Total Parathyroidectomy With Routine Thymectomy and Autotransplantation Versus Total Parathyroidectomy Alone for Secondary Hyperparathyroidism: Results of a Nonconfirmatory Multicenter Prospective Randomized Controlled Pilot Trial.

OBJECTIVE: This randomized controlled multicenter pilot trial was conducted to find robust estimates for the rates of recurrence of 2 surgical strategies for secondary hyperparathyroidism (SHPT) within 36 months of follow-up. BACKGROUND: SHPT is a frequent consequence of chronic renal failure. Total parathyroidectomy with autotransplantation (TPTX+AT) and subtotal parathyroidectomy (SPTX) are the standard surgical procedures. Total parathyroidectomy alone (TPTX) might be a good alternative, as morbidity and recurrence rates are low according to small-scale retrospective studies. METHODS: The trial was performed as a nonconfirmatory randomized controlled pilot trial with 100 patients on long-term dialysis with otherwise uncontrollable SHPT to generate data on the rate of recurrent disease within a 3-year follow-up period after TPTX or TPTX+AT. Parathyroid hormone (PTH) and calcium levels, recurrent or persistent hyperparathyroidism, parathyroid reoperations, morbidity, and mortality were evaluated during a 3-year follow-up. RESULTS: A total of 52 patients underwent TPTX and 48 TPTX+AT. Patient characteristics, preoperative baseline data, duration of surgery (02:29 vs 02:47 hrs, P = 0.17) and mean hospital stay (10 ± 7.1 vs 8 ± 3.7 days, P = 0.11) did not differ significantly. Persistent SHPT developed in 1 TPTX and 2 TPTX+AT patients. None of the TPTX patients required delayed parathyroid AT to treat permanent hypoparathyroidism. Serum-calcium values were similar (2.1 ± 0.3 vs 2.1 ± 0.2, P = 0.95) whereas PTH rose by time in the TPTX+AT group and was significantly higher at the end of follow-up when compared with the TPTX group (31.7 ± 43.6 vs 98.2 ± 156.8, P = 0.02). Recurrent SHPT developed in 4 TPTX+AT and none of the TPTX patients. CONCLUSIONS: TPTX+AT and TPTX seem to be safe and equally effective for the treatment of otherwise uncontrollable SHPT. TPTX seems to suppress PTH more effectively and showed no recurrences after 3 years. The hypothesis that TPTX is superior to TPTX+AT referring to the rate of recurrent SHPT has to be tested in a large-scale confirmatory trial. Nevertheless, TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of SHPT.

[Implementation and evaluation of error prevention measures in surgical clinics: Results of a current online survey]. / Einführung und Beurteilung von Maßnahmen zur Fehlerprävention in chirurgischen Kliniken: Ergebnisse einer aktuellen Online-Befragung.

In the autumn of 2014, more than 3,000 surgeons completed an online questionnaire asking for the prevalence and efficiency of instruments to prevent adverse events within surgical departments in Germany. About 90 % of the respondents stated that perioperative checklists, preoperative marking of the surgical site and the documentation of hospital infections had been implemented in their institution; and 75 % of the institutions had introduced critical incident reporting systems (CIRS), morbidity and mortality conferences and identification bracelets for patients. The surgeons were asked to rank the different instruments for the prevention of adverse events. According to the respondents, preoperative marking of the surgical site and the use of checklists were at the top of the efficacy ranking, followed by an introductory course for surgeons starting work in a hospital or when new devices became available. Only 50 % of the responding surgeons perceived CIRS as being efficient. Overall, the answers showed that instruments to increase patient safety were commonly available in surgical departments. On the other hand, there is still room for improvement in daily practice.

Initial surgery for benign primary hyperparathyroidism: an analysis of 1,300 patients in a teaching hospital.

BACKGROUND: Success rates of initial surgery for primary hyperparathyroidism (pHPT) are greater than 95 % in specialized centers, mostly referring to single-surgeon experiences. The present study was performed to identify changes in clinical manifestations, diagnostic procedures, surgical strategies, and outcome of initial parathyroid interventions in a teaching hospital during the past 25 years with special regard to the surgical expertise. METHODS: Clinical data of patients who underwent an initial neck exploration for benign pHPT between 1985 and 2010 at the University hospital Marburg were retrospectively evaluated. All data were analyzed particularly with regard to the implementation of additional pre- and intraoperative procedures and to the particular surgical strategy. In addition, operative results were furthermore analyzed with regard to the experience of the responsible surgeons. RESULTS: An initial neck exploration for benign pHPT was performed in 1,300 patients. Of these, 1,035 patients had a bilateral cervical exploration (BCE) and 265 patients had a focused, minimally invasive parathyroidectomy (MIP). Cure rates did not differ between focused surgeries and BCE (98.9 vs. 98.3%, p = 0.596) after a mean follow-up of 33.4 (± 44.3) months. Postoperative transient hypoparathyroidism was significantly lower in the MIP group (11 vs. 47%, p < 0.0001). The rate of permanent recurrent laryngeal nerve palsies (0.4 vs. 2%, p = 0.064) and nonsurgical complications (0 vs. 1.4%, p = 0.0875) tended to be lower in the MIP group. Success and complication rates of chief surgeons (n = 2), attending surgeons (n = 20), and residents (56 < 3 years, 30 > 3 years) were similar, despite a significantly shorter operating time in the chief surgeon group (p < 0.01). CONCLUSIONS: Despite the implementation of several diagnostic procedures and significant changes concerning the surgical strategy, high success rates of primary interventions for pHPT did not change over the past three decades. High success rates also can be achieved in a teaching hospital, provided that surgery is supervised by an experienced endocrine surgeon. MIP is the treatment of choice in patients with benign sporadic pHPT and positive preoperative localization studies.

Reoperations for primary hyperparathyroidism--improvement of outcome over two decades.

PURPOSE: Reoperations (R-PTX) for primary hyperparathyroidism (pHPT) are challenging, since they are associated with increased failure and morbidity rates. The aim was to evaluate the results of reoperations over two decades, the latter considering the implementation of Tc(99m)sestamibi-SPECT (Mibi/SPECT), intraoperative parathormone (IOPTH) measurement, and intraoperative neuromonitoring (IONM). PATIENTS AND METHODS: Data of 1,363 patients who underwent surgery for pHPT were retrospectively analyzed regarding reoperations. Causes of persistent (p) pHPT or recurrent (r) pHPT, preoperative imaging studies, surgical findings, and outcome were analyzed. Data of patients who underwent surgery between 1987 and 1997 (group 1; G1) and between 1998 and 2008 (group 2; G2) with the use of Mibi/SPECT, IOPTH, and IONM were evaluated. RESULTS: One hundred twenty-five patients with benign ppHPT (n = 108) or rpHPT (n = 17) underwent reoperations (R-PTX). Group 1 included 54, group 2 71 patients. Main cause of ppHPT (G1 = 65 % vs. G2 = 53 %) and rpHPT (G1 = 80 % vs. G2 = 60 %) was the failed detection of a solitary adenoma (p = 0.2). Group 1 patients had significantly less unilateral/focused neck re-explorations (G1 = 23 % vs. G2 = 57 %, p = 0.0001), and more sternotomies (G1 = 35 vs. G2 = 14 %, p = 0.01). After a median follow-up of 4 (range 0.9-23.4) years, reversal of hypercalcemia was achieved in 91 % (G1) and in 98.6 % in group 2 (p = 0.08, OR 7.14 [0.809-63.1]). The rates of permanent recurrent laryngeal nerve palsy (G1 = G2 = 9 %, p = 1) and of postoperative permanent hypoparathyroidism (G1 = 9 % vs. G2 = 6 %, p = 0.5) were not significantly different. Other complications such as wound infection, postoperative bleeding, and pneumonia were significantly lower in group 2 (p < 0.001). CONCLUSION: Nowadays, cure rates of R-PTX are nearly the same as in primary operations for pHPT. These results can be achieved in high-volume centers by routine use of well-established preoperative Mibi/SPECT and US in combination with IOPTH. However, morbidity is still considerably high.

Call-associated acute fatigue in surgical residents--subjective perception or objective fact? A cross-sectional observational study to examine the influence of fatigue on surgical performance.

BACKGROUND: The effect of acute partial sleep deprivation on surgical proficiency is still controversially discussed. The present study correlated physiological parameters of fatigue with objective technical and cognitive skills, as well as subjective sleepiness of surgical residents. The aim of the study was to assess the effect of acute partial sleep deprivation on surgical performance. METHODS: Thirty-eight surgeons were interviewed on three consecutive mornings: prior to a 24 h call, post-call, and after 24 h of rest. Reported hours of sleep were recorded. Subjective alertness was assessed with the standardized Stanford-Sleepiness-Scale (SSS). Saliva cortisol concentrations and pupillary activity were measured by standardized ELISA and pupillography. The virtual reality (VR)-simulator LapSim was used to assess technical skills through low-fidelity VR-tasks ("cutting," "clip applying") and cognitive skills through high-fidelity VR-tasks ("intracorporeal suturing," "VR-cholecystectomy"). Objective alertness was measured by the standardized d2-Paper-Pencil Test. RESULTS: Recorded hours of sleep (p = 0.001) and subjective alertness (SSS) decreased (p = 0.001) significantly post-call. None of the three factors studied-saliva cortisol concentration (p = 0.313), pupillary activity (p = 0.998), or VR-performance of low-fidelity VR-tasks-differed significantly between assessments. Surprisingly, VR-performance of high-fidelity VR-tasks (error-score p = 0.044, time to complete task p = 0.0001, economy of instrument motion p = 0.0001) and objective alertness (d2-Paper-Pencil Test p = 0.027) significantly improved in the post-call setting. CONCLUSIONS: Acute call-associated fatigue seems to be a predominantly subjective perception. Physiological factors seem to outbalance an anticipated fatigue-associated impairment of technical performances within low-fidelity VR-tasks. In surgical residents, acute partial sleep deprivation seems to have a positive short-term effect on cognitive skills, leading to enhanced technical performance and increased objective alertness within complex tasks.

Development of a formula to predict parathyroid carcinoma in patients with primary hyperparathyroidism.

BACKGROUND: Cure of parathyroid carcinoma (PC) requires initial en bloc resection, including resection of all tumor-bearing tissue, with hemithyroidectomy and dissection of the central lymph node compartment. Unfortunately, no reliable preoperative criteria have yet been assessed to indicate a high likelihood of PC. Thus, the aim of the present study was to develop a formula to indicate preoperatively the presence of PC. METHODS: A prospective database of 1,363 patients with primary hyperparathyroidism (pHPT) was screened for patients with PC. Age, gender, surgical procedures, laboratory data, and follow-up results were evaluated and compared to a group of patients with benign pHPT. Based on preoperative serum calcium (Ca) and parathyroid hormone (PTH) levels, as well as patients' age at the time of diagnosis, a formula was developed by a multivariate logistic model that estimates the individual risk for PC. RESULTS: Between 1987 and 2008, 19 patients with PC were identified. Ca (3.8 ± 0.3 vs 2.9 ± 0.3 mmo/l; p = 0.0002) and PTH levels (1,250 ± 769 vs 194 ± 204 pg/ml; p = 0.0030) were significantly higher in patients with PC than in those with benign pHPT. Patients with PC were also significantly younger than patients with benign pHPT (48.9 ± 12.1 vs 59.1 ± 13.8 years; p < 0.05). With a ≥5 % probability that a given patient suffered from PC, the sensitivity and specificity to identify the disease were 100 and 30 %, respectively, with the new Ca, PTH, and age based logarithmic formula. CONCLUSIONS: The new logarithmic formula can be used to calculate the individual risk for PC. If the calculated individual risk exceeds 5 %, en bloc resection seems to be justified to provide long-term cure in case of PC.

Vascular clips versus ligatures in thyroid surgery--results of a multicenter randomized controlled trial (CLIVIT Trial).

BACKGROUND: New techniques using vascular clips or ultrasonically activated shears have been suggested to shorten operation time without compromising safety. The objective of the CLIVIT Trial was to compare ligatures with vascular clips for hemostasis in elective benign thyroid surgery. METHODS: This multicenter, randomized, controlled, parallel group superiority trial was conducted in 13 German surgical centers. Patients scheduled for at least subtotal resection bilaterally were intraoperatively randomized. The primary endpoint was resection time. Secondary endpoints were the amount of postoperative bleeding, reoperation due to bleeding, wound infection, temporary (reversal within 12 months) and permanent (over 1 year) recurrent laryngeal nerve (RLN) paralysis, length of hospital stay, and safety. REGISTRATION: ISRCTN 96901396. RESULTS: Two hundred fifty patients were treated with ligatures and 241 with vascular clips. No differences in patients' baseline and surgical characteristics were observed. No difference was detected for mean resection time (clip 63.5 min ± 29.6, ligature 66.1 min ± 29.3, P = 0.258). Postoperative bleeding (mean 86 ml ± 93), reoperation due to bleeding (clips 4, ligature 2), wound infections (clips 4, ligature 4), postoperative hospital stay (mean 3.0 ± 1.9), and safety data also did not vary significantly. The rates of temporary and permanent RLN paralysis were 6.9 % (34/491) and 2.9 % (14/491), respectively. Not using a surgical drain (123 patients) was not associated with a higher rate of complications. CONCLUSION: Vascular clips did not reduce the resection time. However, a 2.9 % rate of permanent RLN paralysis is of concern. Drains in elective surgery may be of no benefit.

Microarray analysis reveals differential expression of benign and malignant pheochromocytoma.

The diagnosis of a malignant pheochromocytoma (PC) can only be established by the presence of distant metastases, but a subset of apparently benign PCs develop metastases. We have employed a microarray analysis to identify a typical gene expression profile which distinguishes malignant from benign PC. Total RNA was isolated from fresh-frozen tissue of five benign and five malignant PCs. The reference consisted of laser microdissected tissue from normal adrenal medulla. After generating Cy3- and Cy5-fluorescently labeled cDNAs, F-chips containing 11 540 spots were hybridized. Data were analyzed with the IMAGENE 3.0 software. Gene expression levels were validated by real-time (RT)-PCR and immunohistochemistry (IHC). The analysis revealed a more than twofold difference in expression between benign and malignant PCs in 132 genes: 19 were up-regulated and 113 were down-regulated. Expression differences of six genes (calsequestrin, NNAT, neurogranin, secreted protein acidic and rich in cysteine (SPARC), EGR2, and MAOB) were confirmed by RT-PCR in 25 PCs. IHC for calsequestrin revealed an overexpression in malignant PCs (7/10 vs 1/10, P=0.03). Comparative analysis by microarray of all ten PCs (benign/malignant) versus normal adrenal medulla revealed a more than twofold expression difference in 455/539 and 491/671 genes respectively. Several of these genes are known to participate on adrenal tumorigenesis, potential tumor suppressor genes, and oncogenes. Comprehensive gene expression analysis of malignant and benign PCs revealed different gene profiles, which could be used to discriminate between malignant and benign PCs. Based on these findings, the strategy for further follow-up and treatment could be modified accordingly.

Screening of patients with multiple endocrine neoplasia type 1 (MEN-1): a critical analysis of its value.

BACKGROUND: Screening of multiple endocrine neoplasia type 1 (MEN-1) patients is widely recommended because one-fifth succumb to malignant neoplasms. However, recommendations for screening modalities and intervals are based mostly on nonprospective data. METHODS: Thirty-five of 48 MEN-1 patients were evaluated at least twice by an annual screening program in a single-center, prospective, nonrandomized study between 1997 and 2006. The screening program comprised anamnesis, clinical examination, imaging procedures, and extensive biochemical evaluations. Prospectively diagnosed lesions were evaluated separately from nonprospectively diagnosed lesions at first evaluation. RESULTS: The median age of the patients was 45 years (range = 15-70) at initial assessment. They were followed for a median of 72 months (range = 24-108) by a median of 6 (range = 2-10) evaluations. The vast majority of lesions were nonprospectively diagnosed at initial evaluation: 13 of 17 patients had primary hyperparathyroidism (pHPT), 24 of 29 had pancreatic endocrine tumors (PETs), and 4 of 4 had carcinoids. Vice versa adrenal lesions were mostly prospectively detected (18/23). Malignancy was observed in 10 patients (28%) in the initial assessment and without symptoms in 5 patients (9 PETs, 3 carcinoids). Endoscopic ultrasound (EUS) of 29 patients detected 88 PETs which were followed for 157 patient years. The mean annual growing rate was 13.28 +/- 28.23 mm with respect to the baseline tumor diameter of 9 mm. In 35 patients the mean incidence of newly diagnosed PETs was 0.52/year. Adrenal lesions were invariably nonfunctional. A mean change in diameter of 6.7 +/- 23.44% was monitored and malignant transformation was absent. CONCLUSIONS: Most lesions are detected at initial screening, particularly malignant tumors. Computed tomography of the abdomen and chest did not identify additional lesions. The interval between screenings could be extended to 3 years based on annually calculated growth rates and the incidence of MEN-1-associated lesions. The assessment of calcium, gastrin, and prolactin is sufficient for biochemical screening in MEN-1.

Mutations and polymorphisms in the SDHB, SDHD, VHL, and RET genes in sporadic and familial pheochromocytomas.

The prevalence of germ line mutations within the RET-protooncogene and the tumor suppressor genes SDHB, SDHD, and VHL in pheochromocytomas (PC) varies in recent studies from 12 to 24%, if one look at them collectively. DNA was extracted from frozen tumor tissue as well as from blood leukocytes of 36 PC (26 sporadic/10 MEN2). Exons 1-8 of the SDHB-gene, 1-4 of the SDHD-gene, 1-3 of the VHL-gene, and exons 10, 11, 13, 14, 16 of the RET-gene were amplified by PCR and analyzed by DHPLC with the Transgenomic WAVE-System. Samples with aberrant wave profiles were subjected to direct sequencing. Genetic aberrations were correlated to clinical characteristics. Germ line mutations in sporadic PC were identified in four patients (11%) whereas somatic mutations were observed in two (5%) patients. Nine coding polymorphisms (PM) were identified in seven (19%) patients. Intronic variants were observed in six (17%) patients and were all located in the SHDB gene. Patients with wild type alleles in all assessed genes were older (53 vs. 37 years, P = 0.007) and presented with an increased tumor size (49 vs. 32 mm, P = 0.003) compared to patients with mutations. Malignant PC revealed multiple (>2) genetic alterations more frequently than benign PC (4/7 vs. 4/29, P = 0.03). Interestingly intronic variants of the SDHB gene occur more frequently in malignant than in benign PC (3/7 vs. 2/29, P = 0.04). The frequency of germ line mutations in sporadic pheochromocytomas was lower in our cohort than previously reported. Polymorphisms of the RET gene are common (17%) and occur in familial and sporadic PC. Multiple genetic alterations including mutations, polymorphisms and intronic variants are more frequently observed in malignant PC.

Sonic hedgehog and pancreatic-duodenal homeobox 1 expression distinguish between duodenal and pancreatic gastrinomas.

Some 80-90% of gastrinomas are located in the gastrinoma triangle, which includes the duodenum, the pancreatic head, and the hepatoduodenal ligament. The natural history of the tumors depends on their origin. Duodenal gastrinomas are much less aggressive than pancreatic primaries and infrequently develop liver metastases. The reason therefore is unclear. The transcription factor pancreatic-duodenal homeobox 1 (Pdx1) is important in differentiation and development of the pancreas and duodenum. In embryonic development, Sonic hedgehog (Shh) expression establishes a sharp molecular boundary, which allows for the proper patterning of the duodenal and pancreatic epithelium. Pancreatic polypeptide (PP) is expressed in pancreatic islets and is known to be expressed in pancreatic endocrine tumors. This study aims to clarify the expression pattern of Pdx1, Shh, and PP in duodenal and pancreatic gastrinomas. Tissue from 15 patients with duodenal and from 11 patients with pancreatic gastrinomas that underwent surgery between 1987 and 2007 at our institution because of a gastrinoma were evaluated by immunohistochemistry (IHC). Furthermore, tissue from lymph node metastases from two patients with a so far undetected primary gastrinoma was analyzed. IHC revealed strong Pdx1 expression in pancreatic gastrinomas, but not in duodenal gastrinomas. By contrast, there was no Shh expression detectable in pancreatic gastrinomas, but found in all duodenal gastrinomas. This pattern was also true for associated metastases. Shh expression combined with absence of Pdx1 expression in lymph node metastases from patients with an unknown location of the primary suggests a so far undetected duodenal gastrinoma. We show for the first time that only pancreatic, but not duodenal gastrinomas express Pdx1. Moreover, only duodenal gastrinomas express Shh, suggesting a different genetic background of these two tumors. Whereas the expression of Pdx1 in pancreatic gastrinomas might suggest their endocrine origin from islets, duodenal gastrinomas develop from a Pdx1 negative cell cluster. The expression pattern of Pdx1, Shh, and PP in resected metastases can help to locate an otherwise undetected primary gastrinoma.

Multimodal treatment of sporadic and inherited neuroendocrine tumors of the thymus.

BACKGROUND: Neuroendocrine tumors of the thymus (NETT) are a rare tumor entity of the anterior mediastinum. They belong to the category of foregut carcinoids and are often associated with the multiple endocrine neoplasia type 1 (MEN1) syndrome. Approximately 180 cases have been reported since their first description. NETT reveal an aggressive behavior leading to rapid local invasion and metastatic spread. An aggressive surgical approach may achieve long-term survival. METHODS: Patients presenting from 1990 to 2005 at the Department of Surgery and the Department of Gastroenterology of the Philipps-University Marburg with neuroendocrine tumors were enrolled in a prospective database with a follow-up until 2005. Fifty MEN1-patients were enrolled in a study and screening program. These databases were retrospectively reviewed identifying all patients with NETT. The clinical features, therapeutical approaches and the outcome were analyzed. RESULTS: Six patients were found with NETT, 4 patients suffered from metastases at the time of presentation. All patients were male, with a median age of 41.3 years at presentation. Four out of these 6 patients revealed MEN1 syndrome. All patients underwent tumor resection via sternotomy. Three patients underwent parathyreoidectomy and transcervical thymectomy before the NETT was diagnosed. Median survival was 53 months (range, 24-109). CONCLUSION: Given a frequent association between MEN1 and NETT, all patients with NETT should be screened for MEN1. Since transcervical thymectomy does not prevent all MEN1 patients from developing NETT, existing surveillance guidelines for MEN1 should consider CT scan of the thorax on a regular basis.

Fast-growing pancreatic neuroendocrine carcinoma in a patient with multiple endocrine neoplasia type 1: a case report.

INTRODUCTION: Predictive genetic screening and regular screening programs in patients with multiple endocrine neoplasia type 1 are intended to detect and treat malignant tumors at the earliest stage possible. Malignant neuroendocrine pancreatic tumors are the most frequent cause of death in these patients. However, the extent and intervals of screening in patients with multiple endocrine neoplasia type 1 are controversial as neuroendocrine tumors are usually slow growing. Here we report the case of a patient who developed a fast-growing neuroendocrine carcinoma within 15 months of a laparoscopic distal pancreatic resection. CASE PRESENTATION: We followed a group of 45 patients with multiple endocrine neoplasia type 1 by an annual screening program in the Department of Visceral, Thoracic, and Vascular Surgery at the University Hospital Marburg in cooperation with the Department of Radiology and the Division of Endocrinology. A man with multiple endocrine neoplasia type 1 who was diagnosed with a recurrent primary hyperparathyroidism underwent a distal pancreatic resection for a non-functional neuroendocrine tumor. In the context of our regular screening program, a large non-functional neuroendocrine tumor was diagnosed in the pancreatic head 15 months after the first pancreatic surgery. Therefore, we performed an enucleation and regional lymph node resection. At histology, the diagnosis of a neuroendocrine carcinoma with one lymph node metastasis was established. There was no evidence of recurrence 9 months after re-operation. CONCLUSION: Fast-growing neuroendocrine tumors are rare in patients with multiple endocrine neoplasia type 1. The intervals, both postoperative and in newly diagnosed pancreatic lesions, in patients with multiple endocrine neoplasia type 1 should be reduced to 6 months to establish the early diagnosis of rapidly progressive disease in a small subset of patients.

Multiple primary malignancies in patients with sporadic pancreatic endocrine tumors.

BACKGROUND: To investigate the appearance of multiple primary malignancies in patients with sporadic neuroendocrine pancreatic tumors (NEPTs). METHODS: One hundred forty-five patients with NEPTs were treated at the Department of Surgery, Philipps-University Marburg. Multiple primary malignancies included tumors that were not considered to be a metastasis, invasion, or recurrence of NEPTs. Data on sex, age at diagnosis of cancer, follow-up time after diagnosis, and death rate were collected. RESULTS: Of 115 patients with sporadic NEPTs, 15 (13.0%) patients were identified with at least one malignant tumor, other than a NEPT. The median age at diagnosis of the associated tumor(s) was 57 years (range, 10-72 years). Two of the 15 patients had insulinomas, 5 had gastrinomas and 8 had non-functioning NEPTs, respectively. The risk of developing multiple cancers was the highest for patients with gastrinoma (21.7%), followed by patients with non-functioning NFPTs (20.5%). CONCLUSIONS: In patients with NEPTs multiple primary malignancies are found more frequently than in the general population. The etiology of the increased risk of other primaries is not clearly defined, but it may be the result of accumulated growth stimulation by the secreted hormones or a genetic alteration that leads to tumorogenesis in these patients.

[Simulation of laparoscopic surgery--four years' experience at the Department of Surgery of the University Hospital Marburg]. / Simulation endoskopischer Operationen - Vier Jahre Erfahrung an der Chirurgischen Universitätsklinik Marburg.

It is well known that learning curves are longer for laparoscopic surgery compared to open surgery. Recently, virtual reality (VR) simulation was developed as alternative to conventional training. Such a new training system makes it possible to offer a wide range of repeatable surgical situations, and thus, enable assessments based on direct observation of performance. During the last four years we did several studies using a VR simulator (LapSim). After a constructive validity study - discrimination between novices and experienced laparoscopic surgeons, we were able to show that advanced residents benefit most from a three-day practical course for laparoscopic surgery, while - in a further investigation - we found contrary to training at the Pelvitrainer that novices in laparoscopic surgery have the most benefit from VR training. Minimally invasive surgery is significantly more sophisticated for the surgeon than open surgery. While Research on laparoscopic surgery has focused primarily on the development and assessment of technical skills, non technical skills such as visual-spatial perception and stress coping has received much less attention. We showed that spatial perception as well as stress coping positively correlates with virtual laparoscopic skills. A high degree of spatial perception led to faster adaption to a non-stereo environment and correlated with high level of laparoscopic skills. Furthermore, Ineffective stress-coping strategies correlate with poor virtual laparoscopic performance. VR simulation seems to be a promising tool to improve laparoscopic skills in a modern apprenticeship model. According to patient safety, the development of this instrument for surgery should be advanced professionally just as a flight simulators in aviation.

Are diabetic patients at a greater risk to develop a vocal fold palsy during thyroid surgery than nondiabetic patients?

BACKGROUND: Diabetic neuropathy is reported to be an independent risk factor for the development of a vocal fold palsy (VFP), and nerves in diabetic patients are suspected to have an increased vulnerability to mechanical trauma. This retrospective study was performed to find out whether diabetic patients were at a greater risk to acquire VFP than were nondiabetic patients in a large cohort who underwent thyroid surgery. METHODS: Records of patients who underwent initial thyroid surgery at our institution between 1995 and 1999 were reevaluated. Results of preoperative and postoperative laryngoscopy, repeated laryngoscopy 6 months after operation, and concomitance of diabetes were registered. RESULTS: Six hundred thirty patients were retrospectively analyzed. Preoperative laryngoscopy revealed a unilateral VFP in 3 of 44 diabetic patients (6.8%) and in 4 of 586 (0.7%) nondiabetic patients. Five of 44 diabetic patients (11.4%) and 49 of 586 nondiabetic patients (8.4%) acquired VFP perioperatively, which was permanent in 2 diabetic patients (4.5%) and 8 nondiabetic patients (1.4%). The incidence of preoperative VFP in the diabetic patients was significantly greater than in nondiabetic patients (P = .0091). The incidence of postoperative and permanent VFP did not differ significantly. CONCLUSION: Thyroid surgery can be performed safely in diabetic patients, as they are not at a greater risk to acquire VFP than nondiabetic patients.

Does fine-needle aspiration cytology optimize the surgical management of thyroid disorders in endemic goiter region?

AIM: The aim of this study was to determine the diagnostic value of fine-needle aspiration cytology (FNAC) before thyroidectomy in an endemic goiter region. METHODS: One hundred patients with preoperative FNAC of thyroid nodules who underwent thyroidectomy were recruited. FNAC were classified into five groups. 0, no thyroid cells; 1, normal thyroid cells; 2, degenerative thyroid cells without evidence of malignacy; 3, follicular or oncocytary neoplasia; and 4, malignant thyroid cells. FNAC was compared with postoperative histopathological diagnoses. RESULTS: Only 76% of the FNAC allowed an adequate cytological examination. In 15 patients (15%), carcinomas were found in the postoperative histopathological diagnosis (including four follicular carcinomas). In the 48 patients of FNAC groups 3 and 4, nine carcinomas (18.7%) were found (including four follicular carcinomas). In the 28 patients of groups 1 and 2, there was only one papillary carcinoma (3.5%). In the 24 patients of group 0, there were two papillary, two follicular, and one anaplastic carcinomas (total of 20.8%). The sensitivity, specificity, and likelihood ratio (LR) of the FNAC for benign nodules were 90%, 40.9%, 0.24, respectively. The LR for malignant nodules was 13.2, and that for follicular neoplasia was 0.55. CONCLUSIONS: Despite the high prevalence of carcinoma in an endemic goiter region, FNAC disappointed its diagnostic expectation. The lower specificity of FNAC may be caused by a higher prevalence of thyroid nodules in an endemic goiter region or by the absence of a specialized cytopathologist.

Parathyroidectomy for renal hyperparathyroidism in children and adolescents.

BACKGROUND: Renal hyperparathyroidism (rHPT) almost inevitably develops in pediatric patients with end-stage chronic kidney disease (CKD) and may require parathyroidectomy (PTX) despite intensified conservative therapy. Long-term duration of uncontrolled rHPT may result in disabling osteodystrophy and vascular calcifications. Only a few reports on children undergoing PTX for rHPT are available and mainly consist of case reports with short follow-up periods. To study this entity, we analyzed the course of 23 pediatic patients who underwent PTX for rHPT. METHODS: Twenty-three patients with a mean age of 15 years and who underwent PTX for rHPT between 1986 and 2006 were evaluated. Surgical indications and techniques, specific postoperative management, and follow-up courses are described. RESULTS: Preoperative mean serum (s-) calcium was 2.7+/-0.05 mmol/L (normal range=2.2-2.7 mmol/L); s-phosphate was 1.8+/-0.1 mmol/L (normal range=0.8-1.6 mmol/L), and mean intact parathyroid hormone (PTH) level was 1240.1+/-160.1 pg/ml (normal range=11-65 pg/ml). Twenty-one patients underwent initial PTX and two patients underwent reoperative PTX. Total PTX with parathyroid autotransplantation (AT) was performed in 18 patients. In three patients less than four parathyroid glands were identified and no AT was performed consecutively. Postoperatively, no complications with respect to bleeding or vocal cord damage were recorded. The postoperative values of s-calcium, s-phosphate, and PTH decreased to or below normal range (s-calcium=2.0+/-0.1 mmol/L, s-phosphate=1.2+/-0.1 mmol/L, PTH=50.1+/-11.2 pg/ml). All 15 children below the age of 15 years required calcium intravenously. Follow-up was obtained in all patients 69.6+/-11.4 months after PTX. Bone pain resolved in all previously symptomatic patients. S-calcium was 2.2+/-0.2 mmol/L, s-phosphate was 1.4 +/- 0.3 mmol/L, and PTH was 90.2+/-21.5 pg/ml. No patient required repeated parathyroid autografting, and only one underwent an explantation of his AT six years after initial PTX. CONCLUSION: Total PTX with AT in pediatric patients with rHPT is a safe and effective procedure. It should be considered if rHPT is refractory to conservative treatment, in view of the risk of potentially lethal vascular calcifications developing in the majority of adults with childhood onset of CKD.

Laryngoscopy in thyroid surgery--essential standard or unnecessary routine?

BACKGROUND: Preoperative and postoperative laryngoscopy has been recommended for diagnostic and forensic reasons as a standard procedure in all patients who undergo thyroid surgery. The aim of this study was to find a more selective approach by defining patients at risk of developing vocal fold palsy (VFP). METHODS: The history of neck explorations, results of laryngoscopy, and histology were registered in all patients who underwent thyroid surgery at our institution between 1995 and 1999. Patients with pathologic findings at postoperative laryngoscopy underwent reassessment of voice and vocal fold (VF) mobility 6 months later. RESULTS: Unilateral VFP was detected preoperatively in 13 of 695 patients (1.9%). Of the 13 patients, only 1 patient was asymptomatic, had no history of neck surgery, and had no suspected malignancy. Postoperative laryngoscopy revealed a new development of VFP in 68 of 695 patients (9.8%). All patients with a permanent VFP had symptoms immediately after operation. Asymptomatic VFPs always recovered. CONCLUSIONS: Preoperative laryngoscopy is justified in symptomatic patients who undergo reoperation or in patients when malignancy is suspected. The necessity of a preoperative laryngoscopy in all other patients must be questioned. Postoperative laryngoscopy and additional diagnostic testing should be reserved for symptomatic patients.