Surgical therapy of adrenal tumors: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: Previous guidelines addressing surgery of adrenal tumors required actualization in adaption of developments in the area. The present guideline aims to provide practical and qualified recommendations on an evidence-based level reviewing the prevalent literature for the surgical therapy of adrenal tumors referring to patients of all age groups in operative medicine who require adrenal surgery. It primarily addresses general and visceral surgeons but offers information for all medical doctors related to conservative, ambulatory or inpatient care, rehabilitation, and general practice as well as pediatrics. It extends to interested patients to improve the knowledge and participation in the decision-making process regarding indications and methods of management of adrenal tumors. Furthermore, it provides effective medical options for the surgical treatment of adrenal lesions and balances positive and negative effects. Specific clinical questions addressed refer to indication, diagnostic procedures, effective therapeutic alternatives to surgery, type and extent of surgery, and postoperative management and follow-up regime. METHODS: A PubMed research using specific key words identified literature to be considered and was evaluated for evidence previous to a formal Delphi decision process that finalized consented recommendations in a multidisciplinary setting. RESULTS: Overall, 12 general and 52 specific recommendations regarding surgery for adrenal tumors were generated and complementary comments provided. CONCLUSION: Effective and balanced medical options for the surgical treatment of adrenal tumors are provided on evidence-base. Specific clinical questions regarding indication, diagnostic procedures, alternatives to and type as well as extent of surgery for adrenal tumors including postoperative management are addressed.

Respiratory-induced hemodynamic changes measured by whole-body multichannel impedance plethysmography.

The cardiovascular system is described by parameters including blood flow, blood distribution, blood pressure, heart rate and pulse wave velocity. Dynamic changes and mutual interactions of these parameters are important for understanding the physiological mechanisms in the cardiovascular system. The main objective of this study is to introduce a new technique based on parallel continuous bioimpedance measurements on different parts of the body along with continuous blood pressure, ECG and heart sound measurement during deep and spontaneous breathing to describe interactions of cardiovascular parameters. Our analysis of 30 healthy young adults shows surprisingly strong deep-breathing linkage of blood distribution in the legs, arms, neck and thorax. We also show that pulse wave velocity is affected by deep breathing differently in the abdominal aorta and extremities. Spontaneous breathing does not induce significant changes in cardiovascular parameters.

Refinement of screening for familial pancreatic cancer.

OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. METHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. RESULTS: 253 IAR with a median age of 48 (25-81) years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152) months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45 years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50 years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50 years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12 months (n=180) or IAR that decided to be screened at ≥24 months intervals (n=30). CONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.

Global pollution by organochlorinated endocrine disruptors - possible challenge for mankind at the onset of millennium.

Author of this review submits a comprehensive report of his long-lasting research regarding the global pollution by endocrine disruptors (EDs), EDs and diabetes and obesity, EDs and the thyroid in highly polluted Slovakia, Ah-receptor: the central pivot responsible for such global "EDs disaster", EDs and immune system, EDs and testosterone, EDs in mothers and newborns, EDs and human genome, and EDs at the beginning of the millennium.

Obesogenic and diabetogenic impact of high organochlorine levels (HCB, p,p'-DDE, PCBs) on inhabitants in the highly polluted Eastern Slovakia.

OBJECTIVE: This study was aimed to evaluate possible obesogenic and diabetogenic impact of highly increased serum level of persistent organochlorinated pollutants POPs, such as polychlorinated biphenyls (PCBs), dichlorodiethyl-dichloroethylene (p,p'-DDE), and hexachlorobenzene (HCB), on the level of obesity markers (cholesterol and triglyceride level in serum, and body mass index [BMI]) and diabetes markers (fasting glucose and fasting insulin in serum) in inhabitants of Eastern Slovakia. METHODS: In young (21-40 years) males (n=248) and females (n=330) as well as in old (41-75 years) males (n=586) and females (n=889), the serum levels of 15 polychlorinated biphenyl congeners (Σ15PCBs), p,p'-DDE and HCB, and serum insulin, testosterone, total cholesterol, triglycerides and glucose levels have been estimated by high resolution gas chromatography/mass spectrometry and by the appropriate electrochemiluminiscent immunoassay or chemical methods, respectively. RESULTS: In both age groups of males and females, the levels of Σ15PCBs, p,p'-DDE, and HCB were very high and their mutual interrelations were highly significant (p<0.01). However, it should be noted that no significant changes were found in individual variables related to very high level of Σ15PCBs, except of increased BMI (p>0.05) in females.In all ages and gender groups, defined above general as related to increasing level of individual OCPs in individual age and gender groups, significant increase in cholesterol and triglyceride levels as well as BMI values, supported their obesogenic effect, while significant increase in fasting glucose and insulin in serum, supported their diabetogenic effect. Finally, highly significant decrease in testosterone level, as found in both young and old males, supported the antiandrogenic effect, namely of HCB. However, somewhat less of p,p'-DDE, while PCBs did not show any such effect in spite of their very high level. CONCLUSIONS: Highly increased blood levels of diabetes (fasting glucose and insulin) and obesity markers (cholesterol, triglyceride and BMI) were found in large groups of males and females in highly polluted area of Slovakia. Significant decrease in testosterone level was also observed in males.

In vitro evaluation of aliphatic fatty alcohol metabolites of Perseaamericana seed as potential antimalarial and antimicrobial agents.

Perseaamericana Mill (Lauraceae) is a local medicinal plant used in Nigerian ethnomedicine as antimalarial. The aqueous decoction of the root part is a potent remedy against bacterial infections. Hence, the need to investigate the phytochemical and biological activities (antimicrobial and antiplasmodial) of the root back of Perseaamericana. Chromatographic and spectroscopic techniques were used in the identification and purification of metabolites, which were assayed for antimalarial and antimicrobial activities using Plasmodium falciparum and a panel of microorganisms. From the seeds of P. americana, five known 1, 2, 4-dihydroxy derivatives aliphatic alcohols, called avocadenols were isolated and identified by spectroscopic methods including 1D- and 2D NMR, and comparison with reported data in literature. Antifungal activity for 1, 2, 4-Trihydroxyheptadec-6-en-16-yne (5) (IC50< 8 µg/mL) against all the fungal strains and S. areus, and antimalarial activity for compounds 1, 2, 4-Trihydroxyheptadec-16-ene (1) and 1, 2, 4-tetrahydroxyheptadecane-6, 16-diene(2) (IC50 = 1.6 and 1.4 µg/mL for the D6 clone, respectively, and 2.1 and 1.4 µg/mL for the W2 clone, respectively) was observed. The fatty alcohols 1, 2, 4-tetrahydroxyheptadecane-6, 16-diene(2); 1, 2, 4-Trihydroxyheptadec-16-yne(3) and 1, 2, 4-Trihydroxyheptadecane(4) also exhibited promising in vitro antibacterial activity against a panel of pathogenic bacteria S. areus, methicillin resistant S. areus and E. coli at IC50 values of 21.1, 8, 200 µg/mL), (3.259, 86.32 µg/mL) and (17.18, 8.26 and 200 µg/mL), respectively. The results of this study provide evidence that the fatty alcohols are a promising class of antimalarial and antimicrobial agents.

Multiple small "imaging" branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia?

Most screening programs for familial pancreatic cancer are currently based on endoscopic ultrasonography and/or magnetic resonance imaging (MRI). Cystic lesions, especially those suspicious for small intraductal pancreatic mucinous neoplasms (IPMNs) of the branch ducts, can be visualized in up to 40 % of individuals at risk, but their pathological importance in the setting of FPC is yet not well established. Individuals at risk from a prospective screening program for familial pancreatic cancer with small "imaging" IPMNs of the branch-duct type (BD-IPMN) who underwent pancreatic resection were analysed regarding clinico-pathological data and the locations of pancreatic lesions. Five of 125 individuals at risk who underwent screening had multiple small (size 2-10 mm) unicystic lesions and/or multicystic single lesions in the pancreatic body and tail suspicious for BD-IPMNs upon MRI imaging and decided to undergo surgical resection after interdisciplinary counselling, although none fulfilled the consensus criteria for IPMN resection. Histological examination revealed BD-IPMNs with low or moderate dysplasia of the gastric type in combination with multifocal PanIN2 and PanIN3 lesions in 4 individuals. The remaining patient had only tiny ductectasias in the pancreatic tail with multifocal PanIN 2 lesions in the entire gland and one PanIN3 lesion in the pancreatic head. Intriguingly, the location of the most dysplastic histological lesions (PanIN3) did not correspond to the preoperatively detected lesions and were not visible in preoperative imaging. In the setting of FPC, the presence of multiple small "imaging" BD-IPMNs may indicate the presence of high-grade PanIN lesions elsewhere in the pancreas.

Harmonic scalpel versus conventional dissection technique in pylorus-preserving partial duodenopancreatectomy.

BACKGROUND/AIMS: Pancreatic head resection is performed with low mortality, but morbidity remains high. Extensive preparation, long operating times, intraoperative blood loss and the need for blood transfusions are risk factors for postoperative morbidity. The aim of our study was to evaluate the feasibility and safety of the ultrasonic dissection device in pylorus-preserving duodenopancreatectomy (PPPD). METHODS: Fifty consecutive patients who underwent PPPD with an ultrasonic dissection device (group 1) were compared with a match-controlled group of 50 consecutive patients who underwent PPPD with conventional dissection techniques (group 2). Duration of surgery, intraoperative blood loss, blood units, complications, mortality and duration of hospital stay were analyzed. RESULTS: There was no difference in age, gender or BMI between groups. In group 1, mean blood loss (446 ± 281.8 ml, p = 0.008) and number of blood units (0.32 ± 0.86, p = 0.001) were significantly lower than in group 2 (819 ± 915.4 ml; 1.36 ± 2.83 units). Duration of surgery was shorter in group 1 (345.6 vs. 373 min, p = 0.28). The rate of postoperative complications, mortality and hospital stay were not significantly different. CONCLUSIONS: Use of an ultrasonic dissection device in PPPD might significantly reduce intraoperative blood loss and the need for blood transfusions. These results should be verified in a prospective randomized controlled trial.

Thyroid volume, iodine intake, autoimmune thyroid disorders, inborn factors, and endocrine disruptors: twenty-year studies of multiple effects puzzle in Slovakia.

OBJECTIVE: The aim of this study was to evaluate multiple interrelations between several endogenous and exogenous effects and the thyroid volume and function in large groups of children, adolescents, and adults with a sufficient whole life intake of the iodine. SUBJECTS AND METHODS: The data were obtained either by cross sectioned or longitudinal studies in a total of 4998 children and adolescents (aged 7 to 17 years) and 2501 adults (1071 males and 1430 females aged 20-75 years). Thyroid volume (ThV) was measured by ultrasound, antibodies, and hormones by electrochemiluminiscent immunoassay, and endocrine disruptors (EDs, polychlorinated biphenyls-PCB, dichlorodiethyl-ichloroethylene-DDE, and hexachlorobenzene-HCB) by high resolution gas chromatography/mass spectrometry. RESULTS: 1. In large groups of boys and girls of age 7, 10, 13 or 17 years, the ThV was significantly higher in the 10th decile than in pooled nine lower deciles. Moreover, in 17-year old subjects significantly higher prevalence of hypoechogenicity by ultrasound, positive thyroperoxidase antibodies (TPOab), and increased thyrotropin (TSH) levels were found in the 10th decile. 2. In a small group of children, some individuals revealed consistently higher ThV during the whole 7-year follow-up period irrespective of supplementation with iodine. 3. In 325 sibling pairs of age 10-19 years, born within three years, three groups with different ThV/m2 of body surface were distinguished: Group A (183 pairs having both ThVs small), Group B (103 pairs having both ThVs large); Group C (33 pairs having one ThV small and the other one large). Similar aggregation of ThVs in three groups was observed in 13 pairs of discordant twins and 19 sibling triads in which all the siblings were born within four years. 4. In 42 concordant twins, several pairs had ThV nearly twice as high (in terms of both plain ThV or ThV/m2 of the body surface) as several other pairs of the same age which is assumed to be a result of a genetic background. 5. In large cohorts of males and females, a highly significant positive correlation was found between the ThV and high level of TPOab on one side and EDs on the other side. However, in nearly the same numbers of subjects with low TPOab, negative correlation was seen between ThV and disruptors. These observations may apparently support the synergic effect of the autoimmunity and EDs on the thyroid function. CONCLUSIONS: Several cases of an excessive thyroid growth in the iodine replenished children, adolescents, and adults may apparently result from the autoimmune thyroiditis, probably induced by immunogenic action of iodine in presumably disposed individuals. However, in some cases even simultaneous participation of EDs can not be excluded. Some observations have also suggested that excessive thyroid growth in the iodine replenished adolescent and adult population which was equally exposed to disruptors may also result from other reasons as the unfavorable hereditary background.

Blood testosterone in middle aged males heavily exposed to endocrine disruptors is decreasing more with HCB and p,p'-DDE related to BMI and lipids, but not with Σ15PCBs.

OBJECTIVE: This work was aimed to evaluate the fundamental relations between the blood levels of testosterone (TEST) and persistent organochlorinated pollutants (POPs) related to body mass index (BMI) and blood lipids in a cohort of heavily exposed males from Eastern Slovakia. METHODS: In 429 middle aged (41-55 years) males heavily exposed to POPs the levels of 15 polychlorinated biphenyl congeners (Σ15PCBs), hexachlorobenzene (HCB), and dichlorodiethyl-dichloroethylene (p,p'-DDE) were measured by gas chromatography/mass spectrometry and the total testosterone (TEST) by electrochemiluminiscent immunoassay. RESULTS: After classifying the values of BMI, TEST, HCB, p,p'-DDE, and Σ15PCBs in quintiles and evaluating mutual interrelations of individual quintile counts in pairs of variables with chi-square, statistically significant interrelation was found for BMI/TEST (<0.0001) and HCB/TEST (p<0.001), but not for p,p'-DDE/TEST (p<0.6036) and Σ15PCBs/TEST (p<0.3246). Moreover, highly significant negative correlation was found between HCB and TEST by means of both Pearson (p<0.01) and Spearman rank correlations (p<0.0001). However, similar correlations performed between p,p'-DDE and Σ15PCBs did not reveal statistical significance. Finally, highly significant positive correlations were found between HCB and BMI, age, total lipids, and triglycerides. However, these correlations were less significant for p,p'-DDE and not significant or even negligibly negative for Σ15PCBs. In contrast, correlations of TEST with BMI and lipid fractions were significantly negative. CONCLUSION: It appears that HCB might play a role in a decrease of TEST in males with relatively narrow age range of males highly exposed to POPs. Highly significant positive correlation of HCB with BMI and blood lipids points out the role of BMI as an imaginary compartment closely related to the total body fat mass and representing a depot of POPs which is closely related to the level of POPs and lipids in blood. However, the differences in the affinity of individual POPs to BMI and blood lipids as well as the mechanism of their different relation to blood TEST levels remain to be still explained.

A simple and safe anastomosis for pancreatogastrostomy using one binding purse-string and two transfixing mattress sutures.

Pancreatic anastomotic leakage remains a persistent problem after pancreaticoduodenectomy (PD), especially in the presence of a soft, nonfibrotic pancreas. A modified technique for pancreatogastrostomy was devised, which combines one binding purse-string and two transfixing mattress sutures between the pancreatic stump and the posterior gastric wall. This technique was applied in 35 patients after PD for malignant and benign diseases of whom 10 (28.6%) had a soft pancreas. Median time for the anastomosis was 18 minutes. Operative mortality was zero, and morbidity was 34.3%. Three (8.6%) patients developed a pancreatic fistula (2 type A, 1 type B) as classified according to the International Study Group on pancreatic fistula. All fistulas resolved without further intervention. The described technique is a simple and safe reconstruction procedure after PD that warrants further evaluation.

Peripheral bone mineral density in correlation to disease-related predisposing conditions in patients with multiple endocrine neoplasia type 1.

BACKGROUND AND AIM: Patients with multiple endocrine neoplasia type 1 (MEN1) often have low bone mineral density (BMD) attributed to primary hyperparathyroidism (pHPT). However, in MEN1 patients, other endocrine dysfunctions and conditions such as hypercortisolism, hypogonadism, and GH deficiency due to pituitary manifestation, and surgery on the upper gastrointestinal tract may affect BMD. SUBJECTS AND METHODS: In 23 patients with MEN1 (10 females, 13 males; 46±12 yr), BMD was determined by quantitative computed tomography at the forearm (pqCT), compared to a reference population and related to different conditions suspected to affect bone metabolism in MEN1. RESULTS: In this cohort, Z-score for trabecular BMD was -0.85±1.18 and for total BMD -1.16±1.04. There was a similar trend towards lower BMD in uncontrolled hyperparathyroidism, hypercortisolism, hypogonadism/GH deficiency and the state after surgery at the upper gastrointestinal tract. CONCLUSIONS: These data while confirming previous observations on reduced BMD in patients with MEN1, however, challenge its only or even predominant association with pHPT. Other conditions such as hypercortisolism, somatotrophic/ gonadotrophic pituitary insufficiency, and previous upper gastrointestinal surgery seem to be factors contributing to the risk of developing osteoporosis.

Restoration of nerve agent inhibited muscle force production in human intercostal muscle strips with HI 6.

An important factor for successful therapy of poisoning with organophosphorus compounds (OP) is the rapid restoration of blocked respiratory muscle function. To achieve this goal, oximes are administered for reactivation of inhibited acetylcholinesterase (AChE). Unfortunately, clinically used oximes, e.g. obidoxime and pralidoxime, are of limited effectiveness in poisoning with different OP nerve agents requiring the search for alternative oximes, e.g. HI 6. In view of substantial species differences regarding reactivation properties of oximes, the effect of HI 6 was investigated with sarin, tabun and soman exposed human intercostal muscle. Muscle force production by indirect field stimulation and the activity of the human muscle AChE was assessed. 30 µM HI 6 resulted in an almost complete recovery of sarin blocked muscle force and in an increase of completely inhibited muscle AChE activity to approx. 30% of control. In soman or tabun exposed human intercostal muscle HI 6 (50 and 100 µM) had no effect on blocked muscle force or on inhibited human muscle AChE activity. In addition, HI 6 up to 1000 µM had no effect on soman blocked muscle force indicating that this oxime has no direct, pharmacological effect in human tissue. These results emphasize that sufficient reactivation of AChE is necessary for a beneficial therapeutic effect on nerve agent blocked neuromuscular transmission.

Alpha-fetoprotein, carcinoembryonic antigen and beta2-microglobulin in adult population highly exposed to organochlorinated pollutants (PCB, DDE and HCB).

OBJECTIVE: It is aimed to obtain some general information about the prevalence of certain biomarkers in highly exposed population and on the interrelations between their serum level as related to that of some major organochlorines (OCs). METHODS: The level of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and beta2-microglobulin (beta2-MG) as well as that of polychlorinated biphenyls (Σ15PCBs), dichlorodiphenyl-dichloroethylene (DDE) and hexachlorobenzene (HCB) was estimated in 2046 adults (834 males and 1212 females) from highly polluted Eastern Slovakia. RESULTS: Great majority of blood levels was lower than two specific units used for individual markers, while the prevalence of values higher than two specific units of appropriate markers. At the same time, the prevalence of all markers level higher than 2 specific units was highly significantly increasing with of stratified PCBs level quintiles which were also positively related to these of DDE and HCB. Some significant correlations between biomarkers level and age were also observed. CONCLUSIONS: Although from the data obtained within this multipurpose field survey any notable interrelations between AFP, CEA and beta2-MG and some specific diseases and/or malignant processes could not be retrospectively specified, from the data obtained it appears that some of such interrelations cannot be definitely excluded.

Polychlorinated biphenyls and testosterone: age and congener related correlation approach in heavily exposed males.

OBJECTIVE: It was aimed to evaluate some fundamental correlations of 15 individual PCB congeners and their sum with serum testosterone level in highly and long-term exposed males with special respect to minimize the interfering effect of age. METHODS: A total of 834 males from eastern Slovakia (age range of 21-78 years; median, 75th and 90th percentile of 48, 54 and 58 years, respectively) were examined consisting of 432 males from highly polluted area and 402 males from the area of background pollution. In all of them the serum level of 15 polychlorinated biphenyl congeners (PCBs), hexachlorobenzene (HCB) and dichlorodiethyl-dichloroethylene (DDE) was measured by gas chomatography/mass spectrometry and total testosterone in serum was measured with the aid of electrochemiluminiscent immunoassay. Pearson's correlation coefficients for each individual PCB congener as well as for Sigma15PCBs with testosterone were assessed in the cohort of all 834 males and also in the cohort of 444 males with age range of 41-55 years in which any significant negative influence of age on testosterone level has not been found and thus the interfering effect of aging on that level was apparently minimized. RESULTS: In the cohort of 834 males with high level of Sigma15PCBs (median = 885; range = 211-77,084; 5% - 95% = 377 - 4051 ng/g lipid) and highly significant negative correlation with age (r= 0.303; p<0.000) a significant negative correlation (p<0.05) with testosterone has been observed only for two mono-ortho-congeners (CB-105 and -118). However, in the cohort of 444 males aged 41-55 years any significant correlation for individual PCB congeners and for Sigma15PCBs with testosterone did not appear. CONCLUSION: In a large cohort of highly exposed males with minimized interfering effect of age any significant correlations between 15 PCB congeners analyzed and total testosterone were not found.

Surgery for multiple endocrine neoplasia type 1-associated primary hyperparathyroidism.

BACKGROUND: Surgery in patients with multiple endocrine neoplasia type 1 (MEN1)-associated primary hyperparathyroidism (pHPT) is difficult as the condition it is caused by asymmetrical multiple gland hyperplasia. It is uncertain which operative procedure provides the best outcome with regard to long-term normocalcaemia. METHODS: All patients who had surgery for genetically confirmed MEN1-associated pHPT between 1987 and 2009 were identified from a prospective database. Clinical data, operative procedures and outcome were analysed retrospectively. RESULTS: A total of 47 patients were identified. Twenty-three patients underwent total parathyroidectomy with thymectomy and autotransplantation (TPTX + AT), 11 patients subtotal parathyroidectomy (3-3.5 glands, SPTX) with thymectomy, and 13 patients selective gland excision (fewer than 3 glands, SGE). Rates of persistent disease, recurrent disease and permanent hypoparathyroidism after TPTX + AT were 4 per cent (1 patient), 4 per cent (1 patient) and 22 per cent (5 patients) respectively. Respective rates after SPTX were 0 per cent, 18 per cent (2 patients) and 45 per cent (5 patients), which were not statistically different from those following TPTX + AT. SGE resulted in persistent disease in 23 per cent (3 patients) and a significantly higher rate of recurrent disease (46 per cent, 6 patients; P = 0.004 versus TPTX, P = 0.210 versus SPTX), but permanent hypoparathyroidism did not occur. CONCLUSION: TPTX + AT and SPTX both seem adequate surgical procedures for the treatment of MEN1-associated pHPT and are associated with fewer recurrences than SGE.

Thyrotropin versus thyroid hormone in regulating bone density and turnover in premenopausal women.

OBJECTIVE: This cross-sectional study aimed to evaluate the interrelations between endogenous TSH level on one side and the status of bone mineral density (BMD) and bone metabolic turnover (BMT) on the other in pooled four groups of premenopausal women either without or with a long-term L-thyroxine treatment. METHODS: Serum levels of free thyroxine (FT4), thyrotropin (TSH), calcium (Ca), alkaline phosphatase (ALP), osteocalcin OC) and cross linked N-telopeptide of type 1 collagen (NTx) as well as urinary calcium (U-Ca/24h), bone mineral density of lumbar spine L 1-4 (BMD-L) and femoral hip (BMD-F) were estimated in a cohort of 151 premenopausal women (median 36 years) consisting of four groups: Group 1, 40 healthy untreated women, while three other groups consisted of patients previously treated for about 5 years; Group 2, 41 patients with genuine hypothyroidism treated by L-thyroxine (50-100 microg daily); Group 3, 40 patients with genuine hyperthyroidism treated by Carbimazol (10-15 mg daily); Group 4, 30 patients treated by suppressive doses of L-thyroxine (100-150 microg daily) after thyroidectomy for thyroid cancer (n=10) or because of progressively growing benign goitre (n=20). RESULTS: When using multiple correlation analysis (Pearson's r) in pooled 151 women, TSH showed significant positive correlation with BMD-L (p<0.01) and BMD-F (p<0.001) and, at the same time, significant negative correlation with serum level of BMT markers such as ALP (p<0.05), OC (p<0.05) and NTx (p<0.01), while the correlation of FT4 with BMD-L, BMD-F was significantly negative (p<0.001 for both) and that with all BMT markers was significantly positive (p<0.05 to <0.001). Thus, it appeared that higher TSH level was associated with increased bone mineral density and, at the same, with decreased bone metabolic turnover. These interrelations were further supported by the findings of significantly lower BMD-F (p<0.01), BMD-L (p<0.001) and significantly higher ALP, OC and NTX (all at p<0.001) in the group of 36 women with TSH level<0.3 mU/l as compared to the group of 115 women with TSH level range of 0.35-6.3 mU/l). CONCLUSIONS: Irrespectively of thyroid diagnosis and/or previous long term thyroxine treatment in some groups, this cross sectional study showed that, after the pooled group of 151 women has been redistributed according to the actual TSH level, the bone mineral density and the level of bone turnover markers was significantly more favorable in 115 subjects with TSH level range of 0.35-6.3 mU/l than these in 36 women with TSH<0.3 mU/l.

PALB2 mutations in European familial pancreatic cancer families.

Recently, PALB2 was reported to be a new pancreatic cancer susceptibility gene as determined by exomic sequencing, as truncating PALB2 mutations were identified in 3 of 96 American patients with familial pancreatic cancer (FPC). Representing the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) and the German National Case Collection for Familial Pancreatic Cancer (FaPaCa), we evaluated whether truncating mutations could also be detected in European FPC families. We have directly sequenced the 13 exons of the PALB2 gene in affected index patients of 81 FPC families. An index patient was defined as the first medically identified patient, stimulating investigation of other members of the family to discover a possible genetic factor. None of these patients carried a BRCA2 mutation. We identified three (3.7%) truncating PALB2 mutations, each producing different stop codons: R414X, 508-9delAG and 3116delA. Interestingly, each of these three families also had a history of breast cancer. Therefore, PALB2 mutations might be causative for FPC in a small subset of European families, especially in those with an additional occurrence of breast cancer.

[Mesh-wrapping of a traumatised liver with active bleeding: a subsequent complication--obstruction of the inferior vena cava]. / Hepatorrhaphie mittels Vicrylnetz bei Leberruptur Grad IV - Eine mögliche Komplikation: Verschluss der V. cava inferior.

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.