Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

The advantages and disadvantages of nerve monitoring during thyroid surgery in childhood.

BACKGROUND: Intraoperative damage of the recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (EBSLN) are common and cause complications in thyroid surgery. The method of intraoperative electrophysiological neuromonitoring (IONM) of the RLN and the EBSLN has been used in adults for several years. The question is whether IONM can be used in paediatric surgery for the identification and functional control of the RLN and the EBSLN, and what the advantages and disadvantages of using it are. METHODS: Surgical treatment of benign (n = 9) and malign (n = 2) thyroid diseases was carried out in eleven children (median age: 13 years) with a total of 18 nerves at risk (NAR). The function of the vocal cord was monitored in all children before and after surgery. Intraoperative identification and functional control of RLN and EBSLN was performed using the Neurosign 100. All results before and after resection of the thyroid gland were documented. RESULTS: A clear and reliable identification of the RLN and the EBSLN was possible in all cases. All NAR showed a constant physiological nerve signal before and after surgical resection of the thyroid gland. However, in one young patient the postoperative examination of the vocal cord revealed a partial paralysis on the left side after thyroidectomy, despite the constant intraoperative signal of the RLN. After a period of six months, normal functioning had resumed. CONCLUSION: The IONM of both RLN and EBSLN in adult surgery could be used successfully in paediatric surgery. In this study a clear and positive identification of both nerves was possible in all patients. Therefore the IONM of the RLN and EBSLN could develop into a successful and easy method for the prevention of intraoperative nerve damage during thyroid surgery in childhood and young adolescence. Assuming that a constant IONM signal represents a normal vocal cord, our evaluation showed that there is a small percentage of false negative and positive results.

[New concepts in treatment of gastric carcinoma]. / Neue Konzepte in der Behandlung des Magenkarzinoms.

Despite interdisciplinary approach to gastric cancer the outcome of patients remains poor. Even after curative resection most patients suffer from progression of disease and metastasizing course. Adjuvant treatment like chemotherapy or radiation can not improve survival substantialy. This is discussed to be due to dissemination of tumor cells, which are not affected by most treatment options. The new concept of tumor specific antibody therapy with a monoclonal antibody is discussed as an effective treatment especially to fight disseminated tumor cells and thus might help to improve the outcome in stomach cancer.

[Gastrointestinal stromal tumor of the abdominal wall. An unusual localization of a rare tumor]. / Gastrointestinaler Stromatumor der Bauchwand. Ungewöhnliche Lokalisation eines seltenen Tumors.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. We describe here for the first time a patient with a huge GIST of the abdominal wall without any relation to the gastrointestinal tract, omentum, or mesentery. With regard to the size of 24 cm and a low mitotic index, this GIST is considered an intermediate risk for metastasis. Radical surgical resection was performed with negative pathologic resection margins. The classic immunohistochemical phenotype of the tumor described facilitates the differential diagnosis to exclude abdominal desmoid tumor and solitary fibrous tumor (SFT). In the case of metastasis, therapeutic nihilism no longer seems justified with the availability of imatinib, a tyrosine kinase inhibitor, which shows encouraging results in the therapy of metastatic GIST.

[Not all vocal cord failure following thyroid surgery is recurrent paresis due to damage during operation. Statement of the German Interdisciplinary Study Group on Intraoperative Neuromonitoring of Thyroid Surgery concerning recurring paresis due to intubation]. / Nicht jeder Stimmlippenstillstand nach Schilddrüsenoperation ist eine chirurgischbedingte Rekurrensparese. Stellungnahme der "Interdisziplinären Studiengruppe Intraoperatives Neuromonitoring Schilddrüsenchirurgie" zur Problematik intubationsbedingter Rekurrensparesen.

Since the phoniatrician H. Bauer described the first case of recurrent laryngeal nerve palsy most likely caused by intubation some 45 years ago, several case reports have been published. However, systematic analyses regarding the frequency of recurrent laryngeal nerve palsies due to intubation are scarce, and none of them has used the proper methods to demonstrate clearly that such a mechanism exists. Currently available data justify the assumption that not every recurrent laryngeal nerve palsy following thyroid surgery is due to the operation itself and that the damage caused by intubation, however, may only account for a minority of these cases. The differential diagnosis of postoperative recurrent laryngeal nerve palsy requires the use of specific tools which go beyond simple laryngoscopy and include stroboscopy as well as intra- and extralaryngeal electromyography. A partial palsy of recurrent laryngeal nerve due to intubation would be associated with severe dysphonia or aphonia, not with dyspnea because of the typical intermediate position of the paralyzed vocal folds with a normal electromyographic function of the cricothyroid muscle. The use of these methods to identify the nature of postoperative recurrent laryngeal nerve palsy is recommended in cases of regular intraoperative neuromonitoring but postoperatively impaired function of the vocal cords.

[Effectiveness and results of intraoperative neuromonitoring in thyroid surgery. Statement of the Interdisciplinary Study Group on Intraoperative Neuromonitoring of Thyroid Surgery]. / Zuverlässigkeit und Konsequenzen des intraoperativen Neuromonitorings in der Schilddrüsenchirurgie. Stellungnahme der "Interdisziplinären Studiengruppe Intraoperatives Neuromonitoring Schilddrüsenchirurgie"

Intraoperative neuromonitoring (IONM) has yielded an increasing effect on thyroid surgery. During IONM, the recurrent laryngeal nerve is stimulated electrically and an acoustically transformed electromyographic signal is derived via either a needle electrode placed in the vocalis muscle or an electrode adjusted to the intubation tube. The IONM is used for identifying and predicting the function of the recurrent laryngeal nerve. Especially under difficult anatomic conditions, IONM has proven a valuable tool for identification of recurrent laryngeal nerves. This can lead to decreased occurrence of nerve palsy rates, as shown in numerous studies. The reliability of the IONM signal (defined as the correlation between intraoperative signal interpretation and postoperative vocal cord function) is reflected by a specificity as high as 98.2%, as shown by German multicenter studies. Thus, normal vocal cord function could be demonstrated postoperatively in over 98.2% of patients with intraoperatively unchanged neuromonitoring signals. If the neuromonitoring signal changed during operation, 39% of the patients suffered from transient vocal cord immobility and 12% had permanent loss of vocal cord function.

Immunogenicity of parathyroid allografts in the rat: immunosuppressive dosages effective in passenger leukocyte-rich small bowel transplants are not effective in parathyroid gland transplants with few passenger leukocytes.

BACKGROUND AND AIMS: The passenger leukocytes harboured within an allograft induce a massive allo-immune response that leads to allograft rejection if not countered by immunosuppression. We compared the response to short-term immunosuppression of parathyroid gland transplants possessing few passenger leukocytes with that of passenger leukocyte-rich small bowel transplants. METHODS: Heterotopic parathyroid and orthotopic small bowel transplantation was performed in a Wistar Furth-to-Lewis rat strain combination. Immunosuppression with cyclosporine A (CsA) was administered in different dosages for 14 days. Dysfunctional allografts were examined immunohistologically. RESULTS: CsA more effectively suppressed the immune response provoked by immunogenic small bowel grafts than that induced by less-immunogenic parathyroid grafts. Immunosuppression with 20 mg/kg per day induced long-term survival in the small bowel (165+/-21 days) but not in the parathyroid (28+/-3 days). All rejected grafts featured massive cellular infiltration by activated T cells as a sign of immune rejection. CONCLUSION: Immunosuppressive dosages effective in passenger leukocyte-rich small bowel transplants were not as effective in parathyroid gland transplants harbouring few passenger leukocytes. In spite of the paucity of passenger leukocytes in parathyroid grafts it is more difficult to control by immunosuppression the immune response to them than that to the passenger leukocyte-rich small bowel.

[Solid-pseudopapillary tumor of the pancreas as differential diagnosis in pancreatic tumors of the young]. / Der solid-pseudopapilläre Tumor des Pankreas als Differenzialdiagnose bei Pankreasraumforderungen junger Patienten.

AIM: The presentation of solid pseudopapillary tumors of the pancreas (SPTP) with examples of our own surgical department. SPTP occur typically in young women or in children and are for most of benign behavior. In about 5 % a malignant course with occurrence of metastases can develop. METHODS: Diagnosis, morphological and histological findings and therapeutic approach are described in three cases. The differential diagnosis of other tumors of the pancreas is discussed. FINDINGS: Three women (age 21, 33 and 43) with SPTP have been treated in the Department of Surgery at the University of Würzburg between 1997-1999. All tumors were resected curatively. No adjuvant treatment was performed. The follow up ranged from 31-56 months. No relapse of disease or occurrence of metastases were observed. All resected specimen revealed the typical character of SPTP with areas of solid parts and hemorrhage within the tumor. A panel of immunohistological markers (Vimentin, N-Cam, NSE, Chromogranin, Synaptophysin, Ck7, Ck19, Ck20, EMA) and expression of receptors were investigated. CONCLUSION: The diagnosis of this rare tumor can be made clinically and intraoperatively according to its typical morphology and occurrence, predominantly in young women or in children thus helping to perform adequate surgical therapy.

Presentation of an unusual benign liver tumor: primary hepatic glomangioma.

Glomus organs are small arteriovenous anastomoses chiefly responsible for thermoregulation of the distal portion of the extremities. Glomangiomas are benign tumors of these bodies. They occur preferentially in the fingers and toes, but some case reports describe primary glomangiomas in the respiratory or gastrointestinal tract and genitals. To date, no glomangiomas of the liver have been reported. We report on a 61-year-old patient in whom routine ultrasound disclosed a subcapsular well-defined mass in the liver. Further imaging showed that the mass did not correspond to any of the usual liver tumors. Biopsy finally revealed it to be a primary glomangioma of the liver. Clinically, there was lack of appetite and weight loss over a period of several months. Owing to the possibility of malignant transformation of glomangiomas, as described in the literature, the tumor was excised under existing clinical symptoms and continued slow growth. Further histological evaluation of the tumor did not reveal malignancy. Primary glomangioma of the liver is a new differential diagnosis for benign liver neoplasms. Because there is a potential for malignant transformation, the existence of clinical symptoms and continuing growth are indications for resection.

[Does intraoperative nerve monitoring reduce the rate of recurrent nerve palsies during thyroid surgery?]. / Reduziert das intraoperative Neuromonitoring die Recurrenspareserate bei Schilddrüsenoperationen?

Two different aspects of the influence of neuromonitoring on the possible reduction of post-operative recurrent laryngeal nerve palsies require critical examination: the nerve identification and the monitoring of it's functions. Due to the additional information from the EMG signals, neuromonitoring is the best method for identifying the nerves as compared to visual identification alone. There are still no randomized studies available that compare the visual and electrophysiological recurrent laryngeal nerve detection in thyroid operations with respect to the postoperative nerve palsies. Nevertheless, comparisons with historical collectives show that a constant low nerve-palsy-rate was achieved with electrophysiological detection in comparison to visual detection. The rate of nerve identification is normally very high and amounts to 99 % in our own patients. The data obtained during the "Quality assurance of benign and malignant Goiter" study show that in hemithyreoidectomy and subtotal resection, lower nerve-palsy-rates are achieved with neuromonitoring as compared to solely visual detection. Following subtotal resection, this discrepancy becomes even statistically significant. While monitoring the nerve functions with the presently used neuromonitoring technique, it is possible to observe the EMG-signal remaining constant or decreasing in volume. Assuming that a constant neuromonitoring signal represents a normal vocal cord, our evaluation shows that there is a small percentage of false negative and positive results. Looking at the permanent recurrent nerve palsy rates, this method has a specificity of 98 %, a sensitivity of 100 %, a positive prognostic value of 10 %, and a negative prognostic value of 100 %. Although an altered neuromonitoring signal can be taken as a clear indication of eventual nerve damage, an absolutely reliable statement about the postoperative vocal cord function is presently not possible with intraoperative neuromonitoring.

[A Critical Estimation of Intraoperative Neuromonitoring (IONM) in Thyroid Surgery]. / Kritische Beurteilung und Fehlermöglichkeiten des intraoperativen Neuromonitoring (IONM) bei Operationen an der Schilddrüse.

We investigated 238 patients with 431 nerves at risk (NAR) undergoing thyroid surgery. Positive identification of the recurrent laryngeal nerve was obtained in 99.3 % of NAR with intraoperative neuromonitoring. 19 patients (4.4 % NAR) suffered from unilateral vocal cord dysfunction in the early postoperative phase. A complete restitution of vocal cord function could be demonstrated in 18 of these patients, leaving one patient (0.23 % NAR) with a permanent vocal cord dysfunction. Our data show that reliable predictions concerning the postoperative outcome of nerve function cannot always be made on the basis of the intraoperative findings. Thus, our own data show a specifity of 98.5 % and a negative predictive value of 96.8 %. On the other hand, sensitivity was 23.5 % and positive predictive value was 40 %. Misinterpretation of the intraoperative signal can lead to risky operative manoeuvres. Possible reasons for the misinterpretation of the intraoperative signal and a critical reflection on the possibilities and predictive values of neuromonitoring will be discussed.

[Identification and surgical anatomy of the external branch of the superior laryngeal nerve]. / Der Ramus externus des Nervus laryngeus superior (RELS): Ein Stiefkind in der Chirurgie der Schilddrüse.

Injury to the external branch of the superior laryngeal nerve (EBSLN) during thyroid surgery can cause serious consequences for patients who depend on control of pitch and a clear and forceful voice, like singers or professional speakers. We used the Neurosign 100(R) nerve monitor to identify 157 nerves in 108 patients undergoing thyroid surgery. The EBSLN was successfully identified in 98.7 % of cases. The recording electrode could be placed either into the cricothyroid muscle or the vocal cord. The latter position proved superior if the recurrent laryngeal nerve had to be identified as well. 16 percent of the nerves crossed the branches of the superior thyroid artery at or below the upper pole of the gland, posing a "high risk" for intraoperative lesions. Our data confirm the results of smaller studies reporting this type of nerve course in 12 % to 14 % of patients. The present findings show a significant number of EBSLN to be in danger of injury when the superior thyroid artery is ligated during thyroid surgery. Neuromonitoring proofed to be a reliable method to identify the nerve, which is an important element in concepts to prevent its injury.

[Patient selection criteria for single-sided or minimal invasive operative procedures in primary hyperparathyroidism (pHPT)]. / Kriterien für die Patientenauswahl zur einseitigen bzw. minimal-invasiven chirurgischen Therapie des primären Hyperparathyreoidismus (pHPT).

In 56 postoperative patients with primary hyperparathyroidism we analysed retrospectively whether a single-sided or minimal invasive operative procedure could have been utilized. Additionally the sensitivity of (99m)TC-Sestamibiscintiscanning and ultrasound of the neck region was assessed. Single gland disease was found in 49 patients, 6 patients had primary multiglandular disease and one patient revealed a double adenoma. The overall sensitivity of (99m)TC-Sestamibiscintiscanning and ultrasound was found to be 78 % and 53 % respectively. In 46 patients the operation would have been started minimal invasive, in 7 of these patients a conversion to bilateral exploration would have been necessary because of four gland hyperplasia, double adenoma or misleading preoperative localisation. In 39 patients a successful minimal invasive procedure would have been possible. A primary bilateral exploration would have been necessary in 10 patients because of either coexisting goiter or questionable localisation of the pathological altered gland. Since sensitivity of localisation diagnostics is low with regard to multiglandular disease, parathyroid hormone should be monitored intraoperatively whenever minimal invasive operative procedures are performed.