[Is the timing of completion thyroidectomy for differentiated thyroid carcinoma prognostic significant?]. / Beeinflusst der Zeitpunkt der Restthyreoidektomie die Prognose differenzierter Schilddrüsenkarzinome?

The purpose of this study was to evaluate whether the timing of completion thyroidectomy for differentiated thyroid carcinoma had an influence on the risk of the operation and patient's survival. From January 1, 1985 to March 31, 2001, 230 consecutive patients underwent surgery for differentiated thyroid carcinoma (178 papillary and 52 follicular carcinomas). In this article completion thyroidectomy was defined as the removal of the remaining thyroid tissue after any initial surgical procedure less than total thyroidectomy within an interval ranging from 3 days to 4 months after the initial surgical procedure. Of 99.1 % (n = 228) of the 230 patients the postoperative course is known for 1 month to 36 years with a median follow-up of 5 years. Among 81 patients undergoing thyroidectomy as the initial operation, recurrent laryngeal nerve palsy occurred in 13.5 % (n = 11). In 2 of these patients (2.5 %) recurrent laryngeal nerve palsy was permanent. Transient recurrent laryngeal nerve palsy occurred more frequent in patients who underwent completion thyroidectomy within 8 days to 3 months of the initial surgical procedure (20.5 %) than in patients, in whom completion thyroidectomy was performed either within 7 days of the primary operation or after a minimum of 3 months (5.2 % in each group). Disease-free survival as well as long-term survival was not different after thyroidectomy or completion thyroidectomy for all differentiated thyroid carcinomas and in patients with papillary carcinomas. In order to reduce surgical morbidity we suggest that completion thyroidectomy should be performed either within 7 days of the primary operation or after a minimum of 3 months.

[Intraoperative parathyroid hormone monitoring in neck exploration for renal hyperparathyroidism?]. / Intraoperatives Parathormonmonitoring bei der Halsexploration wegen renalem Hyperparathyreoidismus?

INTRODUCTION: In operations for renal hyperparathyroidism the value of intraoperative parathormone monitoring was investigated. PATIENTS AND METHODS: Intraoperative intact parathyroid hormone levels were determined (PTH Quick assay) in 40 patients undergoing first cervical exploration and in two patients with graft-dependent recurrence of renal hyperparathyroidism. RESULTS: In 33 patients, total parathyroidectomy with autotransplantation was carried out. The median parathormone levels decreased from 652 pg/ml to 120 pg/ml (19% of initial level) 5 min after total parathyroidectomy. In seven patients, fewer than 4 parathyroid glands each were identified during cervical exploration and "total parathyroidectomy (?)" without autotransplantation was performed. Intraoperatively median parathormone level decreased from 1193 pg/ml to 116 pg/ml (10% of initial level). In one of these seven patients, hyperparathyroidism persisted due to an ectopic fourth gland within the carotid sheath. In two of these patients, hypoparathyroidism occurred and a delayed autotransplantation of cryopreserved parathyroid tissue was carried out. On the first day after total parathyroidectomy with autotransplantation and "total parathyroidectomy (?)", median levels of intact parathyroid hormone were 1.9 pg/ml and 82.5 pg/ml, respectively. CONCLUSION: Intraoperative monitoring is not useful in first cervical exploration for renal hyperparathyroidism because it cannot predict complete resection of parathyroid tissue. The parathormone level on the first postoperative day allows precise evaluation of the efficacy of the surgical procedure.

[Drug therapy of carcinoids of the gastrointestinal tract]. / Medikamentöse Therapie bei Karzinoiden des Gastrointestinaltraktes.

Carcinoid tumors are rare and slowly growing neuroendocrine tumors of the foregut, midgut and hindgut. Drug therapy is of special importance in patients with inoperable metastasising disease. This palliative therapy is aimed at reduction of the hormone-dependent symptoms and inhibition of tumor growth. Somatostatin analogues, alpha-interferon and various chemotherapeutic agents are used for this purpose. Drug therapy can be supplemented by surgical and radiological intervention through interdisciplinary cooperation of the surgeon, radiologist, endocrinologist and gastroenterologist.

Postoperative reduction of fibrinolysis as a prognostic factor of fatal outcome.

For the resection of an esophagus carcinoma a mortality rate of 2 to 30% was described. It is still unclear whether an abdominothoracic or transhiatal intervention is superior regarding the outcome. To investigate the prognostic value of fibrinolytic markers, plasmin-alpha2-antiplasmin (PAP) and D-dimer (DD) values were determined daily in the early postoperative period for 11 days. In addition, the course of PAP and DD concentrations was compared with the method of esophagectomy. Of the 28 patients enclosed in the study, 5 died between day 10 and day 34 owing to adult respiratory distress syndrome and septicemia. The PAP and DD concentrations increased in survivors after surgery until day 5 and day 7, respectively. The concentrations were twofold and 10-fold higher than the upper reference level. In contrast, four of five nonsurvivors showed an inadequate increase in PAP concentrations within the reference range, whereas the course of DD was inconspicuous. The sensitivity and specificity of PAP and DD in respect to a fatal outcome was calculated by receiver operating characteristic analysis based on all results: sensitivity 76% (PAP-cut off value 760 microg/L) and 49% (DD 6 mg/L), specificity 77% and 72%, respectively. The biochemical markers showed no significant differences between the abdominothoracic and transhiatal esophagectomy. In the abdominothoracic intervention, lower PAP and higher DD concentrations were observed. The results showed that the PAP concentrations could detect a fatal outcome within the first 5 days after surgery.

[Results of bilateral surgical technique in primary hyperparathyroidism]. / Ergebnisse der bilateralen Operationstechnik bei primärem Hyperparathyreoidismus.

AIM OF THE STUDY: The surgical success rate and clinical outcome after surgery for primary hyperparathyroidism were evaluated in a prospective long-term follow-up study. PATIENTS AND METHODS: 407 patients, 396 with the first manifestation, 6 with recurrent and 5 with persistent disease underwent operation from August 1, 1987 to August 15, 1999. All patients were prospectively investigated in a long-term follow-up study and underwent reexaminations at regular surveillance intervals. The postoperative course is known in 93.9% of all patients. RESULTS: The prevalence of asymptomatic primary hyperparathyroidism was 5.6% in our patients. Surgical cure was obtained in 97.7% of patients after initial neck exploration. In 58% of the patients with hypercalcaemic syndrome recovery occurred within the first month after surgery. Skeletal symptoms persisted in 24% of patients two years after the operation. CONCLUSIONS: In primary hyperparathyroidism bilateral neck exploration yielded a high surgical success rate and provided long-term relief of symptoms. The morbidity of parathyroid surgery was influenced by a concomitant thyroid resection and a relationship was established between the number of intraoperatively identified parathyroid glands and the morbidity of the operation.

[Surgical therapy of primary hyperparathyroidism. Quality of life after 10 years prospective observation]. / Operative Therapie des primären Hyperparathyreoidismus. Lebensqualität nach 10jähriger prospektiver Beobachtung.

AIM OF THE STUDY: The quality of life after surgery for primary hyperparathyroidism was evaluated in a prospective long-term follow-up study. PATIENTS AND METHODS: Altogether 383 patients, 374 with the first manifestation, 6 with recurrent and 3 with persistent disease, who underwent operation from August 1, 1987 to February 15, 1999 were prospectively investigated and included in a long-term follow-up study. All patients underwent reexaminations at regular surveillance intervals. The postoperative course is known in 93.7% of all patients. We carried out 1,504 follow-up examinations (per patient: 1-12, median 4). The follow-up period ranged from 1 month to 10 years with a median of 24 months (mean 34.5 +/- 29.8 months). RESULTS: The true frequency of asymptomatic primary hyperparathyroidism could be confirmed only postoperatively, because a part of the patients were unaware of mild symptoms of hypercalcaemic syndrome prior to surgery. Therefore the prevalence of asymptomatic primary hyperparathyroidism was 5.6% in our patients. Surgical cure was obtained in 97.6% of patients after initial neck exploration. Successful parathyroidectomy provided long-term relief of symptoms in our patients. In 58% of the patients with hypercalcaemic syndrome recovery occurred within the first month after surgery. Bone and joint pain persisted for a longer period of time and was present in 24% of patients two years after the operation. During the follow-up period the mortality of our study population was significantly higher (p = 0.00024) than the expected mortality risk for the German population as a whole. CONCLUSIONS: The present prospective follow-up study yielded conclusive outcome research data after operative therapy for primary hyperparathyroidism. The high biochemical cure rate with long-term relief of symptoms, as well as the increased mortality after successful parathyroidectomy emphasize the importance of early diagnosis and early surgical treatment for primary hyperparathyroidism, even in the absence of manifest symptoms.

Outcome after surgery for primary hyperparathyroidism: ten-year prospective follow-up study.

Clinical outcome after surgery for primary hyperparathyroidism was evaluated in a prospective long-term, follow-up study. From August 1, 1987 to August 31, 1998 a total of 360 patients were prospectively investigated and included in a follow-up study. All patients underwent follow-up examinations at regular surveillance intervals. The postoperative course is known for 94.5% of all patients. Follow-up was 1 month to 10 years (median 24 months; mean 34.5 +/- 29.8 months). Asymptomatic primary hyperparathyroidism was rare (6%), and its true frequency could be confirmed only postoperatively because some of the patients were unaware of mild symptoms of hypercalcemic syndrome prior to surgery. Surgical cure was obtained in 97.7% of patients after initial cervical exploration; and successful parathyroidectomy provided long-term relief of symptoms. Within 2 years postoperatively, 84% of the patients recovered fully from hypercalcemic syndrome: in 58% of these patients recovery occurred within the first month after surgery. Skeletal symptoms persisted in 24% of patients 2 years postoperatively. To date no patient has developed recurrence of primary hyperparathyroidism. During follow-up in our study population mortality was significantly higher than the expected mortality risk for the German population as a whole (p = 0.00024). The present prospective follow-up study yielded conclusive outcome research data after operative therapy for primary hyperparathyroidism. The high cure rate and low morbidity, as well as the increased mortality, in our study population during follow-up after successful operative therapy for the disease emphasize the importance of early diagnosis and early surgical treatment for primary hyperparathyroidism, even in the absence of manifest symptoms.

[Predictive genetic investigations. Individualization of diagnosis and treatment in families with multiple endocrine neoplasia type II]. / Prädiktive genetische Untersuchungen. Individualisierung von Diagnostik und Therapie bei Familien mit multipler endokriner Neoplasie Typ II.

BACKGROUND AND OBJECTIVE: When multiple endocrine neoplasia type 2 (MEN2) is suspected, genetic tests are at the centre of screening procedures. It was the aim of this study to compare the diagnostic value of molecular biological investigations with that of conventional biochemical tests. PATIENTS AND METHODS: The study cohort consisted of all 144 patients cared for in our department since 1990 with the suspected diagnosis of MEN2 (evidence of a medullary thyroid carcinoma [MTC]), coexistence of two MEN2 tumours or a family history of MEN2. 14 of the 144 patients (from 12 families) were already known to have an hereditary MTC, while the remaining 130 had been referred for further diagnostic investigations. RESULTS: An hereditary MTC was diagnosed in 22 of the 130 patients, a sporadic MTC in 32, while no definitive classification was possible in 20 MTC patients without a positive family history and on whom no mutation analysis had been performed. MEN2 was excluded in 56 family members. All 22 patients with newly diagnosed MTC had abnormally high calcitonin levels. A germ-line mutation in the RET proto-oncogene was found in 8 of the 9 families who had undergone molecular biological tests. The investigate results led to a thyroidectomy in 19 of the 22 patients with hereditary MTC; in all of them the surgical specimen showed C-cell hyperplasia and/o MTC. CONCLUSION: These results emphasize the importance of genetic tests in family screening. Preoperative measurement of calcitonin remains essential in MEN2 families in whom a germ-line mutation is not known. The choice of the appropriate diagnostic test must be individualized to the particular patients so that optimal results are obtained.

[Early diagnosis and reoperation in persistent primary hyperparathyroidism]. / Frühdiagnostik und frühzeitige Reoperation des persistierenden primären Hyperparathyreoidismus.

INTRODUCTION: The persistence rate of primary hyperparathyroidism after cervical exploration was estimated and early diagnosis and reoperation were evaluated in a prospective study. METHODS: Between 1 August 1987 and 31 October 1998, 370 patients underwent surgery. The postoperative course is known in 94.6 % of these patients (follow-up 1 month-10 years, median 24 months). RESULTS: Cervical exploration was successful in 97.5 % (n = 353) of the 361 patients with the first manifestation of primary hyperparathyroidism and in all patients with recurrence or persistence of the disease after initial operation elsewhere. In persistent primary hyperparathyroidism serum calcium levels remained elevated 4 days after surgery (n = 9, 2.5 %). Localization studies, preferably with (99m)Tc-MIBI-scintigraphy were attempted during the first postoperative week and could be performed in 4 patients. Four patients wished the procedure to be performed later. CONCLUSION: Within one week after the initial intervention the diagnosis of persistent primary hyperparathyroidism can be established and localization studies as well as cervical reexploration can be carried out. An interval of 3 months from the initial operation to reexploration of the parathyroid area is recommended if the reexploration is impossible within one week. Mediastinal reoperations or surgical interventions in the neck sparing the perithyroid area may be carried out without consideration of specific intervals.

Modified cryopreservation and xenotransplantation of human parathyroid tissue.

INTRODUCTION: A modified cryopreservation technique for human parathyroid tissue was compared with the standard method using a programmed freezer. METHODS: Total parathyroidectomy was performed in three groups of 6-week-old Rowett nude rats. Group I (control) underwent no transplantation of parathyroid tissue (n=9). After 10 days, the rats of groups II (n=15) and III (n=15) underwent xenotransplantation of 20 mg cryopreserved human parathyroid tissue, which had been stored in liquid nitrogen at -196 degrees C for 1-22 months prior to xenotransplantation. The parathyroid tissue was derived from 15 parathyroidectomized patients with renal hyperparathyroidism. Two tissue samples were obtained from every patient. One sample from every patient was cryopreserved by means of the technique of programmed cryopreservation: programmed freezing of human parathyroid tissue at a controlled rate of -1 degrees C/min to -80 degrees C prior to transfer to liquid nitrogen (group II). The second sample from every patient was cryopreserved by means of a modified cryopreservation technique: immediate placement of human parathyroid tissue in a freezer at -20 degrees C and transfer to liquid nitrogen after 2 h (group III). Calcium and intact parathyroid hormone concentrations in serum were determined over a period of 60 days. Furthermore, individual differences in the calcium concentrations were assessed for each rat on the basis of the calcium levels recorded preoperatively and at day 60. RESULTS: All animals in the control group developed hypocalcemia. Serum calcium concentrations returned to normal levels 60 days after xenotransplantation of parathyroid tissue, which had been cryopreserved using the modified technique (group III) in 12 of 15 rats (80%). At day 60, serum calcium had normalized in 10 of 15 rats (67%) after xenotransplantation of parathyroid tissue cryopreserved using programmed freezing (group II). After modified cryopreservation (group III), the median individual difference in the calcium concentrations was -0.16 mmol/l after programmed freezing (group II). At the end of the study, a median level of human intact parathyroid hormone of 3.5 pg/ml and 2.4 pg/ml was estimated for groups II and III, respectively. There was no statistical significant difference of the individual differences in the calcium concentrations or of the levels of human intact parathyroid hormone between groups II and III. CONCLUSION: Human parathyroid tissue was successfully xenografted in the present experimental study. The results obtained after cryopreservation using the described modified technique were equivalent to those recorded after controlled freezing in a programmed freezer. The simplified cryopreservation technique therefore appears to be suitable for human parathyroid tissue.

Prospective study of parathyroid graft function in patients with renal hyperparathyroidism after total parathyroidectomy and heterotopic autotransplantation by measurement of the intact parathyroid hormone concentrations in both antecubital veins.

OBJECTIVE: Evaluation of the value of gradients for intact parathyroid hormone after total parathyroidectomy and heterotopic autotransplantation for renal hyperparathyroidism. DESIGN: Prospective long-term follow-up study. SETTING: Teaching hospital, Germany. SUBJECTS: A total of 115 patients operated on for renal hyperparathyroidism between 1 August 1987 to 15 August 1997. INTERVENTIONS: 100/115 had total parathyroidectomy with autotransplantation. MAIN OUTCOME MEASURES: Analyses of serum calcium, alkaline phosphatase, and intact parathormone in serum 1, 4, 8, 12, 18 and 24 months postoperatively and annually thereafter. Parathormone gradients were calculated as the ratio of the parathormone concentrations in the antecubital venous blood of the grafted and the non-grafted arm. RESULTS: During follow-up (mean 32 months, range 1 month to 9 years), 111 of the 115 patients had one to 10 re-examinations (mean: 4) and in the patients who had had total parathyroidectomy with autotransplantation a total of 437 gradients could be calculated, 91% of which were < or =20. Postoperative hypocalcaemia caused by calcium deficiency of the skeleton led to an increase in parathormone secretion and gradients. Increasing parathormone gradients during follow-up as a result of excessive parathormone secretion in the grafted-arm indicated graft-dependent recurrence. In 6 of the 9 patients with graft-dependent recurrences the gradients exceeded 20. CONCLUSION: The combined sequential assessment of gradients for intact parathyroid hormone and of serum calcium concentrations permits objective evaluation of parathyroid graft function.

[99mTc-MIBI-scintigraphy before parathyroid surgery?]. / 99mTc-MIBI-Szintigraphie vor Eingriffen wegen Hyperparathyreoidismus?

AIM: In a non prospective study the value of preoperative parathyroid imaging with 99mTc-MIBI-scintigraphy was evaluated. PATIENTS AND METHODS: From August 1, 1987 to December 15, 1997 453 patients were operated on for hyperparathyroidism. Preoperatively 116 patients underwent 99mTc-MIBI-scanning, which had been carried out by several institutes. RESULTS: Primary hyperparathyroidism. Sensitivity of MIBI-scintigraphy in solitary parathyroid adenoma (n = 48) and first-time cervical exploration was 54% (25 true positive scans) and overall sensitivity was 50% (25 true positive scans in 53 patients). In 6 patients with persistence or recurrence of primary hyperparathyroidism MIBI-scintigraphy was true positive (sensitivity 100%). Neither the volume nor the weight of the adenomas influenced the result of MIBI-scanning. There was no correlation between preoperative serum concentrations of calcium and intact parathormone and sensitivity of MIBI-scintigraphy. Renal hyperparathyroidism. Before first-time cervical exploration sensitivity of MIBI-scintigraphy (n = 40) for detecting all abnormal parathyroid glands in the presence of diffuse hyperplasia yielded only 10%. In 5 of 7 patients, who underwent reexplorations of the neck or mediastinum for persistence or recurrence of renal hyperparathyroidism MIBI-scintigraphy was true positive (sensitivity 71%). The sensitivity for detection of hyperplastic parathyroid glands correlated with the weight as well as with the volume of the glands (p < 0.001). The weight of imaged glands ranged from 0.21 to 9.76 g, median 1.27 g and their median volume was 1.12 ml (range: 0.04-15.63 ml). For non imaged glands a median weight of 0.49 g and a median volume of 0.3 ml (ranges: 0.03-10.34 g, 0.009-9.8 ml, respectively) could be estimated. CONCLUSIONS: First-time cervical exploration for hyperparathyroidism can be carried out with a high success rate and without any preoperative localization study. Before recurrent parathyroid surgery we recommend 99mTc-MIBI-scintigraphy because of its > 90% sensitivity.

Hyperlactacidaemia in isolated hyperthermic perfusion of tumour bearing rat limbs: a study of feasibility using a novel infusion solution.

PURPOSE: In a methodological study the applicability of hyperlactacidaemia in isolated hyperthermic perfusion of tumour-bearing rat limbs was investigated. METHODS: In 50 Sprague Dawley rats, DS-sarcoma growth was initiated on the right food dorsum by subcutaneous injection of 0.5 ml ascites cells. In the anaesthetized animals isolated limb perfusion was performed under steady state conditions for 60min using a miniature equipment. Thereafter tumour volume was measured daily. (a) Investigation of feasability: 40 rats were allocated to four groups. Group I: Normothermic perfusion at 38 degrees C, n = 10; Group II: Hyperthermic perfusion at 40-41 degrees C, n = 10; Group III: Normothermic perfusion at 38 degrees C and hyperlactacidaemia of 10 mmol/l, n = 10; Group IV: Hyperthermic perfusion at 40-41 degrees C and hyperlactacidaemia of 10 mmol/l, n = 10. (b) Investigation of survival and histological changes: In group V hyperthermic perfusion at 40-41 degrees C and hyperlactacidaemia of 10 mmol/l, n = 10 was performed. After the animals had died, hip disarticulation of the tumour-bearing limb was performed for histological examination. RESULTS: Normothermic and hyperthermic perfusion of tumour-bearing rat limbs using miniature equipment was feasible and tolerated by the animals. Regional hyperlactacidaemia of 10 mmol/l could be maintained throughout the perfusions. After combined treatment with hyperthermia and hyperlactacidaemia, tumour volume decreased and extensive tumour necrosis occurred, while in other animals aggressive tumour growth with bone infiltration could be observed. CONCLUSIONS: The present study demonstrates the applicability of hyperlactacidaemia in hyperthermic isolated limb perfusion in the rat and proved a tumour growth delay due to an induction of tumour necrosis thereafter. Further investigations in other tumour entities and experimental models are required to confirm this impressive therapeutic effect of hyperthermia in combination with hyperlactacidaemia.

Remodeling of peritoneal-like structures by mesothelial cells: its role in peritoneal healing.

BACKGROUND: Intraabdominal adhesions are a common complication following laparotomy. Since the exact mechanisms involved in this processes are unknown we have analyzed in vitro the role of mesothelial cells in peritoneal healing. MATERIAL AND METHODS: Human mesothelial cells from omental tissue were cultivated for 2 weeks in a three-dimensional culture either on or in a collagen type I matrix. The effects of blood and collagen matrix were analyzed by exposing mesothelial cells to an overlying blood clot, simulating intraperitoneal bleeding, or a second collagen layer. The production of collagen types III and IV, fibronectin, and laminin was analyzed with immunohistochemical methods. RESULTS: Mesothelial cells grown on a collagen matrix formed a monolayer of flat or cobblestone-like cells whereas those cultivated in a collagen matrix exhibited spindle-like morphology. Mesothelial cells failed to grow into an overlying collagen matrix, but did grow into a blood clot, emphasizing a potential role of blood clots in peritoneal adhesion formation. Independent of the culture systems mesothelial cells produced collagen type III, fibronectin, and laminin but not collagen type IV. CONCLUSIONS: Our experiments demonstrate remodeling of peritoneal-like structures by mesothelial cells in a three-dimensional culture reflecting their putative role in the reepithelialization after serosal defects, and also in the formation of peritoneal adhesions.

[Somatostatin receptor status in non-medullary thyroid carcinoma]. / Untersuchungen zum Somatostatinrezeptor-Status bei nicht-medullären Schilddrüsenkarzinomen.

AIM: Recent in-vitro and in-vivo studies demonstrated a somatostatin receptor expression in some non-medullary thyroid carcinomas. In this study we investigated the somatostatin receptor status for this particular tumor entity in a larger patient group. SUBJECT AND METHODS: We compared 131-iodine with 111-In-pentetreotide scans in 24 patients with metastasizing, non-medullary thyroid cancer. The findings were correlated with other imaging modalities. Additionally, we performed receptor autoradiography in one patient, octreotide therapy in another patient and administration of 90-Y- and 111-In-DOTATOC in 2 consecutive patients. RESULTS: In the 15 patients with papillary or follicular carcinoma, 111-In-pentetreotide was inferior to 131-I in 8/15, equal in 1/15, and superior in 6/15 patients. In 8/9 of the patients with Hürthle cell carcinoma, metastases showed a 111-In-pentetreotide accumulation of various intensity, while 131-iodine scans were negative except for one patient. 111-In-pentetreotide was equal or superior compared to 201-Tl or 99m-Tc-sestamibi, but for the most part inferior in comparison with 18-F-FDG-PET. The findings of 111-In-pentetreotide scintigraphy correlated well with the receptor autoradiography and the accumulation of DOTATOC, but not with the therapeutic effect of "cold" octreotide on the thyroid cancer metastases. CONCLUSIONS: Several metastases of papillary and follicular carcinoma, and the majority of Hürthle cell cancer metastases can express somatostatin receptors. 111-In-pentetreotide scintigraphy is a promising tool for localization of metastases especially in Hürthle cell cancer or if PET is not available, and may be useful for selection of possible candidates, if therapeutic effective beta-emitting somatostatin analogues will be available for routine application.

Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma: German and Austrian experience.

When mutations of the RETproto-oncogene were found in 1993 to account for hereditary medullary thyroid carcinoma (MTC), surgeons obtained the opportunity to operate on patients prophylactically (i. e., at a clinically asymptomatic stage). Whether this approach is justified, and, if so, when and to which extent surgery should be performed remained to be clarified. A questionnaire was sent to all surgical departments in Germany and Austria. All of the patients who fulfilled the following criteria were enrolled: (1) preoperatively proved RET mutation; (2) age

[Unusual coincidence of partially active endocrine tumors]. / Ungewöhnliche Häufung von partiell endokrin aktiven Tumoren.

We report on a female patient who developed five different tumors between the age of 53 and 62 years. The following tumors were diagnosed, three of which showed endocrine activity: uterine myoma; hemangiopericytoma of the meninges; pleural mesothelioma; preperitoneal leiomyoma; medullary carcinoma of the thyroid (sporadic form) in a hyperthyroid goiter. Coexistence of hyperthyroidism and medullary carcinoma of the thyroid is rare. Paraneoplastically induced hypoglycemia--in this patient induced by the pleural mesothelioma and less by the preperitoneal leiomyoma--is of similarly infrequent occurrence. Tumors of epithelial or mesenchymal origin may cause hypoglycemia as a result of peptide secretion, exerting an insulin-like effect. The detection of IGF-I and IGF-II in the serum confirms the diagnosis. Insulinoma can be differentiated by the absence of hyperinsulinemia.

[Prognostic value of e-cadherin in papillary thyroid carcinoma]. / Prognostische Bedeutung des e-Cadherin beim papillären Schilddrüsencarcinom.

The prognostic significance of e-cadherin in papillary thyroid carcinoma was evaluated in a retrospective study. From September 1985 to December 1996, 113 patients underwent surgery for papillary thyroid carcinoma. Seventy-eight formalin-fixed, paraffin-embedded tissue samples were available for immunohistochemical analysis of e-cadherin expression. In 74 of these 78 patients the postoperative course is known for 2 months to 35.2 years (median 3.6 years, mean: 4.9 +/- 4.8 years). Reduced or negative e-cadherin expression (< or = 20%) was associated with advanced T categories of the primary tumours and higher rates of synchronous lymph node involvement and distant metastasis. During follow-up in this group of patients locoregional tumour recurrence occurred more frequently and survival was shorter than in patients with tumours which exhibited e-cadherin expression of > 20%. Statistical analysis revealed e-cadherin expression (< or = 20%/ > 20%), synchronous distant metastasis (M0/pM1, cM1) and radicality of resection (R0/R1, 2) as significant risk factors for survival. Our findings provide evidence that e-cadherin is a prognostic factor in papillary thyroid carcinoma.

Prospective evaluation of parathyroid graft function after total parathyroidectomy and heterotopic autotransplantation in renal hyperparathyroidism by bilateral determination of intact parathormone in cubital venous blood.

The value of gradients for intact parathyroid hormone (PTH) in the assessment of graft function after total parathyroidectomy/autotransplantation for renal hyperparathyroidism was evaluated in a prospective follow-up study. Altogether 99 patients who underwent operation from August 1, 1987 to December 31, 1996 were prospectively investigated and reexamined postoperatively, including analyses of serum calcium, alkaline phosphatase, and intact PTH in the antecubital venous blood of both arms. The postoperative course is known for all patients. Of the 99 patients included in the study, 95 underwent one to nine reexaminations (median three) over follow-up periods of 1 month to 5 years (median 24 months). Reproducible PTH gradients were established during follow-up. Ninety percent of the calculated gradients were < or = 20. Intermittent postoperative hypocalcemia, due to calcium deficiency of the skeleton in renal osteopathy, led to an increase in PTH secretion and gradients. Increasing gradients > 20 during follow-up make graft-dependent recurrence probable. The presence of a gradient of approximately 1 in bilaterally elevated PTH levels may be an indication of hyperfunctioning parathyroid tissue in the neck or mediastinum. The combined assessment of the course of gradients for intact PTH, hormone levels in both arms, and serum calcium permits an objective evaluation of parathyroid graft function.