ACTH-secreting medullary thyroid cancer: a case series

Summary

Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour that originates from the parafollicular cells of the thyroid gland. The most common presentation of MTC is with a single nodule; however, by the time of diagnosis, most have spread to the surrounding cervical lymph nodes. Cushing's syndrome is a rare complication of MTC and is due to ectopic adrenocorticotrophic hormone (ACTH) secretion by tumour cells. Cushing's syndrome presents a challenging diagnostic and management issue in patients with MTC. Tyrosine kinase inhibitors (TKI) previously used for the management of metastatic MTC have become an important therapeutic option for the management of ectopic ACTH in metastatic MTC. The article describes three cases of ectopic ACTH secretion in MTC and addresses the significant diagnostic and management challenges related to Cushing's syndrome in metastatic MTC.

Learning points:

Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour.

Cushing's syndrome is a rare complication of MTC that has a significant impact on patients' morbidity and mortality.

Tyrosine kinase inhibitors (TKI) provide an important therapeutic option for the management of ectopic ACTH in metastatic MTC.

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Locoregional therapy with α-emitting trastuzumab against peritoneal metastasis of HER2-positive gastric cancer in mice

Abstract

Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found however that locoregionally administered trastuzumab armed with a radionuclide astatine-211 (²¹¹At)-emitting α-particle (²¹¹At-trastuzumab) is effective against HER2-positive PMGC in a xenograft mouse model. We first observed that ²¹¹At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in subcutaneous tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test α-particle radioimmunotherapy with ²¹¹At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the intraperitoneal administration of ²¹¹At-trastuzumab (1 MBq) was a more efficient means of delivery of ²¹¹At into metastatic tumors than intravenous injection; the maximum tumor uptake with intraperitoneal administration was over 60 percent injected dose per gram (%ID/g) compared to about 18%ID/g with intravenous injection. Surprisingly, a single intraperitoneal injection of ²¹¹At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA double-strand breaks, and to drastically reduce the tumor burden in three further mice. No body weight loss, leukocytopenia or significant biochemical changes in liver and kidney function were observed in the treatment group. Accordingly, locoregionally administered ²¹¹At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with ²¹¹At-trastuzumab may offer a new treatment option for HER2-positive PMGC.

This article is protected by copyright. All rights reserved.

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Small bowel obstruction due to ingestion of rubber balls

Abstract

We report a case of a 10-month-old girl who presented with a 10-day history of emesis that became bilious on the last day. The initial evaluation suggested small bowel obstruction. An upper gastrointestinal study confirmed the normal location of the duodenojejunal junction with normal rotation and no evidence of midgut volvulus. Ultrasound (US) evaluation demonstrated two intraluminal lesions that do not follow the typical features of solid or cystic lesions. Two rubber balls were found at surgery to be responsible for the small bowel obstruction. Foreign body ingestion is common in children, but this case demonstrates a unusual foreign object to be ingested as well as the US appearance of this particular foreign body.

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Comparison of the diagnostic accuracy of PET/MRI to PET/CT-acquired FDG brain exams for seizure focus detection: a prospective study

Abstract

Background

There is great interest in positron emission tomography (PET)/magnetic resonance (MR) as a clinical tool due to its capacity to provide diverse diagnostic information in a single exam.

Objective

The goal of this exam is to compare the diagnostic accuracy of PET/MR-acquired [F-18]2-fluoro-2-deoxyglucose (FDG) brain exams to that of PET/CT with respect to identifying seizure foci in children with localization-related epilepsy.

Materials and methods

Institutional Review Board approval and informed consent were obtained for this Health Insurance Portability and Accountability Act-compliant, prospective study. All patients referred for clinical FDG-PET/CT exams of the brain at our institution for a diagnosis of localization-related epilepsy were prospectively recruited to undergo an additional FDG-PET acquisition on a tandem PET/MR system. Attenuation-corrected FDG images acquired at PET/MR and PET/CT were interpreted independently by five expert readers. Readers were blinded to the scanner used for acquisition and attenuation correction as well as all other clinical and imaging data. A Likert scale scoring system (1-5) was used to assess image quality. The locale of seizure origin determined at multidisciplinary epilepsy surgery work rounds was considered the reference standard. Non-inferiority testing for paired data was used to compare the diagnostic accuracy of PET/MR to that of PET/CT.

Results

The final study population comprised 35 patients referred for a diagnosis of localization-related epilepsy (age range: 2-19 years; median: 11 years; 21 males, 14 females). Image quality did not differ significantly between the two modalities. The accuracy of PET/MR was not inferior to that of PET/CT for localization of a seizure focus (P=0.017).

Conclusion

The diagnostic accuracy of FDG-PET images acquired on a PET/MR scanner and generated using MR-based attenuation correction was not inferior to that of PET images processed by traditional CT-based correction.

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Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier

Publication date: Available online 16 May 2017
Source:Cell Stem Cell
Author(s): Gad D. Vatine, Abraham Al-Ahmad, Bianca K. Barriga, Soshana Svendsen, Ariel Salim, Leslie Garcia, Veronica J. Garcia, Ritchie Ho, Nur Yucer, Tongcheng Qian, Ryan G. Lim, Jie Wu, Leslie M. Thompson, Weston R. Spivia, Zhaohui Chen, Jennifer Van Eyk, Sean P. Palecek, Samuel Refetoff, Eric V. Shusta, Clive N. Svendsen
Inactivating mutations in the thyroid hormone (TH) transporter Monocarboxylate transporter 8 (MCT8) cause severe psychomotor retardation in children. Animal models do not reflect the biology of the human disease. Using patient-specific induced pluripotent stem cells (iPSCs), we generated MCT8-deficient neural cells that showed normal TH-dependent neuronal properties and maturation. However, the blood-brain barrier (BBB) controls TH entry into the brain, and reduced TH availability to neural cells could instead underlie the diseased phenotype. To test potential BBB involvement, we generated an iPSC-based BBB model of MCT8 deficiency, and we found that MCT8 was necessary for polarized influx of the active form of TH across the BBB. We also found that a candidate drug did not appreciably cross the mutant BBB. Our results therefore clarify the underlying physiological basis of this disorder, and they suggest that circumventing the diseased BBB to deliver active TH to the brain could be a viable therapeutic strategy.

Graphical abstract

Teaser

Vatine et al. show that human iPSC-based modeling can pinpoint the origin of a neuronal disorder in the brain as a defect in transport of thyroid hormone across the blood-brain barrier, rather than in the neurons themselves.


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Surgical considerations for papillary thyroid microcarcinomas

We reevaluate current treatment recommendations of papillary thyroid microcarcinomas taking into account the indolent behavior of these tumors, and the potential morbidity that may result from an unnecessary surgery. The goals of this communication are to: 1) provide surgeons and endocrinologists with the most up-to-date evidence on management of microcarcinomas, 2) outline appropriate instances for active surveillance, and 3) describe the role of surgical interventions for microcarcinomas including lobectomy, total thyroidectomy, and central neck dissection.

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Liver transplantation for unresectable colorectal liver metastases: A systematic review

The use of liver transplantation (LT) for liver metastases attempted in the early 1990's was associated with poor perioperative outcomes and unacceptably low overall survival. Recently, there has been renewed interest in LT as a treatment option for colorectal liver metastases (CLM) in countries where organ supply is high. To date, no meticulous analysis about the efficacy, safety and outcomes of LT in CLM patients has been published. We present the first systematic review on the subject.

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