. If left untreated, MSUD can result in mental retardation, central nervous system disorders, and even death. Most patients with MSUD are treated with a restricted protein diet and milk from which BCAAs have been removed. LT has been shown effective in patients with MSUD. This report describes the case of a 15‐month‐old boy who received a liver graft from his mother. Transplantation was successful, and the patient was then able to ingest a normal diet. Despite episodes of acute rejection, chylous ascites, and high fever (40 °C), he has shown no evidence of MSUD recurrence. These findings indicate that patients with MSUD can be successfully treated by LDLT, even when the donor is a heterozygous carrier of a mutated BCKDH gene.     

Endolymphatic space size in patients with Meniere’s disease and healthy controls

Conclusions: The incident ratios of cochlear and/or vestibular endolymphatic hydrops (EH) were significantly higher in the affected ears of patients with Meniere’s disease (MD) than in the ears of healthy controls. There were no significant differences between controls and the contralateral ears of MDs. Objectives: The aim was to compare the incidence ratios of EH between unilateral/bilateral MD and controls using 3T magnetic resonance imaging (MRI) with intravenous gadolinium. Methods: A total of 41 patients were diagnosed with MD: 32 with unilateral MD (uMD) and nine with bilateral MD (bMD). Fifteen healthy volunteers were enrolled as controls. The patients underwent 3T MRI 4?h after intravenous injection of gadolinium. Results: Cochlear EH was present in 3.3% of 30 ears of 15 controls, 6.3% of 32 contralateral (contra) ears of 32 uMDs, 62.5% of 32 affected ears of 32 uMDs, and 55.6% of 18 affected ears of nine bMDs. Vestibular EH was observed in 6.7% of control ears, 3.1% of contra-uMD ears, 65.6% of affected uMD ears, and in 55.6% of affected bMD ears. Either cochlear or vestibular EH was present in 10.0% of control ears, 6.3% of contra-uMD ears, 81.3% of affected uMD ears, and 44.4% of affected bMD ears.