[Modern thyroid surgery - the surgeon's endocrine-surgical understanding and his responsibility for the extent of surgery and complication rate]. / Moderne Schilddrüsenchirurgie ­ das endokrin-chirurgische Verständnis des Operateurs und seine Verantwortung für Resektionsausmaß und Komplikationsrate.

High quality thyroid surgery implies a surgeon with an endocrine-surgical understanding aiming at best possible outcome. This includes an appropriate extent of the resection and a low rate of complications. It is important that the surgeon is involved at an early stage being part of the decision process for or against partial or total thyroidectomy. Furthermore, the surgeon should not only be able to perform thyroid and cervical lymph node sonography, but also to be capable to interpret cross-sectional imaging modalities and nuclear medicine imaging procedures. A thorough knowledge of modern principles of radicality is essential.Benign goiters require individualized surgical strategy: solitary nodules can be treated with a tissue-preserving selective nodular resection. However, a multinodular goiter does not necessarily require total thyroidectomy-prevention of a permanent hypoparathyroidism is of paramount importance. For recurrent goiters, removal of the dominant side and therefore, unilateral procedure is favored. Nowadays, there is an increasing tendency to set the indication for thyroid surgery separately for each lobe. Graves' disease requires thyroidectomy, and occasionally, hypertrophic Hashimoto's thyroiditis may also result in surgery.The principles of radical surgical treatment of malignant goiters have changed significantly over the past few years and, so far, strict indication for postoperative radioiodine treatment is being reconsidered. This is especially relevant for papillary thyroid microcarcinomas and minimally invasive follicular tumors. Even the radical surgical treatment of medullary thyroid carcinoma, especially considering synchronous or metachronous lateral neck dissection, is currently under review.Hypoparathyroidism is the most relevant complication in radical thyroid surgery and has devastating influence on the patients' life quality. Nowadays, permanent recurrent laryngeal nerve injury and postoperative hemorrhage rarely occur due to subtle surgical techniques. Extracervical surgical access to the thyroid is still a matter of clinical trials and should be restricted to centers. Radiofrequency ablation is an alternative method for benign lesions or hyperfunctioning nodules in patients with high surgical risk.

Postoperative Hypoparathyroidism in Thyroid Surgery: Anatomic-Surgical Mapping of the Parathyroids and Implications for Thyroid Surgery.

Hypoparathyroidism remains one of the most common complications in thyroid surgery. This study aims for an improved understanding of the complexity of the blood supply and the localisation of the parathyroids compared to the two most important intraoperative landmarks: the inferior laryngeal nerve (ILN) and Zuckerkandl's tubercle (ZT). We examined 103 laryngeal compounds to classify the blood supply and the localisation of the parathyroids. For intraoperative localisation we defined a Cartesian coordinate system with the ZT plane as x-axis and the course of the inferior laryngeal nerve as y-axis. The inferior thyroid artery (ITA) mainly supplies the parathyroids, whereas the superior thyroid artery provides a backup supply. It must be pointed out that 8.2% of parathyroids receive their blood directly from the thyroid gland. 73.5% of all parathyroids lie within 1 cm of the ILN and 1 cm cranial and 2.5 cm caudal to the ZT plane. Our described perimeters mark the most crucial areas during surgery and provide the surgeon with an anatomic mapping showing areas of special carefulness needed. One should keep bearing in mind all possible blood supply types of the parathyroids and therefore all branches should be handled with care.

Current knowledge on the sensitivity of the (68)Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours.

Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three (68)Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these (68)Ga-sstr-binding peptides in the imaging setting. On (68)Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUVmax) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and ß-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUVmax-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUVmax-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with (68)Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.

The nonrecurrent laryngeal nerve: A clinical anatomic mapping with regard to intraoperative neuromonitoring.

BACKGROUND: We investigated the nonrecurrent inferior laryngeal nerve (nrILN), an important variant in the course of the inferior laryngeal nerve (ILN; 0.5-6.0%). Its importance was demonstrated in a clinical case as well as in cadaver specimens, and the pattern was identified with intraoperative neuromonitoring (IONM). METHODS: The ILN and the presence of an nrILN were investigated in 36 formaldehyde-embalmed specimens. Our anatomic findings showed differences in the anatomic course of the ILN and thus produced possible explanations for different IONM signals that would correlate with differences in the anatomic course of the ILN. Preoperative ultrasonographic evaluation of the brachiocephalic trunk and the recurrent laryngeal nerve were used for the exclusion or identification of an nrILN, respectively. RESULTS: We found 2 nrILNs (ascending, horizontal; 6%) in the anatomic specimens. These 2 specimens each showed an aberrant right subclavian artery (lusorial artery) and were, therefore, associated with the absence of a brachiocephalic trunk. The intraoperative case displayed a descending nrILN. Signals derived from the vagus nerve were positive if derived proximal to and negative if derived distal to the branching of an nrILN. By ultrasonographic identification of a normal brachiocephalic trunk, an nrILN could be excluded. CONCLUSION: Surgeons need a working knowledge about nrILNs to avoid recurrent nerve palsy and should be familiar with all the possible course variations in the ILN when IONM signals are absent with vagal stimulation. Moreover, endocrine surgeons need to be able to interpret correctly negative as well as positive signals. Preoperative ultrasonography should ideally be performed, because the presence of a normal brachiocephalic trunk is a quick method to exclude or identify a nrILN.

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma.

PURPOSE: (18)F-Fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTA-TOC) PET. Therefore, we compared (68)Ga-DOTA-TOC and (18)F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. METHODS: A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with (68)Ga-DOTA-TOC PET and (18)F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. RESULTS: Compared with anatomical imaging, (68)Ga-DOTA-TOC PET and (18)F-DOPA PET each had a per-patient and per-lesion detection rate of 100% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of (68)Ga-DOTA-TOC was 100% and that of (18)F-DOPA PET was 56.0%. Overall, (68)Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and (18)F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of (68)Ga-DOTA-TOC PET was 100% (McNemar, P < 0.5), and that of (18)F-DOPA PET was 71.1% (McNemar, P < 0.001). The SUVmax (mean ± SD) of all 32 concordant lesions was 67.9 ± 61.5 for (68)Ga-DOTA-TOC PET and 11.8 ± 7.9 for (18)F-DOPA PET (Mann-Whitney U test, P < 0.0001). CONCLUSION: (68)Ga-DOTA-TOC PET may be superior to (18)F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically inoperable tumours and metastatic or multifocal disease.

Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto's thyroiditis.

BACKGROUND: Alterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto's thyroiditis (HT, n = 18) and healthy controls (HC, n = 70). METHODS: Proportions of peripheral T cells were investigated by flow cytometry. The replicative history was assessed by T cell receptor excision circles (TRECs) and relative telomere length (RTL). Expression of CD62L was analyzed by immunohistochemistry in thyroid sections. The role of CMV was assessed by serology, ELISPOT assay and in situ hybridization. RESULTS: Our results demonstrated a significant increase of CD28-negative T cells, associated with CMV-seropositivity in HT patients. HT showed abundant CD45RO + T cells with peripheral loss of CD62L-expressing CD8 + CD45RA + T cells, the latter mainly depending on disease duration. CD62L was expressed in thyroid lymphocyte infiltrations. The diagnosis of HT and within the HT group CMV-seropositivity were the main determinants for the loss of CD28 expression. RTL was not different between HC and HT. HT showed significantly lower TRECs in CD4 + CD45RA + T cells compared to HC. CONCLUSIONS: Patients with HT display a peripheral T cell phenotype reminiscent of findings in elderly persons or other autoimmune disorders. Whether these mechanisms are primary or secondary to the immunological alterations of autoimmune conditions should be investigated in longitudinal studies which may open research on new therapeutic regimes for treatment of HT and associated autoimmune diseases.

First experience using peptide receptor radionuclide therapy in a patient with urothelial carcinoma.

A 78-year-old man with urothelial carcinoma metastasis after surgical resection of the right kidney, part of the ureter, and urinary bladder in May 2003 and 3 cycles of chemotherapy with cisplatin-gemcitabine was referred for peptide receptor radionuclide therapy (PRRT). Somatostatin-receptor profile was assessed by 68Ga-labeled lanreotide PET, and PRRT was performed using 3738 MBq (101 mCi) of 90Y-DOTA-lanreotide. Because of adequate PRRT response confirmed with MRI and 18F-FDG PET, surgical resection of the solitary cervical metastasis was feasible. Treatment was well tolerated, and the patient remains in complete remission from his urothelial carcinoma.

Intramural duodenal hematoma after upper gastrointestinal endoscopy.

BACKGROUND: Intramural hematoma of the duodenum is a very rare condition. It is mostly seen after blunt abdominal trauma in children. There are only few cases of intramural duodenal hematoma after upper gastrointestinal endoscopy. Most of them are associated with coagulation disorders. The optimal treatment strategy for this condition is still under debate. CASE PRESENTATION: We present the case of a 21-year-old woman who had undergone an upper gastrointestinal endoscopy for dyspepsia and protracted singultus. Work-up included biopsies. Immediately after the procedure, the patient developed an intramural hematoma causing complete duodenal obstruction. The patient was treated conservatively and recovered within three weeks without any sequelae. CONCLUSION: Uncomplicated cases of intramural hematoma may be treated conservatively with total parenteral nutrition, fluid and electrolyte replacement.

CT-MIBI-SPECT image fusion predicts multiglandular disease in hyperparathyroidism.

BACKGROUND: To perform focused or minimally invasive surgery for hyperparathyroidism (HPT) exact preoperative localization is mandatory. Computed tomography-(99m)Tc-sestamibi-single photon emission computed tomography image fusion (CT-MIBI-SPECT) serves this difficult task in single gland HPT to a large extent. The aim of this study was to evaluate whether CT-MIBI-SPECT image fusion is superior to MIBI-SPECT alone and CT alone in detecting abnormal parathyroid tissue in patients with multiglandular disease. PATIENTS AND METHODS: CT-MIBI-SPECT image fusion for preoperative localization was performed in 30 patients with multiglandular disease. There were six patients with primary hyperparathyroidism (four MEN I syndromes and two double adenomas; one of these patients has HRPT2 gene mutation), 14 with secondary, and eight with tertiary HPT, further one patient each suffering from persistent primary and persistent secondary hyperparathyroidism. In both persistent patients only one remaining gland was left from primary surgery. The results of MIBI-SPECT, CT, and CT-MIBI-SPECT image fusion were compared in these patients. The outcome and the exact predicted positions were correlated with intraoperative findings. RESULTS: In five out of six patients with multiglandular primary hyperparathyroidism more than one gland was detected, thus multiglandular disease could be suspected preoperatively. Overall CT-MIBI-SPECT image fusion was able to predict the exact position of all abnormal glands per patient in 14 of 30 (46.7%) cases, whereas CT alone was successful in 11 (36.7%), and MIBI-SPECT alone just in four (13.3%) of 30 patients. CONCLUSION: Multiglandular disease in primary hyperparathyroidism can be suspected preoperatively in a high percentage of patients. Additionally, this study shows that CT-MIBI-SPECT image fusion is superior to CT or MIBI-SPECT alone in preoperative localization of all pathologic glands in patients suffering from multiglandular disease.

Virtual neck exploration: a new method for localizing abnormal parathyroid glands.

BACKGROUND DATA: Computed tomography (CT) together with 99mTc-sestamibi single photon emission computed tomography (MIBI-SPECT) image fusion (CT-MIBI-SPECT image fusion) allows virtual exploration of the neck. The aim of this study was to evaluate whether CT-MIBI-SPECT image fusion is superior to MIBI-SPECT and CT in detecting abnormal parathyroid glands in patients with primary hyperparathyroidism. METHODS: CT-MIBI-SPECT image fusion for preoperative localization was performed in 116 patients with primary hyperparathyroidism (pHPT). Both investigations were performed with reproducible fixation of the patient on a vacuum mattress. At a special work station the neck was virtually explored by viewing the CT images in all 3 dimensions. The MIBI-SPECT images were superimposed on underlying CT images. Only patients with single-gland disease were evaluated (pHPT: 112, persistent pHPT: 1, recurrent pHPT: 1, persistent secondary hyperparathyroidism: 1, tertiary HPT after kidney transplantation: 1). CT-MIBI-SPECT image fusion results were compared with those obtained with CT alone and MIBI-SPECT alone. The predicted positions were correlated with the intraoperative findings. RESULTS: CT-MIBI-SPECT image fusion was able to predict the exact position of the abnormal gland in 102 (88%) of the 116 patients, whereas CT alone showed in 75 (65%) patients and MIBI-SPECT alone in 64 (55%) patients the exact position of the abnormal gland. Sixty-two patients underwent minimally invasive surgery, namely in 21 patients with a unilaterally focused approach and in 33 patients with a bilateral approach (27 of these underwent simultaneous thyroid resection). Sensitivity for CT-MIBI-SPECT image fusion was 88%, for CT alone 70%, and for MIBI-SPECT alone 59%. Specificity for CT-MIBI-SPECT image fusion was 99%, for MIBI-SPECT alone 95%, for CT alone 94%. Overall accuracy for CT-MIBI-SPECT image fusion was 97%, for CT alone 89%, for MIBI-SPECT 87%. CONCLUSIONS: This study provides evidence that CT-MIBI-SPECT image fusion is superior to CT or MIBI-SPECT alone for preoperative localization of enlarged parathyroid glands in patients with single-gland primary hyperparathyroidism.

Virtual neck exploration in patients with hyperparathyroidism and former cervical operations.

BACKGROUND: In surgery for primary hyperparathyroidism, preoperative localization together with intraoperative parathyroid hormone assay is important when minimal invasive operations of the parathyroid glands are intended. In cases of reoperation, correct localization of the abnormal parathyroid glands is extremely instrumental. Computed tomography (CT)-(99m)Tc-sestamibi (MIBI)-single photon emission computed tomography (SPECT) image fusion allows for a virtual exploration of the neck by showing the suspected gland three-dimensionally with all the anatomic landmarks in correct position. The aim of this study was to evaluate whether CT-MIBI-SPECT image fusion is superior to MIBI-SPECT alone in detecting abnormal parathyroid glands in patients with previous neck surgery. PATIENTS AND METHODS: In a prospective study, CT-MIBI-SPECT image fusion for preoperative localization was performed in 28 patients with hyperparathyroidism and previous neck surgery. Twenty-one patients had thyroidectomy and seven patients had surgery for hyperparathyroidism. The results of MIBI-SPECT alone and CT-MIBI-SPECT image fusion were compared in these patients. The outcome and the exact predicted position, not just the predicted side, were correlated with intraoperative findings. RESULTS: CT-MIBI-SPECT image fusion was able to predict the exact position of the abnormal gland in 24 of 28 patients (86%), whereas MIBI-SPECT alone was successful in 12 of 28 cases (43%, p < 0.004) only. CT-MIBI-SPECT image fusion detected all three pathologic glands in their ectopic position. With MIBI-SPECT alone, just one ectopic pathologic gland was found. CONCLUSION: This study provides evidence that CT-MIBI-SPECT image fusion is superior to MIBI-SPECT alone in preoperative localization of enlarged parathyroid glands in patients with hyperparathyroidism and previous neck surgery. This should be kept in mind if the results are compared to earlier studies concerning CT-MIBI-SPECT image fusion.

EpCAM overexpression in thyroid carcinomas: a histopathological study of 121 cases.

Epithelial cell adhesion molecule (EpCAM) is expressed by a broad variety of carcinoma cells. It is recognized by the monoclonal antibody 17-1A, which has already been applied for immunotherapy of several carcinoma types in preclinical and small clinical studies. In the present study the immunohistochemical properties of 17-1A were evaluated in 121 cases of thyroid carcinomas of follicular cell origin, comprising of 75 differentiated (DTC; 35 papillary and 40 follicular carcinomas), 24 poorly differentiated (PDTC) and 22 anaplastic thyroid carcinomas. Overexpression of EpCAM, as recently defined, was found with a distinct membranous staining pattern in 81.3% of DTCs and in 66.6% of PDTCs. In contrast, all anaplastic thyroid carcinomas (0%) completely lacked EpCAM expression. Normal thyroid tissue presented with weak and heterogeneous EpCAM staining. This study demonstrates EpCAM overexpression as a common finding in DTCs and PDTCs, and thus these tumors as possible novel targets for EpCAM-directed immunotherapy. Our findings suggest that patients with recurrent or advanced tumor disease and metastatic spread could benefit from this modern therapeutic regime, especially after insufficient radioiodine therapy.

Insular-type component follicular thyroid carcinoma in a 10-year-old girl--case report.

Insular-type carcinoma of the thyroid is a rare form of undifferentiated thyroid cancer. The manifestation of disease occurs mainly in adults and is extremely rare in children. Prognosis of this type of thyroid carcinoma is unfavorable in childhood. Because of its rarity, it is not yet clear whether these tumors carry the same risk of progression. Therapy of choice is total thyroidectomy combined with a cervical lymph node dissection. In children, surgery is associated with a higher risk of recurrent nerve palsy and loss of parathyroid glands than in adults. Therefore, identification and protection of the recurrent laryngeal nerve using electrical neuromonitoring as well as exact preparation of parathyroid glands may reduce these risks. The history of a 10-year-old girl with insular-type thyroid carcinoma is presented. Surgical considerations such as total thyroidectomy vs less-than-total thyroidectomy with unilateral or bilateral cervical lymph node dissection are presented. Prognosis concerning morbidity, pointing out the aspect of electrical neuromonitoring and precaution of parathyroid glands, and survival rate of this extremely rare entity are discussed.

Accuracy of preoperative pinhole subtraction single photon emission computed tomography for patients with primary and recurrent hyperparathyroidism in an endemic goiter area.

PURPOSE: Bilateral parathyroid exploration is still the standard therapeutic procedure for primary and recurrent hyperparathyroidism (HPTH). Since a unilateral surgical strategy that reduces surgical complications should not increase the risk of missing enlarged parathyroid glands, reliable preoperative imaging is the first requirement for this approach. This study was conducted to assess the accuracy of preoperative (99m)TcO(4)-(201)T1 pinhole subtraction single photon emission computed tomography (SPECT) compared with sonography. METHODS: The study population consisted of 15 patients with primary (n = 13) or recurrent (n = 2) HPTH who underwent preoperative (99m)TcO(4)-(201)T1 pinhole subtraction SPECT. Preoperative sonography was also done in 14 of these patients. RESULTS: (99m)TcO(4)-(201)T1 pinhole subtraction SPECT was significantly more accurate than sonography. It had an overall accuracy of 80% in detection of enlarged parathyroid glands. The accuracy of localization increased to 92.3% in patients with solitary adenomas, and to 100% in those with solitary adenomas and no previous parathyroid exploration. CONCLUSIONS: The high accuracy of preoperative localization with (99m)TcO(4)-(201)T1 pinhole subtraction SPECT in patients with primary and recurrent HPTH allows for an imaging-guided unilateral operative strategy in most patients, even those with concomitant nodular goiters. This may reduce the risk of surgical complications and expand the use of minimally invasive techniques in parathyroid surgery.

Neuroendocrine tumors and second primary malignancy--a relationship with clinical impact?

BACKGROUND: Neuroendocrine tumors (NET) are frequently associated with synchronous or metachronous secondary primary malignancies (SPM). The aim of this study was to report on 14 patients with NET and SPM from a series of 96 patients with NET. PATIENTS AND METHODS: Fourteen patients with NET and synchronous or metachronous SPM were reviewed for primary site and characteristics of NET and associated SPMs as well as the outcome of these combined malignancies. RESULTS: From 1987 to 2002, 14 (14.6%) out of 96 patients with NET were identified with SPM. The median age of the patients at diagnosis of NET was 69 years (range: 56-86 yrs). There were nine female and five male patients. The localization of NET was: four in appendix, three ileum, two duodenum, one stomach, one jejunum, one pancreatic tail, one rectum and one lung. Five patients had synchronous SPM (two colon cancers with one double colon cancer, one gastric cancer, one bladder cancer, one ovarian cancer) and nine metachronous SPM (two basal cell carcinomas, one colon cancer, two breast cancer, one gastric MALT-lymphoma, one ductal pancreatic adenocarcinoma, one bladder cancer, one hepatocellular carcinoma), three months to five years after diagnosis of NET. Five patients died of metastatic tumor (three SPM: 1, 7, 10 yrs; two NET: 1, 9 yrs), two patients died of other causes (1, 7 yrs), three patients are alive with metastatic tumor (two NET: 5, 6 yrs; one SPM: 10 yrs) while four patients are tumor-free (6 ms, 2, 9, 10 yrs). CONCLUSION: NET is associated to a high degree with gastrointestinal and genitourinary SPM. In 5/14 (36%) patients SPM was diagnosed synchronously, while in 8/14 (57%) patients SPM was diagnosed metachronously. In 8/14 patients (57%) primary symptoms were caused by SPM. As a consequence, every NET should be regarded as an index tumor and risk-adapted follow-up with thorough investigation, mainly of the GI and genitourinary tracts, is to be recommended.

Catestatin--a novel neuropeptide in carcinoid tumors of the appendix.

BACKGROUND: The aim of the study was to investigate the immunohistochemical distribution of the novel neuropeptide catestatin in carcinoid tumors. Catestatin, a novel 21 amino acid neuropeptide derived from chromogranin A, was determined immunohistochemically in 30 carcinoid tumors of the appendix and various carcinoid tumors of other localities. MATERIALS AND METHODS: Paraffin-embedded tissues from 30 carcinoid tumors of the appendix and 16 other carcinoid tumors (5 bronchus-, 5 stomach-, 2 small bowel-, 4 large bowel carcinoid tumors) were incubated with antibodies specific for catestatin, chromogranin A and chromogranin B. Immunohistochemical staining of catestatin was compared to staining with chromogranin A and B. Western blot analysis was performed in one patient with ileal carcinoid. RESULTS: Thirty patients (20 women, 10 men) with carcinoid tumors of the appendix and 16 patients with other localized carcinoid tumors were investigated. Twenty-six of the appendiceal tumors were localized in the apex of the appendix and 4 tumors in the midportion; none of the tumors was localized at the base of the appendix. Median tumor diameter was 10.7 mm (range 4-18 mm). Immunoreactivity to catesatatin was positive in 28 patients (negative in 2, 0-10% in 11 patients, 11-50% in 14 patients, 51-100% in 3 patients). In 16 patients with carcinoid tumors in various other localizations, catestatin was also expressed. Western blot analysis of ileal carcinoid showed abundant catestatin reactivity with accelerated processing of chromogranin A in the tumor tissue. CONCLUSION: Catestatin derived from chromogranin A, which is the most widely distributed marker of neuroendocrine tumors, is expressed in high frequency in carcinoid tumors of the appendix (93.3%).

Computed axial tomography-MIBI image fusion for preoperative localization in primary hyperparathyroidism.

BACKGROUND: An imaging-guided unilateral surgical approach in patients with primary hyperparathyroidism (HPTH) requires reliable preoperative localization procedures. Using present imaging techniques, 60% to 80% of patients with primary HPTH can be treated successfully with limited surgery. Thus, further improvement of diagnostic accuracy is required. Computed axial tomography (CAT)-MIBI image fusion was introduced as a new technique for localizing enlarged parathyroid glands. We describe the new method and present its first results. METHODS: Six consecutive patients with primary HPTH underwent CAT-MIBI image fusion for preoperative parathyroid localization. CAT and technetium-99m-sestamibi scan were performed separately. The patient's head and neck were fixed with the noninvasive Vogele-Bale-Hohner Head Holder (VBH HeadFIX; Medical Intelligence, Schwabmünchen, Germany) and the BodyFIX (Medical Intelligence) vacuum cushion. Radiographic and scintigraphic markers were mounted at the head holder and the patient. CAT and MIBI images were fused by overlaying radiographic markers using a commercial software and workstation. RESULTS: In 5 patients, localization and dimension of the solitary adenomas were exactly predicted. In 1 patient with multiglandular disease (3 enlarged glands), CAT-MIBI image fusion was not able to predict multiple gland involvement. However, in a retrospective analysis of the localization study, the other two enlarged parathyroid glands could be correctly identified regarding their site and size. CONCLUSIONS: First results of CAT-MIBI image fusion are promising. The new technique provides a higher image resolution and better delimitation of enlarged parathyroid glands and adjacent anatomic structures than conventional scintigraphic methods.

CT-MIBI image fusion: a new preoperative localization technique for primary, recurrent, and persistent hyperparathyroidism.

BACKGROUND: Successful minimally invasive or imaging-guided operations in patients with primary, recurrent, and persistent hyperparathyroidism are based on the reliability of preoperative parathyroid localization studies. The CT-MIBI image fusion promises a higher diagnostic accuracy than current imaging procedures. The aim of our study was to assess its reliability in correctly detecting enlarged parathyroid glands. METHODS: In a prospective study 24 consecutive patients underwent CT-MIBI image fusion as preoperative parathyroid localization procedure. The results of technetium 99m sestamibi single photon emission computed tomography (MIBI-SPECT) alone, today the standard method in parathyroid imaging, and CT-MIBI image fusion were analyzed by a blinded reviewer, and the imaging results were compared with the intraoperative findings. RESULTS: For CT-MIBI image fusion a sensitivity of 93% and a specificity of 100% in correctly detecting the position of enlarged parathyroid glands was calculated and compared with a sensitivity of MIBI-SPECT of 31% and a specificity of 87% (P<.001). This new imaging technique enabled us to successfully treat 22 of our patients (92%) with imaging-guided surgery. Twenty (83%) underwent unilateral or minimally invasive operations. CONCLUSIONS: CT-MIBI image fusion appears to be superior to MIBI-SPECT in preoperative parathyroid imaging. CT-MIBI image fusion can be performed on existing CT- and MIBI-SPECT units. We recommend this method for preoperative localization in patients with primary, recurrent and persistent hyperparathyroidism.

Her2/neu expression in C-cell hyperplasia and medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) are rare neoplasms derived from the calcitonin-producing thyroid parafollicular C-cells. Interestingly about 20% of cases are related to inherited tumor syndromes. As precursor lesion, C-cell hyperplasia can be detected in numerous MTCs. In our series of 6 patients with MTC, including 5 patients with adjacent C-cell hyperplasia, Her2/neu levels were immunohistochemically evaluated on formalin-fixed, paraffin-embedded tissues using c-erbB-2/Her-2/neu Oncoprotein Ab-17 monoclonal antibody(mAb). Statistically, a highly significant correlation was found between high Her2/neu levels and extrathyroidal growth. C-cell hyperplasias always presented with higher amounts of stained cells than their corresponding invasive MTCs. Whereas in hyperplastic areas large stained cell clusters were found, the invasive tumors showed mainly single cells reacting in areas of variable size. These results present the impact of Her2/neu oncoprotein concerning development and biological behaviour, especially aggressive growth, of invasive MTCs and suggest a major role of hyperplastic C-cell areas in the development of these malignant tumors.

Her2/neu expression in poorly-differentiated and anaplastic thyroid carcinomas.

The Her2/neu expression in poorly-differentiated thyroid carcinomas (PDTC) and in anaplastic thyroid cancer (ATC) was investigated retrospectively. Tumors of 25 patients suffering from PDTC and 25 from ATC were evaluated, including 15 cases of PDTC with highly-differentiated tumor parts. Her2/neu levels were immunohistochemically detected on formalin-fixed, paraffin-embedded tissues using c-erbB-2/Her2/neu Oncoprotein Ab-17 monoclonal antibody(mAb). In statistical analysis using 1-way ANOVA, Her2/neu protein overexpression was highly significantly correlated with the differentiation status of the investigated tumor parts. Whereas ATCs showed only few positive tumor cells, PDTCs presented with large reacting tumor areas and highly-differentiated parts of PDTCs revealed the highest staining intensity. These findings suggest a decreasing impact of Her2/neu oncoproteins correlating to dedifferentiation, reflecting the aggressive biological behaviour of these tumors.