Bruno Niederle

Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: Foregut, midgut, hindgut, and unknown primary

a DRK Kliniken Westend, Berlin , Germany; b UFR Bichat-Beaujon-Louis Mourier, Service de Chirurgie Digestive, Hopital Louis Mourier, Colombes , France; c Medicine and Surgery, General Surgery Section, MED/18 – General Surgery and d Department of Pathology, University of Verona, Verona , Italy; e Netherlands Cancer Centre, Amsterdam , and f Department of Nuclear Medicine, Erasmus University Medical Center, Rotterdam , The Netherlands;

Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters

As incidence data on gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have so far only been retrospectively obtained and based on inhomogeneous material, we conducted a prospective study in Austria collecting all newly diagnosed GEP-NETs during 1 year. Using the current WHO classification, the tumor, nodes, metastases (TNM) staging and Ki67 grading and the standard diagnostic procedure proposed by the European Neuroendocrine Tumor Society (ENETS), GEP-NETs from 285 patients (male: 148; female: 137) were recorded. The annual incidence rates were 2.51 per 100,000 inhabitants for men, 2.36 per 100,000 for women. The stomach (23%) was the main site, followed by appendix (21%), small intestine (15%) and rectum (14%). Patients with appendiceal tumours were significantly younger than patients with tumours in any other site. About 46.0% were classified as benign, 15.4% as uncertain, 31.9% as well differentiated malignant and 6.7% as poorly differentiated malignant. Patients with benign or uncertain tumours were significantly younger than patients with malignant tumours. Among the malignant tumours of the digestive tract, 1.49% arose from neuroendocrine cells. For malignant gastrointestinal NETs, the incidence was 0.80 per 100,000: 40.9% were ENETS stage I, 23.8% stage II, 11.6% stage III and 23.8% stage IV. The majority (59.7%) were grade 1, 31.2% grade 2 and 9.1% grade 3. NETs of the digestive tract are more common than previously reported; the majority show benign behaviour, are located in the stomach and are well differentiated. G3 tumours are very rare.

ENETS Consensus Guidelines for the Management of Patients with Neuroendocrine Neoplasms from the Jejuno-Ileum and the Appendix Including Goblet Cell Carcinomas

a Division of Hepatology and Gastroenterology, Department of Internal Medicine, Campus Virchow-Klinikum, Charite-Universitatsmedizin Berlin, Berlin , Germany; b Department of Pathology, Universitatsspital, Zurich , Switzerland; c Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; d Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem , Israel; e Department of Internal Medicine, Philipps University, Marburg , Germany; f Hopital Sirio Libanes, Centro de Oncologia, Sao Paulo , Brazil; g Department of Radiology, Campus Virchow-Klinikum, Charite, University Medicine Berlin, Berlin , Germany; h Department of Oncology, Institut Catala d’Oncologia (IDIBELL), Barcelona , Spain; i Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford , UK

Gastrinoma (Duodenal and Pancreatic)

a Digestive Diseases Branch, NIH, Bethesda, Md. , USA; b Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; c Department of Hepatology and Gastroenterology, CHV A Pare Hospital, Boulogne , France; d Department of Gastroenterology, North Hampshire Hospital, Hampshire , UK; e Department of Surgery, Vivantes Humboldt Hospital, Berlin , Germany; f Department of Radiology, Royal Marsden Hospital, Sutton , UK; g Department of Pathology, Verona University, Verona , Italy; h Department of Radiology, Uppsala University, Uppsala , Sweden; i Department of Pathology, Universitatsspital Zurich, Zurich , Switzerland; j Department of Endocrinology and Metabolism, Hadassah University, Jerusalem , Israel; k Department of Oncology, Alexander Fleming Institute, Buenos Aires , Argentina; l Laboratory of Molecular Imaging and Experimental Radiotherapy, Universite Catholique de Louvain, Brussels , Belgium; m Department of Pathology, University Hospital of Kiel, Kiel , Germany

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.

Prophylactic Thyroidectomy in 75 Children and Adolescents with Hereditary Medullary Thyroid Carcinoma: German and Austrian Experience

Abstract. When mutations of theRETproto-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 ≤ 20 years, (3) clinically asymptomatic thyroid C cell disease; and (4) TNM classification pT0–1/pNX/pN0–1/M0. Seventy-five patients were identified, and fifteen mutations were detected in six codons. Two adolescents had unilateral pheochromocytomas as part of the multiple endocrine neoplasia II (MEN-II) syndrome. No hyperparathyroidism was noted. All patients underwent total thyroidectomy, and 57 patients went on to have lymph node dissection. Parathyroid glands were removed in 34 patients and autografted in 11. Histopathology revealed MTC in 46 patients (61%, youngest 4 years); C cell hyperplasia (CCH) only was detected in the other 29 patients. Three patients had lymph node metastases (LNMs) the youngest being age 14 years. Calcitonin levels were not useful for differentiating between CCH and MTC, but in all patients with LNMs at least the stimulated calcitonin levels were assayed. After surgery, five patients (6.7%) sustained permanent hypoparathyroidism, and one patient (1.3%) had a permanent unilateral recurrent nerve palsy. All but three patients (96%) were biochemically cured. In conclusion, prophylactic total thyroidectomy can be performed safely in experienced centers. We recommend prophylactic total thyroidectomy at age 6. Cervicocentral lymph node dissection should be included when calcitonin levels are elevated or if patients are older than 10 years. Bilateral lymph node dissection should be performed if LNMs are suspected or when patients with elevated calcitonin are older than 15 years.

Well-differentiated pancreatic tumor/carcinoma: Insulinoma

a Department of Internal Medicine, Section of Endocrinology, Erasmus MC, Rotterdam, The Netherlands; b Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; c Hospices Civils de Lyon, Hopital Edouard-Herriot Service Central d‘Anatomie et Cytologie Pathologiques, Lyon , France; d Centre de Medecine Nucleaire, Universite Catholique de Louvain, Brussels , Belgium; e Department of Pathology, University of Kiel, Kiel , Germany; f B Unit of Surgery, Department of Surgery, University of Verona, Verona , Italy; g Department of Nuclear Medicine, Erasmus MC, Rotterdam , The Netherlands; h Department of Endocrine Oncology, University Hospital, Uppsala , Sweden; i Department of Internal Medicine, Division of Hepatology and Gastroenterology, Interdisciplinary Center of Metabolism and Endocrinology, Charite, Campus Virchow Hospital, University for Medicine Berlin, Berlin , Germany; j Service de Gastroenterologie-Pancreatologie, Pole des Maladies de l‘Appareil Digestif, Hopital Beaujon, Clichy , France; k Department of Pathology and Laboratory Medicine, Universita degli Studi, Parma, Italy; l Department of Endocrinology, Genoa University, Genoa , Italy

Primary hyperparathyroidism: Incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy

PURPOSE This prospective study was designed to assess the effect of primary hyperparathyroidism on heart muscle, valves, and myocardial function. Echocardiography was used to evaluate changes in mechanical performance, the thickness of the left ventricular wall, myocardial calcific deposits, and valvular calcifications in patients with primary hyperparathyroidism. METHODS Echocardiography was performed in 54 patients with hyperparathyroidism prior to surgery and 12 +/- 2 months after successful parathyroidectomy. A matched control group was followed for comparison. RESULTS In a blinded fashion, aortic and mitral valve calcifications were detected in 63% and 49% of patients with primary hyperparathyroidism (controls: 12% and 15%, respectively). Calcific deposits in the myocardium were found in 69% of patients with hyperparathyroidism and 17% of the control subjects. After parathyroidectomy and 12 months of normocalcemia, a significant regression of left ventricular hypertrophy (p < 0.001) was observed. CONCLUSIONS The present data show a high incidence of left ventricular hypertrophy, calcific deposits in the myocardium, and/or aortic and mitral valve calcification in patients with primary hyperparathyroidism. A 1-year follow-up after parathyroidectomy (and restoration of normocalcemia) discloses regression of hypertrophy, while calcifications persist without evidence of progression.

Risk Factors for Malignancy of Thyroid Nodules Initially Identified as Follicular Neoplasia by Fine-Needle Aspiration: Results of a Prospective Study of One Hundred Twenty Patients

Indeterminate or suspicious findings on fine-needle aspiration (FNA) of nodular thyroid disease (i.e., findings that neither give immediate indication for surgery nor lead to clear-cut conservative management) have been the key diagnostic problem in thyroid cytology for which the inability to differentiate cytologically benign from malignant follicular growth has been one reason. The aim of this cohort study of 120 consecutive (103 females, 17 males) patients with palpable nodular thyroid disease diagnosed as follicular neoplasia (FN) by FNA (defined by the triad of high numbers of follicular cells, microfollicular arrangement, and scanty or absent colloid) was to identify patients at high risk for malignancy based on the prospective evaluation of clinical features and to characterize the histologic entities of FN. Based on a 100% surgery rate we found an 18% malignancy rate (12 papillary carcinomas, 9 follicular carcinomas). Previously suggested factors with elevated risk for malignancy such as extremes of age, male gender, and large nodule size were not associated with increased risk as were cold nodules by 99mTc-scintigraphy (relative risk: 1.2, 95% confidence interval [CI] 0.4-3.3). However, hard lesions to palpation (relative risk 2.6, 95% CI: 1.2-5.6), solitary (relative risk: 2.6, 95% CI: 1.7-4.0), and hypoechoic FNs (relative risk: 3.4, 95% CI: 2.0-5.7) by ultrasound showed elevated risks of malignancy. In summary, suspicious palpation or ultrasound results may help to define a subgroup of patients with elevated risk of malignancy when FNA indicates the diagnosis of follicular neoplasm of the thyroid.

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.