Central neck dissection in differentiated thyroid cancer: technical notes.

Differentiated thyroid cancers may be associated with regional lymph node metastases in 20-50% of cases. The central compartment (VIupper VII levels) is considered to be the first echelon of nodal metastases in all differentiated thyroid carcinomas. The indication for central neck dissection is still debated especially in patients with cN0 disease. For some authors, central neck dissection is recommended for lymph nodes that are suspect preoperatively (either clinically or with ultrasound) and/or for lymph node metastases detected intra-operatively with a positive frozen section. In need of a better definition, we divided the dissection in four different areas to map localization of metastases. In this study, we present the rationale for central neck dissection in the management of differentiated thyroid carcinoma, providing some anatomical reflections on surgical technique, oncological considerations and analysis of complications. Central neck dissection may be limited to the compartments that describe a predictable territory of regional recurrences in order to reduce associated morbidities.

Ultrasound dye-assisted surgery (USDAS): a promising diagnostic and therapeutic tool for the treatment of cancer recurrences in the neck.

The evolution of new techniques for cancer surgery has led to important changes in cancer care in recent years. The endpoint of cancer treatment is now to treat the patient with minimum discomfort while respecting quality of life. New techniques, such as mini-invasive surgery, must respect the correct oncological indications, when technically feasible. The surgery for nodal spread or recurrence of disease, after previous surgery on T or T and N for neck cancer, can represent a diagnostic and therapeutic challenge, especially in the neck, which is characterized by small spaces and noble structures. Often lesions become enveloped in scar tissue and can be difficult to visualize during surgery, representing a genuine problem for the surgeon. Ultrasound dye-assisted surgery is a procedure that combines ultra-sound localization of pathological nodes with the use of methylene blue to mark diseased structures to simplify their visualization (and thus removal) in the surgical field. The technique is simple and can be used in surgically and oncologically experienced hands, even in hospitals that do not have sophisticated technology.

Identification of patients at high risk for hypocalcemia after total thyroidectomy.

Hypocalcemia is a major post-operative complication of total thyroidectomy, causing severe symptoms and increasing hospitalization time. The primary cause is secondary hypo-parathyroidism following damage to, or devascularisation of, one or more parathyroid glands during surgery. Aim of the study was to develop a simple and reliable method for predicting post-operative hypocalcemia in total thyroidectomy patients. A retrospective analysis was made of immediate pre-operative and early post-operative calcium levels in 100 patients. It was found that a marked decrease in blood calcium, immediately after surgery, was a sensitive predictor of hypocalcemia. In a subsequent prospective series of 67 patients, the efficacy was assessed of early administration of calcium plus Vitamin D in reducing symptomatic hypocalcemia in patients in whom the difference (Δ) between pre- and post-operative blood calcium was ≥ 1.1 mg/dl. This treatment was part of a protocol in which normo-calcemic patients were discharged immediately after drainage removal (third post-operative day). In the retrospective series, 84% of patients who developed hypocalcemia had Δ ≥ 1.1 and 54% of patients who did not develop hypocalcemia had Δ < 1.1 (p < 0.0001). Mean duration of hospitalization was 6.2 days. In the prospective series, 76% of patients who developed hypocalcemia had Δ ≥ 1.1 mg/dl; of the patients who did not develop hypocalcemia 75% had Δ < 1.1 mg/dl (p = 0.0013); mean hospitalization was 4.7 days (p < 0.0001). Use of the 1.1 mg/dl cut-off for deciding whether to start early prophylaxis allowed most patients to avoid symptomatic hypocalcemia (and the associated anxiety), while permitting a significantly reduced hospital stay, resulting in lower hospitalization costs.

Management and follow-up of thyroid cancer in pregnant women.

Thyroid cancer, the most common endocrine malignancy, is often detected in young female patients. Therefore, pregnancy following thyroid cancer is not infrequent, and about 10% of thyroid cancers occurring during the reproductive years are diagnosed during pregnancy or in the early post-partum period. Differentiated thyroid cancer (DTC) in young people generally has an excellent prognosis, and disease-free survival among women with DTC diagnosed during pregnancy may not differ from that in age-matched non-pregnant women with similar disease. However, thyroid cancer detected during pregnancy may cause anxiety about the optimal timing of recommended treatments and about both maternal and neonatal morbidity, as weel as pregnancy following a diagnosis of thyroid cancer obviously needs both maternal and foetal management. The main objectives in clinical monitoring of pregnant thyroid cancer patients are: 1) to reach an adequate balance of maternal calcium and thyroid hormones that is absolutely required by the foetal central nervous system for normal maturation; 2) to maintain optimal levels of maternal thyroxin to avoid possible recurrence or spread of disease; and 3) to perform safe follow-up visits for the mother and to plan further therapy when needed. Data from a review of the literature and the authors' own experience show that in patients undergoing either suppressive or substitutive thyroxine therapy foetal thyroid growth is normal at ultrasound study, newborn thyroid status is normal, and the incidence of maternal morbidity is not influenced by the pregnancy. In this review, the authors underline that regular adjustment of levo-thyroxine and calcium therapy is of outmost importance for both maternal and foetal well-being and offer some insight, very interesting from a practical point of view, to provide a clear and simple pathway for the management of pregnancy-associated thyroid cancer.

Role of prophylactic central neck dissection in cN0 papillary thyroid cancer.

Prophylactic central neck dissection in papillary thyroid cancer is controversial. In this retrospective cohort study, the aim was to assess possible advantages of prophylactic central neck dissection with total thyroidectomy in cN0 papillary thyroid cancer. A total of 244 consecutive patients with papillary thyroid cancer, without clinical and ultrasound nodal metastases (cN0), were evaluated out of 1373 patients operated for a thyroid disease at the Istituto Europeo di Oncologia, Milan, Italy from 1994 to 2006. Of these 244 patients, 126 (Group A) underwent thyroidectomy with central neck dissection, while 118 (Group B) underwent thyroidectomy alone. Demographic, clinical and pathological features were analysed. Overall recurrence rate was 6.3% (8/126) in Group A and 7.7% (9/118) in Group B, with a mean follow-up of 47 (Group A) and 64 (Group B) months. In Group A patients, 47% were pN1a and all patients with recurrence had nodal involvement (p = 0.002). Survival rate did not differ in the two groups. Nine patients were lost to follow-up. Group A patients were older and their tumours were larger in size; according to the pT distribution, a higher extra-capsular invasion rate was observed. The two groups were equivalent as far as concerns histological high risk variants and multifocality. Nodal metastases correlated with stage: pT1-2 vs. pT3-T4a, p = 0.0036. A lower risk of nodal metastases was related to thyroiditis (p = 0.0034). In conclusion, central neck metastases were predictive of recurrence without influencing prognosis. From data obtained, possible greatest efficacy of central neck dissection in pT3-4 papillary thyroid cancer without thyroiditis is suggested.

Compartmental surgery in tongue tumours: description of a new surgical technique.

The aim of curative surgical oncology is to remove the primary tumour with a wide margin of normal tissue. What constitutes a sufficiently wide margin particularly in oral cancer is fundamentally unclear. The currently accepted standard is to remove the primary lesion with a 1.5-2 cm circumferential macroscopic margin. In the last ten years, anatomical considerations in the approach to primary, advanced and untreated tumours of the tongue led us to develop and improve a new surgical approach to their demolition and reconstruction. From July 1999 to July 2009, at the European Institute of Oncology in Milano, Italy, 155 patients were treated, while defining and refining the concept of compartmental tongue surgery (CTS) and its main components: 1) anatomical approach to the disease that requires removal of the primary lesion and all of the potential pathways of progression--muscular, lymphatic and vascular; 2) identification of a distinct territory at risk of metastatic representation of the disease: the parenchymal structures between the primary tumour and the cervical lymphatic chain that include the muscular (mylohyoid), neuro-vascular (lingual nerve and vein) and glandular (sublingual and submandibular) tissues; 3) preparation for a rational reconstruction in consideration of a functional defect resulting from this anatomical demolition.

Thyroid stem cells--danger or resource?

The thyroid gland has long since been known for its self-renewal ability, mainly in cases of hyperplastic disease such as goitre. Recently the amazing improvement in knowledge about stem cells has explained this potentiality. Some stem cell features and their clinical usefulness are summarized here, reviewing data from the literature: (1) the proven presence of adult stem cells in thyroid tissue, either normal, goitrous or neoplastic, bring with it important implications regarding tissue regeneration and oncogenesis; (2) modifying culture conditions and micro-environment stem cells have led to mature tissue with specialized functions. This has considerably changed the attitude of regenerative medicine and cancer research; (3) finally, identification of stem cells and stem cell markers in thyroid cancer, gives hope for the development of new therapeutic approaches in recurrent or treatment-resistant thyroid cancer.

Occult thyroid carcinoma.

Some medical definitions remain the same for many years, others change due to the progress in the diagnostic tools, which are able to distinguish markers and symptoms until then undetectable. Occult thyroid carcinoma is a general term indicating clinically different situations, whereas the incidentally detected papillary thyroid microcarcinoma is the most important from the clinical point of view. It is fundamental, for therapeutic management, to determine biological parameters which would define a small group of papillary thyroid microcarcinomas with aggressive biological behaviour. The most promising genetic and molecular markers for papillary thyroid carcinoma risk stratification are discussed in this review. Preoperative evaluation of these markers, obtained through analysis of ultrasonography-guided fine needle biopsy specimens of papillary thyroid microcarcinoma, could be very valuable in guiding treatment of this type of cancer.

Pregnancy and thyroid cancer: ultrasound study of foetal thyroid.

Thyroid cancer is the most common endocrine malignancy, more frequently diagnosed in young women during childbearing age and approximately 10% of all thyroid cancers are diagnosed during pregnancy or in the early post-partum period. Thyroid cancer in young people has generally an excellent prognosis, and survival among women with thyroid cancer diagnosed during pregnancy may not differ from that in age-matched non-pregnant women with similar cancer. Pregnancy after treatment of thyroid carcinoma requires both maternal and foetal controls. Of utmost importance is to ensure adequate maintenance of maternal levels of levothyroxine, needed by both the foetal central nervous system for its normal maturation and the mother to avoid possible recurrence or spread of the disease. In the present investigation, to confirm normal foetal growth and foetal thyroid development, an ultrasound study of the foetal thyroid was performed in 40 full term pregnancies in 32 women receiving levothyroxine treatment for previously treated thyroid cancer. In patients undergoing either suppressive or substitutive levothyroxine treatment, foetal thyroid growth was noted to be normal in all the cases, newborn thyroid status was always normal, and the incidence of maternal morbidity was not influenced. In the present study group, pregnancy does not appear to compromise mother's disease-free interval, nor to be compromised by thyroid cancer treatment. Results of the present study confirm that regular adjustment of levothyroxine treatment is of utmost importance for both maternal and foetal well-being and that foetal thyroid ultrasound study may add useful and reassuring data about child well-being.

Thyroid cancer: possible role of telemedicine.

Telemedicine is extremely useful when distance could hinder diagnostic procedures, disease management, or when severe side-effects may occur in patients not within easy reach of medical care and requiring prompt action and specific therapies. Telemedicine has been successfully adopted in the management of chronic patients, particularly in those with cardiologic or oncologic diseases. In the treatment of differentiated thyroid cancer, requiring long-term check-ups and visits as well as administration of high doses of levothyroxine (TSH - thyroid-stimulating hormone - suppression), also in elderly patients, telemedicine seems particularly indicated. Moreover, these distant monitoring techniques could not only reduce long-term management costs but also considerably decrease cardiovascular risks associated with these patients. The present review aims to provide some general information on telemedicine and its possible fields of action with regard to distant monitoring of patients with differentiated thyroid carcinoma.

Preoperative determination of serum thyroglobulin to identify patients with differentiated thyroid cancer who may present recurrence without increased thyroglobulin.

Thyroglobulin is considered a reliable marker of recurrent disease in patients with well-differentiated thyroid carcinoma. However, some patients present recurrence with no increase in serum thyroglobulin. In the attempt to identify patients who might present recurrence with no such sign of the disease, thyroglobulin levels have been determined pre-operatively in 185 consecutive patients scheduled for primary treatment for well-differentiated thyroid carcinoma from June 1997 to May 2002 at the Head and Neck Division of the European Institute of Oncology. In 22 patients (11.9% of total), serum thyroglobulin was undetectable. In none of these 22 cases was thyroglobulin detected during follow-up, either during thyroxin suppressive therapy or during withdrawal for radioiodine scan. One of these low-thyroglobulin patients developed recurrent disease involving cervical lymph nodes, with positive radioiodine scan: thyroglobulin remained undetectable. On the contrary, in the patients with high or normal thyroglobulin presenting recurrence, the recurrence was indicated, in all cases, by increased thyroglobulin levels. From these findings it may be concluded that pre-operative assessment of serum thyroglobulin may identify patients who might present recurrence without increased thyroglobulin, and in whom standard follow-up by monitoring thyroglobulin serum levels is inadequate.

Thyroid disease in northern Italian children born around the time of the Chernobyl nuclear accident.

BACKGROUND: The Chernobyl nuclear accident of 1986 caused a dramatic increase in the incidence of thyroid cancers in exposed children in Belarus. Airborne radioactivity from the reactor spread over northern Italy, where rainout gave rise to low levels of radioactivity at ground level. PATIENTS AND METHODS: As the latency between exposure to ionising radiation and development of thyroid cancer is thought to be about 10 years, in 1996/1997 all children born in 1985 and 1986 and attending school in an area of Milan, Italy were examined for thyroid nodules. A total of 3949 children were examined by two physicians blinded to the examination and diagnosis of the other. The children were to be reassessed in 2001/2002. RESULTS: In total, 1% had palpable nodules. The nodule diagnoses were: Hurtle cell adenoma (one), thyroglossal duct cyst (one), thyroid cyst (four) and thyroiditis (four). The prevalence of thyroid disease in the cohort was indistinguishable from that of populations not exposed to radioactive pollution. Only 10 children re-presented for examination 5 years later; all were negative. The direct costs of the study were estimated at 21,200 Euros. CONCLUSION: The high cost of the study in relation to reassuring lack of increase in thyroid nodule prevalence suggests that further studies are not justified.

Timing of breast cancer surgery in relation to the menstrual cycle: an update of developments.

It is well-established that hormones have multiple effects on breast cancer. Some, but not all studies indicate that the phase of the menstrual cycle (and hence hormonal status) at the time of breast surgery may influence survival. In this paper we review the literature in this area, explore how it is possible that such an association may occur, and note that randomised studies which unambiguously determined the phase of the cycle at the time of the operation are lacking. We go on to describe an ongoing self-randomised trial designed to address this problem and present preliminary results which show that only about 75% of the women ovulated during the cycle in which the operation took place, and that the established prognostic factor Ki-67 varied with the phase of the cycle in women who ovulated. It is too early to assess the significance of this finding.

Papillary carcinoma in thyroglossal duct remnants: presentation of four cases and decision procedure for prophylactic thyroid gland dissection.

Papillary carcinoma in thyroglossal duct remnants is a rare and usually unexpected finding. It is controversial whether or not prophylactic thyroid gland dissection is necessary in such circumstances. We present our experience of four cases. Based on this, a consideration of published risk factors, and evaluation of the likelihood of a primary versus metastatic origin of the malignancy, we present a therapeutic decision procedure. When the thyroid is normal, the patient presents low-risk factors for thyroid cancer, and there is evidence that the malignancy is primary, removal of all thyroglossal duct remnants by the Sistrunk procedure is sufficient.