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.

[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.

[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.

[In-transit metastasis in melanoma: Efficacy of topical imiquimod combined with carbon dioxide laser or with electrocautery]. / Métastases en transit du mélanome : efficacité de l'imiquimod topique combiné au laser CO2 ou à l'électrocoagulation.

BACKGROUND: In-transit metastases in cutaneous melanoma are common and difficult to manage. Therapy is mainly palliative. Use of topical imiquimod has been assessed for surface metastases. PATIENTS AND METHODS: We report on four patients with cutaneous melanoma metastases treated with topical imiquimod associated with carbon dioxide laser in the first two patients and with electrocoagulation in the two others. For two patients, we noted complete regression of the lesions after 15 and 18 months. For the two others, treatment was stopped after 9 to 10 months because of progression of subcutaneous metastasis and distant metastasis. DISCUSSION: Topical imiquimod is an alternative treatment used in superficial in-transit metastasis of melanoma. Its use as a monotherapy is sometimes ineffective. We elected to use combined pre-treatment with carbon dioxide laser or electrocoagulation in order to potentiate the action of imiquimod. This simple and inexpensive therapeutic strategy constitutes a palliative treatment that can allow prolonged local control of cutaneous metastasis.

[Nodular cutaneous amyloidosis associated with Sjögren's syndrome]. / Amylose cutanée nodulaire et syndrome de Gougerot-Sjögren.

BACKGROUND: Cutaneous nodular amyloidosis is rare, and association with Sjögren's syndrome has been reported. We discuss the possible link between these two diseases based on a case we saw. PATIENTS AND METHODS: A 78-year-old woman with Sjögren's syndrome ongoing for 17 years presented for evaluation of a waxy infiltrated lesion on her left leg that had appeared 6 months earlier. Histopathological examination revealed a deposit of homogenous eosinophilic material throughout the dermis consistent with amyloidosis. Immunohistochemical study showed these deposits to be AL immunoglobin light chains. DISCUSSION: The association of cutaneous nodular amyloidosis and Sjögren's syndrome appears to be a distinct disease entity reflecting the polymorphic clinical spectrum of lymphoproliferative diseases related to Sjögren's syndrome.

Pheochromocytoma and abdominal paraganglioma.

Pheochromocytomas (PHEO) and paragangliomas (PGL) are tumors derived from the sympathetic and parasympathetic nervous system. The parasympathetic-associated paragangliomas arising in the neck are usually non-functioning and are rarely encountered by general and visceral surgeons. The sympathetic-associated PHEO and PGL are usually functioning and most often arise in the abdomen. Because they harbor very specific characteristics (hypersecretion of catecholamines, familial origin in up to 30% of them, multiple locations, etc.) their perioperative management needs to be known by surgeons taking care of these patients in order to avoid operative disasters. Surgery can lead to perioperative hemodynamic modifications and sometimes catecholamine storm even in normotensive patients with PHEO and PGL. This emphasizes the need to exclude PHEO before any adrenal surgery as well as to medically prepare all patients with PHEO and PGL preoperatively. We review in this paper the pathophysiology and current perioperative management of patients with apparently sporadic PHEO and PGL.

[Mohs micrographic surgery in two children with dermatofibrosarcoma protuberans]. / Chirurgie micrographique de Mohs dans le dermatofibrosarcome de Darier-Ferrand de l'enfant.

Dermatofibrosarcoma protuberans is a rare low-grade malignant tumor. The pseudopodia structure of the tumor requires 3-5 cm surgical margins. Mohs micrographic surgery (MMC) can reduce these margins to 1.3 cm while controlling all the histological excision margins. Children seem to be a good indication for this technique because it reduces the amount of skin removed. We report 2 cases of pediatric DFS treated with CMM to illustrate the usefulness of this technique in pediatrics. Two girls, aged 12 and 13 years, had a dermatofibrosarcoma located on the breast and sternum, respectively. CMM was proposed. One operative session was needed with direct closure in a second phase. MMS is a useful surgical technique for childhood tumors. If dermatofibrosarcoma is a very good indication in children, other skin tumors could benefit from this approach.

[Recurrent neutrophilic panniculitis in a patient with chronic myelogenous leukaemia treated with imatinib mesilate and dasatinib]. / Panniculite neutrophilique récidivante chez une patiente traitée par imatinib mésilate puis dasatinib pour une leucémie myéloïde chronique.

BACKGROUND: Tyrosine kinase inhibitors are now established as valuable therapy in chronic myelogenous leukaemia (CML). They induce several types of cutaneous side effect, the most common being non-specific maculopapular rash and periocular oedema. Rare cases of panniculitis have been described in patients with CML treated with imatinib mesilate and dasatinib. We report a case of recurrent panniculitis in a patient with CML treated successively with imatinib mesilate and dasatinib. CASE REPORT: An 81-year-old woman diagnosed with chronic CML experienced two episodes of neutrophilic panniculitis following imatinib mesilate therapy, as well as relapse following replacement of imatinib mesilate by dasatinib. Several skin biopsies showed a neutrophilic infiltrate throughout the fatty tissue lobules, without vasculitis and without any evidence of bacterial infection. The symptoms gradually subsided without discontinuation of tyrosine kinase inhibitor therapy. DISCUSSION: Neutrophilic panniculitis is uncommon among patients treated with tyrosine kinase inhibitors and has only been described in patients treated for chronic myeloid leukaemia. We discuss the potential causative role of imatinib mesilate and dasatinib in onset of the disease, as well as differential diagnosis of neutrophilic panniculitis, which resembles subcutaneous Sweet's syndrome.

Randomized controlled trial of bilateral superficial cervical plexus block versus placebo in thyroid surgery.

BACKGROUND: Bilateral superficial cervical block during thyroid surgery can reduce postoperative pain but its value is unclear. This randomized clinical trial assessed the efficacy of such regional anaesthesia on postoperative pain after thyroid surgery performed under general anaesthesia. METHODS: Patients undergoing thyroid surgery were randomized to one of four groups in a double-blind fashion. Patients received a cervical block with placebo or bupivacaine at the start or end of surgery. Postoperative pain, analgesic use and length of hospital stay were assessed. RESULTS: There were 159 patients eligible for analysis. The bupivacaine group had significantly less pain than the placebo group (P = 0.016). The timing of bupivacaine administration did not significantly influence pain (preoperative versus postoperative, P = 0.723). There was no difference between groups in the amount of analgesic used. Length of hospital stay was the same in the bupivacaine and placebo groups (P = 0.925) and when bupivacaine was administered at the beginning or end of surgery (P = 0.087). CONCLUSION: Bilateral superficial cervical block with bupivacaine combined with general anaesthesia significantly reduced postoperative pain after thyroid surgery. REGISTRATION NUMBER: NCT00472446 (http://www.clinicaltrials.gov).

Diagnosis and treatment of small follicular thyroid carcinomas.

BACKGROUND: Follicular thyroid microcarcinomas (mFTCs) of 10 mm or less in size rarely manifest clinically and their clinical significance is controversial. This study assessed their characteristics and incidence, and analysed treatment modalities used for mFTC. METHODS: Members of the German Association of Endocrine Surgeons were asked to review patients with mFTC operated on between 1990 and 2005. RESULTS: Data for 90 patients from 26 institutions were reported. Histopathological slides were available for re-evaluation in 35 patients. Most initial diagnoses had to be revised because of incorrect size assessment or incorrect diagnosis (benign adenoma, papillary thyroid carcinoma (PTC), follicular variant of PTC). The diagnosis of mFTC was confirmed in only four patients. As a result of the incorrect histopathological diagnosis, unnecessary completion thyroidectomy and radioiodine ablation were performed in 17 and 20 patients respectively. The incidence of mFTC was calculated to be 0.12 per million population per year. CONCLUSION: mFTC is exceptionally rare. Such tumours are overdiagnosed, resulting in unnecessary treatment associated with avoidable morbidity. Histopathological re-evaluation by an experienced pathologist is recommended before embarking on further treatments when a diagnosis of mFTC is made.

Human papillomavirus 16-specific T cell responses in classic HPV-related vulvar intra-epithelial neoplasia. Determination of strongly immunogenic regions from E6 and E7 proteins.

Cell-mediated immunity directed against human papillomavirus 16 (HPV-16) antigens was studied in 16 patients affected with classic vulvar intra-epithelial neoplasia (VIN), also known as bowenoid papulosis (BP). Ten patients had blood lymphocyte proliferative T cell responses directed against E6/2 (14-34) and/or E6/4 (45-68) peptides, which were identified in the present study as immunodominant among HPV-16 E6 and E7 large peptides. Ex vivo enzyme-linked immunospot-interferon (IFN)-gamma assay was positive in three patients who had proliferative responses. Twelve months later, proliferative T cell responses remained detectable in only six women and the immunodominant antigens remained the E6/2 (14-34) and E6/4 (45-68) peptides. The latter large fragments of peptides contained many epitopes able to bind to at least seven human leucocyte antigen (HLA) class I molecules and were strong binders to seven HLA-DR class II molecules. In order to build a therapeutic anti-HPV-16 vaccine, E6/2 (14-34) and E6/4 (45-68) fragments thus appear to be good candidates to increase HPV-specific effector T lymphocyte responses and clear classic VIN (BP) disease lesions.

[Lichen striatus with nail dystrophy in an infant]. / Lichen striatus avec dystrophie unguéale chez un nourrisson.

BACKGROUND: Lichen striatus is an acquired eruption that develops in a linear pattern along Blaschko's lines, most commonly on the limbs. It is most often seen in children aged between 3 and 10 years. Nail involvement is uncommon. We report the case of an infant with lichen striatus and nail involvement. CASE REPORT: A 10-month-old boy was referred for evaluation of acquired onychodystrophy on his right third and fourth fingers present for 2 months. On physical examination, lateral longitudinal ridging and splitting were seen on the right third and fourth fingernails with onychodystrophy. Linear bands of bright pink papules were seen on the inside and outside edges of the third and fourth fingers. Skin biopsy revealed a lymphocytic infiltrate in the superficial dermis with exocytosis and very few dyskeratotic cells, suggesting lichen striatus. Skin and nails lesions resolved spontaneously over 9 months. DISCUSSION: Nail involvement in lichen striatus is uncommon and is frequently associated with typical skin lesions. Thirty cases have been reported in the literature since 1941. None of the subjects affected was younger than 2-years-old. Nail involvement was more frequent on the fingers, especially the thumb. As in the present case, longitudinal ridging, splitting and thinning with onychodystrophy are common clinical features of nail involvement. The diagnosis of lichen striatus is based on the presence of skin lesions and can be confirmed by biopsy.

[Disseminated BCG infection revealing X-linked severe combined immunodeficiency]. / BCGite disséminée révélant un déficit immunitaire combiné sévère lié à l'X.

BACKGROUND: Live attenuated Bacillus Calmette-Guérin (BCG) vaccine is rarely responsible for disseminated infection. We report a case of X-linked severe combined immunodeficiency (SCID) revealed by a disseminated skin infection. PATIENTS AND METHODS: A 4-month-old baby was hospitalized for prolonged gastroenteritis. He was in poor general condition, with prolonged fever, oral and gluteal candidiasis and purple nodules associated with ulceration of the BCG scar. The absence of a thymus, T-cells and NK-cells, and the presence of nonfunctional B-lymphocytes led to a diagnosis of SCID. Biopsies of nodules revealed a dermal infiltrate without necrosis. A Ziehl-Neelson stain was highly positive and the culture grew Mycobacterium bovis. Treatment consisted of a four-drug antibiotic regimen directed against M. bovis combined with gamma interferon, immunoglobulins and antibiotic prophylaxis by cotrimoxazole and was followed by a haploid-identical bone marrow transplant without rejection at six months. The early death of the child's maternal uncle from sepsis suggested X-linked transmission, which was subsequently confirmed by genetic analysis. DISCUSSION: BCG vaccination can cause serious infections in immunocompromised subjects. Skin involvement is extremely rare but may be the first sign of SCID, of which the X-linked form is the most common and corresponds to a variety of mutations in the gene coding for the gamma chain common to several interleukin receptors. Genetic counselling is essential to identify female carriers and allow early antenatal diagnosis. Bone marrow transplantation is the only treatment.

National survey on the management of primary hyperparathyroidism by Swiss endocrinologists.

BACKGROUND: From the endocrine surgeon's perspective, it is important to know how endocrinologists manage patients with primary hyperparathyroidism (pHPT). The aim of this survey was to evaluate the preoperative diagnostic workup and referral pattern for parathyroidectomy by Swiss endocrinologists. MATERIALS AND METHODS: The survey was conducted by mailing a questionnaire to all members of the Swiss Society for Endocrinology and Diabetes in spring 2005. RESULTS: The questionnaire was sent back by 68 of 124 endocrinologists (55%). The median annual case volume of patients with pHPT was 6 (range 1-50). The mean fraction of these patients referred for surgery was 59 +/- 24%. This fraction was significantly higher in the German-speaking part of Switzerland than in the French-speaking part (67 +/- 21% vs 51 +/- 27%). When considering surgery for asymptomatic pHPT, 62% of the endocrinologists rely routinely on the recommendations of the NIH consensus conference and 86% on the subsequent guidelines of the workshop in 2002. Sixty-seven percent of the endocrinologists routinely perform localization studies before possible referral for surgical exploration. Typically, they consisted of an ultrasonography of the neck (93%) and a (99m)Tc-MIBI scintigraphy (80%). The impact of the availability of a minimally invasive surgical procedure on the number of patients referred for surgery seems to be considerable. Sixty-one percent of the participants would expand the indication for surgery if the operation could be done by a limited surgical approach. CONCLUSIONS: In a relevant fraction of patients with pHPT, endocrinologists still do not regard curative therapy as mandatory. Surprisingly, there are significant cultural differences concerning referral patterns to surgery between the German-speaking and the French-speaking parts of Switzerland. Minimally invasive procedures seem to lower the threshold for referral for surgical therapy.