The role of radioactive iodine in the management of patients with differentiated thyroid cancer - An oncologic surgical perspective.

With improved understanding of the biology of differentiated thyroid carcinoma its management is evolving. The approach to surgery for the primary tumour and elective nodal surgery is moving from a "one-size-fits-all" recommendation to a more personalised approach based on risk group stratification. With this selective approach to initial surgery, the indications for adjuvant radioactive iodine (RAI) therapy are also changing. This selective approach to adjuvant therapy requires understanding by the entire treatment team of the rationale for RAI, the potential for benefit, the limitations of the evidence, and the potential for side-effects. This review considers the evidence base for the benefits of using RAI in the primary and recurrent setting as well as the side-effects and risks from RAI treatment. By considering the pros and cons of adjuvant therapy we present an oncologic surgical perspective on selection of treatment for patients, both following pre-operative diagnostic biopsy and in the setting of a post-operative diagnosis of malignancy.

Ethical issues in non-intervention trials for thyroid cancer.

In recent years, the increasing numbers of small, apparently indolent thyroid cancers diagnosed in the world have encouraged investigators to consider non-intervention as an alternative to surgical management. In the following pages, the prospect of a non-intervention trial for thyroid cancer is considered with attention to the ethical issues that such a trial might raise. Such a non-intervention trial is analyzed relative to 7 ethical considerations: the social or scientific value of the research, the scientific validity of the trial, the necessity of fair selection of participants, a favorable risk-benefit ratio for trial participants, independent review of the trial, informed consent, and allowing the study participants to withdraw from the trial. A non-intervention trial for thyroid cancer is also considered relative to the central concept of equipoise.

Altered regulatory T cell phenotype in latent autoimmune diabetes of the adults (LADA).

Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of ß cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (Tregs ) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating Tregs in LADA patients early during disease progression. Flow cytometric analysis was performed on whole blood and peripheral mononuclear cells (PBMC) from patients diagnosed with LADA prior to insulin deficiency (n = 39) and from healthy volunteers (n = 20). Overall, we found the frequency and activation status of peripheral putative Tregs to be altered in LADA patients compared to healthy controls. While total T cells and CD4(+) T cells expressing high levels of CD25 (CD4(+) CD25(hi) ) were unchanged, the frequency and total numbers of CD4(+) T cells expressing an intermediate level of CD25 (CD4(+) CD25(int) ) were decreased in LADA patients. Interestingly, the expression of the Treg -specific marker forkhead box protein 3 (FoxP3), as well as the activation and memory makers CD69, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), CCR4 and CD45RO were increased in CD4(+) CD25(+) T cells of the patients. Our data depict phenotypical changes in T cells of LADA patients that may reflect a derangement in peripheral immune regulation contributing to the slow process leading to insulin-dependent diabetes in these patients.

Paraneoplastic syndromes in patients with oral cancer.

The diagnosis of a paraneoplastic syndrome (PNS) may precede, follow or be concurrent with the diagnosis of a malignant tumor. There is increasing knowledge of association between PNS and head and neck cancers, but the relationship between oral cancer and paraneoplastic disease has not been previously investigated. PNS associated with head and neck cancer can be divided into six main groups: endocrine, cutaneous or dermatologic, hematologic, osteoarticular or rheumatologic, neurologic, and ocular syndromes. We have comprehensively reviewed the literature to evaluate the incidence of occurrence of PNS with oral cancer, and conclude that only endocrine and dermatologic PNS have been associated with oral cancer. Humoral hypercalcemia is the most frequent PNS related to oral cancer, and has a negative prognostic significance. Dermatologic PNS are less common, but when they occur, they may precede the diagnosis of the oral tumor. Awareness of these conditions is important for clinicians who deal with cancer.

Paraneoplastic syndromes in patients with nasopharyngeal cancer.

Paraneoplastic syndromes (PNS) represent the clinical manifestation of the remote and indirect effects produced by tumor metabolites or other products. Paraneoplastic effects are not directly mediated by tumor invasion of normal tissue, or by the disruption of normal function of the involved organ, or by distant metastases. More than 260 cases of nasopharyngeal carcinoma (NPC) associated with PNS have been reported in the literature. These syndromes can be divided into six main groups: cutaneous or dermatologic, endocrine, hematologic, osteoarticular or rheumatologic, neurologic, and ocular. The most common dermatologic manifestation is dermatomyositis, while the syndrome of inappropriate secretion of antidiuretic hormone and occasionally Cushing's syndrome due to ectopic ACTH production are the endocrinologic manifestations. Tumor fever and leukemoid reaction, osteoarticular or rheumatic syndromes, including clubbing of the fingers and toes, sensory neuropathy and demyelinating motor polyneuropathy, and rarely optic neuritis represent the most prominent examples of the other groups of syndromes. PNS may occur before the NPC is manifest, or while it is in an occult stage, and thus the possibility of NPC should be considered in patients with these various disorders. While some PNS will respond to direct treatment, most often the PNS subsides in parallel to response of the NPC, and thus may be useful for monitoring tumor response or recurrence.

Squamous carcinoma arising in a branchial cleft cyst: have you ever treated one? Will you?

The existence of primary branchiogenic carcinoma - that is, carcinoma arising in a pre-existing branchial cleft cyst (a benign developmental cyst) - has in recent decades been the subject of increasing scepticism. Recognition of the propensity of a variety of head and neck sites - including in particular the tonsil - to give rise to cervical metastases while the primary tumours themselves remain undetected has given rise to the idea that virtually all cystic carcinomas of the neck represent metastatic deposits, whether or not their primary sites are found. A diagnosis of primary branchiogenic carcinoma should be viewed with extreme scepticism, and every effort should be made (e.g. imaging, panendoscopy, elective tonsillectomy) to exclude the existence of a primary site elsewhere, before considering a diagnosis of primary branchiogenic carcinoma.

Renkioi: a forgotten Crimean War hospital and its significance.

Renkioi Civil Hospital was built late in the Crimean War (1854-6) in Turkey on the Dardanelles. Designed by Isambard Kingdom Brunel, its prefabricated structure was a brilliant engineering innovation. As a civil hospital for military patients, it was staffed by experienced civilian doctors, thereby relieving the shortage of military doctors. Renkioi is remembered as an astonishing early prefabricated structure. However the war was soon to end and it was never used to near capacity. Thus, its other successful features are largely forgotten. It demonstrated the advantages of a doctors, rather than a military officer, being in complete command of a hospital and this was later accepted by the army. Renkioi also showed how infection could be reduced by able staff in a well administered, properly designed hospital with good sanitation. After the war, Dr. Edmund Parkes, its Medical Superintendent, became the first Professor of Hygiene at the new Army Medical School, ensuring that "the prevention of disease and the promotion of health" became the first function of the Army Medical Services.

Juvenile hormone regulates de novo isoprenoid aggregation pheromone biosynthesis in pine bark beetles, Ips spp., through transcriptional control of HMG-CoA reductase.

Evidence is presented for transcriptional regulation of de novo pheromone biosynthesis in Ips spp. bark beetles, but the comparative biochemical and molecular approach reveals a dichotomy between species in the pini and grandicollis subgeneric groups. Radiotracer studies with 14C-acetate demonstrate that feeding on host phloem stimulates biosynthesis in males of three Ips spp. However, treatment with juvenile hormone III (JH III) stimulates biosynthesis only in Ips pini. Thus, two species in the grandicollis subgeneric group (I. grandicollis and I. paraconfusus) appear to have a different mode of regulation related to JH III than does I. pini. Between 16 and 20 hr after feeding has commenced, pheromone production, as measured by accumulation in abdominal tissue, is stimulated about 150- (I. pini) and 350-times (I. paraconfusus) above the control level of 1-10 ng/male measured at 0 hr. Treatment with JH III results in accumulation in I. pini that is 3-4 times more than in phloem-fed males, whereas the identical treatment results in only weak accumulation in I. paraconfusus (45-times less than phloem-fed males). Comparative studies of gene expression and enzyme activity related to biosynthesis also support different modes of JH III-related regulation in I. pini and I. paraconfusus. In males of both species, feeding on host phloem results in increased transcript abundance and increased activity for the key de novo isoprenoid pathway enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R). However, while JH III treatment results in comparable maximal increases in HMG-R transcript levels in both species (similar to feeding), the activity of HMG-R in crude extracts from JH III-treated male I. paraconfusus is low in comparison with male I. pini. Hypothetical explanations for the interspecific dichotomy in the regulation of pheromone biosynthesis include a second hormone or factor in grandicollis group species that functions either alone or with JH III; in both cases acting after HMG-R has been transcribed.

Laryngeal and sinonasal paragangliomas.

Laryngeal paragangliomas are classified as supraglottic and infraglottic. This article defines each type of paraganglioma, discusses the clinical features and diagnoses, and covers the surgical management. This article also addresses sinonasal paragangliomas, including their clinical features, diagnosis, and treatment.

Incidence and sites of distant metastases from head and neck cancer.

The incidence of distant metastases in head and neck squamous cell carcinoma (SCC) is relatively small in comparison to other malignancies. Distant metastases adversely impact survival and may significantly affect treatment planning. The incidence of distant metastases is influenced by location of the primary tumor, initial T and N stage of the neoplasm, and the presence or absence of regional control above the clavicle. Patients with advanced nodal disease have a high incidence of distant metastases, particularly in the presence of jugular vein invasion or extensive soft tissue disease in the neck. Primary tumors of advanced T stages in the hypopharynx, oropharynx and oral cavity are associated with the highest incidence of distant metastases. Pulmonary metastases are the most frequent in SCC, accounting for 66% of distant metastases. It may be difficult to distinguish pulmonary metastasis from a new primary tumor, particularly if solitary. Other metastatic sites include bone (22%), liver (10%), skin, mediastinum and bone marrow. An important question remains as to how intensely pre- and postoperative screening for distant metastases should be performed. Preoperative chest X-ray is warranted in all cases. If the primary tumor and nodal status place the patient at high risk for pulmonary metastasis, then preoperative computed tomography scan of the chest should be done. Screening for distant metastases at other sites is usually not indicated in SCC of the upper aerodigestive tract. Postoperatively, annual X-rays of the chest are usually sufficient, but in high-risk situations a chest X-ray performed every 3-6 months may be beneficial. Certain histologic types of primary tumor have greater or lesser propensity to metastasize distantly, and have a different natural history. Adenoid cystic carcinoma metastasizes frequently, even in the absence of extensive local or regional disease. Basaloid squamous cell carcinoma and neuroendocrine carcinomas also metastasize widely. Extensive evaluation for distant metastases is justified for these tumors. Knowledge of the natural history of various neoplasms and the factors that contribute to distant metastases as well as good judgement are essential for cost-effective treatment planning and decision-making with regard to pre- and postoperative evaluation for distant metastases in cancer of the head and neck.

Surgical management of the neck in thyroid cancer.

Thyroid cancer is a relatively common clinical problem. The American Cancer Society has estimated 1,050,000 newly diagnosed cancers in 1999 in the United States, of which 16,000 are expected to be of thyroid origin. Although most thyroid cancers have an excellent prognosis as compared with other malignant tumors, it is estimated that approximately 1,225 deaths will be attributed to the disease [1].

The role of partial laryngeal resection in current management of laryngeal cancer: a collective review.

A spectrum of treatment plans and surgical procedures is available for management of early and moderately advanced laryngeal cancer. While the approach of chemotherapy and irradiation, or irradiation alone, followed by total laryngectomy for failure is often employed in practice by present day clinicians, the options of conventional conservation surgery (CCS), transoral endoscopic laser surgery (TLS) and supracricoid partial laryngectomy (SCPL) provide a wide choice of treatments that may help attain the goal of cure with preservation of laryngeal function and integrity of the airway. While CCS has been supplanted for many early-stage lesions by TLS and for more advanced stages by SCPL, centres throughout the world have reported favourable results with CCS, which is often modified to include resection of more extensive tumours than was previously possible. During the past decade a number of extended CCS procedures have been developed for management of glottic tumours involving both vocal cords and the anterior commissure, the paraglottic space and with vocal cord fixation, and for supraglottic tumours involving the glottis or hypopharynx. TLS has proved an effective, minimally invasive and functionally satisfactory procedure for management of suitable T1 and T2 glottic cancers, and stage I-III supraglottic cancers. The procedure may be effectively employed in combination with neck dissection and postoperative radiotherapy when necessary, particularly for moderately advanced supraglottic carcinomas. SCPL has proven effective in management of glottic and supraglottic cancers of all stages, even with involvement of paraglottic space and thyroid cartilage, provided at least one arytenoid unit can be preserved with clear margins. Invasion of cricoid cartilage is the most significant limitation for this procedure. All three surgical approaches have been employed for irradiation failure, but with greatly increased failure and complication rates compared with the results of treatment of non-irradiated patients. Thus a decision to treat laryngeal cancer initially with irradiation may preclude a satisfactory result from partial laryngectomy should radiation fail. The treatment of laryngeal cancer should be individualized according to the size and extent of the tumour, the age and physical condition of the patient, and the skill and experience of the surgeon with various treatment modalities and surgical procedures.

Ecological validity of neuropsychological assessment in childhood traumatic brain injury.

Empirical investigation of the degree to which testing predicts children's real-world functioning following traumatic brain injury (TBI) is sparse. This article reviews the research in neuropsychology, which offers only moderate correlations between test scores and everyday functioning. This line of research is hindered by several methodological issues: difficulty translating performance on standardized testing into real-world capacities, measurement of real-world functioning, developmental factors, and the influence of intervening variables in the natural environment. Ecologically valid assessment may require multiple data sources. More research is needed to respond effectively to questions about children's everyday functioning after traumatic brain injury.

Surgical treatment of the neck in cancer of the larynx.

Current concepts in management of the clinically negative and clinically positive neck in laryngeal cancer are reviewed. Occult disease in the neck not detected by physical and radiographic examination may also be difficult to identify on routine histologic examination. Immunohistochemistry or molecular analysis may detect metastatic involvement not apparent by light microscopy. The surgeon should be aware of the relatively high incidence of micrometastases in patients with laryngeal cancer to establish optimal treatment approaches. Elective treatment of the neck is recommended for supraglottic tumors staged T2 or higher, and glottic or subglottic tumors staged T3 or higher. The neck may be treated electively by either surgery or irradiation, but irradiation is best reserved for cases where that modality is employed for the primary tumor. Elective neck dissection provides important information for prognostic purposes and therapeutic decisions, by establishing the presence, number, location and nature of occult lymph node metastases. The selective lateral neck dissection (levels II, III and IV), unilateral or bilateral, is the procedure of choice for elective treatment. Paratracheal nodes (level VI) should be dissected in cases of advanced glottic and subglottic cancer. Complete radical or functional neck dissections are excessive in extent, as levels I and V are almost never involved. Sentinel lymph node biopsy may fail to detect tumor on frozen section examination or may not reveal 'skip' metastases. The clinically involved neck is usually treated by complete radical or functional neck dissection of levels I through V. Selective neck dissection has been employed successfully in selected cases, particularly for N1 or occasionally N2 nodal involvement. The selective neck dissection can be extended to include structures at risk. More advanced disease has been treated in this manner often in association with adjuvant chemotherapy and/or irradiation. While the benefit of adjuvant treatment is difficult to assess, it appears most useful in cases with extranodal spread of disease, a factor associated with the worst prognosis.