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HighlightsThe developed downforce test stand simulated varying disc loads based on actual field data.The planter’s downforce control system was able to maintain the target gauge wheel load 94% of the time.The planter’s downforce control system managed disc load variations of up to 667 N within 1.3 s.Abstract. In recent years, precision planters have incorporated automatic control of the row unit downforce to reduce sidewall soil compaction, maintain proper seeding depth, and control row unit ride quality. By applying an appropriate row unit downforce, more uniform emergence and increased yield can be obtained. However, little research exists on evaluating the response and accuracy of downforce control systems during planting. Therefore, the objectives of this study were to (1) develop a laboratory-scale row unit downforce test stand and (2) use the test stand to evaluate the downforce control system response time and the load distribution between the gauge wheels, opening discs, and closing wheels using simulation scenarios based on real-world soil and terrain data. The downforce test stand was able to distribute the applied downforce to the row unit gauge wheels, opening discs, and closing wheels. It was also capable of varying the row unit ride height. The simulation scenarios using the test stand showed that the downforce control system maintained the target gauge wheel load (GWL) of 379 N within ±223 N for more than 94% of the time during all simulations. The downforce control system was also able to manage the GWL within 1.3 s for disc load variations up to 667 N. Keywords: Automatic downforce control, Downforce test stand, Gauge wheel load, Simulation.

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.

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.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.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%, p0.0001). 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 (563 years, 303 years) were similar, despite a significantly shorter operating time in the chief surgeon group (p0.01).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.

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.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.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.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.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.

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. 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. 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. 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.

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.

In multiply traumatised patients injuries of the -liver are frequently seen. Depending on location and extent of the trauma, different techniques can be applied. In the presented case of a central liver trauma in a 21-year-old man with active bleeding, mesh-wrapping of both liver lobes was applied to achieve control of the bleeding. Postoperatively the patient developed constant hypertension, oliguria and severe anasarka of the lower half of the body caused by a near total obstruction of the inferior vena cava. After removal of the wrappings, all symptoms slowly disappeared. This case and the findings in similar cases in the literature suggest that there is an indication for wrapping a traumatised liver rather with diffuse and peripheral bleeding than with a central liver trauma.

Surgical research in Germany occupies a lower position in international ranking than expected. According to the size of the population, the economic impact, the gross domestic product and the research funding capacity, the impact of German surgical research should be much higher. Reasons are a more intensive commitment to patient care, structural differences and a changing lifestyle in younger doctors in comparison to many leading countries. If the situation is to be improved all factors have to be evaluated and, if possible, changed. Overall, German surgeons are underrepresented as readers and authors in the scientific market, which is mostly in the English language.

The effect of varying calcium concentrations on PTH release from dispersed cells of adenomatous parathyroid tissues (n = 15) was studied. During high calcium concentrations PTH secretion was inhibited up to 62.5% as compared to low calcium concentrations. There was no correlation between iPTH secretion rate and suppressibility. Each adenoma had a different iPTH secretion rate. Three adenomas showed a high suppressibility (28.0%, 53.8%, and 62.5%). The supernates of their media were chromatographed and examined by midregion and C-terminal specific PTH-RIAs. Carboxyl-terminal PTH fragments were found to be released by two adenomas. There was no evidence for the release of midregion PTH fragments. Comparison of incubation media revealed that the adenoma with the lowest suppressibility released the highest amount of intact PTH (per 100,000 cells/ml). This adenoma exclusively secreted intact PTH, whereas PTH fragments were only released from two adenomas with higher suppressibility. In these media the ratio of PTH fragments to intact PTH increased with the calcium content of the media. The ratio was also dependent on the suppressibility of the adenomas; i.e. the ratio was greater when the suppressibility was higher. This suggests that in adenomas the intracellular hormone degradation is responsible for the degree of PTH suppression. As the suppressibility of PTH secretion is reduced in hyperfunctioning parathyroid tissue, diminished intracellular hormone degradation seems to be involved in the pathogenesis of primary hyperparathyroidism.

We compared a midregion (44-68) human parathyroid hormone (hPTH) specific radioimmunoassay (M-RIA) with a C-terminal (65-84) hPTH specific radioimmunoassay (C-RIA). The M-RIA discriminated 21 of 23 patients with primary hyperparathyroidism from 95 normals (normal range: 22.4-106.5 pmol/l). With the C-RIA 12 patients including the 2 patients not discriminated by the M-RIA had immunoreactive PTH (iPTH) values within the normal range of this assay (normal range: undetectable to 88.6 pmol/l). To investigate the reasons for these different abilities of separation, hyperparathyroid sera were subjected to gel-filtration and analyzed using the two assays. Intact PTH appeared to have a major influence on the immunoreactivity of circulating PTH in the M-RIA. In contrast, the C-RIA showed the highest immunoreactivity with midregion-C-terminal PTH fragments. Hyperparathyroid sera not discriminated by the C-RIA but with elevated iPTH in the M-RIA showed decreased amounts of midregion-C-terminal PTH fragments, while intact PTH comprised the highest amount of total circulating PTH immunoreactivity in the M-RIA. From the present results we conclude that the superiority of the M-RIA is due to the determination of intact PTH which is preferable for clinical measurements with relation to the diagnosis of primary hyperparathyroidism.

The effect of the muscarine-like acting parasympathomimetic drug oxotremorine and its antagonist atropine on PTH release was tested using single cell suspensions obtained from a) primary parathyroid adenomas, and b) secondary hyperplastic parathyroid tissue from patients undergoing chronic hemodialysis. For both cell-types we found a dose-dependent suppression of PTH release with oxotremorine. The suppressive activity could be antagonized with atropine, suggesting that parasympathomimetic nerval impulses play a suppressive role in the regulation of PTH release. Muscarine-receptors appear to be responsible for this mechanism.

Serum calcitonin (CT), parathyroid hormone (PTH), and calcium levels were measured in 23 patients with primary hyperparathyroidism. PTH was determined by a midregion (M-RIA) and a carboxyl-terminal (C-RIA) specific PTH-RIA. Only 2 patients had elevated CT levels. In contrast to the findings in 46 healthy controls, the CT levels did not correlate with calcium levels. Patients who had the highest iPTH values showed a negative correlation between CT and iPTH (M-RIA (n = 7): R = -1.0000, p less than 0.001; C-RIA (n = 13): R = -0.5604, p less than 0.05). The results of the C-RIA were subtracted from those of the M-RIA. In 12 patients with the highest levels of intact PTH (M-RIA - C-RIA), serum PTH concentration was inversely correlated with serum CT concentration (R = -0.7343, p less than 0.01). In the same patients a negative correlation between CT and calcium was found (R = -0.6783, p less than 0.02). These findings suggest that high PTH levels may have a direct suppressive effect on CT concentration and this may be, at least in part, responsible for failure of CT concentrations to rise in many patients with primary hyperparathyroidism.

Localisation of parathyroid tissue in hyperparathyroidism may be difficult with standard methods. Immunoscintigraphy, using radiolabeled antibodies against epitopes of human parathyroid cells, could be a promising alternative. Therefore, we studied the necessary preconditions, whether the so-called BB5-antibody, directed against parathyroid cell membranes possesses sufficient specificity and affinity to be employed in immunoscintigraphy. Specificity was tested immunohistochemically with APAAP-staining of 39 different human tissues. Additionally, an immunoscore-based quantitative comparison was performed to test the affinity of BB5-antibody for normal and pathologic parathyroid tissue. Specificity was proven by the fact that of all 39 tested tissue-types only the parathyroid tissue was BB5-positive. Normal parathyroid tissue showed a significantly higher affinity to the BB5-antibody than pathologic parathyroid tissue (p < 0.03). However, all tissue samples from primary or secondary hyperparathyroidism exhibited sufficient staining. We conclude that the BB5-antibody fulfills the necessary conditions to be tried for immunoscintigraphical localisation of the parathyroid glands.

Permanent hypoparathyroidism is one of the most difficult of all endocrine disorders to treat medically. While autotransplantation of parathyroid tissue is clinically established, allotransplantation without immunosuppression is still at the level of animal experiments. Although persons affected by hypoparathyroidism are facing a clearly reduced quality of life, hypoparathyroidism rarely is a life threatening condition. Therefore, systemic immunosuppression for recipients of allotransplants is not justified. A conceptional alternative would be protecting the tissue to be transplanted from the immunologic response by coating it with a semipermeable membrane (microencapsulation). In 1994, we succeeded in iso-, allo- and xenotransplantation of microencapsulated parathyroid tissue in an animal model. Unfortunately, prior to the first clinical use, further analysis of the coating substance (alginate) demonstrated that it has mitogenic properties. Here, we report on the first successful transplantation of microencapsulated parathyroid tissue using a purified, non-mitogenic alginate which is suitable for clinical use.

Thyroid stimulating hormone (TSH) causes differentiation and epidermal growth factor (EGF) causes dedifferentiation of thyroid cells in vitro. In undifferentiated thyroid cancer cell lines, TSH stimulates tumor cell migration and invasion, a dedifferentiated function, presumably due to an escape of tumor cells from the control of differentiating growth factors. In a highly differentiated thyroid carcinoma cell line of Hurthle cell origin (XTC), we tested the hypothesis that TSH would stimulate thyroglobulin secretion (a differentiated function) more than EGF, and EGF would stimulate invasion (a de-differentiated function) more than TSH. Proliferation, adhesion, cell migration and invasion were measured by the MTT assay, human thyroglobulin by RIA and protease activity by substrate-gel zymography. TSH induced differentiated morphologic changes in XTC cells and stimulated secretion of human thyroglobulin in a dose dependent manner, whereas EGF did not. The effects of TSH on growth, adhesion, migration and invasion were dose dependent and biphasic, with an increase at low and a decrease at high concentrations of TSH. These effects were always more pronounced than those observed with EGE Gelatinolytic activity, consistent with metalloproteinase activity was revealed by zymography, but the pattern of secretion was not altered by neither TSH nor EGF. These results suggest, that TSH has pleiotropic effects on differentiated thyroid cancer cells in vitro that involve differentiated morphology and function but also affect features commonly associated with the malignant in vitro phenotype.

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.

Information management is becoming an increasingly challenging task for farmers, especially in terms of the amount of data and the complexity of processes in precision farming. One of the most demanding functions is data acquisition. Mobile farm equipment featuring different sensors is able to collect a large amount of data while working. Automated process-data acquisition can be the basis for information-steered agricultural production. But use of these data is restricted today by hardware and software compatibility, different data formats, the lack of a concept for reusing data, and the amount of data. This paper presents a prototype implementation of an agricultural process-data service (APDS). It is part of an infrastructure for data management in information-driven plant production, developed in the Pre agro joint research project. Data are recorded in an ISOBUS environment and transferred to a server. There they are analyzed and aggregated to jobs. Data can be requested for further use via a web portal and a web service interface.

In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT–PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time–PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.

Precision agriculture (PA) is an innovative, integrated and internationally standardized approach aiming to increase the efficiency of resource use and to reduce the uncertainty of decisions required to control variation on farms. Worldwide, investments in research and technology on PA have considerably increased during the past decades. Advances in agricultural research, combined with application of PA on grasslands, could provide major economic and environmental benefits. However, most of the available technology is currently being applied on arable land but not on grassland although the latter contributes substantially to agricultural land use as well as to capital and income. The authors hypothesise that heterogeneity of grassland among and within fields is a major constraint to PA application and that understanding such heterogeneity would enable to implement PA where competitive and cost efficient. In this paper, current developments and future perspectives of digital image processing, remote sensing, yield measurement, and site-specific management on grassland are discussed. At fine scales, on-board sensors can provide information on sward properties that application techniques could respond to. At larger scales, remotely sensed information can provide digital maps of type and status of vegetation that allow a precise management, although the mix of spatial coverage and spatial resolution is not yet ideal. The site-specific management on arable land, however, has not yet proven its applicability in different environments. On grassland, some of these technologies are either already implemented as prototypes into research projects or under development with a short-term perspective to be introduced into practice. Grassland scientists can significantly contribute to the current development and, in return, benefit from latest sensor technology and so enable rapid data acquisition and improvement of experimentation and knowledge. Also existing computer simulation models can contribute to make PA on grassland a success. Animal husbandry is strongly linked to grassland utilization and can also benefit from present PA technology through animal production and health control and animal guidance with appropriate electronic stimuli. Considerable interdisciplinary research is required to link existing knowledge on PA technology with grassland science and with animal science. This could mainly be accomplished by the interpretation of signal–object interaction that is needed to set up suitable configurations on grassland.

BACKGROUND AND OBJECTIVE: "Critical incident reporting systems” (CIRS) are voluntary systems which, within the framework of risk management, provide pointers to the type and origin of critical incidents (including "errors”). The interest in introducing a CIRS is great, but whether it can fulfill its promises remains to be clarified. The aim of this study was to answer the question of whether an CIRS in a structured form would be acceptable to staff and whether it would be suitable for introducing targeted measures for achieving improvements. METHODS: The introduction of a CIRS in the Department of Visceral, Thoracic and Vascular Surgery proceeded according to the recommendations of the Action Alliance for Patients' Safety (Aktionsbundnis fur Patientensicherheit e.V.). RESULTS: During a period of 13 months we received a total of 96 reports, 29.3% from various levels of carers/nurses, while 35.4% were from doctors. 40.6% of the incidents had been observed by the reporting person, in 38.5% of cases the reporting person had been involved in the incident and in 12.5% this person had helped in dealing with the incident. 38.5% of the reported critical incidents occurred between 06.00 and 12.00, while 34.4% occurred between 12:00 and 18:00 o/c. In 32.3% of cases the estimated duration of dealing with the incident was under four hours and between four and eight hours in 26%. During the first year of this study 12 actions were started and continued in consequence of an analysis of the reported critical incidents. CONCLUSION: After one year of the study it was found that a CIRS can be reliably introduced into a surgical department in accordance with the recommendations of the Action Alliane for Patients' Safety. When introduced correctly CIRS provides valuable information, which will lead to risk reduction in surgery.

A patient with high-grade osteoporosis had elevated levels of ACTH, cortisol and carcinoembryonic antigen (CEA). Computed tomography demonstrated enlarged adrenal glands. Despite intensive search no ACTH-producing tumour was found. A central Cushing's syndrome was thus possible, and a radiologically normal sella turcica made a microadenoma of the hypophysis a possibility. However, a one-time hypertensive crisis with elevated catecholamines raised the suspicion of an additional phaeochromocytoma and thus provided the first pointer to a multiple endocrine neoplasia. Bilateral phaeochromocytomas, discovered at adrenalectomy, as well as raised serum-calcitonin levels, strongly suggested coexistence of a C-cell carcinoma, which previously had not been demonstrated either by thyroid scanning or fine-needle biopsy. A total thyroidectomy revealed a multifocal and metastasizing C-cell carcinoma. On extraction it contained a high concentration of calcitonin, typical for a C-cell carcinoma. An unusual finding was of ACTH in extracts of both the C-cell carcinoma and the phaeochromocytoma. It was immunologically identical with the synthetic ACTH used as a standard.

Pheochromocytoma scanning using 131J-meta-benzylguanidine was done in one patient with metastasizing paraganglioma, one patient with multiple endocrine neoplasia type IIb. No activity of tumour tissue could be demonstrated in the patient with metastasizing paraganglioma, whereas the pheochromocytoma could be clearly defined in the patient with multiple endocrine neoplasia type IIa. The female with multiple endocrine neoplasia type IIb showed a suspect space-occupying lesion of the left adrenal using computed tomography. Pheochromocytoma could be excluded by 131J-benzylguanidine scanning, selective estimation of catecholamines in adrenal venous blood as well as the glucagon stimulation and clonidine suppression.

Following the third operation, aparathyroidism occurred in a 70-year-old female with primary hyperparathyroidism due to parathyroid hyperplasia. Part of the parathyroid obtained during the last operation was cryopreserved immediately after resection and replanted successfully after 15 days into the lower arm muscles. The function of the transplanted tissue was demonstrated by successful stepwise reduction of hormone substitution. Parathyroid hormone concentrations in the blood of the veins draining the transplanted tissue were more than double in comparison with the contralateral side. Functional and morphological investigations of the defrosted tissue prior to transplantation showed vitality and intact morphology.

On the basis of 70 re-operations in 55 patients (34 women, 21 men, median age 58 [43-83] years) suffering from primary hyperparathyroidism the reasons for failure of the first operations were analysed. The main reasons were inadequate exploration of the neck (failure to identify all four glands), failure to recognize multiple gland involvement, or inadequate resection in cases where more than one gland was affected. An abnormally situated gland was a less common cause, as shown by the fact that 41 out of the 73 glands removed at the last re-operation were situated in the normal position or in its immediate vicinity; in 20 cases the surgeon had failed to recognise multiple gland disease. Next in order of importance were anatomical variations in the location (32 out of 73 tumours) or the number of the glands (9 patients with hyperplasia of 5 glands). At the re-operations 89% of the parathyroid tumours were found in the neck region or would have been accessible from the neck at the time of the first operation. Overall, the hypercalcaemia was permanently rectified in 96.6% of the patients. During the last 10 years 94% of patients have been normocalcaemic postoperatively, thanks mainly to the re-implantation of autologous parathyroid tissue, preserved by low-temperature storage. The incidence of permanent unilateral recurrent nerve paresis attributable to the re-operations was 6%.

Implantation of self-expandable metal stents was planned for 21 patients (12 women, 9 men; mean age 64.7 +/- 11.6 [38-80] years) with malignant obstructive jaundice due to complex hilar biliary obstruction (Bismuth II: n = 5, Bismuth III: n = 13, Bismuth IV: n = 1, state after hepaticojejunostomy: n = 2). Stents were implanted bilaterally in 18 patients (one each on the right and left, n = 12; two stents on right, one stent on left, n = 6), one patient had three stents on one side, another had one unilateral stent. Thus there was a 93.3% success rate (46 of 49 planned stent implantations). The mean bilirubin level fell from 14.7 +/- 7.7 mg/dl before stent implantation to 3.9 +/- 5.4 mg/dl afterwards (P = 0.0001). One patient experienced late bleeding with haemorrhagic shock and consumption coagulopathy after a failed drainage attempt. She died despite superselective embolization, operative suturing of the puncture site, and wide-ranging intensive care measures. Procedure-related death rate was thus 4.8%, the 30-day death rate 9.5%. During the follow-up period, averaging 145 +/- 152 (16-529) days, jaundice recurred in six patients (30%) and was successfully treated by re-intervention in five. 13 patients died after a mean survival time of 98 +/- 119 (16-432) days. It is concluded from these data that self-expandable metal stents provide minimally invasive palliative treatment of complex biliary hilar obstruction in the type of case in which plastic stents are known to fail.

An 86-year-old man was admitted to hospital because of transitory cramp-like abdominal pain of 6 days' duration. Immediately preceding admission he had suffered a short episode of vomiting and diarrhoea. There was no history of previous abdominal operation. On examination there were signs of incomplete mechanical ileus. Ultrasonography revealed an abnormal cockade with triple ring phenomenon at the ileocaecal junction and the "duck-beak phenomenon" as signs of enterocolic intussusception. Immediate laparotomy demonstrated a submucous lipoma of the terminal ileus as its cause.--If there is clinical suspicion of intussusception, even in the presence of atypical abdominal symptoms, ultrasonography is the procedure of choice to provide rapid diagnosis. In adults treatment is always surgical.

HISTORY AND CLINICAL FINDINGS: A 73-year-old woman was hospitalised because of increasing dyspnoea and hoarseness after a bout of acute tracheobronchitis. She had been receiving levothyroxine for a growing grade III nodular goitre. At the ages of 26 and 29 she had been treated for cervical lymph node tuberculosis with local excision and percutaneous radiotherapy of 8 Gy each time. On examination she was found to have a bulging neck profile and a hard, practically immobile node in the left lobe of the thyroid. INVESTIGATIONS: Laboratory tests showed a euthyroid metabolic state, while ultrasound demonstrated a mass. 40 mm in diameter, scintigraphically a cold nodule. A fine-needle biopsy was cytologically highly suspicious of neoplasm. TREATMENT AND COURSE: Surgical exploration of the neck and mediastinum revealed an insular follicular carcinoma (10 cm in diameter), involving the right recurrent laryngeal nerve and surrounding the brachiocephalic trunk. The latter had to be removed and a Gore-Tex graft was interposed. Postoperative radiotherapy was given (150 mCurie I131). CONCLUSION: An enlarging nodular goitre, occurring after a latent period of years following radiotherapy to the neck region for benign and (or) malignant disease, especially when it had been administered in childhood or young adulthood, should raise the suspicion of a radiogenic thyroid carcinoma. Definitive diagnosis by fine-needle biopsy is essential.

Pancreatitis occurred in 13 (5.6%) of 234 patients (76 men, 158 women; mean age 63 [2-83] years) who were operated on for primary hyperparathyroidism (pHPT) between 1987 and 1992. The pancreatitis patients had a significantly higher median level of parathormone (340 pg/ml), of serum calcium (3.2 mmol/l) and of thyroid weight (1.7 g) than the remaining 221 patients (135 pg/ml; 2.9 mmol/l; 1.0 g, respectively: P < 0.05 for each). In ten patients pHPT had been diagnosed during an attack of pancreatitis: pancreatitis had been the diagnostic clue to pHPT. After conservative treatment of the pancreatitis and parathyroidectomy seven of the ten patients were free of symptoms during the follow-up. In one patient pancreatitis recurred postoperatively and two patients died of the consequences of haemorrhagic necrotizing pancreatitis. Cholelithiasis, as another possible causative factor for pancreatitis, was present in five of the 13 patients (38%). None of the patients was an alcoholic. These data indicate that there is a positive correlation between advanced pHPT and pancreatitis. Pancreatitis may be the expression of much advanced hyperparathyroidism which has been diagnosed too late.

Between 1987 and 1991, 16 patients (13 females, three males; mean age 52.4 [33-73] years) with Zollinger-Ellison syndrome (ZES) were treated according to a standardized surgical concept. The diagnostic work-up consisted of measuring serum gastrin levels, pre-operative localization by ultrasound and abdominal computed tomography, as well as extensive staging by laparotomy. As complete a tumour resection as possible was the aim of treatment in 15 patients, while in one patient it was to reduce the tumour mass. In six patients who had resection of a solitary tumour there was no evidence of recurrence after 6-42 months of follow-up. Exploration of the duodenum made it possible to identify and then remove a small gastrinoma of the duodenal wall in three patients. No gastrinoma was found in one patient despite extensive exploration. In a further four patients the laparotomy was purely exploratory, because diffuse metastasization was found. In four patients the primary tumour and, where present, the regional lymph nodes were removed, but the signs of ZES persisted, i.e. the intervention was merely palliative. In one female patient, reduction of tumour mass was necessary because the symptoms could not be controlled by conservative measures: she died postoperatively from toxic hepatitis. This experience indicates that standardized surgical intervention achieves potentially curative results in nearly 40% of patients. Including the duodenum in the surgical exploration allows the identification of even small gastrinomas of the duodenal wall. It is concluded that all patients with ZES but no evidence of diffuse metastases should undergo surgical treatment.

Over the period of two weeks a 19-year-old man developed gradually increasing painless jaundice with dark urine and light-coloured soft stools (6-7 times daily), as well as loss of appetite, nausea and nagging itch. Biochemical tests indicated marked cholestasis (alkaline phosphatase 800 U/l, gamma-GT 206 U/l). Abdominal ultrasound examination revealed high-grade stenosis of the distal choledochal duct caused by an enlargement of the head of the pancreas and computed tomography confirmed a tumour in this location. Endoscopic retrograde cholangiopancreatography demonstrated filiform stenosis of the major pancreatic duct and prepapillary stenosis of the choledochal duct. Several needle biopsies failed to establish a definitive diagnosis. A Whipple operation was performed: the stomach was preserved but about 40% of pancreatic tissue resected. Histologically there was chronic suppurative pancreatitis of the head of the pancreas. The patient was symptom-free 6 months after the operation. The case illustrates that it is not always possible in a painless pancreatic tumour to distinguish between pancreatitis and malignant tumour.

BACKGROUND AND OBJECTIVE: Mutations in the MEN 1 gene were recently discovered as the causative genetic defect of the autosomal dominantly inherited multiple endocrine neoplasia type 1. It was the aim of this study to evaluate the spectrum of MEN 1 mutations in our own series of patients in order to obtain a basis for predictive family screening.PATIENTS AND METHODS: Genomic DNA from peripheral blood of 21 patients with MEN 1, members of 14 non-related MEN 1 families, was examined for MEN 1 germ-line mutations by means of single-strand conformation variant analysis (SSCP) and direct DNA sequencing. In addition, blood from 20 asymptomatic family members of five families was tested for its predictive value.RESULTS: Eleven different heterozygotic germ-line mutations, among them eight frameshift, two missense and one nonsense mutations, were identified. In four of the 20 asymptomatic members from five MEN 1 families who had been tested after appropriate genetic counselling, the MEN 1 mutation characteristic for the particular family was found. Clinical screening programme in three mutation carriers revealed abnormal findings in all three: one primary hyperparathyroidism, one prolactinoma and one nonfunctioning pancreatic tumour each. The 16 family members without MEN 1 mutation were spared further unnecessary screening investigations.CONCLUSION: Although the function of the MEN 1 gene is not yet known, molecular genetic tests provide a basis for genetic counselling, predictive genetic screening and clinical management of MEN 1 families. (Less)

Perioperative data on 284 patients who had simultaneously undergone cholecystectomy and surgical exploration of the bile duct were analysed. The procedures had been performed electively in 234 patients (145 females, 89 males; median age 61.5 [20-84] years). Freedom from stone was achieved in 96.2%; complication rate was 25.2% and death rate 2.6%. There was no death among patients without any or only one risk factor, while the morbidity rate for them was 18%. There were five deaths among 34 patients with four or more risk factors, and 13 (38.2%) had complications. Three of the patients who had died had been operated on because of septic, obstructive cholangitis with fever greater than 37.5 degrees C and bilirubin levels greater than 5 mg/dl. The operation was performed as an emergency in 50 patients (32 females, 18 males; median age 71.5 [24-93] years. 94% of them were free of stone afterwards; death rate was 10%, complication rate 44%. These data suggest that indications for the double surgical procedure in case of cholecysto-choledocholithiasis should be related to risk factors. In an emergency and in patients at risk, endoscopic papillotomy and stone extraction should precede cholecystectomy. But the one-time and thus definitive double surgical procedure remains the management of choice for patients with few or no risk factors.

Over a five-year period (1.1.89-31.12.93), a duodenopancreatectomy (Whipple's operation) was performed without hospital or 30-day death in 54 consecutive patients (22 women, 32 men; mean age 62 [27-82] years). The postoperative morbidity was 39% (21 of 54 patients). The indications for the operation were malignant tumour (n = 41), mainly ductal adenocarcinoma of the pancreas (n = 30), benign tumour (n = 5) or inflammatory head of the pancreas tumour in chronic pancreatitis (n = 6). A classical Whipple's operation was performed in 36 patients, while the stomach-preserving variant was undertaken in 18. The main complications were postoperative disorders of gastric emptying (n = 13), bleeding (n = 7), abscess (n = 4), leakage at the pancreas anastomosis (n = 3) and pancreatic fistula (n = 2). All complications were successfully overcome by early use of interventional methods or relaparotomy. -The low mortality rate of Whipple's operation (0-5% in selected centres) justifies the use of this operation even in advanced malignancies.