An update on thyroid surgery

An update on thyroid surgery O. Gimm, M. Brauckhoff, P. N. Thanh, C. Sekulla, H. Dralle Universitäts- und Poliklinik für Allgemein-, Viszeral- und Gefäßchirurgie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle, Germany Published online: 11 July 2002 © Springer-Verlag 2002

Abstract. Surgery has been the treatment of choice for many disorders of the thyroid gland, both benign and malignant, for many decades. However, surgery has not been invariable but has continued to change in accordance with research results. In benign cases, surgery has generally evolved to be as organ preserving as possible. In several instances, however, a more radical extent of resection seems justified in order to ensure that the risk of recurrence is as low as possible. For instance, total thyroidectomy may be beneficial in patients with endemic multinodular goitre or young patients with Graves’ disease and accompanying cold nodules or high levels of autoantibodies. Several tools, e.g. magnifying glasses, bipolar coagulation forceps and neuromonitoring, are available to identify and preserve the recurrent laryngeal nerve and the parathyroid glands, hence keeping the morbidity at a low level. Most recently, minimally invasive surgery has been successfully used in treating both benign and malignant disorders of the thyroid gland. In the case of malignant disorders, minimally invasive surgery may become an attractive alternative to open surgery if a limited surgical extent is justified, e.g. in patients with micro-PTC (papillary thyroid carcinoma, diameter less than 1 cm). Whether a limited surgical approach is also justified in other cases, e.g. in any patient with intrathyroidal PTC or patients with micro-FTC (follicular thyroid carcinoma), remains to be shown and is the subject of ongoing investigations. One of the most intriguing recent discoveries is the identification of genotype-phenotype correlations in patients with hereditary medullary thyroid carcinoma. In these patients, the timing and extent of surgery may depend not only on the patient’s age and serum levels of the tumour marker calcitonin but also on the specific germline RET proto-oncogene mutation. Surgery will certainly continue to play an important role in the treatment of thyroid diseases and O. Gimm (✉) Universitäts- und Poliklinik für Allgemein-, Viszeralund Gefäßchirurgie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle, Germany e-mail: [email protected] Tel.: +49-345-5572314, Fax: +49-345-5572551

may be increasingly based on individual findings instead of general recommendations. Keywords: Thyroid – Surgery – Advances Eur J Nucl Med (2002) 29 (Suppl. 2): S447–S452 DOI 10.1007/s00259-002-0913-3

Introduction The Swiss surgeon Emil Theodor Kocher can be called the father of endocrine surgery, and especially thyroid surgery. Before he and Theodor Billroth set out to improve surgery of the thyroid gland, it had been performed only in life-threatening situations since the mortality rate was reported to be as high as 40%. Due to Kocher’s growing surgical expertise, his own mortality rates dropped from about 14% in 1884 to 2.4% in 1889 and 0.18% in 1898. In addition, morbidity rates dropped dramatically and surgery became an effective therapeutic tool for thyroid diseases, both benign and malignant. In 1909, Kocher received the Noble Prize for his achievements concerning the physiology, pathology and surgery of the thyroid gland. Almost 100 years later, surgery is still the treatment of choice for many thyroid disorders. In this article, we give a brief summary on the current surgical practice in patients with thyroid diseases, with particular focus on recent developments concerning strategies of surgical resection and surgical techniques.

Extent of resection Benign goitre In general, surgery of benign thyroid disorders has evolved to be as organ preserving as possible. However, several disorders may be best treated by performing a more radical resection (Table 1). This issue has been addressed by several recent publications. For instance, pa-

European Journal of Nuclear Medicine Vol. 29, Supplement 2, August 2002

S448 Table 1. What’s new in thyroid surgery? Extent of resection

Surgical technique

1. Benign goitre

Aim: Minimising the risk of surgical morbidity while maintaining the quality of conventional techniques

1.1. Follicular adenoma

1. Recurrent laryngeal nerve: identification/preservation of the nerve recommended; neuromonitoring may be helpful in the hand of a less experienced surgeon

Lobectomy recommended (not proven by studies)

2. Parathyroid glands: preservation of at least 2 glands (in situ or autotransplanted) minimises the risk of hypoparathyroidism significantly

1.2. Graves’ disease and multinodular goitre

3. Minimally invasive surgery: can be performed without increasing the morbidity; benefit not clear

Total vs subtotal resection: tendency towards a more extended resection 2. Malignant tumours 2.1. Differentiated thyroid carcinoma Papillary thyroid carcinoma Limited resection (pT1 tumour) vs radical resection (pT2–4 tumour) Lymph node dissection: central compartment mandatory, beyond central compartment optional Follicular thyroid carcinoma Limited resection in pT1 tumours? (Not proven by studies) Lymph node dissection: extent to be determined in studies 2.2. Medullary thyroid carcinoma Sporadic: Limited resection in pT1 tumours? (Success proven in single studies) Hereditary: Time and extent of surgery may depend on the patient’s age, calcitonin level and RET mutation (genotype-phenotype correlation) 2.3. Undifferentiated thyroid carcinoma Extended surgery in combination with radiation (>30 Gy) may be beneficial for pN0, R0/R1 patients

tients with Graves’ disease may benefit from total thyroidectomy as compared with less than total thyroidectomy for the following reasons: (a) there is no risk of recurrence; (b) total thyroidectomy may have a beneficial effect on endocrine ophthalmopathy; (c) the risk of malignant thyroid tumours in patients with Graves’ disease is generally low (about 4%), though it may be up to 15% if cold nodules are present [1]. It needs to be taken into account that subtotal thyroidectomy generally is accompanied by decreased morbidity as compared with total thyroidectomy. The risk of recurrence, however, is increased in patients with high serum levels of autoantibodies and a young age (30%) present initially. Their significance for survival appears to be uncertain. However, an influence on the rate of recurrence is widely accepted. Hence, the CAEK guidelines recommend routine dissection of lymph nodes of the cervicocentral compartment. The indication for performance of lymph node dissection beyond this compartment is, however, less clear. If lymph node metastases are present, the indication is certainly given. However, lymph node metastases of PTC may be very small and not identifiable preoperatively or intraoperatively. Still, lymph node involvement of the cervicolateral lymph node compartment has been found in up to 25%–30% of patients with PTC, while lymph node metastases in the upper mediastinum are rare. The latter may, however, be found more frequently in patients with pT4 tumour (extrathyroidal tumour extension). In patients with PTC, lymph node dissection should be performed en bloc, i.e. lymph nodes should be resected with the surrounding adipose tissue while nerves, vessels and muscles are preserved. This technique is also known as systematic lymph node dissection. Systematic lymph node dissection should be performed since many lymph node metastases are small and hence not identifiable intraoperatively (see above). In addition, soft tissue infiltrates, which would remain in situ in the case of selective lymph node dissection (“berry picking”), have been found in up to 13% [3]. Since pre- and intraoperative techniques often fail to identify lymph node metastases, the search for more reliable techniques is ongoing. Sentinel lymph node biopsy has been shown to be of value in determining the extent of lymph node dissection in patients with melanoma and breast cancer. In thyroid cancer, however, the value of the sentinel lymph node is less clear. The success rate in identifying a sentinel lymph node in thyroid cancer ranges from 65% to 95%. The false negative rate has been reported to be as high as 17% [4]. However, well-designed studies are still lacking, and the value of sentinel node dissection in thyroid cancer remains to be determined. Medullary thyroid carcinoma In contrast to DTC, medullary thyroid carcinoma (MTC) derives from parafollicular C cells. C cells secrete calcitonin, which may serve as a sensitive and specific tumour marker at diagnosis and during follow-up. About one-quarter of all MTCs are hereditary and part of the multiple endocrine neoplasia syndrome type 2 (MEN 2). Activating germline mutations in the RET proto-oncogene have been found in >95% of these patients.


S450 Fig. 1. Timing and extent of surgery in hereditary MTC

There is no doubt that patients with hereditary MTC should undergo total thyroidectomy since every single C cell harbours the potential risk of becoming malignant. However, the necessity of total thyroidectomy in patients with sporadic MTC has recently been questioned [5] (Table 1). It has been shown that excellent results can be achieved in patients with sporadic MTC by means of unilateral surgery of the thyroid gland together with cervicocentral and ipsilateral cervicolateral lymph node dissection. Similar to PTC, lymph node metastases may often (>50%) be present in patients with MTC. In general, lymph node metastases in MTC are believed to affect both recurrence rate and survival. Hence, routine lymph node dissection of at least the cervicocentral compartment is recommended. The indication for lymph node dissection of the cervicolateral compartments, however, is less clear. Nevertheless, routine cervicolateral dissection has been recommended by several authors both in patients with sporadic and in those with hereditary MTC because metastases are often found (30%–50% of cases). An exception may be young screening patients, i.e. asymptomatic patients harbouring a germline RET mutation. In these patients, timing and surgical extent may depend on calcitonin levels, age and the specific RET mutation (Fig. 1). As in patients with PTC, lymph node dissection should be performed en bloc.

Surgical technique To keep the complication rate as low as possible, precise surgical techniques and bloodless operation should be aimed for. Today, many helpful tools exist, such as magnifying glasses, neuromonitoring and bipolar coagulation forceps. They facilitate the identification, preparation and preservation of important structures (e.g. parathyroid glands, nerves). The most commonly observed complications following surgery of the thyroid gland are hypocalcaemia and paresis of the recurrent laryngeal nerve. Depending on the extent of lymph node dissection, additional complications (e.g. paresis of the accessory nerve, Horner’s syndrome) may also be observed. Recurrent laryngeal nerve paresis Risk factors Paresis of the recurrent laryngeal nerve is a serious complication which may prevent the affected individual from continuing his/her profession (e.g. in the case of teachers or singers). Several factors that increase the risk of permanent laryngeal nerve paresis have been identified, including recurrent goitre (3.4-fold) and extent of surgical resection (2.1-fold) [7].

Undifferentiated thyroid carcinoma DTC may dedifferentiate and may even become undifferentiated. Whether UTC can develop directly from follicular cells is not known. The overall survival rate is extremely low: less than 5% of affected individuals survive the first year after diagnosis. Cure is rarely possible, and can only be achieved in patients undergoing surgery. Most patients present with a primary tumour beyond the thyroid gland (pT4 tumour). It could be shown that these patients only benefit from an extended surgical approach in the absence of lymph node metastases and in the case of a macroscopically radical tumour resection (R0 or R1) [6] (Table 1).

Identification For decades, there was controversy over whether identification of the laryngeal nerve can lower the rate of recurrent laryngeal nerve palsy or whether such attempts in fact have a deleterious effect on preservation of the nerve’s function. In experienced hands, however, it has repeatedly been shown that identification of the nerve is not accompanied by an increased rate of nerve palsy. Recently, analysis of the data concerning more than 7,500 patients in a large, prospective multicentre study has shown that identification of the recurrent laryngeal nerve


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reduces the risk of recurrent laryngeal nerve paresis by 1.6-fold [7]. This holds true not only for malignant but also for benign disorders. Only in rare instances (e.g. enucleation of a thyroid adenoma in the ventral thyroid lobe) may identification of the nerve be unnecessary. Neuromonitoring The benefit of monitoring the integrity of the recurrent laryngeal nerve intraoperatively has recently been shown in several studies. Despite different methods, the rate of paresis of the recurrent laryngeal nerve has been reported to be as low as 0%–0.6% [8, 9, 10]. That neuromonitoring can significantly reduce the rate of permanent laryngeal nerve paresis could also be shown in a large, prospective multicentre study analysing the data of more than 7,500 patients [11]. Neuromonitoring itself may be helpful not only in reducing the rate of recurrent laryngeal nerve paresis but also in identifying the nerve. Successful identification of the nerve has been reported in >97% of patients [8]. Neuromonitoring has also been shown to be of help in patients with non-recurrent laryngeal nerves [12]. Hypocalcaemia Even though unpleasant, the symptoms of hypocalcaemia can easily be treated by calcium intake either orally or via intravenous injection. However, the long-term effects are often underestimated. Hence, the development of hypocalcaemia must be avoided. In a large, prospective multicentre study, several risk factors have been identified that are associated with an increase risk of hypocalcaemia: female gender (2.1-fold), Graves’ disease (2.8-fold), experience of the surgical department (1.5fold), recurrence of goitre (1.9-fold) and extent of resection (1.8-fold) [7]. It could also be shown that identification of at least two parathyroid glands intraoperatively results in a 2.5-fold reduction in the risk of developing hypocalcaemia [13]. Minimally invasive surgery The technique of minimally invasive surgery has now been well established for several organs and diseases (e.g. cholecystitis, appendicitis). In endocrine surgery, laparoscopic or endoscopic techniques have been used for years to treat neoplasms of the adrenal gland. Very recently, minimally invasive video-assisted parathyroidectomy (MIVAP) was introduced by Miccoli and colleagues from Italy. The same group [14] and others [15, 16] have also shown the feasibility of minimally invasive video-assisted thyroidectomy (MIVAT). At first, only benign thyroid diseases were treated. The operation time has been reported to be as low as 80–100 min [14],

though others have reported longer operating times of 120–330 min [16]. The complication rates have generally been low. Conversion to open surgery was necessary in 3%–10% of cases. In the meantime, several different endoscopic approaches have been developed. Such approaches were initially developed to limit discomfort for the patient while keeping the cervical incision as small as possible, but others have made modifications due to “national” requirements. For instance, since even a small cervical scar in some Asian women may render them less likely to get married, subclavian and axillary approaches have been reported. The usefulness and safety of these procedures remains to be shown. References 1. Kraimps JL, Bouin-Pineau MH, Mathonnet M, De Calan L, Ronceray J, Visset J, Marechaud R, Barbier J. Multicentre study of thyroid nodules in patients with Graves’ disease. Br J Surg 2000; 87:1111–1113. 2. Mishra A, Agarwal A, Agarwal G, Mishra SK. Total thyroidectomy for benign thyroid disorders in an endemic region. World J Surg 2001; 25:307–310. 3. Machens A, Hinze R, Lautenschlager C, Thomusch O, Dralle H. Prophylactic completion thyroidectomy for differentiated thyroid carcinoma: prediction of extrathyroidal soft tissue infiltrates. Thyroid 2001; 11:381–384. 4. Dixon E, McKinnon JG, Pasieka JL. Feasibility of sentinel lymph node biopsy and lymphatic mapping in nodular thyroid neoplasms. World J Surg 2000; 24:1396–1401. 5. Miyauchi A, Matsuzuka F, Hirai K, Yokozawa T, Kobayashi K, Kuma S, Kuma K, Futami H, Yamaguchi K. Unilateral surgery supported by germline RET oncogene mutation analysis in patients with sporadic medullary thyroid carcinoma. World J Surg 2000; 24:1367–1372. 6. Machens A, Hinze R, Lautenschlager C, Thomusch O, Dunst J, Dralle H. Extended surgery and early postoperative radiotherapy for undifferentiated thyroid carcinoma. Thyroid 2001; 11:373–380. 7. Thomusch O, Machens A, Sekulla C, Ukkat J, Lippert H, Gastinger I, Dralle H. Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany. World J Surg 2000; 24: 1335–1341. 8. Jonas J, Bahr R. Intraoperative electromyographic identification of the recurrent laryngeal nerve [in German]. Chirurg 2000; 71:534–538. 9. Hemmerling TM, Schurr C, Dern S, Schmidt J, Braun GG, Klein P. Intraoperative electromyographic recurrent laryngeal nerve identification as a routine measure [in German]. Chirurg 2000; 71:545–550. 10. Lamade W, Meyding-Lamade U, Buchhold C, Brauer M, Brandner R, Uttenweiler V, Motsch J, Klar E, Herfarth C. First continuous nerve monitoring in thyroid gland surgery [in German]. Chirurg 2000; 71:551–557. 11. Thomusch O, Sekulla C, Dralle H. Thyroid surgery with intraoperative neuromonitoring of the recurrent laryngeal nerve: a prospective study in Germany with 7617 patients. Br J Surg 2000; 87:1276–1277.


S452 12. Brauckhoff M, Gimm O, Brauckhoff K, Ukkat J, Thomusch O, Dralle H. Calcitonin kinetics in the early postoperative period of medullary thyroid carcinoma. Langenbecks Arch Surg 2001; 386:434–439. 13. Thomusch O, Sekulla C, Dralle H. Risk analysis for hypoparathyroidism in thyroid surgery. Prospective study with a multiple logistic regression analysis. Langenbecks Arch Surg 2000; 385:431. 14. Miccoli P, Berti P, Raffaelli M, Conte M, Materazzi G, Galleri D. Minimally invasive video-assisted thyroidectomy. Am J Surg 2001; 181:567–570.

15. Mourad M, Ngongang C, Saab N, Coche E, Jamar F, Michel JM, Maiter D, Malaise J, Squifflet JP. Video-assisted neck exploration for primary and secondary hyperparathyroidism: initial experience. Surg Endosc 2001; 15:1112– 1115. 16. Gagner M, Inabnet WB 3rd. Endoscopic thyroidectomy for solitary thyroid nodules. Thyroid 2001; 11:161–163.
