Diagnostic Utility of Galectin-3 in Thyroid Cancer

Galectin-3 (Gal-3), which has received significant recent attention for its utility as a diagnostic marker for thyroid cancer, represents the most well-studied molecular candidate for thyroid cancer diagnosis. Gal-3 is a protein that binds to β-galactosidase residues on cell surface glycoproteins and has also been identified in the cytoplasmic and nuclear compartment. This marker has been implicated in regulation of normal cellular proliferation and apoptosis, as well as malignant transformation and the metastasis of cancer cells. We here present a mechanistic review of Gal-3 and its role in cancer development and progression. Gal-3 expression studies in thyroid tissue and cytologic tumor specimens and their methodological considerations are also discussed in this article. Despite great variance in their methodology, the majority of immunohistochemical studies found that Gal-3 was differentially expressed in thyroid carcinoma compared with benign and normal thyroid specimens, suggesting that Gal-3 is a good diagnostic marker for thyroid cancer. Recent studies have also demonstrated improved methodological reliability. On the other hand, Gal-3 genomic expression studies have shown inconsistent results for diagnostic utility and are not recommended. Overall, the development of Gal-3 as a diagnostic marker for thyroid cancer represents a promising avenue for future study, and its clinical application could significantly reduce the number of diagnostic thyroid operations performed for cases of indeterminant fine needle aspiration biopsy cytology, and thus positively impact the current management of thyroid nodular disease.Thyroid cancer represents one of the few cancer types that remains a diagnostic dilemma for the clinician. Thyroid nodules are extremely common in the general population, being identified in 5% of patients by palpation and 50% by ultrasound examination.¹ Fine needle aspiration biopsy (FNAB) represents the critical initial diagnostic test used for evaluation of thyroid nodules. However, diagnosis of thyroid cancer still remains uncertain in a large number of cases. In a review of more than 18,000 thyroid FNABs performed at the Mayo Clinic, FNAB had a reported sensitivity of 83%, specificity of 92%, and accuracy of 95%.² Furthermore, in up to 15% of cases, the diagnosis of cancer cannot be definitively determined by FNAB. This occurs in certain histological types of thyroid tumors in which benign and malignant thyroid lesions have overlapping cytomorphologic characteristics. There are also currently no patient or tumor characteristics that can reliably predict the presence of cancer in individuals diagnosed with a thyroid neoplasm of Hurthle cell or follicular subtype.^3,4Thus, when a thyroid tumor with this indeterminate cytology is identified by FNAB, the current recommended approach is a diagnostic operation for removal of either a portion of or the entire thyroid gland.^3,4,5 In addition to the emotional distress experienced by patients who undergo surgery for a possible cancer diagnosis, thyroid resection carries a low but significant risk of permanent injury to associated parathyroid glands and nerves that may lead to the need for life-long calcium supplementation or voice dysfunction, and extremely uncommonly the need for a long term tracheostomy. Indeed, only approximately one in five patients undergoing thyroid resection for indeterminant FNAB cytology will eventually be diagnosed with a thyroid cancer by histopathological evaluation.³Study of the molecular characteristics of thyroid cancer has allowed for the development of potential molecular diagnostic tools. In the largest thyroid cancer diagnostic marker panel study reported to date, we recently found Galectin-3 (Gal-3) to be the most accurate stand-alone marker for differentiated thyroid cancer diagnosis (DTC) when compared with a panel of 56 other molecular markers.⁶ The study used a tissue microarray containing 100 benign and 105 malignant thyroid tumors that was stained for expression of 57 markers. The most useful markers for DTC diagnosis were Gal-3, Cytokeratin 19, vascular endothelial growth factor, androgen receptor, p16, Aurora-A, and Hector Battifora mesothelial antigen-1 (HBME-1). Furthermore, the classification performance of Gal-3 alone (accuracy of 86.9%) was almost as good as the best multimarker panel (accuracy of 91.0%) determined by a Random Forests algorithm using marker combinations from the entire molecular marker panel.Gal-3 is one of the best studied molecular markers for thyroid cancer diagnosis. Numerous studies have elucidated the mechanistic role of Gal-3 in normal physiology and cancer. More than 60 protein expression studies, evaluating more than 6000 thyroid specimens, have been reported in the current literature that investigate the utilization of Gal-3 as a thyroid cancer diagnostic marker. The aim of this review is to present: (1) a mechanistic overview of Gal-3 in thyroid cancer, (2) an evaluation of Gal-3 expression studies with focus on a Gal-3 immunohistochemical (IHC) testing methodologies, and (3) an overview of studies reporting utilization of Gal-3 expression for thyroid cancer diagnosis.     

Reassortant avian influenza virus (H5N1) in poultry, Nigeria, 2007

Genetic characterization of a selection of influenza virus (H5N1) samples, circulating in 8 Nigerian states over a 39-day period in early 2007, indicates that a new reassortant strain is present in 7 of the 8 states. Our study reports an entirely different influenza virus (H5N1) reassortant becoming predominant and widespread in poultry.     

Air enema reduction of intussusception: a registrar-led, protocol-driven service is safe and effective

Purpose

In the UK, air enema reduction of intussusception is predominantly performed by consultant radiologists. At our institution, it is usually performed by a team involving radiology and surgical registrars. The purpose of this study was to assess who performs air enemas in the UK and the efficacy and safety of our registrar-led service.

Methods

A telephone survey of paediatric surgical centres in the UK was performed asking who performs air enema in these institutions. Following this, a retrospective review of all air enemas at our institution between January 2005 and 2011 was performed. Cases were identified from radiology databases and reviewed for grade of radiologist, perforation and outcome.

Results

At all 25 centres, consultant radiologists performed air enemas. At our institution 145 enemas were performed in 6 years. 141 were analysed (54 girls, 87 boys). Median age was 9 months (range 3–107 months). 82 % were performed by the registrar-only team. Over 6 years the registrar-led reduction rate was 77.5 % and in the last 3 years 84 %. The perforation rate was 0.9 %.

Conclusion

A paediatric surgical registrar-led service for air enema reduction can be safe and effective ensuring a team approach is adopted, equipment is efficient and a strict protocol is applied.     

Depression among Nigerian women following pregnancy loss

Objective

To determine the level of depression in Nigerian women following spontaneous pregnancy loss and the coping strategies used.

Methods

A questionnaire survey of 202 Nigerian women who had involuntary pregnancy loss over a 1-year period. The Zung Self-Rating Depression Scale was used to assess the women.

Results

Two-thirds of the pregnancy losses occurred before 20 weeks of gestation and one-third occurred after 20 weeks. The majority of respondents (74.3%) had minimal depressive symptoms (scoring 50-59 on the depression scale), 3% had moderate symptoms (scoring 60-69), and 13.9% had severe symptoms (scoring 70-80). Risk factors for moderate to severe depression included being married, previous pregnancy loss, loss of a male fetus, childlessness, and losses after 20 weeks (P < 0.05). Presence of a woman's husband, children, parents and relatives, friends, and religious observance were identified as positive coping strategies.

Conclusion

Most Nigerian women suffer some level of depression following pregnancy loss, with no living children and losses after 20 weeks being the most significant risk factors.     

Endotoxic activity and enterotoxigenicity of human strains of Campylobacter jejuni isolated from patients in a Nigerian hospital

Limulus gelation assay and dermal Schwartzman reaction provided a sensitive and reproducible means of testing the endotoxic activity of hospital strains of Campylobacter jejuni in Lagos, Nigeria. All the 22 isolates of Campylobacter jejuni tested for the limulus gelation assay were positive for the production of endotoxin. Furthermore, the Campylobacter suspensions caused a positive dermal Schwartzman reaction in rabbits. The area of skin reaction was less extensive than that produced by Escherichia coli 01114B and E7539/77 which served as positive controls. Five local strains of Campylobacter jejuni tested for enterotoxin production showed negative reaction in the infant mouse test whereas enterotoxin production was observed in Campylobacter jejuni strain 11168 and Escherichia coli E7539/77. Consequently, the infant mouse test may not be suitable for enterogenicity testing of our local isolates of Campylobacter jejuni.     

Two species of antiganglioside antibodies in a patient with a pharyngeal-cervical-brachial variant of Guillain-Barré syndrome.

A patient with a pharyngeal-cervical-brachial variant of Guillain-Barré syndrome had anti-GT1a and anti-GD1a antibodies (IgG) in the serum. The activities of anti-GT1a antibodies were stronger than anti-GD1a antibodies and their activities declined later in the clinical course. These two different antibodies bound independently to each ganglioside in an absorption study with polystyrene beads coated with GT1a or GD1a.