Surgery during pregnancy - results of a German questionnaire.

OBJECTIVES: Worldwide, not only the number of female medical students, but also of female surgeons increases. Simultaneously, younger generations take a closer look to their work-life balance. With this in mind, it seems necessary to evaluate the expectations of female surgeons in particular with respect to pregnancy during their surgical career. METHODS: Therefore, a nationwide survey was conducted in Germany from July to December 2016 under the auspices of the German Society of Surgery as well as the Professional Board of German Surgeons. The questionnaire involved 2,294 female surgeons and 1,843 complete records were evaluated. RESULTS: Of the analyzed answers, 62% of the women (n=781) were operating during pregnancy. The joy of surgery (91.6%), followed by team spirit (57.1%), were the main motivations to perform operations while pregnant. Operative activity decreased from 30.8% in the first 3 months of pregnancy to 21.5% during the last three months. Regarding the possible complaints, e.g., leg edema, back pain, premature labor and vaginal bleeding, there were no significant differences between the women with or without activity in the operating room. Sick leave due to pregnancy (1-10 days) was stated by 40.4% of respondents. CONCLUSION: Despite strong legal regulations for pregnant surgeons, the survey showed that most female surgeons are eager to operate despite their pregnancy. The results also demonstrate no significant differences regarding complications during pregnancy- or pregnant-dependent absence from work. Hospitals and surgical departments are asked to establish proper working conditions for pregnant surgeons and pregnancy should not be an obstacle for a career in surgery.

Influence of Parathyroidectomy on Bone Metabolism and Bone Pain in Patients with Secondary Hyperparathyroidism.

BACKGROUND: After parathyroidectomy (PTX), hungry bone syndrome leads to hypocalcemia due to bone remineralization. The aim of this pilot study was to analyze changes in markers of bone metabolism in patients with secondary hyperparathyroidism (sHPT) after PTX and to correlate these markers with bone pain measured with a validated questionnaire. MATERIALS AND METHODS: All patients who underwent PTX for sHPT between March 2010 and February 2012 at out institution were included in this prospective observational pilot study. At the day before surgery and on the 3rd day thereafter, levels of parathyroid hormone (PTH), calcium, osteocalcin, alkaline phosphatase (AP), bone-specific AP (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), osteoprotegerin (OPG), sclerostin, fibroblast growth factor 23, and Klotho were measured. Additionally, all patients were requested to answer the Brief Pain Inventory preoperatively and on the 5th postoperative day. RESULTS: A total of 35 patients with a mean age of 49.8 years were analyzed. A significant difference between the pre- and postoperative values could be detected in PTH, calcium, BAP, TRAP5b, and sclerostin. The highest correlation of laboratory markers with bone pain was found for preoperative PTH (r = 0.3), postoperative OPG (r = 0.4), postoperative BAP (r = -0.4), and postoperative Klotho (r = -0.4). CONCLUSIONS: The present study revealed significant perioperative changes in PTH, BAP, sclerostin, and TRAP5b after PTX. These markers may serve as laboratory markers to monitor bone metabolism in patients with sHPT. PTH, OPG, and sclerostin were the parameters with the closest correlation to bone pain. However, larger prospective trials with a longer follow-up are required to confirm these results.

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.

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.

The influence of parathyroidectomy on restless legs syndrome in patients with renal hyperparathyroidism.

BACKGROUND: Restless legs syndrome (RLS) is a common and poorly understood movement disorder that leads to unpleasant leg sensations. Although RLS can be idiopathic, secondary etiologies such as iron deficiency and renal failure are common. The aim of this prospective cohort study was to evaluate whether RLS is a common feature in patients undergoing parathyroidectomy for renal hyperparathyroidism (rHPT) and if RLS-related symptoms can be influenced by surgery. METHODS: After providing written consent, patients who underwent a parathyroidectomy for rHPT between January and November 2011 answered a validated RLS-screening-questionnaire (RLSSQ). If this was suggestive for RLS a confirming questionnaire (IRLS) was also completed on the day before surgery, on the fifth postoperative day, and again during follow-up (minimum 12 months). Perioperative parathyroid hormone and calcium levels, as well as the scores of the questionnaires were analyzed. RESULTS: Twenty-one patients (14 men, 7 women) with a mean age of 47.8 ± 3.2 years underwent total parathyroidectomy with bilateral cervical thymectomy and parathyroid autotransplantation for rHPT. The mean score of the RLSSQ of all 21 patients prior to operation was 6.1 ± 0.5. In 10 of 21 patients (47.6 %) the results of the RLSSQ were suggestive for RLS with a mean score of 8.0 ± 0.3. The consecutive scores of the IRLS in these latter patients significantly dropped from 26.6 ± 1.4 to 19.0 ± 2.2 between the preoperative and postoperative settings (p < 0.05). After a mean follow-up of 17.3 ± 3.7 months the mean scores of the RLSSQ and the IRLS were 6.1 ± 0.6 and 16.3 ± 1.8. CONCLUSIONS: rHPT may play a major role in the severity of RLS-associated symptoms in patients with renal failure. Consequently, parathyroidectomy may prove to be a valuable tool to reduce RLS-associated morbidity in affected patients. However, larger prospective trials are required to confirm the possible relation between RLS and rHPT seen in the present study

Relevance of bilateral cervical thymectomy in patients with renal hyperparathyroidism: analysis of 161 patients undergoing reoperative parathyroidectomy.

BACKGROUND: The most frequent location of ectopic or supernumerary inferior parathyroid is the thymus. Bilateral cervical thymectomy has therefore been recommended as an essential part of the initial surgery for renal hyperparathyroidism (rHPT) to avoid persistent or recurrent cervical disease. The aim of this study was to evaluate how often reoperation might have been avoidable if an appropriate cervical thymectomy had been performed during initial surgery. METHODS: A prospective database of patients with rHPT was screened for patients on permanent dialysis who underwent reoperative parathyroidectomy (PTX) between 1976 and 2010. Data were retrospectively analyzed for the performance of bilateral cervical thymectomy during previous surgeries and the presence of ectopic and/or supernumerary intrathymic parathyroid glands during reoperative PTX. RESULTS: Of 161 patients who underwent reoperative PTX, 95 had neck reexploration. Among them were 29 patients with total PTX and autotransplantation, seven with subtotal PTX (3.5 glands resected), and 59 with incomplete PTX during the initial surgery. Bilateral cervical thymectomy during the initial PTX was performed in only 12 of 95 patients (12.6 %). It was revealed to be incomplete in six of them, inheriting an intrathymic parathyroid gland during reoperative interventions. Reoperative PTX revealed intrathymic parathyroid glands in 27 of 95 patients (28.4 %). The intrathymic parathyroid glands were ectopic in 17 (63.0 %) patients and supernumerary in 8 (29.6 %). Both ectopic and supernumerary intrathymic parathyroid glands were found in two patients (7.4 %). CONCLUSIONS: The risk for persistent and recurrent disease based on intrathymic parathyroid glands is a relevant problem during initial surgery for rHPT. Thus, routine bilateral cervical thymectomy that is as complete as possible is essential during the initial PTX for rHPT.

The calcitonin levels can sometimes mislead parathyroid surgeons in patients with chronic kidney disease and renal hyperparathyroidism: report of a case.

Renal hyperparathyroidism (rHPT) as a consequence of an abnormal calcium balance is a frequent complication in patients with chronic kidney disease (CKD). However, calcium homeostasis is also regulated by calcitonin. The relevance of elevated calcitonin levels in patients with rHPT is unclear. This report presents a case of a patient with CKD and mild rHPT scheduled for thyroidectomy for a suspected medullary thyroid carcinoma (MTC) within a mononodular goiter. A hemithyroidectomy with resection of both adjacent parathyroid glands and unilateral central lymph node dissection was performed. Histopathology revealed no evidence of MTC. The rHPT, calcitonin and pentagastrin test subsequently normalized and follow-up revealed no evidence for MTC within the remaining right thyroid lobe. Elevated calcitonin levels in patients with CKD may reflect a physiological response to rHPT than rather represent MTC. The thresholds for calcitonin levels need to be better defined in affected patients to determine the optimal extent of surgical resection.

Total versus near-total thyroidectomy in Graves' disease and their outcome on postoperative transient hypoparathyroidism: study protocol for a randomized controlled trial?

BACKGROUND: Graves' disease is an independent risk factor for transient postoperative hypoparathyroidism. Besides the disease itself, preparation techniques are influential. Transient postoperative hypoparathyroidism has severe consequences for patients' physical and psychological state. It can be life threatening during the acute phase and may impair patients' health, psyche and quality of life thereafter. For the surgical therapy of Graves' disease, total thyroidectomy is recommended according to the national S2-guideline. The evidence- based on a metaanalysis- is criticized by the Cochrane diagnostic review commentary for substantial methodological deficits. Two randomized controlled trials lead to the hypothesis that a near-total resection with bilateral remnants of ≤ 1g on each side compared to total thyroidectomy will significantly reduce the occurrence of transient postoperative hypoparathyroidism with equal therapeutic safety. METHODS/DESIGN: Patients with Graves' disease indicated for definite surgery are eligible for the trial. Trial-specific exclusion criteria are: conservative treatment, malignancy, previous thyroid surgery and coincident hypoparathyroidism. The trial is created for therapeutic purpose through process innovation. It is designed as a prospective randomized controlled patient and observer blinded multicentered trial in a parallel design including an active comparator and an intervention group. The intervention addresses the surgical procedure: near-total thyroidectomy leaving bilateral remnants of ≤ 1g on each side in the intervention group and total thyroidectomy in the control group. The occurrence of transient postoperative hypoparathyroidism is defined as primary endpoint. Secondary endpoints are: reoperations due to bleeding, recurrent laryngeal nerve palsy, permanent hypoparathyroidism, recurrent disease, changes of endocrine orbitopathy and quality of life within a one-year follow-up period. The primary efficacy analysis follows the intention-to-treat principle. A binary logistic regression model will be applied. Complications and serious adverse events will be descriptively analyzed. DISCUSSION: The trail is expected to balance out the shortcomings of the current evidence. It will define the surgical gold standard for the surgical therapy of Graves' disease. Patients' safety and quality of life are assumed to be enhanced. Therapy costs are likely to be reduced and health care optimized. The conduction of the trial is feasible through the engagement and commitment of the German association of endocrine surgeons and the National Network for Surgical Trials. TRIAL REGISTRATION: German clinical trials register (DRKS) DRKS00004161.

Cryopreservation of parathyroid tissue after parathyroid surgery for renal hyperparathyroidism: does it really make sense?

BACKGROUND: Metachronous autotransplantation of cryopreserved parathyroid tissue is a technique for treating postoperative hypoparathyroidism after parathyroid surgery for renal hyperparathyroidism (rHPT). The aim of the present study was to evaluate our institution's experience with metachronous autotransplantation to analyze the role of cryopreservation in the treatment of rHPT and to determine for whom and when cryopreservation of parathyroid tissue should be deemed necessary. METHODS: A prospective database of patients with rHPT who underwent surgery between 1976 and 2011 was screened for patients with hypoparathyroidism who received a metachronous autotransplantation. Data were analyzed regarding clinical data, histopathological findings of the cryopreserved parathyroid tissues, and patient outcome after metachronous replantation of parathyroid tissue. RESULTS: Fifteen of 883 patients with rHPT underwent a metachronous autotransplantation under local anesthesia at a mean time of 23 months following the last cervical surgery. Histopathology of the parathyroid tissue chosen for transplantation revealed a necrosis rate of 0 % in 14 and 70 % in one patient. Mean preoperative serum calcium and parathyroid hormone (PTH) levels were 2.0 mmol/l and 3.7 pg/ml, respectively. Autotransplantation raised mean serum calcium and PTH levels to 2.2 mmol/l and 97.5 pg/ml, respectively, after a mean follow-up of 78 months. CONCLUSIONS: Metachronous autotransplantation following parathyroid surgery in patients with rHPT effectively normalizes PTH and calcium levels. The success rate is high if an adequate cryopreservation procedure is applied. However, it is rarely necessary, and therefore the cryopreservation of parathyroid tissue in all patients has to be questioned, at least from an economic point of view.

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.

Initial parathyroid surgery in 606 patients with renal hyperparathyroidism.

BACKGROUND: The aim of the present study was to evaluate the outcome of different surgical procedures for patients on permanent dialysis who underwent initial parathyroidectomy for renal hyperparathyroidism (rHPT). METHODS: Out of a prospective database of patients who underwent parathyroid surgery for rHPT between 1976 and 2009, patients on permanent dialysis who underwent initial parathyroidectomy were further analyzed regarding perioperative biochemical changes and postoperative outcome. RESULTS: A total of 606 patients were analyzed. Total parathyroidectomy with autotransplantation (group A) was performed in 504 patients, total parathyroidectomy without autotransplantation in 32 (group B), subtotal parathyroidectomy in 21 (group C), and incomplete parathyroidectomy in 49 (group D). After surgery, mean calcium levels dropped from 2.76 to 1.91 mmol/l in group A, from 2.67 to 2.11 mmol/l in group B, from 2.70 to 2.09 mmol/l in group C, and from 2.65 to 1.94 mmol/l in group D. The parathyroid hormone level dropped from 1,371.4 pg/ml to 28.8 pg/ml in group A, from 1,078.4 pg/ml to 27.0 pg/ml in group B, from 2,377.9 pg/ml to 61.4 pg/ml in group C, and from 1,010.2 pg/ml to 99.5 pg/ml in group D. Persistent rHPT occurred in 2/504 patients from group A (0.4%), 0/32 patients from group B (0%), 1/21 patients from group C (4.8%), and 2/49 patients from group D (4.1%). After a mean follow-up of 57.6 months, recurrent rHPT occurred in 27/504 patients from group A (5.4%), in 0/32 patients from group B (0%), in 2/21 patients from group C (9.5%), and in 3/49 patients from group D (6.1%). CONCLUSIONS: Total parathyroidectomy with or without autotransplantation is a feasible and safe surgical procedure for patients on permanent dialysis with otherwise uncontrollable rHPT.

Frequency of ectopic and supernumerary intrathymic parathyroid glands in patients with renal hyperparathyroidism: analysis of 461 patients undergoing initial parathyroidectomy with bilateral cervical thymectomy.

BACKGROUND: The frequency of intrathymic parathyroid glands (IPGs) in patients undergoing parathyroidectomy for renal hyperparathyroidism (rHPT) varies considerably between 14.8% and 45.3%. Total parathyroidectomy with autotransplantation and subtotal parathyroidectomy are the most accepted surgical procedures to treat patients with rHPT. However, routine bilateral cervical thymectomy (BCT) is still discussed, although controversially. METHODS: From a prospective database of patients who underwent parathyroid surgery for rHPT between 1975 and 2009, patients with routine BCT at initial PTX were further analyzed regarding the frequency of ectopic and supernumerary IPGs. Duration of hemodialysis and stage of chronic kidney disease were correlated with the frequency of supernumerary IPGs to elucidate a potential role of long-standing proliferation stimuli to any surplus parathyroid tissue. RESULTS: Initial parathyroidectomy with BCT was performed in 461 patients. IPGs were resected in 205 of them (44.5%). They were ectopic in 181 (39.3%) and supernumerary in 30 patients (6.5%). The frequency of supernumerary IPGs in patients on permanent hemodialysis was 7.4% (29/392), 3.9% (1/26) in predialysis patients, and 0% (0/43) in patients after successful kidney transplantation. This differences reached no statistical significance. CONCLUSIONS: BCT is essential in patients with fewer than four parathyroid glands identified at typical positions. Because of the low frequency of supernumerary IPGs and a suspected low proliferation stimulus, the relevance of BCT after resection of four glands in predialysis patients and those after successful kidney transplantation must be questioned. Nevertheless, routine BCT seems to be acceptable and can be recommended in patients on permanent hemodialysis not awaiting kidney transplantation until proven otherwise by prospective trials.

Calcitonin-secreting pancreatic endocrine tumors: systematic analysis of a rare tumor entity.

OBJECTIVE: Pancreatic endocrine tumors (PETs) are characterized by the presence of hormone syndromes. Reports focusing on calcitonin-secreting PET (CTsPETs) are very rare. This study aimed to define a CTsPET-associated syndrome in regard to chemical, anatomical, and developmental aspects. METHODS: A computerized MEDLINE search was conducted under the search items: "pancreatic endocrine tumor," "calcitonin," "neuroendocrine pancreatic tumor," and "pancreas." Results of clinical, histopathological, immunohistochemical, and biochemical assessments of all patients identified with CTsPET were registered and statistically analyzed. RESULTS: Thirty-seven patients with CTsPET were identified. Mean serum calcitonin was elevated to the 89.2-fold of the upper reference value. Main symptoms were watery diarrhea (51.4%) and abdominal pain (35.1%). Most patients (59.5%) presented with metastatic spread at the time of diagnosis. Of all patients, 66.7% were alive after a mean follow-up of 28.9 months. Survival was higher in patients who underwent more aggressive surgical therapies independent from tumor sizes and in those with no metastases at the time of diagnosis. CONCLUSIONS: High calcitonin levels should always raise suspicion of medullary thyroid carcinomas. However, when thyroid examination remains without pathological findings, a CTsPET should be excluded. An aggressive surgical approach even in cases with large primary tumor sizes may lead to a longer survival.

An economic comparison of surgical and medical therapy in patients with secondary hyperparathyroidism--the German perspective.

BACKGROUND: Treatment options for secondary hyperparathyroidism were significantly amended with the introduction of cinacalcet and paricalcitol. Limitations of resources in public health systems demand detailed analyses of accruing costs. The aim of this study was to compare the costs of these new treatment modalities to surgery. METHODS: Patients who underwent initial parathyroidectomy (n = 91) and patients treated with cinacalcet or paricalcitol (n = 100) at an ambulatory dialysis center between 01/2003 and 12/2006 were analyzed. The revenues of both therapies for the funding agencies were calculated by a cost-cost analysis. The real arising costs of the supplier were analyzed and compared to the revenues. RESULTS: Treatment costs for cinacalcet (60 mg/day/year) were 5828.40€ and 4485.20€ for paricalcitol (15 µg/week/year). Revenues for inpatient surgical treatment according to the German DRG system were 3755.38€/case. Additionally, costs for postoperative ambulatory therapies were 545.05€ for the first year and 384.97€ for the following. CONCLUSION: Due to linearly increases, expenses of medical treatment with cinacalcet for more than 9 months or paricalcitol for more than 12 months exceeded the costs of surgical therapy. The indication of these new medical therapies should be restricted to patients as an interim solution ahead of surgery or in patients considered unfit for surgery.

Long-term control of parathyroid hormone and calcium-phosphate metabolism after parathyroidectomy in children with chronic kidney disease.

BACKGROUND: Hyperparathyroidism (HPT) is an essential contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). Pharmacological and dietary interventions are of limited efficacy; calcimimetics are not yet recommended in children. Parathyroidectomy (PTX) is ultimately performed if HPT becomes refractory to conservative measures; the long-term results and the impact of subsequent kidney transplantation (NTX), however, have not yet been evaluated. METHODS: We analyzed the postsurgical course of 18 paediatric CKD patients with refractory HPT who underwent PTX and autotransplantation of tissue fragments. PTX was successful in all but one patient with an ectopic fifth gland; median follow-up time was 8.3 (range 2.8-19) years. RESULTS: Parathyroid hormone (PTH) dropped within 1 year after PTX from 1030 +/- 108 to 98 +/- 18 pg/ml, Ca*P from 59.5 +/- 3 to 49 +/- 2 mg(2)/dl(2). Oral calcium supply transiently increased from 18.7 +/- 4.2 to 24.1 +/- 4.8 mg/kg/day within the first 6 months (all P < 0.05). Haemoglobin increased from 10.7 +/- 0.4 to 11.5 +/- 0.3 g/dl (P < 0.01), despite similar erythropoietin dose and ferritin levels. In patients on long-term dialysis, Ca*P increased again after 18 months; three patients required a second PTX after 3.8, 12 and 12.3 years. Twelve patients underwent NTX 1.8 (0.3-3.8) years after PTX, which decreased mean PTH and Ca*P into the target range throughout the entire post-NTX observation period. Postoperative complications included one transient recurrent nerve palsy, one hypocalcaemic seizure and a case of haemopericardium. At present, no patient has clinical signs of bone disease. CONCLUSIONS: PTX accomplishes long-term control of HPT and calcium-phosphate metabolism in children with CKD and following PTX and may thus mitigate uraemic bone and cardiovascular disease. This has to be taken into account if alternative long-term therapy with calcimimetics (with as yet unknown effects on longitudinal growth and pubertal development) is considered.

Unique expression pattern of the EMT markers Snail, Twist and E-cadherin in benign and malignant parathyroid neoplasia.

BACKGROUND: Epithelial and mesenchymal transitions (EMT) are essential for embryonic development and progression of non-invasive tumor cells into malignant, metastatic carcinomas. During embryogenesis, the parathyroid glands develop from pharyngeal pouches and migrate to their final destinations, densely enclosed by mesenchymal neural crest cells. In this study, we examined the expression of the EMT markers Snail, Twist and E-cadherin in normal parathyroid glands and benign and malignant parathyroid diseases. METHODS: Using immunohistochemistry, we compared expression of E-cadherin, Snail and Twist in 25 patients with parathyroid adenoma, 25 patients with parathyroid hyperplasia, and nine patients with parathyroid cancer with normal parathyroid glands. RESULTS: Normal parathyroid glands, parathyroid adenomas, and parathyroid hyperplasias showed a typical membranous E-cadherin staining pattern. Expression of Snail was found in 22/25 parathyroid adenomas and in all parathyroid hyperplasias. Twist was expressed in 22/25 of parathyroid adenomas and in 20/25 parathyroid hyperplasias. Snail and Twist positive cells were homogeneously distributed throughout the gland. However, in all nine parathyroid carcinomas, membranous E-cadherin staining was lost. In addition, the expression pattern of Snail and Twist was changed and mostly limited to the invasive front of cancer tissue samples. CONCLUSION: Expression of Snail and Twist at the invasive front and consecutive loss of E-cadherin in parathyroid carcinomas suggests a key role of EMT in the tumorigenesis of this cancer. The unique expression pattern could help to distinguish between an adenoma and a non-metastatic carcinoma. Loss of E-cadherin and change of the expression pattern of Snail and Twist together should result in an en bloc resection or a close follow-up.

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.

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.