Impact of autofluorescence for detection of parathyroid glands during thyroidectomy on postoperative parathyroid hormone levels: parallel multicentre randomized clinical trial.

BACKGROUND: Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. METHODS: This parallel multicentre RCT investigated the use of Fluobeam® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery. RESULTS: Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam® LX was reported. CONCLUSION: The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients. Registration number: NCT04509011 (http://www.clinicaltrials.gov).

A Case of simultaneous occurrence of Marine - Lenhart syndrome and a papillary thyroid microcarcinoma.

BACKGROUND: Marine-Lenhart syndrome is defined as the co-occurrence of Graves' disease and functional nodules. The vast majority of autonomous adenomas are benign, whereas functional thyroid carcinomas are considered to be rare. Here, we describe a case of simultaneous occurrence of Marine-Lenhart syndrome and a papillary microcarcinoma embedded in a functional nodule. CASE PRESENTATION: A 55 year-old, caucasian man presented with overt hyperthyroidism (thyrotropin (TSH) <0.01 µIU/L; free thyroxine (FT4) 3.03 ng/dL), negative thyroid peroxidase and thyroglobulin autoantibodies, but elevated thyroid stimulating hormone receptor antibodies (TSH-RAb 2.6 IU/L). Ultrasound showed a highly vascularized hypoechoic nodule (1.1 × 0.9 × 2 cm) in the right lobe, which projected onto a hot area detected in the 99mtechnetium thyroid nuclear scan. Overall uptake was increased (4.29%), while the left lobe showed lower tracer uptake with no visible background-activity, supporting the notion that both Graves' disease and a toxic adenoma were present. After normal thyroid function was reinstalled with methimazole, the patient underwent thyroidectomy. Histological work up revealed a unifocal papillary microcarcinoma (9 mm, pT1a, R0), positively tested for the BRAF V600E mutation, embedded into the hyperfunctional nodular goiter. CONCLUSIONS: Neither the finding of an autonomously functioning thyroid nodule nor the presence of Graves' disease rule out papillary thyroid carcinoma.

Preoperative calcitonin testing improves the diagnosis of medullary thyroid carcinoma in female and male patients.

AIM: Calcitonin (Ctn) measurement in patients with thyroid disease could potentially increase the detection rates of medullary thyroid carcinoma (MTC) but remains a controversial issue. The aim of this study was to evaluate routine preoperative Ctn measurements. METHODS: All patients with thyroid surgery documented in the prospective StuDoQ|Thyroid registry between March 2017 and September 2020 were included. Cutoff levels for Ctn were determined with receiver-operating characteristic analyses to assess the preoperative diagnosis of MTC in subgroups for females and males. FINDINGS: In 29 590 of 39 679 patients (75%) participating in the registry, routine preoperative Ctn testing was performed. In 357 patients (227 females and 130 males), histopathology confirmed MTC with a mean tumor size of 14.7 mm (±12.43). Biochemical cure was achieved in 71.4% of the patients. Ctn levels between 11 and 20 pg/mL were seen in 2.6% of the patients, and only 0.7% of the patients had Ctn levels above 21 pg/mL. Cutoff levels for the diagnosis of MTC were 7.9 pg/mL for females and 15 pg/mL for males (P < 0.001). The sensitivity and specificity for females were 95 and 98%, and 96 and 97% for males, respectively. CONCLUSION: Routine Ctn testing is a reliable predictor for MTC and provides the opportunity for earlier thyroidectomy before lymph node metastases occur, resulting in a better prognosis. Females with Ctn levels >7.9 pg/mL and males >15 pg/mL without any other extrathyroidal sources for an elevated Ctn should be monitored. Thyroid surgery should be considered if Ctn levels are increasing or ultrasound detects suspicious thyroid lesions.

The laryngeal twitch response - Can it avoid unnecessary two-stage thyroidectomy? - A retrospective cohort study.

BACKGROUND: The objective of this study was to determine if the laryngeal twitch response, when compared to neuromonitoring, can predict postoperative vocal cord function and can thus be used in case of technical failure of the EMG-recording electrode. METHODS: A total of 640 nerves at risk were included in this study based on a prospective protocol. The laryngeal twitch response and the EMG-records were compared with the results of the postoperative laryngoscopy. RESULTS: Of the 640 nerves at risk, 582 showed a normal postoperative vocal cord function. A recurrent laryngeal nerve paralysis (no vocal fold movement) was observed in 39 cases and recurrent laryngeal nerve paresis (reduced vocal cord movement) was diagnosed in 19 cases. The overall negative predictive value (NPV) in final vagus nerve stimulation (V2) was 95.0% for the EMG-records and 94.8% for the laryngeal twitch response. When pareses were excluded, the NPV was 96.8% and 96.6% respectively. The positive predictive value (PPV) of vagus nerve stimulation lies between 51.4% and 57.1% excluding the pareses. It rises to values between 60.0% and 65.1% if they are included. CONCLUSIONS: The laryngeal twitch response and the EMG-records show similar results, and the NPV is good in both. Thus, in case of technical failure or displacement of the EMG-recording electrode, the laryngeal twitch can be used in decision-making for or against a two-stage thyroidectomy.

Complete and incomplete recurrent laryngeal nerve injury after thyroid and parathyroid surgery: Characterizing paralysis and paresis.

BACKGROUND: Injury of the recurrent laryngeal nerve and consequent disorder of vocal fold movement is a typical complication in thyroid and parathyroid surgery. During postoperative laryngoscopy we observed not only a complete standstill (vocal fold paralysis), but also a hypomobility (paresis). In this prospective study, we investigated the difference in incidence and prognosis as well as risk-factors, intraoperative neuromonitoring, and symptoms between vocal fold paralysis and vocal fold paresis. METHODS: Data were prospectively collected and analyzed in a single high-volume thyroid center between 2012 and 2016. Vocal fold paresis was defined as hypomobility in abduction or adduction, a reduction in range and speed of vocal fold movement. Vocal fold paralysis was defined as asymmetry and missing purposeful vocal fold movement. RESULTS: The study included 4,707 surgeries and 7,992 at-risk nerves at risk. Vocal fold paralysis was diagnosed in 374 patients (4.68% of 7,992 nerves at risk) and vocal fold paresis in 114 patients (1.43%). Exclusively in the paralysis group, 36 patients (0.45%) developed permanent loss of vocal fold function (P < .001). In follow-up, vocal fold paresis patients regain normal vocal fold function significantly earlier than vocal fold paralysis (mean duration: 6.96 ± 6.506 vs 10.77 ± 7,827 weeks) and presented with significantly less symptoms like hoarseness, diplophonia, dysphagia, and dyspnea (68.8% vs 95.9 %). In intraoperative neuromonitoring, vocal fold paresis showed a significantly higher postresectional N. vagus amplitude than vocal fold paralysis patients (0.349 mV vs 0.114 mV, P < .001). CONCLUSION: After thyroidectomy, vocal fold paresis must be distinguished from vocal fold paralysis and should be implemented as a separate outcome parameter in the postoperative quality assessment.

Parathyroidectomy improves concentration and retentiveness in patients with primary hyperparathyroidism.

BACKGROUND: Many patients with primary hyperparathyroidism (PHPT) show symptoms of hypercalcemia syndrome, including psychologic and psychiatric disorders. The aim of this study was to find out whether parathyroidectomy improves cognitive performance with regard to concentration and retentiveness in patients with PHPT. METHODS: . Twenty patients with PHPT underwent psychologic testing preoperatively as well as 6 and 12 weeks postoperatively. Concentration under stress (timing) was proved by the d2-Test of Attention. To evaluate retentiveness, parts of the Wilde Intelligence Test were used. Patients were tested under identical circumstances with regard to time, location, and tester to minimize exterior influences. RESULTS: The patients' concentration enhanced significantly postoperatively (P <.001). The same applied to the total number of items processed (P <.01). Improvement of patients' ability to memorize numbers reached statistical significance when comparing the preoperative with the postoperative result (P =.0396); furthermore, there was a tendency to perform the tests more carefully and accurately (P =.069). CONCLUSIONS: Parathyroidectomy not only betters physical symptoms of PHPT but can also positively influence the patients' cognitive performance. These findings reflect the clinical observation of the patients' improved mental capacity after parathyroidectomy.

Follicular variant of papillary thyroid carcinoma: a long-term follow-up.

HYPOTHESIS: The clinical behavior of the follicular variant of papillary thyroid carcinoma (FVPTC) is similar to pure papillary thyroid carcinoma (PPTC) and completely different from follicular thyroid carcinoma (FTC). DESIGN: Retrospective analysis of prospectively documented data. SETTING: Referral center of a university hospital. PATIENTS: Two hundred thirty-seven consecutive patients with follicular cell-derived thyroid carcinomas were operated on in our institution during a 15-year period, from January 1, 1980, to December 31, 1994. Of the 154 PTC patients, 37 (24%) had FVPTC. The mean follow-up was 128.2 months (10.7 years). MAIN OUTCOME MEASURES: Demographic features, tumor characteristics, local and distant spread, persistence or recurrence of disease, and carcinoma-related mortality were compared between the groups with FVPTC, PPTC, and non-Hürthle cell FTC (NHFTC). RESULTS: The frequency of multicentricity was significantly higher in the FVPTC group than in the PPTC group (P =.03) or in the NHFTC group (P =.01) (12 [32%] of 37 patients vs 17 [15%] of 117 patients vs 6 [10%] of 58 patients, respectively). The incidence of cervical lymph node metastases was lower in the FVPTC group than in the PPTC group (P =.30) and higher than in NHFTC group (P =.004) (12 [32%] of 37 patients vs 53 [45%] of 117 patients vs 6 [10%] of 58 patients, respectively). At diagnosis, no patient with FVPTC showed distant metastases, compared with 5 patients (4%) with PPTC (P =.34) and 19 (33%) with NHFTC (P<.001). There was no carcinoma-related death in the FVPTC group. The strikingly poorer prognosis for the NHFTC group was statistically significant (P<.001), whereas the difference in carcinoma-specific survival between the PPTC and the FVPTC groups did show a trend toward better survival in the FVPTC group. CONCLUSION: The clinical behavior of the FVPTC group did not differ significantly from that of the PPTC group, whereas compared with the NHFTC group, the FVPTC group showed statistically significant differences for most of the analyzed variables.

Applicability of laparoscopic adrenalectomy in a prospective study in 150 consecutive patients.

HYPOTHESIS: Within a decade, laparascopic adrenalectomy has become the new "gold standard" for the surgical treatment of most adrenal lesions. Designed as a single-center project focused on patients with adrenal lesions, this study should provide an indication of the number of patients requiring surgery who can safely undergo laparoscopy, after consideration of such selection criteria as tumor size and benign or malignant lesion status at magnetic resonance imaging. Furthermore, the access-related complications were analyzed. DESIGN: According to a prospective protocol, 150 consecutive patients selected for adrenal surgery were assigned to transperitoneal endoscopic or open adrenalectomy. SETTING: University hospital section of endocrine surgery. RESULTS: One hundred two patients (68%) were selected for a laparoscopic approach that had to be converted to open surgery in 5 patients (5%). Two malignant cortisol-secreting lesions were operated on laparoscopically because of their small size and benign appearance at magnetic resonance imaging. During histological examination, 14 (29%) of 48 patients assigned to transperitoneal open adrenalectomy had lesions deemed malignant (16 [11%] of 150 patients). The laparoscopic group had significantly fewer complications (9%) than did the open group (21%; P =.04). CONCLUSIONS: By applying defined selection criteria for the treatment of adrenal lesions, transperitoneal endoscopic adrenalectomy can be a safe procedure and may be performed in at least two thirds of patients. The choice of endoscopic or open approach in larger tumors should depend on the results of preoperative imaging studies and the endocrine surgeon's experience in endoscopic adrenal surgery.

Thyroid surgery in the geriatric patient.

BACKGROUND: Although age itself is no contraindication for major surgical procedures, few patients 75 years and older undergo thyroid surgery. HYPOTHESIS: Thyroid surgery in the geriatric patient can be performed with low morbidity and mortality. DESIGN: Retrospective analysis of prospectively documented data. SETTING: University hospital referral center. PATIENTS: We included 738 patients undergoing thyroid surgery within 5 years, of whom 55 (7.5%) were 75 years or older (group 1) (mean +/- SD age, 79.9 +/- 4.1 years). MAIN OUTCOME MEASURES: Indication for surgery, surgical strategy, morbidity, and mortality were analyzed and compared with those in younger patients (<75 years; group 2). RESULTS: Malignancy was suspected or verified in 29 patients (52.7%) in group 1; 21 (38.2%) had mechanical symptoms due to large bilateral nodular goiters; and 5 (9.1%) presented with benign nodular goiter. The main indication in group 2 (n = 683) was benign nodular goiter in 455 (66.6%); 142 patients (20.8%) presented with suspected malignancy and 21 (3.1%) with mechanical symptoms (P<.001). Most patients underwent total thyroidectomy, hemithyroidectomy, or near-total thyroidectomy (n = 50 [90.9%; group 1] vs n = 597 [87.4%; group 2]; P =.53). Frequency of malignancy was higher in group 1 ([n = 20 [36.4%] vs n = 179 [26.2%]; P =.17). Morbidity of thyroid surgery was comparable in both groups. One (2.3%) of 44 patients in group 1 had permanent hypoparathyroidism, compared with 10 (2.0%) of 502 in group 2 (P =.61); permanent recurrent laryngeal nerve paralysis occurred in 1 (1.05%) of 95 nerves at risk in group 1 compared with 3 (0.26%) of 1172 nerves at risk in group 2 (P =.22). There was no perioperative mortality in either group. CONCLUSIONS: Thyroid surgery in patients 75 years or older can be performed with low morbidity. The guarantees for success include an individual risk-and-benefit analysis and careful preoperative preparation.

Impact of localization studies on feasibility of minimally invasive parathyroidectomy in an endemic goiter region.

BACKGROUND: A localized single-gland disease is the basis for minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (PHPT). (99m)Tc sestamibi scanning (MIBI) and high-resolution Doppler ultrasonography (US) are well-established techniques used to localize enlarged parathyroid glands. Additionally, US enables physicians to diagnose subclinical thyroid abnormalities. The aim of this study was to optimize localization results, applying a combined interpretation of MIBI and US, and to analyze the influence of these results on the feasibility of MIP (endoscopic/video-assisted and open) in an endemic goiter region. STUDY DESIGN: One hundred fifty consecutive patients with sporadic PHPT were prospectively subjected to MIBI and US to localize parathyroid lesions and to review the morphology of the thyroid gland. Bilateral cervical exploration was performed in all patients. The feasibility of MIP was calculated retrospectively on the basis of surgical findings and biochemical outcomes at least 12 months postoperatively (normocalcemia in 148 of 150 patients [99%]). RESULTS: Forty-five percent of patients (67 of 148) would have been suitable for minimally invasive endoscopic or video-assisted parathyroid exploration. These procedures would have succeeded in 38% of patients (56 of 148). Sixty-four percent (94 of 148) would have been suitable for minimally invasive open parathyroidectomy, which would have succeeded in 55% (82 of 148 patients). CONCLUSIONS: Not all patients are suitable for MIP. A combined interpretation of MIBI and US results is helpful in planning targeted exploration. In an endemic goiter region minimally invasive open parathyroidectomy is applicable in significantly more patients than is endoscopic and video-assisted MIP.

Advantages of recurrent laryngeal nerve identification in thyroidectomy and parathyroidectomy and the importance of preoperative and postoperative laryngoscopic examination in more than 1000 nerves at risk.

OBJECTIVES/HYPOTHESIS: Recurrent laryngeal nerve palsy (RLNP) is a major obstacle in thyroid and parathyroid surgery. Therefore, methods that reduce the number of temporary and, especially, permanent recurrent laryngeal nerve palsies are of great interest. One promising way to ensure the integrity of the recurrent laryngeal nerve (RLN) is to identify the nerve always. The first question raised in the present study was whether RLN preparation reduces the number of recurrent laryngeal nerve palsies or whether it introduces additional risks. Second, from former cases we know that the absence of postoperative hoarseness does not exclude RLNP, nor does postoperative hoarseness exclusively imply RLNP. Besides, misdiagnosis is not uncommon. Therefore, preoperative and postoperative laryngoscopic examination was given attention. STUDY DESIGN: Patients were investigated 1 to 7 days before and 3 to 7 days after surgery. When an RLNP was identified, patients were followed up in a 2-week rhythm the first few times and every 6 to 8 weeks thereafter until RLNP resolved or it was considered permanent after 2 years. METHODS: We prospectively investigated 608 surgical patients with 1080 nerves at risk. Because different diseases might have different rates of postoperative RLNP, we analyzed benign thyroid disease (680 nerves at risk), thyroid malignoma (321 nerves at risk), and hyperparathyroidism (79 nerves at risk) separately. Patients undergoing primary surgery (no prior thyroid surgery) and secondary interventions (there were one or more thyroid operations before this intervention) were evaluated separately. RESULTS: We found 3.4%, 7.2%, and 2.5% of temporary recurrent laryngeal nerve palsies per nerve in the benign thyroid disease, thyroid malignoma, and hyperparathyroidism groups, respectively. The prevalence of recurrent laryngeal nerve palsies in these groups was 0.3%, 1.2%, and 0%, respectively. Conforming with other studies, the total number of recurrent laryngeal nerve palsies (temporary and permanent) was not increased compared with cases with no RLN preparation, whereas the number of permanent recurrent laryngeal nerve palsies was markedly reduced. An RLN was always identifiable. Astonishingly, the restitution of an RLNP was up to 2 years in duration; however, most restitutions occurred within the first 6 months. Thirty cases of hoarseness appeared or were intensified after surgery and were not caused by RLNP. Eleven cases of postoperative RLNP had no detectable hoarseness. CONCLUSIONS: Besides indirect laryngoscopy, videostroboscopy should be performed in all cases with no evident bilateral normal laryngeal function or normal voice. Otherwise, the incidence of false-positive or false-negative diagnosis of RLNP is likely to be increased.

Surgical strategy in adrenal masses.

OBJECTIVE: Endoscopic adrenalectomy represents the "New Golden Standard" in the surgical treatment of benign adrenal lesions up to 6 cm. Open adrenalectomy is recommended for patients with suspected malignant disease and tumors larger than 6 cm. METHODS AND MATERIAL: The surgical technique of trans- and retroperitoneal adrenalectomy is described. Reviewing literature the importance of the endoscopic approach and its role in the surgical treatment of adrenal lesions is analyzed. RESULTS: As in open adrenalectomy different endoscopic approaches to the adrenals were developed: adrenal tumors can be removed endoscopically using a transperitoneal (patient in a supine or lateral decubitus position) or extraperitoneal route (patient in a lateral decubitus or prone position). Reviewing literature the endoscopic transperitoneal adrenalectomy is documented in 1425 patients. 4.6% (66 patients) had to be converted to an open procedure. Five hundred and forty-four tumors were removed by an extraperitoneal access. The conversion rate was 4.4% (24 patients). CONCLUSION: The basis of excellent results are careful patient selection, evaluation and preoperative preparation in a center with experience in the open techniques and at least 20 endoscopic adrenalectomies per year.

[Minimally invasive endocrine surgery: aspects of diagnostic imaging]. / Minimal-invasive Chirurgische Endokrinologie: Aspekte der Radiodiagnostik.

Since 1997 minimally invasive surgical techniques are used for the treatment of diseases of the adrenals, thyroid, parathyroid and the endocrine pancreas. In contrast to open surgical procedures special radiological examinations are the basis for minimally invasive techniques after biochemical testing. The basis of excellent results are a careful evaluation and preparation of the patient in a centre with experience in the open techniques and a frequency of at least 20 endoscopic adrenalectomies a year. Adrenal tumours can be removed endoscopically through a transperitoneal or an extraperitoneal route. The endoscopic exploration of the parathyroids in patients with biochemically proven primary hyperparathyroidism was modified to video-assisted exploration because of the long operating times. An alternative to the video-assisted procedure is the minimally invasive open exploration. With this technique reoperations can be performed and ipsilateral thyroid nodules (found in more than 50% in middle Europe) can be removed. Small solitary thyroid nodules are the indication for an endoscopic or video-assisted exploration of the thyroid. A laparoscopic exploration of the pancreas was performed in 68 patients with neuroendocrine pancreatic tumours. The experience of the surgical team improves the postoperative long term results, thus minimally invasive endocrine surgery should be performed in centres with great experience in the treatment of endocrine tumours and with the possibility of close contact to other specialists interested in this topic.

Hypoparathyroidism after total thyroidectomy: a prospective study.

HYPOTHESIS: Combined measurement of intact parathyroid hormone (iPTH) and serum calcium (sCa) levels is useful for predicting postoperative hypocalcemia with minimal laboratory effort and low costs. DESIGN: Prospective analysis of 170 consecutive patients. SETTING: University hospital referral center. PATIENTS: One hundred seventy patients underwent total thyroidectomy. Defining hypoparathyroidism as albumin-adjusted sCa levels of less than 1.9 mmol/L with or without clinical symptoms or subnormal sCa levels (1.9-2.1 mmol/L) with neuromuscular symptoms, the influences of central lymph node dissection, experience of the surgeon, and parathyroid autotransplantation were observed. We measured the sCa and iPTH levels separately and in combination and the postoperative sCa slope to predict patients who were at risk of hypoparathyroidism. MAIN OUTCOME MEASURES: Predictive values for iPTH and sCa levels were compared to identify postoperative hypoparathyroidism. RESULTS: Of the 170 study patients, 41 developed transient hypoparathyroidism and 2 developed permanent hypoparathyroidism. The morphologic features and function of the thyroid gland, central neck dissection, experience of the surgeon, and parathyroid autotransplantation did not influence development of postoperative hypoparathyroidism. The best sensitivity for predicting postoperative hypoparathyroidism was 97.7% for measurement of iPTH levels, and the best specificity was 96.1% for measurement of sCa levels. Negative and positive predictive values reached their best (99.0% and 86.0%, respectively) when we combined sCa and iPTH values. CONCLUSIONS: Patients with iPTH levels of 15 pg/mL or less and sCa levels of 1.9 mmol/L or less are at increased risk of developing postoperative hypoparathyroidism. Measuring iPTH levels 24 hours after total thyroidectomy in combination with sCa levels on the second postoperative day allows the prediction of hypoparathyroidism with a high sensitivity, specificity, and positive predictive value.

Application of staging systems for differentiated thyroid carcinoma in an endemic goiter region with iodine substitution.

OBJECTIVE: To evaluate and compare staging systems for differentiated thyroid carcinoma and predicted outcome in an endemic goiter region with iodine substitution and to examine the risk profile of differentiated thyroid carcinoma and compare it against nongoiter regions. SUMMARY BACKGROUND DATA: Differentiated (papillary or follicular) thyroid carcinoma has a favorable prognostic outcome. In numerous studies prognostic factors have been identified and staging systems created, particularly in Anglo-American centers (nonendemic goiter regions), to evaluate individual prognostic outcome. METHODS: In a retrospective study, the authors assessed 440 patients with differentiated thyroid carcinoma (papillary, n = 293; follicular, n = 147) and a long-term follow-up of median 10.6 years to determine the predictive accuracy of nine staging systems applicable to the study population; the systems were compared by calculating the proportion of variation explained. RESULTS: With regard to cause-specific mortality, the difference between the respective stages and/or risk groups was highly significant for every staging system. By means of calculating the proportion of variation explained, MACIS scoring supplied the most reliable prognostic information for differentiated thyroid carcinoma (relative importance 16.93%). EORTC and UICC/AJCC systems had a relative importance of 16.34% and 13.96%, respectively, also a high level of accuracy; this implies that they are superior to the other six staging systems. If we separate papillary and follicular carcinoma, for the former the MACIS score with a relative importance of 15.05% is clearly superior to the other staging systems, whereas for the latter the EORTC score and the UICC/AJCC staging system, with relative importance of 17.04% and 16.58%, respectively, yield the best prognostic information. CONCLUSIONS: By applying staging systems in an endemic goiter region with iodine substitution, the best prognostic information for papillary thyroid carcinoma has been achieved with the MACIS score, while for follicular thyroid carcinoma the EORTC score and the UICC/AJCC system have the best prognostic accuracy. Because of the individual factors, which are easy to obtain and generally available (age, T, N, M classification), the uncomplicated handling, and the widespread use and the good predictive accuracy, the UICC/AJCC classification is the staging system of choice for comparing published results.

How to pass on expertise: pancreatoduodenectomy at a teaching hospital.

Pancreatoduodenectomy (PD) has become a routine procedure. Recent series report perioperative mortality rates of 5% or less, moderate morbidity, and even improved long-term survival. Nevertheless, being one of the most complex abdominal operations, a certain number of surgical procedures (i.e., personal caseload) seems essential for acceptable results. The objectives of this retrospective study were to evaluate whether PD can be safely performed as a teaching operation, and if the personal caseload of the senior surgeon affects morbidity and mortality. A series of 128 consecutive PDs carried out at a large academic teaching hospital were analyzed. The 49 operations performed by 11 residents of the surgical department as teaching operations under supervision of an experienced (senior) surgeon (ES) were compared with operations performed by an ES (group 2, n = 79). Three patients died from non-procedure-related causes (two in group 1). Eleven patients of group 2 had to be reoperated, in contrast to three in group 1 (NS). The total number of complications and number of pancreatic fistulas were comparable in the two groups. Surgeons performing less than one PD per year had significantly more complications. Under direct supervision of an experienced surgeon PD can be performed safely as a teaching operation. A caseload of at least one resection per year seems necessary for consistently good results.

Long-term follow-up of patients with bone metastases from differentiated thyroid carcinoma -- surgery or conventional therapy?

OBJECTIVE: Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This study was performed (1) to analyse retrospectively patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bone metastases on survival. PATIENTS AND DESIGN: We analysed 41 consecutive patients with bone metastases from differentiated thyroid carcinoma who had undergone thyroid surgery at Vienna University Hospital since 1966. The median follow-up time was 12 years. There were 24 females and 17 males with a mean age of 60 +/- 12 years. Primary tumour histology was follicular in 35 and papillary in six patients. Radioiodine treatment was performed in 32 with a mean administered activity of 27 +/- 24 GBq 131I. Metastases restricted to the skeleton were found in 22 whereas in 19 individuals additional extraskeletal distant metastases were seen. Twenty-seven patients had multiple bone metastases. In 21 individuals, up to five bone metastases were surgically removed with the intention of cure. RESULTS: Univariate analysis identified total thyroidectomy (P = 0.003), lymph node surgery (P = 0.001), radioiodine therapy (P = 0.036), and the absence of extraskeletal distant metastases (P = 0.017) as significant predictors of survival. Multivariate analysis failed to identify significant prognostic factors. In the subgroup of patients with distant metastases limited to the bones, univariate analysis identified, in addition to thyroid and lymph node surgery, the surgical extirpation of the bone metastases as a significant prognostic factor associated with improved survival (P = 0.025). CONCLUSIONS: These findings indicate that in patients without additional extraskeletal distant metastases, the radical surgical extirpation of bone metastases from differentiated thyroid carcinoma might be associated with improved survival.

Construction of cDNA libraries from microdissected benign and malignant thyroid tissue.

cDNA libraries were constructed from thyroid epithelial cells gained by laser capture microdissection for gene expression analysis of the progression of thyroid cancer. Six histologically diverse thyroid tissue specimens were used. A mean of 93 ng of total RNA was gained per tissue sample from a mean estimated number of 25,000 microdissected cells per sample. Analysis of randomly selected clones from six libraries showed an average insert size of 600 (range, 300-1500) bp. Preliminary sequencing of clones selected from the six libraries indicates a range of 46% to 62% known genes per library, 4% to 25% anonymous expressed sequence tags per library, and 15% to 43% novel expressed sequence tags per library. Thyroglobulin was found in normal thyroid epithelium and follicular thyroid adenoma, whereas calcitonin precursor transcripts were found in medullary thyroid carcinoma. We demonstrate production of high-quality cDNA libraries of microdissected tissue of the thyroid, which should prove useful for gene expression analysis of human thyroid tumors.

Can dynamic gadolinium-enhanced magnetic resonance imaging with chemical shift studies predict the status of adrenal masses?

Endoscopic adrenalectomy represents the new gold standard in the surgical treatment of benign adrenal lesions up to 6 cm. In some cases lesions larger than 10 cm have been removed laparoscopically to offer the patient the advantages of the minimally invasive technique. The larger the diameter of an adrenal lesion, the greater the probability of malignancy. In a prospective study 130 consecutive patients (88 women, 42 men; mean age 47.8 years) with 137 adrenal lesions earmarked for surgery underwent preoperative gadolinium-enhanced magnetic resonance imaging (MRI) with chemical shift studies (CSS). The aim of this study was to predict the status (benign, borderline, malignant) of adrenal lesions by MRI irrespective of tumor size. There were 14 patients with malignant tumors, 3 had borderline tumors (epithelial tumors with high malignant potential), and the remaining 120 had benign adrenal lesions. Five malignant lesions (36%) had a diameter < 6 cm. MRI correctly predicted 11 of 14 malignant tumors (1 malignant pheochromocytoma and 2 adrenocortical carcinomas had false-negative results), 117 of 120 benign lesions, and 2 of 3 borderline lesions. All but two malignant tumors were operated on using open surgery; 82 (68%) of 120 benign adrenal lesions were treated using the transperitoneal laparoscopic approach. Tumor size alone is not suitable for predicting the status of adrenal lesions. Dynamic gadolinium-enhanced MRI with CSS can predict the status of at least 95% of adrenal lesions. Tumors> 6 cm classified as benign by preoperative MRI may be removed laparoscopically by endocrine surgeons experienced in endoscopic adrenalectomy.

Treatment of small intestinal neuroendocrine tumors: is an extended multimodal approach justified?

Neuroendocrine tumors (NETs) of the small bowel are known for their low malignant behavior. Although most cases are diagnosed in an advanced stage, natural life expectancy is significantly higher than with intestinal carcinomas. The question arises if there are any benefits to combining extended (radical or debulking) surgery, interventional treatment, and medical treatment with respect to life expectancy, and quality of life. A series of 58 patients (34 men, 24 women; mean age 61 +/- 12 years, range 37-87 years) with NETs of the small bowel were retrospectively reviewed and prospectively followed over 63 +/- 53 months. Clinical presentation, tumor characteristics, and postoperative medical treatment were documented. Quality of life was additionally analyzed using a questionnaire. Survival probability and quality of life were compared for tumor stages and type of treatment performed. In 47 of 58 (81%) patients the NET was diagnosed based on the presence of intestinal stenosis or endocrine symptoms. Of 16 patients without liver metastases, 15 (94%) were cured by radical surgery. Multiple liver metastases were evident in 40 of 58 (69%) patients and decreased the 5- and 10-year cumulative survival to 64% +/- 10% and 22% +/- 10% (M0 vs. M1: p <0.05). The 5- and 10-year survival rates after multimodal treatment (surgery, bio/immunotherapy, transarterial embolization of liver metastases) were 64% +/- 11% and 28% +/- 12% compared to 61% +/- 15% and 0% in patients without (p = NS). In patients with small intestinal NETs, a consistent multimodal treatment helps to improve the overall survival and, in most patients, the quality of life.