Recent Publications by CFE Educators

BACKGROUND

Minimal access thyroid surgery, using various techniques, is increasingly being reported. The present study reviews our experience with thyroid surgery using a lateral focused mini-incision approach, and assesses its safety and feasibility.

METHODS

The study group comprised all patients undergoing minimal access thyroid surgery (MATS) during the period May 2002-May 2003. Data were prospectively gathered, including patient demographics, indication for surgery, operation performed, nodule size, final pathology, and complications. Exclusion criteria for this procedure included: family history of thyroid cancer, previous neck irradiation or surgery, carcinoma on fine needle aspiration, presence of significant thyroiditis, multinodular goitre, and nodule size >3 cm. The operation was carried out through a 2.5-cm lateral incision placed directly over the nodule, with exposure gained by dissecting the plane between the sternomastoid muscle and the lateral edge of the strap muscles.

RESULTS

Twenty-five patients underwent MATS, 22 women and three men. Nineteen patients underwent hemithyroidectomy, five underwent isthmectomy, and one underwent local nodule excision. The average measured incision size was 2.63 cm at the end of the procedure. The average nodule size was 2.2 cm, and the average thyroid lobe resected measured 4.7 cm in maximal length. Final pathology revealed benign nodules in 21 patients and four thyroid cancers (two follicular and two papillary). There was one wound infection and two patients had temporary recurrent laryngeal nerve neuropraxia.

CONCLUSION

Minimal access thyroid surgery is a safe and feasible alternative to open thyroid surgery in selected cases.

Peripheral nerve damage results in loss of sensation in the affected region of the body. Oaklander and Brown now report that, in the rat, transection of a peripheral nerve in only one side of the body also results in profound loss of the innervation of the same region on the opposite side of the body. Peripheral nerve damage may also produce persistent (neuropathic) pain conditions that are presumed to arise from maladaptive reorganization of the central nervous system. Thus, the possibility that comparable bilateral changes occur in patients and that such changes contribute to neuropathic pain conditions must be considered.

The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and gamma rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly (131)I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose-response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.

Radiation therapy occupies an important role in the treatment of gynecologic malignancies. Unfortunately, traditional approaches result in the irradiation of large volumes of normal tissues exposing patients to many toxicities and precluding dose escalation in select patients. A novel approach to the planning and delivery of radiation therapy, known as intensity-modulated radiation therapy (IMRT), has been introduced. Unlike conventional approaches, IMRT conforms the prescription dose to the shape of the target in three dimensions, thus sparing the surrounding normal tissues. Multiple studies have demonstrated the clear superiority of IMRT planning in these patients in terms of normal tissue sparing. Promising clinical results have also been published, suggesting that IMRT reduces the incidence of acute and chronic toxicity in these women. Ongoing studies are focusing on tumor control and patient outcome. Although further work is needed, these results suggest that IMRT may represent a major advancement in the planning and delivery of radiation therapy in patients with gynecologic malignancies.

Endomorphin-2 (EM2) is a tetrapeptide with remarkable affinity and selectivity for the mu-opioid receptor. In the present study, we used double-fluorescence and electron microscopic immunocytochemistry to identify subsets of EM2-expressing neurons in dorsal root ganglia and spinal cord dorsal horn of adult rats. Within the lumbar dorsal root ganglia, we found EM2 immunoreactivity mainly in small-to-medium size neurons, most of which co-expressed the neuropeptide substance P (SP). In adult rat L4 dorsal root ganglia, 23.9% of neuronal profiles contained EM2 immunoreactivity and ranged in size from 15 to 36 microM in diameter (mean 24.3 +/- 4.3 microM). Double-labelling experiments with cytochemical markers of dorsal root ganglia neurons showed that approximately 95% of EM2-immunoreactive cell bodies also label with SP antisera, 83% co-express vanilloid receptor subtype 1/capsaicin receptor, and 17% label with isolectin B4, a marker of non-peptide nociceptors. Importantly, EM2 immunostaining persisted in mice with a deletion of the preprotachykinin-A gene that encodes SP. In the lumbar spinal cord dorsal horn, EM2 expression was concentrated in presumptive primary afferent terminals in laminae I and outer II. At the ultrastructural level, electron microscopic double-labelling showed co-localization of EM2 and SP in dense core vesicles of lumbar superficial dorsal horn synaptic terminals. Finally, 2 weeks after sciatic nerve axotomy we observed a greater than 50% reduction in EM2 immunoreactivity in the superficial dorsal horn. We suggest that the very strong anatomical relationship between primary afferent nociceptors that express SP and EM2 underlies an EM2 regulation of SP release via mu-opioid autoreceptors.

The vanilloid receptor-like 1 protein (VRL-1, also called TRPV2) is a member of the TRPV family of proteins and is a homolog of the capsaicin/vanilloid receptor (VR1, or TRPV1). Although VRL-1 does not bind capsaicin, like VR1 it is activated by noxious heat (>52 degrees C). Unlike VR1, however, VRL-1 is primarily expressed by medium- and large-diameter primary afferents, which suggests that nociceptive processing is but one of the functions to which VRL-1 contributes. To provide information on the diverse spinal circuits that are engaged by these VRL-1-expressing primary afferents, we completed a detailed immunocytochemical map of VRL-1 in rat spinal cord, including light and electron microscopic analysis, and generated a more comprehensive neurochemical characterization of VRL-1-expressing primary afferents. Consistent with previous reports, we found that VRL-1 and VR1 are expressed in different dorsal root ganglion (DRG) cell bodies. Almost all VRL-1-expressing cells labeled for N52 (a marker of myelinated afferents), consistent with VRL-1 expression in Adelta and Abeta fibers. EM analysis of the DRG and dorsal roots confirmed this and revealed two categories of neurons based on the intensity of immunolabeling. The densest VRL-1 immunoreactivity in the spinal cord was found in lamina I, inner lamina II, and laminae III/IV. This is consistent with the expression of VRL-1 by myelinated nociceptors that target laminae I and IIi and in nonnociceptive Abeta fibers that target laminae III/IV. Dorsal rhizotomy reduced, but did not eliminate, the immunostaining in all dorsal horn laminae, which indicates that VRL-1 expression derives from both DRG cells and from neurons intrinsic to the brain or spinal cord. Spinal hemisection reduced immunostaining of the ipsilateral dorsal columns in segments rostral to the lesion and in the dorsal column nuclei, presumably from the loss of ascending Abeta afferents, but there was no change caudal to the lesion. Thus, supraspinal sources of dorsal horn VRL-1 immunoreactivity are likely not significant. Although we never observed VRL-1 immunostaining in cell bodies in the superficial dorsal horn, there was extensive labeling of motoneurons and ventral root efferents-in particular, in an extremely densely labeled population at the lumbosacral junction. Finally, many ependymal cells surrounding the central canal were intensely labeled. These results emphasize that VRL-1, in contrast to VR1, is present in a diverse population of neurons and undoubtedly contributes to numerous functions in addition to nociceptive processing.

BACKGROUND

Frontotemporal dementia (FTD) is a clinically heterogeneous condition that can be associated with clinical manifestations of an extrapyramidal disorder or motor neuron disease. A range of histologic patterns has been described in patients with FTD. The most common familial form of this condition is caused by mutations in the microtubule-associated protein tau gene (MAP tau) and is associated with neuronal or glial tau inclusions.

OBJECTIVES

To determine the clinical, anatomic, and pathological features of San Francisco family A and to map the mutation responsible for disease in this family.

DESIGN

A systematic clinical, neuropsychologic, neuroimaging, and chromosome segregation analysis of San Francisco family A was performed. A pathological and biochemical assessment of a family member was made.

SETTING

Family study.

PATIENTS

San Francisco family A, with FTD, variable extrapyramidal symptoms, and prominent motor neuron disease. Afflicted family members do not have a MAP tau coding or splice regulatory sequence mutation, and the MAP tau is genetically excluded.

MAIN OUTCOME MEASURES

Comparison of clinical, neuropsychologic, neuroimaging, and linkage findings of San Francisco family A with other familial forms of FTD and amyotrophic lateral sclerosis (ALS).

RESULTS

The most probable location for the mutation responsible for this condition is on chromosome arm 17q, distal to the MAP tau. All previously identified susceptibility loci for FTD and ALS are excluded. Autopsy findings from an afflicted family member show distinctive tau and alpha-synuclein inclusions. Another unique feature is that the insoluble tau protein consists predominantly of the 4R/0N isoform.

CONCLUSION

The condition affecting members of San Francisco family A is clinically, pathologically, and genetically distinct from previous familial forms of FTD and ALS.

As the number of cancer survivors in the United States continues to grow, clinicians must be aware of the possible therapy-related second primary malignancies to which their patients are susceptible. No guidelines have been established for the routine screening of cancer survivors for thoracic malignancies, such as lung cancer, esophageal cancer, and pleural mesothelioma. In general, clinicians should remain cognizant of the fact that previous radiation for a variety of malignancies may have increased their patient's risk for developing a therapy-induced second primary tumor within the thorax. Potential signs and symptoms of thoracic malignancies should be approached with heightened vigilance in any patient who has a history of radiation exposure, regardless of how remote.