Anaplastic thyroid carcinoma: changing trends of treatment strategies and associated overall survival.

PURPOSE: The prognosis of anaplastic thyroid cancer (ATC) is poor. Despite various attempts to modify common treatment modalities, including surgery, external beam radiation (EBRT) and chemotherapy (CTX), no standardized treatment is yet established. This study aimed to analyze the changing trends of treatment concepts and associated overall survival (OS) over the last two decades. METHODS: A retrospective analysis was conducted on 42 patients with histologically confirmed ATC. The outcome measures included the evaluation of clinical characteristics and treatments performed with regard to OS. RESULTS: Median OS for all tumor stages was 6 (range 1 week-79) months, 6.5 months for stage IVA/B and 4 months for stage IVC carcinoma patients. Twenty-one patients with stage IVA/B carcinomas underwent curative treatment, including thyroidectomy with lymphadenectomy (TTX plus LAD, n = 11) or multimodal treatment with TTX plus LAD and EBRT plus/minus CTX (n = 10). The median OS of patients with stage IVA/B carcinomas was significantly prolonged after multimodal treatment than after surgery alone (25 vs. 3 months, p = 0.04). Fifteen of 18 patients with stage IVC carcinomas received palliative, 3 patients multimodal treatment. The median OS of stage IVC patients after trimodal therapy was not significantly longer than after debulking procedures (6 vs. 7 months, p = 0.25). In the time period 1999-2009, only 4 (21%) patients received multimodal treatment compared to 9 (39%) in the period from 2009 to 2019, but this did not result in a significantly prolonged survival in the latter period (8.5 vs. 15 months, p = 0.61). CONCLUSION: Concurrent radio- and/or chemotherapy in combination with surgery seems to result in improved survival in stage IVA/B ATC, whereas this is not the case in patients with stage IVC tumors. Novel treatment regimens are urgently needed to improve the dismal prognosis of ATC.

[Update of the S2k guidelines : Surgical treatment of benign thyroid diseases]. / Aktualisierung der S2k-Leitlinie : Operative Therapie benigner Schilddrüsenerkrankungen.

Thyroid resections represent one of the most common operations with 76,140 interventions in the year 2016 in Germany (source Destatis). These are predominantly benign thyroid gland diseases. Recommendations for the operative treatment of benign thyroid diseases were last published by the CAEK in 2010 as S2k guidelines (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. [AWMF] 003/002) against the background of increasingly more radical resection procedures. Hemithyroidectomy and thyroidectomy are routinely performed for benign thyroid disease in practice. The operation-specific risks show a clear increase with the extent of the resection. Therefore, weighing-up of the risk-indications ratio between unilateral lobectomy or thyroidectomy necessitates an independent evaluation of the indications for both sides. This principle in particular has been used to update the guidelines. In addition, the previously published recommendations of the CAEK for correct execution and consequences of intraoperative neuromonitoring were included into the guidelines, which in particular serve the aim to avoid bilateral recurrent laryngeal nerve paralysis. Moreover, the recommendations for the treatment of postoperative complications, such as hypoparathyroidism and postoperative infections were revised. The updated guidelines therefore represent the current state of the science as well as the resulting surgical practice.

The actual role of classic bilateral cervicotomic approach for primary hyperparathyroidism in the era of minimally invasive surgery.

UNLABELLED: Recent advances in preoperative localisation of parathyroid adenomas and intraoperative prove of complete removal of hyperfunctioning parathyroid tissue have fostered less invasive operative procedures which directly target the diseased gland. Such strategies have partially replaced the previous gold standard procedure of bilateral neck exploration. We herein report on our own series of 1099 consecutive operations for primary hyperparathyroidism performed in a 16 year period and provide information and arguments for primary bilateral exploration in selected cases. 97.1% of patients were cured by the primary operation. From 1999 through 2001, 200 patients underwent bilateral neck exploration, whereas 63 unilateral operations were performed (33 patients were treated by minimally invasive video-assisted parathyroidectomy (MIVAP) and 30 by minimally invasive open parathyroidectomy (MIOP). In the remaining 200 patients minimally invasive unilateral parathyroid surgery was not feasible due to concomitant goiter (n = 102), lack of preoperative localisation (n = 30), previous thyroid surgery (n = 10), suspected multiglandular disease (n = 10), or other reasons (n = 8). In 40 patients the decision for bilateral neck exploration was made despite feasibility of a unilateral approach. CONCLUSION: Whereas unilateral exploration produced excellent cure rates in older patients, it is not recommended in patients with a high likelihood of multiglandular disease, presence of a large or multinodular goitre, high PTH levels, giant adenoma, unclear MIBI scans or an unreliable OPTH assay. Contrasting recent reports on a dramatic shift of technique towards minimally invasive procedures unilateral parathyroid surgery may not be preferably advisable in a majority of patients from countries with insufficient iodine supplementation.

[Surgery of euthyroid nodular goiter: special considerations in surgery of recurrent struma]. / Chirurgie der euthyreoten Knotenstruma: Besonderheiten bei der Operation der Rezidivstruma.

Indications for surgery need individual risk-analysis. Operative strategy is more conservative with unilateral procedures, more radical with total lobectomy. The crucial risk is recurrent laryngeal nerve paralysis (r.l.n.p.). In 434 operations with 647 nerves at risk (1985-2001) we classified the anatomical situation of the nerve prospectively: X: not identified, A: not in scar and B: within scar (B1, B2 and B3 dorsally, laterally or ventrally). The risk of r.l.n.p. increased from types A to type B to X, and from B1 to B3. Up to now, intraoperative neuromonitoring did not reduce this risk, additionally.

Primary hyperparathyroidism--early diagnosis in patients referred for thyroid surgery.

BACKGROUND AND AIMS: From 1986 to 1998, 190 patients presented for first-time operations for sporadic, non-malignant, non-multiple endocrine neplasia primary hyperparathyroidism. Of these patients, 54% had been classified as "asymptomatic", 41% as symptomatic and 5% as acute. One hundred and thirty-five patients (71%) were referred to us for parathyroid surgery. Fifty-five patients (29%) were referred for thyroid surgery with hitherto unknown hyperparathyroidism. This corresponds to a prevalence of primary hyperparathyroidism of 1% in patients referred for thyroid surgery (5450 patients during the same period of time). PATIENTS/METHODS: Patients referred for parathyroid surgery (group I, n=135) were compared with patients originally referred for thyroid surgery (group II, n=55). Group II was divided into group IIa: hyperparathyroidism preoperatively biochemically evident (n=26), and group IIb: borderline biochemistry, parathyroid enlargement evident at the operation (n=29). The groups were compared regarding clinical manifestations, serum calcium and parathyroid hormone, pathologic-anatomical substrates, operative complications and outcome. RESULTS: Renal, osseous and gastrointestinal manifestations were more frequent in group I than in groups IIa and IIb (P<0.05). However, cardiovascular and neuromuscular symptoms were present in groups IIa and IIb in more than one-third of patients. Patients from group IIb were younger (49+/-12 years) than patients from groups IIa (60+/-13 years) and I (60+/-14 years). Adenomas were found in 85% of group I patients, in 45% of group IIa patients and in 21% of group IIb patients (P<0.01). In all other cases, hyperplasia was confirmed histologically. Serum calcium was higher in group I (3.0+/-0.42 mmol/l) than in groups IIa (2.63+/-0.16 mmol/l) and IIb (2.46+/-0.14 mmol/l) (P<0.01). Serum PTH was higher in group I (median 11.0 pmol/l) than in groups IIa and IIb (median 7.1 and 6.4 pmol/l, respectively) (P<0.05). Postoperatively, hypercalcemia persisted in two patients (1.1%) belonging to group I, with mediastinal adenomas. Serum calcium at discharge showed no differences between groups (group I: 2.22+/-0.16; group IIa: 2.22+/-0.15; group IIb: 2.20+/-0.11 mmol/l). Recurrent laryngeal nerve paralysis occurred early (4.2% of "nerves at risk") and remained permanent (0.8% of "nerves at risk") without significant differences between groups. CONCLUSION: Diagnostic efforts regarding parathyroid function should be mandatory before thyroid operations. "Asymptomatic" patients frequently (more than 30%) present with cardiovascular and neuromuscular, "unspecific" symptoms. Simultaneous parathyroid exploration is obvious in cases with biochemically evident primary hyperparathyroidism, but should also be performed in patients with borderline biochemistry.

Differentiated operative therapy of thyroid autonomy (Plummer's disease).

The operative therapy of the autonomous thyroid deals almost exclusively with nodular goiters. There are only rare situations with purely diffuse autonomy in surgical patients. The endpoint of operative therapy is permanent elimination of clinically relevant autonomous function and thereby irreversible abolition of thyrotoxicosis, even in their latent form. Clinically relevant autonomous function normally ist linked to nodular structures of different size and different distribution, so that this aim corresponds automatically with the aim of complete removal of nodular structures, both in autonomous and in non-autonomous goiters. Function is best preserved by leaving a homogenous remnant of considerable size. In different particular clinical situations (for example pregnancy, suspicion of malignancy, recurrent goiter, intrathoracic goiter, thyrotoxic crisis, Marine-Lenhart-syndrome) the basic principal of operative strategy is varied according to the respective situations. Unsatisfactory operative results are mainly caused by incomplete removal of nodules, based on insufficient surgical performance of morphological and functional diagnostics, which is related to operative uniformity. An operative strategy, which ist "fitted to morphology" and "regarding function" and which we call "selective strategy", in our opinion ist highly appropriate, to avoid remnant nodules and remnant autonomy and to preserve an normal remnant, even in different position and of different size. This selective surgery ist applicable both to autonomous and non-autonomous goiter. Compared with the classic subtotal, uniform procedure the incidence of remnant nodules is reduced from about 50% to about 5 %. Remnant autonomy is almost excluded, when mistakes are avoided (about 1%). The incidence of recurrent goiter and recurrent thyrotoxicosis is lowered to under 5%--but up to now there are too few reliable long-term follow-up studies. The selective surgery strategy demands flexibility regarding operative tactics, which can be simply classified into 5 basic situations, which we relate to the operative procedure per thyroid lobe. It requires experience and competence in carefully dissecting and--when necessary--manipulating the recurrent laryngeal nerve und the parathyroid glands. Under these conditions it is followed by a comparatively low rate of complications (permanent recurrent laryngeal nerve paralysis and hypoparathyroidism under 1%, respectively). Thus, the old dilemma of thyroid surgery can be solved, which consists of radical operation with higher morbidity and lower frequency of recurrent disease on the one hand and more limited operative procedures with fewer complications but more frequent recurrencies on the other hand.

[Differentiated thyroid gland carcinoma p-T2/T3--extent of lymphadenectomy]. / Das differenzierte Schilddrüsenkarzinom p-T2/T3--Ausmass der Lymphadenektomie.

Systematic lymphadenectomy, which is compartment-orientated, from central node dissection to (modified) radical neck dissection, is not controversial in cases with intra-operative macroscopic node involvement. General "prophylactic" dissection, at least of the ipsilateral central compartment, is advocated due to a high incidence of "occult", microscopic positive nodes, and the elevated risk regarding recurrency and survival which is connected to node-positivity, and lowered recurrence rates with systematic lymphadenectomy. Nevertheless, the biological impact of occult positive nodes, as an independent risk-factor, is not yet clear, with important differences between papillary and follicular carcinoma ("marker" or "governor" of the disease?). Enhanced operative morbidity by extensive lymphadenectomy, especially hypoparathyroidism, must be taken into account.