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Henning Dralle,
Thomas J Musholt,
Jochen Schabram,
Thomas Steinmüller,
Andreja Frilling,
Dietmar Simon,
Peter E Goretzki,
Bruno Niederle,
Christian Scheuba,
Thomas Clerici, [......],
Andreas Zielke,
Wolfram Karges,
Markus Luster,
Kurt W Schmid,
Dirk Vordermark,
Hans-Joachim Schmoll,
Reinhard Mühlenberg,
Otmar Schober,
Harald Rimmele,
Andreas Machens
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ABSTRACT: INTRODUCTION: Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable ("low risk") papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages. METHODS: The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization. RESULTS: The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases. CONCLUSION: These evidence-based recommendations for surgical therapy reflect various "treatment corridors" that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.
Langenbeck s Archives of Surgery 03/2013; · 1.81 Impact Factor
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ABSTRACT: PURPOSE: Calcitonin screening aims at uncovering occult medullary thyroid cancer (MTC) in patients with nodular thyroid disease. Elevated basal calcitonin serum levels call for calcitonin stimulation, the level of which may direct the extent of surgery. Because pentagastrin has become restricted, calcium has increasingly been used instead for stimulation. This study identified a new spectrum of patients demonstrating a false-positive hypercalcitoninemia in the absence of C-cell disease, carrying multinodular goiter (MNG), thyroiditis, and non-MTC thyroid malignancy, and endeavored to explore the feasibility of extrapolating pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. METHODS: Altogether, 43 (9.5 %) of 455 patients with nodular thyroid disease revealed increased basal calcitonin serum levels between 2005 and 2012, for which they underwent intravenous stimulation with pentagastrin (31 patients) or calcium gluconate (12 patients) before and after primary thyroidectomy. RESULTS: Stimulation with calcium gluconate resulted in significantly higher and more variable preoperative calcitonin serum levels after 2 (241.2 vs. 104.9 pg/mL; P = 0.018) and 5 min (240.6 vs. 87.4 pg/mL; P = 0.007) than stimulation with pentagastrin. Stimulation with calcium gluconate produced 10-fold (nodular goiter), 15-fold (thyroiditis), and 21-fold (thyroid neoplasia other than MTC) calcitonin increases over baseline, as opposed to 5-fold, 10-fold, and 8-fold increases after stimulation with pentagastrin. None of the 43 patients, all of whom reverted to undetectable calcitonin serum levels after thyroidectomy, had immunohistochemical evidence of C-cell disease. Subgroup analyses according to gender and thyroid disease, being limited by the low number of patients in each subgroup, did not yield significant differences. CONCLUSIONS: Calcium stimulation yields significantly greater calcitonin levels than pentagastrin stimulation, precluding generalization of pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. After calcium stimulation, false-positive findings appear to be more common in patients of female gender and patients with thyroiditis and thyroid neoplasia other than MTC, potentially effecting surgical overtreatment.
Langenbeck s Archives of Surgery 02/2013; · 1.81 Impact Factor
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ABSTRACT: Context:In multiple endocrine neoplasia type 2, American Thyroid Association (ATA) management guidelines recommend continuous biochemical screening for pheochromocytoma and/or primary hyperparathyroidism. This implicit assumption of linear tumor development is difficult to reconcile with current thinking that cells accrue somatic mutations stochastically, yielding a bell-shaped distribution.Objective:This investigation aimed at evaluating the age distribution of pheochromocytoma and primary hyperparathyroidism in gene carriers at risk of developing multiple endocrine neoplasia type 2.Design:ATA class D, C, B, and A mutations, with or without pheochromocytoma and/or primary hyperparathyroidism, were plotted against carrier age at the time of diagnosis or last follow-up.Setting:The setting was a surgical referral center.Patients:Included were 474 carriers of ATA class D (37 patients), C (170 patients), B (112 patients), and A (155 patients) mutations. Eighty-four carriers (17.8%) developed pheochromocytoma (bilateral in 42 patients) and 20 carriers (4.2%) primary hyperparathyroidism.Interventions:Interventions were adrenalectomy and/or parathyroidectomy.Main Outcome Measures:Main outcome measures were multiple endocrine neoplasia type 2-associated tumors.Results:Bell-shaped age distribution curves were obtained for unilateral and bilateral pheochromocytoma (ATA class D, C, and B) and primary hyperparathyroidism (ATA class C and B). Owing to the rarity of events, the bell shape of the distribution curve was faint but consistent with a random distribution for ATA class A mutations (unilateral pheochromocytoma and primary hyperparathyroidism). With decreasing penetrance, the bell-shaped distribution curve, becoming narrower and flatter, shifted to the right toward higher age groups.Conclusions:These data, revealing phases of greater amidst phases of lower penetrance, support adjustment of biochemical screening to carrier age and ATA class.
The Journal of clinical endocrinology and metabolism 01/2013; · 6.50 Impact Factor
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ABSTRACT: The aim of this study was to investigate the effect of short hairpin RNA (shRNA) targeting autotaxin (ATX) on the migratory and invasive capability of AGS human gastric cancer cells and the growth of xenografts in nude mice. pSUPER-ATX and pSUPER-mock (non-specific), which were constructed corresponding to the ATX-shRNA and negative control mock-shRNA synthesized based on gene sequence, were transfected with blank plasmid pSUPER-control into AGS human gastric cancer cells using Lipofectamine. At 24, 48 and 72 h post-transfection, the cells were harvested and analyzed. The endogenous ATX mRNA and protein of the different groups of AGS cells were detected by RT-PCR and western blot assays. Cell proliferation was measured by MTT assay. In vitro Transwell and Matrigel assays were used to detect the cell migratory and invasive capabilities. A tumor xenograft model was generated by subcutaneous injection of AGS cells into the dorsum of nude mice. The growth of xenograft tumors was monitored and measured; changes in tumor morphology and the organs of mice were observed by H&E staining. The expression of ATX, MMP-2 and MMP-9 protein in xenograft tumor tissues was detected by immunohistochemistry and western blotting. In vitro, both the mRNA and protein levels of ATX in the pSUPER-ATX group were significantly downregulated (P<0.01), and the cell proliferative, migratory and invasive capabilities were also significantly decreased. In vivo, no obvious damage to the organs was found. pSUPER-ATX significantly suppressed the tumor volume and weight from the 7th week after cell transplantation, compared to the pSUPER-mock, pSUPER-control and WT groups; the inhibition rates were approximately 50% (P<0.05). However, no significant differences in these parameters were found among the WT, pSUPER-mock and pSUPER-control groups. Furthermore, ATX, MMP-2 and MMP-9 were expressed at significantly lower levels in the pSUPER-ATX group compared to the levels in the other three groups (P<0.05), and a significant correlation between ATX and MMP-2 expression was found (r=0.869, P<0.01). The specific shRNA targeting ATX downregulated the endogenous ATX of AGS human gastric cancer cells, and inhibited AGS cell proliferative, migratory and invasive potentials. Moreover, shRNA targeting ATX inhibited the growth of human gastric cancer xenografts in nude mice.
Oncology Reports 12/2012; · 1.84 Impact Factor
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ABSTRACT: OBJECTIVETWENTY YEARS AGO, THE GROUND-BREAKING DISCOVERY THAT REARRANGED DURING TRANSFECTION (RET) MUTATIONS UNDERLIE MULTIPLE ENDOCRINE NEOPLASIA 2 (MEN 2) AND FAMILIAL MEDULLARY THYROID CANCER (FMTC) USHERED IN THE ERA OF PERSONALIZED MEDICINE. MEN2-ASSOCIATED SIGNS, TAKING TIME TO MANIFEST, CAN BE SUBTLE. THIS STUDY SOUGHT TO CLARIFY TO WHAT EXTENT CONVENTIONAL ESTIMATES OF 1:200,000-500,000 UNDERESTIMATE THE INCIDENCE OF RET MUTATIONS IN THE POPULATION.DESIGNINCLUDED IN THIS RETROSPECTIVE INVESTIGATION WERE 333 RET CARRIERS BORN BETWEEN 1951 AND 2000 AND OPERATED ON AT THE LARGEST GERMAN SURGICAL REFERRAL CENTER (286 CARRIERS) OR ELSEWHERE (47 CARRIERS).METHODSTO ESTIMATE THE INCIDENCE OF RET MUTATIONS, THE NUMBER OF RET CARRIERS BORN IN GERMANY IN FIVE DECADES (1951-1960, 1961-1970, 1971-1980, 1981-1990, AND 1991-2000) WAS DIVIDED BY THE CORRESPONDING NUMBER OF GERMAN LIVE BIRTHS.RESULTSOWING TO IMPROVED DIAGNOSIS AND CAPTURE OF FMTC AND MEN2 PATIENTS, MINIMUM INCIDENCE ESTIMATES INCREASED OVER TIME: overall from 5.0 (1951-1960) to 9.9 (1991-2000) per million live births and year (P=0.008), and by American Thyroid Association/ATA class from 1.7 to 3.7 for ATA class C (P=0.008); from 1.8 to 2.7 for ATA class A (P=0.017); from 1.5 to 2.2 for ATA class B (P=0.20); and from 0 to 1.4 for ATA class D mutations per million live births and year (P=0.008). Based on 1991-2000 incidence estimates, prevalence in Germany approximates 1:80,000 inhabitants.Conclusions
The molecular minimum incidence estimate of ≈ 1:100,000 was 2-5-fold greater than conventional estimates of 1:200,000-500,000.
European Journal of Endocrinology 12/2012; · 3.42 Impact Factor
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ABSTRACT: BACKGROUND: Intermittent intraoperative neuromonitoring cannot prevent preparative surgical damage or predict imminent recurrent laryngeal nerve (RLN) damage with subsequent development of loss of electromyogram (EMG) signal during thyroid surgery. In case the nerve is stressed, i.e., from traction near the ligament of Berry, the nerve injury is only detected after it has occurred, not allowing the surgeon to correct the mechanical maneuver and salvage nerve function intraoperatively. METHODS: The unusual clinical scenario of sacrifice of a tumor-infiltrated RLN was used to study real-time evolution of RLN injury caused by mechanical distention. The ipsilateral vagus nerve (VN) was continuously stimulated with a new stimulation probe, and changes in EMG response were correlated with the varying levels of stretch and traction. RESULTS: Mechanical traction induced an intermittent depression of EMG amplitudes as a sign of impaired propagation of axon potentials or synaptic transmission. Prolonged mechanical stress caused a long-lasting depression of EMG response. When the mechanical distention was relieved, neurotransmission was gradually restored, with reappearance of singular muscle depolarization of full magnitude interspersed between the barely detectable deflections in the EMG recording. These responses of full amplitude appeared with increasing frequency, until the regular continuous EMG pattern was completely restored. CONCLUSIONS: Only continuous VN stimulation serves to detect early changes in EMG response that indicate imminent danger to RLN functional integrity and alerts the surgeon to immediately correctable surgical actions, thus possibly preventing nerve damage or transforming damage into a reversible event.
World Journal of Surgery 11/2012; · 2.36 Impact Factor
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ABSTRACT: BACKGROUND: Conventional intraoperative nerve monitoring, predicated on intermittent stimulation, can predict recurrent laryngeal nerve (RLN) palsy only after the damage has been done. METHODS: Fifty-two patients (52 nerves at risk) who underwent continuous intraoperative nerve monitoring (CIONM) for thyroid surgery via vagus nerve stimulation had their electromyographic (EMG) tracings recorded and correlated with surgical maneuvers and postoperative RLN function. RESULTS: There was 1 imminent loss of signal (LOS) with intraoperative signal recovery and there were 4 losses of signal with corresponding unilateral transient RLN palsy. When EMG amplitude decreased >50% and EMG latency increased >10%, LOS and postoperative RLN palsy were noted in 4 of 8 patients (50%) who had multiple combined events. In 9 of 13 patients (70%) who developed adverse EMG changes, modification of the causative surgical maneuver resulted in recovery of those EMG changes and aversion of impending RLN palsy. CONCLUSION: CIONM reliably signaled impending nerve injury, enabling immediate corrective action. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
Head & Neck 11/2012; · 2.40 Impact Factor
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ABSTRACT: PURPOSE OF REVIEW: The lateral neck compartment is the second most frequent target region for metastatic papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC). Lateral lymph node metastases are associated with locoregional recurrence and, when they involve either side of the neck, with mediastinal and distant metastases. RECENT FINDINGS: For tumors originating from the upper thyroid pole, the first nodal basin is not invariably the central compartment (as for primaries arising from the inferior thyroid pole) but often the upper part of the ipsilateral lateral compartment. Lymph node dissection of the first basin may differ depending on the location of the primary tumor. Involvement of the contralateral lateral compartment is seen in PTC with extensive central compartment involvement, and in MTC with preoperative basal calcitonin levels more than 200 pg/ml (normal limit <10 pg/ml). SUMMARY: After lateral lymph node dissection for metastatic thyroid cancer, dysfunction of lateral neck nerves is fairly common. This observation underpins the importance of striking a balance between oncological benefit and surgical risk. Lateral lymph node dissection may be warranted for an upper thyroid pole primary, for a tumor with extensive involvement of the central compartment, and for an MTC with increased basal calcitonin level of 20-200 pg/ml (ipsilateral dissection) or more than 200 pg/ml (bilateral dissection).
Current opinion in oncology 10/2012; · 4.09 Impact Factor
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ABSTRACT: Context:A prognostic classification system based on aggregate numbers of lymph node metastases may better estimate the risk of distant metastasis.Objective:This investigation sought to evaluate a papillary thyroid cancer (PTC) patient's risk of distant metastasis.Design:This was a retrospective analysis.Setting:The setting was a tertiary referral center.Patients:Included were 972 PTC patients.Intervention:The intervention was compartment-oriented surgery.Main Outcome Measure:The main outcome measure was lung, bone, and liver metastasis.Results:Eighty-seven (9.0%) of the 972 PTC patients had distant metastases to lung (79 patients), bone (16 patients), liver (two patients), brain and skin (one patient each). For distant metastasis, more than 20 lymph node metastases had a specificity of 90.8% and a negative predictive value of 92.7%, whereas sensitivity and positive predictive value were low (27.6 and 22.9%). On multivariate logistic regression, 1-5, 6-10, and 11-20 involved nodes denoted a moderate risk of lung metastasis [odds ratio (OR), 9.9, 10.6, and 13.8; P ≤ 0.004], whereas more than 20 involved nodes indicated a high risk of lung metastasis (OR, 25.0; P < 0.001). Mediastinal lymph node metastasis carried a moderate risk of lung metastasis (OR, 7.5; P = 0.001). When these numeric categories of lymph node metastases were exchanged for current tumor node metastasis (TNM) N categories, the OR decreased from 25.0 (for > 20 lymph node metastases) to 16.4 (N1b), and from 9.9-13.8 (for 1-20 lymph node metastases) to 4.7 (N1a).Conclusion:In PTC, categories of 0, 1-20, and more than 20 lymph node metastases correlate better with lung metastasis than current TNM N categories N0, N1a, and N1b.
The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
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ABSTRACT: OBJECTIVE:: This investigation aimed at exploring the prospects of a cure for persistent medullary thyroid cancer (MTC) stratified by basal calcitonin levels before reoperation and the number of lymph node metastases previously removed at outside facilities. BACKGROUND:: There is no evidence-based information supporting the balance of surgical benefit and risk in persistent MTC. METHODS:: This retrospective study of 334 patients with persistent MTC referred to a tertiary surgical center, who were compared with 367 patients with previously untreated MTC referred to that institution during the same time period, evaluated biochemical cure rates after systematic lymph node dissection. RESULTS:: The relationship between the incremental serum calcitonin level before reoperation and the number of lymph node metastases at reoperation and biochemical cure was strong after previous removal of 0 (r = 0.74 and 77%-0%) and 1 to 5 lymph node metastases (r = 0.61 and 60%-0%) elsewhere. It disappeared once more than 5 lymph node metastases had been cleared at other hospitals (nonsignificant and 5%). When serum calcitonin levels were 1000 pg/mL or lower before reoperation, biochemical cure rates were 44% (59 of 133 patients) and 18% (12 of 65 patients) after previous removal of 0 and 1 to 5 lymph node metastases, respectively. These rates plummeted to 5% (2 of 43 patients) after a previous clearance of more than 5 lymph node metastases. When serum calcitonin levels exceeded 1000 pg/mL before reoperation, a biochemical cure was exceptional (1%; 1 of 76 patients). CONCLUSIONS:: With serum calcitonin levels of 1000 pg/mL or lower before reoperation and the previous removal of 5 or fewer lymph node metastases, systematic lymph node dissection seems worthwhile for persistent MTC. These findings will need to be validated in independent series before being adopted more widely as a new standard of care.
Annals of surgery 09/2012; · 7.90 Impact Factor
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ABSTRACT: OBJECTIVE:: This institutional study aimed at quantifying a medullary thyroid cancer (MTC) patient's risk of lung, liver, or bone metastasis. BACKGROUND:: Without quantitative information regarding risk factors for lung, liver, and bone metastasis, risk stratification is liable to be haphazard, resulting in poor cost-effectiveness of screening programs. METHODS:: Included in this study were 715 patients with MTC for whom histopathologic information was available for each lymph node removed. RESULTS:: Seventy-two patients (10.1%) were diagnosed with lung metastasis, 58 patients (8.1%) with liver metastasis, and 34 patients (4.8%) with bone metastasis. Multivariate analyses were limited to patients revealing no more than 1 type of distant metastasis to avoid confounding by other distant metastasis. Extrathyroidal extension and 1 to 10 involved nodes indicated a small risk of lung metastasis [3%-4%; odds ratio (OR) 3-4], tumors greater than 40 mm and 11 to 20 involved nodes implied an intermediate risk (13%; OR 6), and more than 20 involved nodes entailed a high risk (26%-30%; OR 14-16). In the multivariate logistic regressions on liver and bone metastasis, in which the number of involved nodes was omitted on statistic grounds, extrathyroidal extension signified a strong risk of liver metastasis (19%, OR 23), whereas no clinical-pathologic variables were significantly associated with bone metastasis. Cumulative rates of lung, liver, and bone metastasis, plotted against the number of lymph node metastases, were similar. DISCUSSION:: N categories encompassing 1 to 10 (N1), 11 to 20 (N2), and more than 20 (N3) lymph node metastases are important prognostic classifiers that should be incorporated into MTC staging systems for better risk stratification.
Annals of surgery 09/2012; · 7.90 Impact Factor
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Karin Frank-Raue,
Andreas Machens,
Gudrun Leidig-Bruckner,
Susanne Rondot,
Christine Haag,
Egbert Schulze,
Angela Lorenz,
Michael Kreissl, Henning Dralle,
Friedhelm Raue,
Kurt W Schmid
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ABSTRACT: Background: Medullary thyroid carcinoma (MTC) is characterized by the synthesis and secretion of calcitonin (Ct). MTC without Ct secretion has been reported on rare occasions. The aim of this study was to analyze the prevalence and clinical spectrum of nonsecretory MTC in two tertiary centers that cared for 839 patients with sporadic MTC. Methods: Clinical, biochemical, histological and immunohistological findings, and somatic RET mutations were analyzed, and long-term follow-up was documented. Results: Seven patients with nonsecretory MTC were identified among 839 patients with sporadic MTC; thus, the prevalence rate of of nonsecretory MTC was 0.83%. In these seven patients, Ct and carcinoembryonic antigen (CEA) levels were normal when the patients were initially diagnosed with MTC, despite advanced tumor stage. Ct and CEA levels remained undetectable in four patients, recurrence was indicated in one patient after 10 years of follow-up by routine anatomic imaging and increased CEA levels, and Ct levels became slightly elevated during follow-up, despite massive tumor load, in the remaining two patients. The diagnosis of MTC was confirmed by positive immunohistochemistry for Ct, CEA, and chromogranin A. A high Ki-67 proliferation index (three patients) and a high proportion of RET 918 mutated cells (four patients), as well as poorly differentiated histology, were associated with aggressive biological behavior of the MTC. The prognosis for nonsecretory MTC varied between long-term survival (12.5 years) and rapid progression leading to death within 1.75 years after diagnosis. Conclusions: The prevalence of nonsecretory MTC was low (0.83% of patients with MTC). Diagnosis was often made at a clinically advanced tumor stage. The histological and immunohistological characteristics and the clinical course and prognosis of nonsecretory MTC are markedly heterogeneous. A high Ki-67 proliferation index and a large proportion of cells with RET 918 mutations is associated with a poor prognosis.
Thyroid: official journal of the American Thyroid Association 09/2012; · 2.60 Impact Factor
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ABSTRACT: Survivin is a novel apoptosis inhibitor. Its gene is related to the baculovirus gene, which is believed to play a crucial role in fetal development and in cancer. We attempted to determine the expression of survivin in both thyroid goiter and carcinoma tissues, and to evaluate its prognostic value in human thyroid disease. In the present study, we applied small interfering RNA (siRNA) directed against survivin to determine the effects of decreasing the high constitutive levels of this protein in the FTC-133 thyroid follicular cancer cell line. Using reverse transcription PCR and immunohistochemistry, we compared the expression of survivin with relevant clinical and pathological data of 90 postsurgical specimens from patients with primary thyroid carcinoma and patients with benign goiter (33 with papillary thyroid cancer, 24 with follicular thyroid cancer, 18 with undifferentiated thyroid cancer and 15 cases with goiter). For the siRNA treatment in a human follicular thyroid carcinoma cell line, fluorescein-labeled double-stranded ultrapure siRNAs were used. RT-PCR identified the survivin transcript in 67/75 (89.3%) tumor samples and in 4/15 benign goiter samples. Immunohistochemical analysis showed positive immunoreactivity in 65/75 (86.7%) carcinomas while no expression was noted in all of the 15 benign goiter tissues. Survivin mRNA and protein levels were significantly higher in cancer tissues compared to benign goiter tissues (P<0.001). Higher survivin expression was found in the tumor tissues of pT3/pT4 and in the tumors with lymph node metastasis (P<0.05). Tumors with distant metastasis demonstrated higher survivin expression compared to the tumors without distant metastasis. Additionally, the expression of survivin in undifferentiated carcinomas was higher than that in differentiated ones. There was no significant correlation between survivin expression and age, gender, histological subtype and pathological stage. Our additional studies demonstrated that siRNA directed against survivin markedly decreased the protein expression of survivin. In conclusion, we conclude that survivin expression indicates more aggressive behavior and metastatic ability in thyroid cancer cells in vivo. Survivin can be used as a diagnostic and therapeutic marker for thyroid carcinoma and an important target in the strategy of thyroid cancer therapy. Our results of siRNA silencing indicate that siRNA may have potential as a therapeutic modality in the treatment of human thyroid cancer.
International Journal of Molecular Medicine 06/2012; 30(3):465-72. · 1.98 Impact Factor
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ABSTRACT: PurposeThis study aimed at definition of normal quantitative parameters in intraoperative neuromonitoring during thyroid surgery.
Only few and single center studies described quantitative data of intraoperative neuromonitoring. Definition of normal parameters
in intraoperative neuromonitoring is believed to be a prerequisite for interpretation of results and intraoperative findings
when using this method. Moreover, these parameters seem important in regard to the prognostic impact of the method on postoperative
vocal cord function.
Material and methodsIn a prospective multicenter study, quantitative analysis of vagal nerve stimulation pre- and postresection was performed
in thyroid lobectomies. A standardized protocol determined set up and installation of neuromonitoring and defined assessment
of quantitative parameters. Data of intraoperative neuromonitoring were respectively print-documented and centrally analyzed.
ResultsIn six participating centers a total of 1,289 patients with 1,996 nerves at risk underwent surgery for benign and malignant
thyroid disease. Median amplitude was significantly larger for the right vs. left vagal nerve, latency was significantly longer
for left vs. right vagal nerve and duration of the left vs. right vagal nerve significantly longer. Age disparities were only
present in form of significantly higher amplitude in patients below 40years; however, there is no continuous increase with
age. Regarding gender, there was significantly higher amplitude and smaller latency in women compared to men. Duration of
surgery revealed a reduction of amplitude with operative time; contrarily, latency and signal duration remained stable. The
type of underlying thyroid disease showed no influence on quantitative parameters of intraoperative neuromonitoring.
ConclusionsSystematic data of multicenter evaluation on quantitative intraoperative neuromonitoring parameters revealed differences between
left and right vagal nerves in regard to amplitude, latency and duration of signal, gender, and age. The nature of thyroid
disease showed no significant influence on quantitative parameters of intraoperative neuromonitoring. This study presents
for the first time collective data of a large series of nerves at risk in a multicenter setting. It seems that definitions
of “normal” parameters are prerequisite for the interpretation of quantitative changes of intraoperative neuromonitoring during
thyroid surgery to enable interpretation of influence on surgical strategy and prediction of postoperative vocal cord function.
KeywordsIntraoperative neuromonitoring-Thyroid surgery-Quantitative parameters-Definition normal values
Langenbeck s Archives of Surgery 04/2012; 395(7):901-909. · 1.81 Impact Factor
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ABSTRACT: Hintergrund:
Klinisch relevante Schilddrüsenkarzinome sind in 5–6% der operierten Knotenstrumen zu finden. Multinodöse Strumen weisen zudem
häufig autonome Areale auf. Daher bedarf es effektiver rationaler differentialdiagnostischer Methoden und Entscheidungsalgorithmen,
um unter der großen Zahl der Schilddrüsenknoten diejenigen Knoten mit einem erhöhten Karzinomrisiko oder einer Schilddrüsenautonomie
zu identifizieren.
Methodik:
Darstellung einer aktuell überarbeiteten Leitlinie und weiterer Leitlinien und Konsensusstellungnahmen sowie selektive Literaturübersicht.
Ergebnisse:
Bereits mittels Anamnese, Sonographie und TSH-Bestimmung (thyreoideastimulierendes Hormon) sind eine erste Risikobeurteilung
und Selektion für die weitere Schilddrüsendiagnostik möglich. Die Feinnadelbiopsie (FNB) ist die Methode mit der besten Sensitivität
und Spezifität für die Dignitätsabklärung sonographisch darstellbarer, szintigraphisch normal speichernder oder kalter Schilddrüsenknoten
> 1 cm. Voraussetzungen für einen effektiven Einsatz der FNB in der klinischen Routine sind allerdings eine adäquate Ausbildung
und umfangreiche Erfahrungen von Punkteur und Zytopathologe.
Schlussfolgerung:
Während malignitätsverdächtige solitäre Schilddrüsenknoten unverzüglich dem Chirurgen zugeführt werden müssen, kann bei fehlenden
klinischen, sonographischen und zytologischen Malignitätshinweisen, normalem Calcitonin sowie Euthyreose der Verlauf – ggf.
unter Medikation – beobachtet werden, wenn nicht eine chirurgische Therapie aufgrund lokaler Beschwerdesymptomatik, trachealer
Beteiligung oder mediastinaler Ausdehnung begründet ist.
Background:
Clinically relevant thyroid carcinomas can be found in 5–6% of nodular goiters which undergo surgery. Moreover, multinodular
goiters fre- quently contain hot areas. Therefore, efficient and rational methods for the differential diagnosis and decision
are required to identify those nodules with an increased cancer risk or those which are hot among the many thyroid nodules.
Methods:
Description of a newly revised and further guidelines and consensus statements as well as selected literature search.
Results:
Already history, ultrasound and TSH (thyroid-stimulating hormone) determination do allow a first risk assessment for the further
diagnostic work-up. Fine-needle biopsy (FNB) offers the best sensitivity and specificity for the distinction between benign
and malignant thyroid nodules. The combination of several clinical and ultrasound criteria and laboratory determinations (calcitonin)
can help with the selection of thyroid nodules with scintigraphically normal or decreased uptake > 1 cm for FNB. However,
the efficiency of FNB requires sufficient training and experience of both the cytopathologist and the person performing FNB.
Conclusion:
Whereas solitary thyroid nodules with a suspicion for malignancy should be referred to the surgeon, euthyroid thyroid nodules
without clinical ultrasound or cytological indicators of malignancy may be followed up – possibly under medication –, if surgery
is not indicated by local complaints, tracheal or mediastinal involvement.
Schlüsselwörter:
Schilddrüsenknoten-Schilddrüsenfeinnadelbiopsie-Szintigraphie-TSH-Autonomes Adenom-Kalter Schilddrüsenknoten-Konservative Therapie-Operation-Radiojodtherapie-Chirurgie
Key Words:
Thyroid nodules-Thyroid fine-needle biopsy-Scintigraphy-TSH-Hot nodule-Cold thyroid nodule-Conservative treatment-Surgery-Radioiodine therapy
04/2012; 105(2):80-87.
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ABSTRACT: The objective of this study was to define a novel type of mycotic aneurysm of the carotid artery arising after cervical reoperation.
We retrospectively analyzed all staphylococcal mycotic aneurysms of the common carotid artery. These aneurysms had developed
after reoperative thyroid or parathyroid surgery, including resection of the central lymph node compartment and cervical reexploration.
Mycotic aneurysms were found in three patients, with an incidence of 0.77% (2/261) and 0.62% (1/161) for thyroid and parathyroid
reoperations, respectively. Postoperatively, a lymphatic fistula and cervical hematoma emerged in all patients, as did cervical
wound infections on days 3, 4, and 6. Deep wound infections were noted on surgical revision. Cultures grew exclusivelyStaphylococcus aureus, which was resistant to methicillin (MRSA) in one patient. Mycotic aneurysms were identified 1 week after cervical reoperation.
One aneurysm was discovered incidentally on planned lavage. The other two aneurysms presented as severe arterial hemorrhages,
resulting in exsanguination in one patient. The other two patients had their aneurysms replaced by saphenous venous autografts.
There seems to be accelerated arterial media destruction with formation of mycotic aneurysms in staphylococcal wound infections
after cervical reoperation. It is important to recognize this novel type of mycotic aneurysm, as it must be repaired immediately
to anticipate imminent rupture.
Objective: Définir un nouveau type d’anévrysme mycosique de l’artère carotide observé après ré-operation du cou.Méthodes: Une analyse rétrospective de tous les anévrysmes mycosiques en rapport avec des infections staphylococciques développés
aux dépens de l’artère carotide commune. Ces anévrysmes se développent après réopération sur la thyroïde ou la parathyroïde,
y compris les adénolymphadénectomies cervicales centrales et les réexplorations cervicales.Résultats: On a observé trois cas d’anévrysme mycosique, pour une incidence de 0.77% (2/261) et 0.62% (1/161) pour, respectivement,
les réinterventions sur la thyroïde et sur la parathyroïde. En postopératoire, les fistules lymphatiques et un hématome cervical
ont été retrouvés chez tous les patients, de même que des infections de la plaie cervicale aux jours 3, 4 et 6. Lors de la
révision chirurgicale, les infections profondes du cou ont été notées. Par les cultures, on a mis en évidence uniquement des
staphylocoques dorés, résistants à la méthicilline (MRSA) chez un patient. Les anévrysmes mycosiques ont été identifiés une
semaine après la réopération cervicale. Un anévrysme a été découvert par hasard lors d’une réexploration pour lavage. Les
deux autres anévrysmes se sont présentés comme des hémorragies sévères d’origine artérielle, résultant en une exsanguination
chez un patient. Chez deux autres patients, les anévrysmes ont été remplacés par des autogreffes veineuses de la saphène.Conclusions: En cas d’infection staphylococcique de plaie après réopération cervicale, il semble exister une destruction accélérée de
la média artérielle avec formation d’un anévrysme mycosique. II est important de reconnaître ce nouveau type d’anévrysme mycosique
qui doit être replacé immédiatement afin de prévenir la rupture imminente.
Objetivo: Describir un nuevo tipo de aneurisma micótico de la arteria carótida producido tras cirugía cervical. Métodos: Análisis
retrospectivo de todos los aneurismas micóticos por estafilococos de la arteria carótida. Estos aneurismas se desarrollaron
tras reintervenciones tiroideas, paratiroideas e incluso, tras resecciones de los ganglios linfáticos del compartimiento central
de cuello y/o reexploraciones quirúrgicas cervicales. Resultados: En 3 pacientes encontramos un aneurisma micótico. Dos, tras
reintervenciones tiroideas (2/261, frecuencia 0.77%) y uno, tras reintervención paratiroidea (1/161, incidencia 0.62%). En
todos estos pacientes se desarrollaron seromas, hematomas cervicales o infecciones de la herida en los dias 3, 4 y 6 del periodo
postoperatorio. Se constató, al efectuar una revisión quirúrgica, una infección profunda de la herida. En los cultivos sólo
crecieron “estafilococus aureus”, que en un paciente eran resistentes a la meticilina (MRSA). Los aneurismas micóticos se
descubrieron una semana después de la reintervención cervical; uno de ellos, se detectó casualmente al efectuar una irrigación
programada de una cavidad incisional. Los otros dos, se diagnosticaron al producirse una grave hemorragia arterial que, en
un caso, originó la muerta del paciente por exanguinación. Los otros dos aneurismas fueron reparados utilizando autoinjertos
de la vena safena. Conclusiones: Tras reintervenciones cervicales, la infección de la herida por estafilococos, parece acelerar
la destrucción de la capa media arterial, provocando un aneurisma micótico. Es muy importante conocer y diagnosticar precozmente
esta nueva forma de aneurismas, para tratarlos de urgencia, anticipándonos así a su ruptura, que entraña gravísimas consecuencias.
World Journal of Surgery 04/2012; 25(9):1113-1116. · 2.36 Impact Factor
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Markus Luster,
Wolfram Karges,
Katrin Zeich,
Sandra Pauls,
Frederik A. Verburg, Henning Dralle,
Gerhard Glatting,
Andreas K. Buck,
Christoph Solbach,
Bernd Neumaier,
Sven N. Reske,
Felix M. Mottaghy
[show abstract]
[hide abstract]
ABSTRACT: PurposeIn detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor 18F-fluorodihydroxyphenylalanine (18F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions;
therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate
whether combined 18F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone.
Methods
18F-DOPA PET, CT and 18F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine
neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored
the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical
history and, when available, histology.
ResultsOf the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively
localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO
in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive
for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On
a per-patient basis, the sensitivity of 18F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive
value.
Conclusion
18F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do 18F-DOPA PET or CT alone.
KeywordsPheochromocytoma-Multiple endocrine neoplasia type 2 (MEN2)-
18F-fluorodihydroxyphenylalanine (18F-DOPA)-Positron emission tomography (PET)-Computed tomography (CT)-Staging
European journal of nuclear medicine and molecular imaging 04/2012; 37(3):484-493. · 4.99 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Few investigations have addressed malpractice litigation after thyroid surgery. The purpose of this medico-legal review was to provide a more comprehensive picture of medico-legal trends in thyroid surgery.
Reviewed were all expert opinions on claims of malpractice after thyroid surgery, commissioned between 1995 and 2010 at 1 tertiary center, and their corresponding verdicts.
Forty-three of 75 malpractice claims involved recurrent laryngeal nerve (RLN) palsy (21 unilateral and 22 bilateral palsies), with a 45% tracheostomy rate for bilateral RLN palsy. Twenty-one claims concerned permanent hypoparathyroidism. Since 2007, intraoperative nerve monitoring (IONM) has become the subject of pleading in 4 of 7 malpractice claims involving unilateral or bilateral RLN palsy. In none of these cases did IONM follow international standards, resulting in 3 plaintiff verdicts.
The growing appreciation that standardized IONM can prevent bilateral RLN palsies after signal loss on the initial side of resection may become increasingly relevant to malpractice litigation. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
Head & Neck 03/2012; 34(11):1591-6. · 2.40 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The clinical relevance of medullary thyroid microcarcinoma, a calcitonin-secreting malignancy, as a valid target for biochemical screening programs has been called into doubt.
This investigation aimed at clarifying the intensity of lymphatic spread and exploring the potential for biochemical cure in medullary thyroid microcarcinoma.
This was a retrospective analysis.
The setting was a tertiary referral center.
Included were 233 patients with hereditary (126 patients) or sporadic (107 patients) medullary thyroid microcarcinoma.
The intervention was compartment-oriented surgery.
Clinical-histopathological variables were stratified by primary tumor diameter (2-mm increments) and biochemical cure.
With incremental tumor diameter, increasingly more patients with medullary thyroid microcarcinoma harbored lymph node metastases: from 6 to 62% of patients (P < 0.001) for hereditary and from 13 to 43% of patients (P = 0.01) for sporadic disease. The corresponding biochemical cure rates declined from 96 to 71% (P = 0.001) and from 85 to 77% (P = 0.01). Distant disease (two instances of lung metastasis and one instance of bone and liver metastasis) was exceptional, affecting 1.3% of patients with medullary thyroid microcarcinoma. Strongest predictors of a patient's failure to achieve normal calcitonin serum levels were positive nodal status (79 vs. 11% in hereditary and 79 vs. 12% in sporadic disease; both P < 0.001) and the number of involved nodes (means of 6.6 vs. 0.3 nodes in hereditary and 8.8 vs. 0.4 nodes in sporadic disease; both P < 0.001).
Sporadic and hereditary medullary thyroid microcarcinoma carry a significant risk of lymph node metastasis and postoperative calcitonin elevation.
The Journal of clinical endocrinology and metabolism 03/2012; 97(5):1547-53. · 6.50 Impact Factor
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The Journal of clinical endocrinology and metabolism 03/2012; 97(3):721-2. · 6.50 Impact Factor
