Surgery for primary hyperparathyroidism in Germany, Switzerland, and Austria: an analysis of data from the EUROCRINE registry.

PURPOSE: EUROCRINE is an endocrine surgical register documenting diagnostic processes, indication for surgical treatment, surgical procedures, and outcomes. The purpose was to analyse data for PHPT in German speaking countries regarding differences in clinical presentation, diagnostic workup, and treatment. METHODS: All operations for PHPT performed from 07/2015 to 12/2019 were analysed. RESULTS: Three thousand two hundred ninety-one patients in Germany (9 centres; 1762 patients), Switzerland (16 centres; 971 patients) and Austria (5 centres; 558 patients) were analysed. Hereditary disease was seen in 36 patients in Germany, 16 patients in Switzerland and 8 patients in Austria. In sporadic disease before primary operation, PET-CT showed the highest sensitivity in all countries. In re-operations, CT and PET-CT achieved the highest sensitivities. The highest sensitivity of IOPTH was seen in Austria (98.1%), followed by Germany (96.4%) and Switzerland (91.3%). Operation methods and mean operative time reached statistical significance (p<0.05). Complication rates are low. Overall, 656 (19.9%) patients were asymptomatic; the remainder showed bone manifestations, kidney stones, fatigue and/or neuropsychiatric symptoms. CONCLUSION: Early postoperative normocalcaemia ranged between 96.8 and 97.1%. Complication rates are low. PET-CT had the highest sensitivity in all three countries in patients undergoing primary operation as well as in Switzerland and Austria in patients undergoing re-operation. PET-CT could be considered a first-line preoperative imaging modality in patients with inconclusive ultrasound examination. The EUROCRINE registry is a beneficial and comprehensive data source for outcome analysis of endocrine procedures on a supranational level.

Omission of lateral lymph node dissection in medullary thyroid cancer without a desmoplastic stromal reaction.

BACKGROUND: Medullary thyroid cancer can be subdivided during surgery into tumours with or without a desmoplastic stromal reaction (DSR). DSR positivity is regarded as a sign of disposition to metastasize. The aim of this study was to analyse whether lateral lymph node dissection can be omitted in patients with DSR-negative tumours. METHODS: This was a retrospective cohort study of a prospectively maintained database of patients with medullary thyroid cancer treated using a standardized protocol, and subdivided into DSR-negative and -positive groups based on the results of intraoperative frozen-section analysis. Patients in the DSR-negative group did not undergo lateral lymph node dissection. Long-term clinical and biochemical follow-up data were collected, and baseline parameters and histopathological characteristics were compared between groups. RESULTS: The study included 360 patients. In the DSR-negative group (17.8 per cent of all tumours) no patient had lateral lymph node or distant metastases at diagnosis or during follow-up, and all patients were biochemically cured. In the DSR-positive group (82.2 per cent of all tumours), lymph node and distant metastases were present in 31.4 and 6.4 per cent of patients respectively. DSR-negative tumours were more often stage pT1a and were significantly smaller. The median levels of basal calcitonin and carcinoembryonic antigen were significantly lower in the DSR-negative group, although when adjusted for T category both showed widely overlapping ranges. CONCLUSION: Lymph node surgery may be individualized in medullary thyroid cancer based on intraoperative analysis of the DSR. Patients with DSR-negative tumours do not require lateral lymph node dissection.

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.

Surgical therapy of adrenal tumors: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: Previous guidelines addressing surgery of adrenal tumors required actualization in adaption of developments in the area. The present guideline aims to provide practical and qualified recommendations on an evidence-based level reviewing the prevalent literature for the surgical therapy of adrenal tumors referring to patients of all age groups in operative medicine who require adrenal surgery. It primarily addresses general and visceral surgeons but offers information for all medical doctors related to conservative, ambulatory or inpatient care, rehabilitation, and general practice as well as pediatrics. It extends to interested patients to improve the knowledge and participation in the decision-making process regarding indications and methods of management of adrenal tumors. Furthermore, it provides effective medical options for the surgical treatment of adrenal lesions and balances positive and negative effects. Specific clinical questions addressed refer to indication, diagnostic procedures, effective therapeutic alternatives to surgery, type and extent of surgery, and postoperative management and follow-up regime. METHODS: A PubMed research using specific key words identified literature to be considered and was evaluated for evidence previous to a formal Delphi decision process that finalized consented recommendations in a multidisciplinary setting. RESULTS: Overall, 12 general and 52 specific recommendations regarding surgery for adrenal tumors were generated and complementary comments provided. CONCLUSION: Effective and balanced medical options for the surgical treatment of adrenal tumors are provided on evidence-base. Specific clinical questions regarding indication, diagnostic procedures, alternatives to and type as well as extent of surgery for adrenal tumors including postoperative management are addressed.

Vaginal prolapse surgery with transvaginal mesh: results of the Austrian registry.

INTRODUCTION AND HYPOTHESIS: Several mesh repair systems for pelvic organ prolapse (POP) were introduced into clinical practice with limited data on safety, complications or success rates, and impact on sexual function. The Austrian Urogynecology Working Group initiated a registry to assess the use of transvaginal mesh devices for POP repair. We looked at perioperative data, as well as outcomes at 3 and 12 months. METHODS: Between 2006 and 2010 a total of 20 gynecology departments in Austria participated in the Transvaginal Mesh Registry. Case report forms were completed to gather data on operations, the postoperative course, and results at 3 and 12 months. RESULTS: A total of 726 transvaginal procedures with 10 different transvaginal kits were registered. Intra- and perioperative complications were reported in 6.8%. The most common complication was increased intraoperative bleeding (2.2%). Bladder and bowel perforation occurred in 6 (0.8%) and 2 (0.3%) cases. Mesh exposure was seen in 11% at 3 and in 12% at 12 months. 24 (10%) previously asymptomatic patients developed bowel symptoms by 1 year. De novo bladder symptoms were reported in 39 (10%) at 3 and in 26 (11%) at 12 months. Dyspareunia was reported by 7% and 10% of 265 and 181 sexually active patients at 3 and 12 months postoperatively respectively. CONCLUSIONS: The 6.8% rate of intra- and perioperative complications is in line with previous reports. Visceral injury was rare. The 12% rate of mesh exposure is consistent with previous series.

Tropane-derived (11) C-labelled and (18) F-labelled DAT ligands.

Radiolabelling of cocaine-derived 3-phenyltropanes for dopamine transporter positron emission tomography with (18) F and (11) C is reviewed.

pHH3 and survivin are co-expressed in high-risk endometrial cancer and are prognostic relevant.

BACKGROUND: Phosphohistone-H3 (pHH3) is a promising reliable mitotic count biomarker. Our purpose was to study the relationship between the novel proliferation marker pHH3 and the established anti-apoptotic marker survivin and consider their prognostic relevance in endometrial cancer. METHODS: A total of 106 patients with endometrial cancer (type I/endometrioid, n=81; type II carcinomas, n=18) and simple hyperplasia without atypia (n=7) were investigated. pHH3 and survivin expression were assessed using immunohistochemistry from paraffin-embedded tissue blocks. RESULTS: A strong positive correlation was observed between pHH3 and survivin expression (P<0.0001). Patients with high-grade tumours and patients with type II carcinomas expressed significantly more pHH3 and survivin than low grade and endometrioid tumours (P<0.0001, P<0.0001, P<0.0001, and P<0.0001, respectively). In univariate survival analysis, overexpression of pHH3 and survivin were associated with increased recurrence and mortality (P<0.0001, P<0.0001, P<0.0001, and P<0.0001, respectively), in the multivariable Cox regression analyses both pHH3 and survivin could be identified as independent parameters for overall survival (P=0.004, and P=0.023, respectively). CONCLUSION: In endometrial cancer, pHH3 and survivin were strongly positive correlated and were both associated with type II and high-grade tumours. Increasing expression levels of pHH3 and survivin were associated with adverse prognostic factors.

Bone metabolism in patients with primary hyperparathyroidism before and after surgery.

Primary hyperparathyroidism (PHPT) is accompanied with a reduced bone mineral density (BMD) and an increased risk of fracture. Surgery is the only option for cure. It is hypothesized that in patients with PHPT bone metabolism normalizes after parathyroidectomy (PTX) and that BMD gradually increases. Fifty-two patients with PHPT who underwent surgery were prospectively followed for 1 year. Biochemical analyses were performed at baseline and 1, 4, 7 days; 6 weeks; and 3, 6, and 12 months, and BMD before and one year after surgery. Parathyroid hormone (PTH), calcium, and the bone resorption marker dropped immediately, but transiently after PTX, bone formation decreased more slowly. Osteoprotegerin (OPG) as well as cathepsin K did not show significant changes. BMD of the lumbar spine, but not of the femoral neck, increased significantly within one year after surgery. Moderate correlations existed between the changes of total calcium, ionized calcium, as well as bone-specific alkaline phosphatase and changes of the lumbar BMD. Patients who needed postoperative supplementation with calcium and vitamin D had significantly higher PTH levels. Some gender-specific differences in patients with PHPT were observed. In patients with PHPT, males appear to be more severely affected than females. Within the first year after PTX, bone metabolism normalized, and BMD of the lumbar spine increased. Patients who needed a supplementation with calcium and vitamin D after PTX preoperatively had higher serum levels of PTH.

Accuracy of concepts in female pelvic floor anatomy: facts and myths!

The pelvic floor is characterized by a complex morphology because different functional systems join here. Since a clear understanding of the pelvic floor region is crucial for female pelvic surgery and fundamental mechanisms of urogenital dysfunction and treatment, we here describe the accurate and functional anatomy of important pelvic structures and landmarks, clarify their terminology and point out possible errors or misunderstandings as to their existence.

How I treat medullary thyroid cancer.

Medullary thyroid cancer (MTC) represents a rare neuroendocrine neoplasm originating from neoplastic C-cells in the thyroid gland. While localized disease is potentially curable with an optimized surgical approach, the number of relapses is high, and a considerable number of patients present with primary metastatic disease. Multidisciplinary management including standardized surveillance following surgery, but also early involvement of medical oncologists, is therefore important. Several oncogenic pathways are involved in the pathogenesis of MTC including vascular endothelial growth factor receptor, epidermal growth factor receptor, MET, and most importantly RET, and the multi-tyrosine kinase inhibitors vandetanib and cabozantinib have been approved for advanced MTC based on data from phase III studies. As activating RET mutations represent the most important driver, specific RET inhibitors were introduced and suggest high response rates with limited off-target toxicities. The current review provides a practical overview on clinical presentation and management from early to advanced MTC.

[EUROCRINE®: adrenal surgery 2015-2019- surprising initial results]. / EUROCRINE®: Nebennierenoperationen 2015 bis 2019 ­ überraschende erste Ergebnisse.

BACKGROUND: Since 2015 operations performed in the field of endocrine surgery have been entered into the European registry EUROCRINE®. The aim of this analysis was a description of the current healthcare situation for adrenal surgery in a homogeneous healthcare environment corresponding to the German-speaking countries-or to the presence of the working group on surgical endocrinology (CAEK) of the German society for general and visceral surgery (DGAV)-and to assess the adherence to current international treatment guidelines. METHODS: An analysis of the preoperative diagnostics, the applied operative techniques and the underlying histological entities was carried out for all operations on adrenal glands in Germany, Switzerland and Austria, which were registered in EUROCRINE® from 2015 to 2019. RESULTS: In the total of 21 participating hospitals from the German-speaking EUROCRINE® countries, 658 operations on adrenal glands were performed. In 90% of cases unilateral adrenalectomy was performed, in 3% bilateral adrenalectomy and in 7% other resection procedures. In 41% the main histological diagnosis was an adrenocortical adenoma. In 15% malignant entities were detected on final histology, including 6% adrenocortical carcinoma (ACC) and 8% metastases to the adrenal glands. 23% of the operations were performed for pheochromocytoma. This entity was primarily resected using minimally invasive approaches (82%), whereas minimally invasive techniques were applied in 28% for ACC and in 66% for metastases to the adrenal glands. CONCLUSION: Surprisingly, following adrenocortical adenoma and pheochromocytoma, the third most common histological entity was metastasis of different extra-adrenal primary tumors to the adrenal gland. Of the operations for ACC 28% were scheduled for minimally invasive techniques, but conversion to open surgery was necessary in 20%. The analysis revealed discrepancies between treatment reality and international guideline recommendations that raise questions, which will be addressed by an updated version of the EUROCRINE® module for the documentation of adrenal surgery.

Effect of intraoperative nerve monitoring on postoperative vocal cord palsy rates after thyroidectomy: European multicentre registry-based study.

BACKGROUND: Intraoperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) predicts the risk of vocal cord palsy (VCP). IONM can be used to adapt the surgical strategy in order to prevent bilateral VCP and associated morbidity. Controversial results have been reported in the literature for the effect of IONM on rates of VCP, and large multicentre studies are required for elucidation. METHODS: Patients undergoing first-time thyroidectomy for benign thyroid disease between May 2015 and January 2019, documented prospectively in the European registry EUROCRINE®, were included in a cohort study. The influence of IONM and other factors on the development of postoperative VCP was analysed using multivariable regression analysis. RESULTS: Of 4598 operations from 82 hospitals, 3542 (77·0 per cent) were performed in female patients. IONM was used in 4182 (91·0 per cent) of 4598 operations, independent of hospital volume. Postoperative VCP was diagnosed in 50 (1·1 per cent) of the 4598 patients. The use of IONM was associated with a lower risk of postoperative VCP in multivariable analysis (odds ratio (OR) 0·34, 95 per cent c.i. 0·16 to 0·73). Damage to the RLN noted during surgery (OR 24·77, 12·91 to 48·07) and thyroiditis (OR 2·03, 1·10 to 3·76) were associated with an increased risk of VCP. Higher hospital volume correlated with a lower rate of VCP (OR 0·05, 0·01 to 0·13). CONCLUSION: Use of IONM was associated with a low rate of postoperative VCP.

ANTECEDENTES: La monitorización nerviosa intraoperatoria (intraoperative nerve monitoring, IONM) del nervio laríngeo recurrente (recurrent laryngeal nerve, RLN) predice el riesgo de parálisis de la cuerda vocal (vocal cord palsy, VCP). La IONM se puede utilizar para adaptar la estrategia quirúrgica con el objetivo de prevenir la VCP bilateral y la morbilidad asociada. La literatura describe resultados controvertidos de la influencia de la IONM sobre las tasas de VCP, por lo que se requieren grandes estudios multicéntricos para aclararlo. MÉTODOS: De mayo de 2015 a enero de 2019, las tiroidectomías efectuadas como primera intervención quirúrgica por patología tiroidea benigna - documentadas prospectivamente en el registro europeo EUROCRINE© - se incluyeron en un estudio de cohortes. La influencia de la IONM y otros factores sobre el desarrollo de VCP postoperatoria fueron analizados utilizando un análisis de regresión multivariable. RESULTADOS: De 4.598 operaciones efectuadas en 82 hospitales e incluidas en el estudio, 3.542 (77,0%) fueron realizadas en mujeres. La IONM se utilizó en 4.182 de 4.598 (91,0%) operaciones independientemente del volumen del hospital. La VCP postoperatoria se diagnosticó en 50 de 4.598 (1,1%) pacientes. La utilización de IONM se asoció con un menor riesgo de VCP postoperatoria en el análisis multivariable (razón de oportunidades, odds ratio, OR 0,34 (i.c. del 95% 0,16-0,73)). La detección de lesión del RLN durante la cirugía (OR 24,77 (12,91 a 48,07)) y la tiroiditis (OR 2,03 (1,10 a 3,76)) se asociaron con un riesgo aumentado de VCP. Un elevado volumen de casos se correlacionó con menor frecuencia de VCP (OR 0,05 (0,01 a 0,13)). CONCLUSIÓN: La utilización de la IONM se asoció con una baja tasa de VCP postoperatoria.

Experiences with the standardized classification of surgical complications (Clavien-Dindo) in general surgery patients.

BACKGROUND: The standardized Clavien-Dindo classification of surgical complications is applied as a simple and widely used tool to assess and report postoperative complications in general surgery. However, most documentation uses this classification to report surgery-related morbidity and mortality in a single field of surgery or even particular intervention. The aim of the present study was to present experiences with the Clavien-Dindo classification when applied to all patients on the general surgery ward of a tertiary referral care center. METHODS: We analyzed a period of 6 months of care on a ward with a broad range of general and visceral surgery. Discharge reports and patient charts were analyzed retrospectively and reported complications rated according to the most recent Clavien-Dindo classification version. The complexity of operations was assessed with the Austrian Chamber of Physicians accounting system. RESULTS: The study included 517 patients with 817 admissions, of whom 463 had been operated upon. Complications emerged in 12.5%, of which 19% were rated as Clavien I, 20.7% as Clavien II, 13.8% as Clavien IIIa, 27.6% as Clavien IIIb, 8.6% as Clavien IVa, and 10.3% as Clavien V. No Clavien grade IVb complication occurred within the investigation. Patients having undergone more complex surgery or with higher scores experienced significantly longer lengths of hospital stay. CONCLUSION: The Clavien-Dindo classification can easily be used to document complication rates in general surgery, even though this collective was not included in the original validation studies of Clavien et al. and consisted of more heavily impaired patients.

[Update of the S2k guidelines : Surgical treatment of benign thyroid diseases]. / Aktualisierung der S2k-Leitlinie : Operative Therapie benigner Schilddrüsenerkrankungen.

Thyroid resections represent one of the most common operations with 76,140 interventions in the year 2016 in Germany (source Destatis). These are predominantly benign thyroid gland diseases. Recommendations for the operative treatment of benign thyroid diseases were last published by the CAEK in 2010 as S2k guidelines (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. [AWMF] 003/002) against the background of increasingly more radical resection procedures. Hemithyroidectomy and thyroidectomy are routinely performed for benign thyroid disease in practice. The operation-specific risks show a clear increase with the extent of the resection. Therefore, weighing-up of the risk-indications ratio between unilateral lobectomy or thyroidectomy necessitates an independent evaluation of the indications for both sides. This principle in particular has been used to update the guidelines. In addition, the previously published recommendations of the CAEK for correct execution and consequences of intraoperative neuromonitoring were included into the guidelines, which in particular serve the aim to avoid bilateral recurrent laryngeal nerve paralysis. Moreover, the recommendations for the treatment of postoperative complications, such as hypoparathyroidism and postoperative infections were revised. The updated guidelines therefore represent the current state of the science as well as the resulting surgical practice.

Nucleolar organizer regions as markers of endometrial proliferation: a study of normal, hyperplastic, and neoplastic tissue.

Nucleolar organizer regions (NORs) are loops of DNA that transcribe to ribosomal RNA. They can be visualized as intranuclear black dots by histochemical staining with a colloid silver solution. We applied this method to 78 sections of endometrial tissue obtained either from curettage or from hysterectomy specimens. The histological diagnoses were as follows: normal proliferative (N = 9) or secretory (N = 5) endometrium, simple hyperplasia (N = 10), complex hyperplasia (N = 18), atypical hyperplasia (N = 8), and adenocarcinoma (N = 28). Mean silver-stained NOR (AgNOR) counts per cell were 3.2 (standard error of the mean [SEM], 0.2) in normal proliferative and 2.7 (SEM, 0.2) in normal secretory epithelium, and increased to 4.1 (SEM, 0.3) in simple hyperplasia, to 5.4 (SEM, 0.4) in complex hyperplasia, to 8.1 (SEM, 0.7) in atypical hyperplasia, and finally to 10.0 (SEM, 0.5) in endometrial carcinoma. The differences were significant (one-factor analysis of variance [ANOVA], P < .001). A slight increase but no significant difference was seen between the mean AgNOR counts in endometrial carcinomas of different histological grades. Our study suggests that AgNOR counts are reliable markers of endometrial proliferation and allow a clear distinction between benign, premalignant, and malignant epithelial changes. Our AgNOR findings in endometrial hyperplasia support the concept of various degrees of hyperplasia that can be differentiated on morphological grounds.