[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.

[Diagnostics and treatment of primary hyperparathyroidism]. / Diagnostik und Therapie des primären Hyperparathyreoidismus.

Primary hyperparathyroidism is a disease that occurs more frequently than generally thought and is often overlooked. Classical symptoms are bone pain and osteoporosis, renal calculi and peptic ulcers. Many patients are asymptomatic or have unspecific complaints. It is easy to establish the biochemical diagnosis based on calcium and parathormone (PTH) levels and 24-h urine calcium excretion. The most sensitive localization procedures for parathyroid adenomas are sonography and Tc-99m-MIBI scintigraphy. The indication for surgery is undisputed in symptomatic patients; however, there is controversy concerning patients without classical symptoms. Operative therapy is highly successful. Focused operative procedures are currently available besides the traditional 4­gland exploration. When focused techniques are used, the operative success should be confirmed by intraoperative determination of the parathormone level.

[Bilateral vocal cord paresis after total thyroidectomy]. / Bilaterale Stimmlippenparese nach totaler Thyreoidektomie.

A 66-year-old female patient complained of hoarseness and dyspnea under exertion following total thyroidectomy. Due to a faulty operating technique both nerves to the vocal cords were damaged. From the operation report it emerged that the dissection was carried out by protecting the border lamellae but the recurrent laryngeal nerve could not be found on both sides. This article presents the external expert opinion, the decision of the arbitration board and the assessment of the case by two specialist physicians.

Successful treatment of solid-pseudopapillary tumor of the pancreas with multiple liver metastases.

The solid-pseudopapillary tumor (SPT) is a very rare pancreatic neoplasm that predominantly affects young females. About 450 cases have been described in the world literature and approximately 20% of the reported patients were children. The occurrence of SPT with distant metastases in children is extremely rare with only two previously reported cases. We now report a 16-year-old Asian girl with a large SPT and synchronous multiple liver metastases who was successfully treated in a 2-step strategy, including initial pylorus-preserving partial duodenopancreatectomy, right hemicolectomy, resection and allografting of the portal vein and secondary resection of 12 liver metastases. The patient is disease free after a follow-up of 18 months after resection of the primary tumor, suggesting that an aggressive surgical treatment might also be justified for metastasized SPT.

Evaluation of the development of lung hypoplasia in the premature lamb.

BACKGROUND: The death rate from human diaphragmatic hernia (CDH) ranges from 50 to 80%, mainly due to the associated lung hypoplasia. To prevent these irreversible pathological and physical defects, the question of intrauterine surgical intervention arises. The histological changes of the lung tissue after inducement of a diaphragmatic hernia were examined. Of special interest was the time elapsing until the development of lung hypoplasia. METHODS: A model of intrauterine inducement of diaphragmatic hernia was established using five fetal lambs to study consecutive pulmonary hypoplasia. Inducement of a diaphragmatic hernia was undertaken between 105 and 108 days' gestation. Lung tissue was examined histologically on postoperative days 8, 17, 21, 22, and 25 after inducement of the defect. RESULTS: On postoperative days 8, 17, and 21, no signs of pulmonary hypoplasia were found on histological examination. A pulmonary hypoplasia was found in two fetuses (on the 22nd and 25th postoperative day). The pathological and anatomical examination of a unilateral pulmonary hypoplasia after a short period of time shows that the artificially created diaphragmatic defect is a good model for producing a congenital diaphragmatic hernia. DISCUSSION: The severity of the pulmonary hypoplasia is related to the duration of lung compression by the herniated organs. The time elapsing until the development of lung hypoplasia is shorter than expected. Tracheal occlusion seems to be an effective strategy for treatment of the defect CDH, but the best technique for achieving occlusion, and particularly the ideal point in time to carry out "Fetendo," are unknown. Further research into this congenital illness is required in order to treat it.

Conventional bilateral cervical exploration versus open minimally invasive parathyroidectomy under local anaesthesia for primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) has been introduced for the treatment of patients with primary hyperparathyroidism (pHPT). Thus far, only one randomized trial has compared video-assisted MIP with conventional bilateral cervical exploration (BCE). The value of open MIP is therefore not known. METHODS: Fifty patients with a solitary parathyroid adenoma localized before surgery by sestamibi scintigraphy were randomized to undergo BCE under general anaesthesia (n = 25) or targeted MIP via a 2-cm incision using local anaesthesia (n = 25). Postoperative hypocalcaemia was the primary endpoint. Secondary outcome measures were operating time, complications, postoperative analgesia and recurrent disease. Follow-up was carried out at 1 and 6 months. RESULTS: All patients who underwent BCE and 24 of those who had MIP were cured by the primary operation. Operating time was 22 min shorter in the MIP group (P = 0.024). Serum levels of calcium were slightly lower during the first 4 days after surgery in the BCE group (P = 0.022). No other no significant differences were found. CONCLUSION: Targeted MIP using local anaesthesia reduces operating time and causes less postoperative biochemical hypocalcaemia compared with bilateral neck exploration.

[Multiple endocrine neoplasia type 1. Surgical therapy of primary hyperparathyroidism]. / Multiple endokrine Neoplasie Typ 1. Chirurgische Therapie des primären Hyperparathyreoidismus.

Primary hyperparathyroidism (pHPT) occurs in about 90% of patients with multiple endocrine neoplasia type 1 (MEN1). In contrast to sporadic pHPT, multiple gland disease is most common in MEN1. The appropriate surgical approach is still controversial. The aim of this study was to analyze the results of surgical therapy of pHPT in patients with genetically confirmed MEN1. In an observational study, preoperative data, operative procedures, long-term results, and a possible genotype-phenotype correlation were analyzed in patients with pHPT and genetically confirmed MEN1. According to our results, tPTX+T (total parathyroidectomy+thymectomy+autotransplantation) seems to be a more favorable surgical approach in patients with MEN1 pHPT than sDE (selective gland exstirpation) and stPTX (subtotal parathyroidectromy) without cervical thymectomy, because recurrences or persistence of the disease are rare. A prospective randomized trial is needed to compare stPTX including cervical thymectomy vs tPTX+T. A genotype-phenotype correlation could not be identified.

[Hyperaldosteronism persisting after subtotal adrenalectomy]. / Persistenz eines primären Hyperaldosteronismus nach subtotaler Adrenalektomie.

BACKGROUND: Primary aldosteronism is known to be caused by aldosterone-producing adenoma (APA). Total adrenalectomy is the standard procedure. In contrast to bilateral adrenal diseases (e.g., MEN II pheochromocytomas), there is no consensus about the effect of subtotal adrenalectomy. CASE REPORT: A 44-year-old patient with primary aldosteronism caused by APA underwent subtotal adrenalectomy including removal of one adenoma. Because hypertension and hypokalemia did not disappear and hyperaldosteronism persisted, the patient had to undergo reoperation in which the adrenalectomy was completed. DISCUSSION: Subtotal adrenalectomy in patients with Conn's syndrome is an interesting therapeutic option,whereas its effect is much higher in hereditary diseases of the adrenal gland. The benefit of preserved adrenal tissue has to be weighed against a possible persistence of hyperaldosteronism, especially in cases with normal opposite adrenal glands.

High diagnostic accuracy of adrenal core biopsy: results of the German and Austrian adrenal network multicenter trial in 220 consecutive patients.

Incidentally detected adrenal tumors are a common finding during abdominal ultrasonography, computed tomography, and magnetic resonance imaging. Although most of these lesions are benign adenomas, adrenocortical carcinomas and metastases constitute 5% to 10% of all tumors. Adrenal biopsy may be helpful, but its diagnostic value is controversial and disputed, and prospective studies have not yet been performed. Therefore, the diagnostic accuracy of adrenal core biopsy was evaluated in a prospective multicenter study involving 8 surgical centers in Germany and Austria. A total of 220 biopsies from surgical specimens of the adrenal gland were punctured in an ex vivo approach and processed for pathohistologic diagnosis using paraffin sections, routine staining, and immunohistochemistry (keratin KL1, vimentin, S100 protein, chromogranin A, synaptophysin, neuron-specific enolase, D11, MiB-1, and p53 protein). The evaluating pathologist was blinded for clinical data from the patients. A total of 89 adrenal adenomas (40.5%), 22 adrenal carcinomas (10.0%), 55 pheochromocytomas (25.0%), 15 metastases (6.8%), 16 adrenal hyperplasias (7.2%), and 23 other tumors (10.5%) were studied. Nine cases were excluded due to incomplete data (n = 2) or insufficient biopsy specimen (n = 7). In the remaining 211 tumors, compared with the final diagnoses of the surgical specimen, bioptic diagnoses were absolutely correct in 76.8% of the cases, nearly correct in 13.2% of the cases, and incorrect in 10% of the cases. Pheochromocytomas were correctly diagnosed in 96% of the cases, cortical adenomas were correctly or nearly correctly reported in 91% of the cases, cortical carcinomas were correctly or nearly correctly reported in 76% of the cases, and metastases were correctly or nearly correctly reported in 77% of the cases. Of the 39 malignant lesions, only 4 were misclassified, 2 as benign and 2 as possibly malignant. This resulted in an overall sensitivity for malignancy of 94.6% and specificity of 95.3%. Our findings suggest that adrenal core biopsy is a useful method for identifying and classifying adrenal tumorous lesions if sufficient biopsy specimens can be obtained. However, in clinical practice it remains to be shown whether the benefits of biopsy outweigh the risks of the procedure.

Familial ACTH-independent Cushing's syndrome with bilateral macronodular adrenal hyperplasia clinically affecting only female family members.

Primary adrenal hyperplasia, which may occur as a familial disorder, is a rare cause of ACTH-independent Cushing's syndrome. In most of these cases the underlying pathology is primary adrenocortical micronodular dysplasia. Very few cases of familial Cushing's syndrome due to primary macronodular adrenal hyperplasia have been described. We report a family with seven affected family members. The pedigree indicates an autosomal dominantly inherited disorder. Interestingly only female family members developed the clinically apparent syndrome. The only available obligatory male gene carrier failed to adequately suppress his plasma cortisol level on overnight dexamethasone suppression test. His adrenal glands showed nodular enlargement on abdominal computed tomographic imaging. Screening of the MEN 1 gene and genetic analysis of the hot spot regions of the GNAS 1 (codons 201 and 227) and GNAI 2 (codons 179 and 205) genes did not show any mutations in the constitutional DNA or the adrenal tissue DNA of the index patient. In conclusion, this family is the largest kindred reported in the literature with ACTH-independent Cushing's syndrome due to autosomal dominant inherited macronodular adrenocortical hyperplasia. Four currently alive and affected family members in two generations and further careful observation of the yet unaffected members of the third available generation might offer the opportunity to identify the still unknown gene defect in the future.

Predictive genetic screening and clinical findings in multiple endocrine neoplasia type I families.

Germline mutations of the MEN1 gene have been identified as the causative genetic defect of multiple endocrine neoplasia type I (MEN-I), an autosomal dominantly inherited condition. To establish the basis for predictive family screening we evaluated the spectrum of MEN1 gene mutations in MEN-I patients treated at our institution. Relatives at risk were subjected to predictive genetic screening after genetic counseling. Gene carriers were subjected to extensive clinical screening for MEN-I, including biochemical tests for basal hormone concentrations in blood and urine, a standardized meal stimulation test and imaging procedures (ultrasonography, computed tomography, magnetic resonance imaging). Among index patients of 15 independent MEN-I kindreds, 14 heterozygous MEN1 germline mutations were identified by single-strand conformational variant analysis (SSCV) and direct DNA sequence analysis. Of 51 individuals at risk, 26 predictively tested relatives with the wild-type MEN1 gene could be excluded from further screening procedures because they had not inherited the disease. In all previously presumed unaffected relatives with the mutant gene, our extensive clinical screening program revealed at least one manifestation of MEN-I. Furthermore, 22 additional diagnoses could be established in identified MEN-I patients. We show that mutation analysis enables predictive genetic screening for MEN-I families, providing a valuable tool for genetic counseling and clinical management. An extensive clinical screening program focusing on genetically proven individuals at risk allows detection of MEN-I manifestations at an early, asymptomatic stage of the disease. Controlled, prospective studies are now required to prove whether timely appropriate treatment on the basis of predictive screening might help improve disease-related quality of life and prolong life expectancy in MEN-I kindreds.

[Outcome of minimally invasive surgery. Qualitative analysis and evaluation of the clinical relevance of study variables by the patient and physician]. / Outcome nach minimal-invasiver Chirurgie. Qualitative Analyse und Bewertung der klinischen Relevanz von Studienendpunkten durch Patient und Arzt.

INTRODUCTION: Mechanistic study endpoints, evaluated exclusively by the physician, are mostly used in clinical studies evaluating new treatment modalities (e.g. laparoscopic cholecystectomy). Those endpoints often lack clinical relevance. The patient's opinion concerning the importance of a study endpoint is particularly important in the evaluation of minimally invasive procedures, which place special emphasis on patient comfort. METHODS: In a first step it was evaluated by meta-analysis, which clinical endpoints have been used for comparison of laparoscopic and conventional cholecystectomy. Furthermore, using a qualitative analysis it was investigated how important the individual study endpoints are for patients and physicians. Ten patients and five surgeons were questioned in a structured interview. RESULTS: Of all outcome variables used world-wide, approximately one third were hermeneutic study endpoints, depending on the quality of the study, but often the method of evaluation was insufficient. Only three of 215 endpoints (< 2%) were quality of life scores, an integrated concept of outcome was missing completely. The qualitative analysis confirms the claimed difference between isolated and integrated evaluation of treatment goals. The importance of postoperative death is underestimated by patients and physicians; postoperative pain is overestimated. Patients ranked the outcome variable "restoration of full physical fitness" as the most important study endpoint after avoidance of complications and death. It is underestimated in isolated evaluation and has not been used in the world literature at all. CONCLUSION: The analysis of clinical relevance of study endpoints should be the first and not the last step of studies to evaluate surgical technology. It cannot be based purely on intuition; it must make use of scientifically accepted techniques (e.g. qualitative analysis).

Adrenocortical carcinoma--our experience with 11 cases.

BACKGROUND AND AIMS: Adrenocortical carcinoma (ACC) is a rare tumour with an incidence of approximately 0.5-2 cases per million per year. Diagnosis is mostly delayed and prognosis is poor. We report our experiences with 11 patients operated on within the last 10 years. PATIENTS/METHODS: The data of the patients with ACC were reviewed and presenting symptoms, diagnostic procedures, treatment and results of follow-up were evaluated. RESULTS: The group of patients consisted of eight women and three men with a mean age of 40.2 (15-57) years. Median follow-up was 16 (1-71) months. Six patients presented with Cushing's syndrome, two presented with virilism and hirsutism caused by androgen-producing tumours. Three patients had hormonally inactive tumours. At the time of diagnosis, five tumours were classified as stage II, two as stage III and four as stage IV. Four patients had tumours with intravascular extension, prompting recurrence in two cases. Eight adrenalectomies, one resection of local recurrence, one adrenalectomy with splenectomy and one adrenalectomy and resection of a liver metastasis were performed. Five patients received additional chemotherapy. Five of the 11 patients are still alive (three stage II, one stage III and one stage IV at the time of diagnosis), three of whom have no evidence of disease (14, 48 and 71 months after surgery). The other six patients died after a median postoperative period of 10 (1-21) months. CONCLUSIONS: Venography should be performed prior to surgery to detect or exclude thrombotic tumour masses in the suprarenal vein, renal vein or inferior vena cava. Radical surgery is the only curative approach and is recommended for all patients with resectable tumours, including those patients with recurrent disease. There is no consensus concerning adjuvant therapy. The value of multidisciplinary strategies needs to be assessed in multicentre trials.

Pancreaticoduodenal endocrine tumors in multiple endocrine neoplasia type 1: surgery or surveillance?

BACKGROUND: The management of pancreaticoduodenal endocrine tumors (PETs) remains controversial in multiple endocrine neoplasia type 1 (MEN 1). METHODS: Twenty-one patients with MEN 1 and PETs were analyzed for outcome of surgery and surveillance with special regard to the genotype based on MEN1 gene mutation analysis. RESULTS: Nine patients had gastrinomas, 5 had nonfunctioning tumors, 4 had insulinomas, 2 had insulinomas and gastrinomas, and 1 had a VIPoma. Seven patients (33%) had malignant tumors. Sixteen patients (76%) were initially treated by pancreatic resections or tumor enucleations or both. Six patients underwent reoperations for recurrences or lymph node metastases or both. Fifteen of the 16 operated patients are alive, and 12 have no evidence of disease after a median follow-up of 78 months (range, 1-198 months). Five patients with gastrinomas or nonfunctioning tumors, but no symptoms, underwent surveillance; 1 of them developed lymph node metastases. Patients with truncating mutations in the N- or C-terminal region (exons 2, 9, or 10) of the MEN1 gene had a significantly higher rate of malignant tumors (55% vs 10%; P <.05) than patients with other mutations. CONCLUSIONS: An aggressive surgical approach is justified for PETs in patients with MEN 1. However, MEN1 gene mutations in exons 3 to 8 seem to be associated with mild behavior of PETs, possibly allowing surveillance in asymptomatic patients.

How asymptomatic is asymptomatic primary hyperparathyroidism?

We observed several cases of patients who believed they were free of symptoms or signs of primary hyperparathyroidism (pHPT) preoperatively. reported a change of complaints following parathyroidectomy (PTX). We, therefore, decided to examine a larger group of patients to discover if these findings were incidental or of more general significance. The role of PTX in these patients with asymptomatic pHPT remains controversial. In 1991 criteria were defined at a NIH-consensus conference, according to which patients qualify for either operative therapy or long term medical surveillance. Until now, it was generally believed that the majority of asymptomatic patients would never develop symptoms. In a epidemiological cohort-study, the perioperative data of 582 consecutive patients with pHPT, including 116 asymptomatic patients (20.9%), who underwent parathyroidectomy between 1987 and 1998 were evaluated by uni- and multivariate analysis. At a median of 72 months postoperatively, all patients underwent a planned follow-up which included a standardised, validated questionnaire, physical examination and laboratory investigations. Eighty-six patients who were asymptomatic preoperatively were available for follow-up. Only eight (9.3%) were definitely asymptomatic, 4.6% of the entire, representative cohort. Postoperative improvement was reported in 81.4% of the "asymptomatic" patients. Multivariate analysis did not reveal a single or a set of preoperative measurements, that would allow to predict the retrospectively definitely asymptomatic patient. PTX resulted in normocalcaemia in 98.8% of preoperatively asymptomatic patients, with an operative morbidity of 1.2% and no mortality. Many apparently asymptomatic patients with pHPT will only realise that they did in fact have preoperative symptoms in retrospect, following PTX. This study suggests that using an up-to-date definition of asymptomatic pHPT, there are only a small number of truly asymptomatic patients and that these cannot be predicted preoperatively, as their symptoms may become apparent only after PTX. "Asymptomatic" patients with pHPT may share the same objective and subjective benefits from PTX as symptomatic patients. They should be operated as soon as the diagnosis is established.