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H Dralle

Publications and source records attributed to H Dralle.

At least 55 records · Page 3Linked to original sources
PubMed2003

HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours.

BACKGROUND: Hyperparathyroidism is a common endocrinopathy characterised by the formation of parathyroid tumours. In this study, we determine the role of the recently identified gene, HRPT2, in parathyroid tumorigenesis. METHODS: Mutation analysis of HRPT2 was undertaken in 60 parathyroid tumours: five HPT-JT, three FIHP, three MEN 1, one MEN 2A, 25 sporadic adenomas, 17 hyperplastic glands, two lithium associated tumours, and four sporadic carcinomas. Loss of heterozygosity at 1q24-32 was performed on a subset of these tumours. RESULTS: HRPT2 somatic mutations were detected in four of four sporadic parathyroid carcinoma samples, and germline mutations were found in five of five HPT-JT parathyroid tumours (two families) and two parathyroid tumours from one FIHP family. One HPT-JT tumour with germline mutation also harboured a somatic mutation. In total, seven novel and one previously reported mutation were identified. "Two-hits" (double mutations or one mutation and loss of heterozygosity at 1q24-32) affecting HRPT2 were found in two sporadic carcinomas, two HPT-JT-related and two FIHP related tumours. CONCLUSIONS: The results in this study support the role of HRPT2 as a tumour suppressor gene in sporadic parathyroid carcinoma, and provide further evidence for HRPT2 as the causative gene in HPT-JT, and a subset of FIHP. In light of the strong association between mutations of HRPT2 and sporadic parathyroid carcinoma demonstrated in this study, it is hypothesised that HRPT2 mutation is an early event that may lead to parathyroid malignancy and suggest intragenic mutation of HRPT2 as a marker of malignant potential in both familial and sporadic parathyroid tumours.

Adult↗
PubMed2003

Multicenter study differentiated thyroid carcinoma (MSDS). Diminished acceptance of adjuvant external beam radiotherapy.

AIM: The Multicenter Study Differentiated Thyroid Carcinoma (MSDS) is an ongoing study in Germany, Austria, and Switzerland on the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated thyroid carcinoma (DTC) in TNM stages pT4 pN0/1/x M0/x (5th ed. 1997). METHODS: MSDS was designed as a prospective randomized trial. Patients receive thyroidectomy, radioiodine therapy (RIT) to ablate the thyroid remnant, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical iodine-131 uptake (http://msds-studie.uni-muenster.de). RESULTS: 311 patients were enrolled between January 2000 and March 2003. 279 patients met the trial's inclusion criteria. 45 consented to randomization, of whom 17 were randomized into treatment arm A (RTx) and 18 into arm B (no RTx). Advised by the trial's independent Data Monitoring and Safety Committee, the MSDS steering committee decided to terminate randomization in April 2003 and continue MSDS as a prospective cohort study. 23 of the 234 patients in the observation arm of the trial were prescribed RTx by their physicians. Thus, 14% of the trial cohort were randomized or assigned to receive RTx (in-tention-to-treat analysis). In contrast, at least 44% of all patients with pT4 papillary DTC in Germany in the nation-wide PCES study underwent RTx in 1996 (p <0.001, chi(2)-test). CONCLUSIONS: Acceptance of external beam RTx as a treatment modality for DTC has receded to a degree that accrual of a sufficient number of patients for a randomized trial has been impossible. Observation of the trial cohort is continued in order to assess clinical event rates with and without RTx and chronic RTx toxicity.

Combined Modality Therapy↗
PubMed2002

An update on thyroid surgery.

Surgery has been the treatment of choice for many disorders of the thyroid gland, both benign and malignant, for many decades. However, surgery has not been invariable but has continued to change in accordance with research results. In benign cases, surgery has generally evolved to be as organ preserving as possible. In several instances, however, a more radical extent of resection seems justified in order to ensure that the risk of recurrence is as low as possible. For instance, total thyroidectomy may be beneficial in patients with endemic multinodular goitre or young patients with Graves' disease and accompanying cold nodules or high levels of autoantibodies. Several tools, e.g. magnifying glasses, bipolar coagulation forceps and neuromonitoring, are available to identify and preserve the recurrent laryngeal nerve and the parathyroid glands, hence keeping the morbidity at a low level. Most recently, minimally invasive surgery has been successfully used in treating both benign and malignant disorders of the thyroid gland. In the case of malignant disorders, minimally invasive surgery may become an attractive alternative to open surgery if a limited surgical extent is justified, e.g. in patients with micro-PTC (papillary thyroid carcinoma, diameter less than 1 cm). Whether a limited surgical approach is also justified in other cases, e.g. in any patient with intrathyroidal PTC or patients with micro-FTC (follicular thyroid carcinoma), remains to be shown and is the subject of ongoing investigations. One of the most intriguing recent discoveries is the identification of genotype-phenotype correlations in patients with hereditary medullary thyroid carcinoma. In these patients, the timing and extent of surgery may depend not only on the patient's age and serum levels of the tumour marker calcitonin but also on the specific germline RET proto-oncogene mutation. Surgery will certainly continue to play an important role in the treatment of thyroid diseases and may be increasingly based on individual findings instead of general recommendations.

Adenocarcinoma, Follicular↗
PubMed2002

Management of mycoses in surgical patients -- review of the literature.

Fungal infections have been recognized as major cause of morbidity and mortality in neutropenic and non-neutropenic surgical intensive care patients. The incidence of Candida has increased: it is now the fourth most often isolated pathogen in bloodstream infections. The incidence of Aspergillus infection in transplant patients is highest in heart and lung transplants: 19-26%. Most invasive fungal infections in surgical patients are caused by Candida spp. and Aspergillus spp., less by Cryptococcus spp. and may be classified as local or organ-related, as (chronic) disseminated, and as fungemia. There is no highly specific and sensitive routine test for the diagnosis of Candida and Aspergillus infections available; clinical signs of fungal infections are rather unspecific. The significance of colonization remains undetermined. In non-neutropenic surgical patients central venous access and broad-spectrum antibiotics are independent risk factors for the development of fungal infection. Immunsuppression, e.g., transplantation, burn injury, can render patients susceptible to fungal infection. This has lead to the introduction of antifungal prophylaxis in transplant and burned patients which has reduced the mortality for Candida spp. infection significantly. There is no prophylaxis available against Aspergillus spp. and Cryptococcus spp. Treatment of fungal infections consists of surgical and medical treatment for most organ-related infections. Recommendations for the management of fungal infections exist mostly for neutropenic patients, only few reports address the fungal infection of the surgical intensive care patient. Amphotericin B has been recommended as first line treatment for most severe fungal infections with fluconazole as follow-up treatment. In case of the development of toxic side effects of amphotericin B, mostly fluconazole or lipid formulations of amphotericin were favored. However, a shift in Candida strains towards non-albicans spp. and more resistant species was observed during recent years. This has lead to treatment failures in severe Candida and Aspergillus infections. The prognosis for invasive Aspergillus infections remains poor despite amphotericin B treatment. Newer azoles, e.g. voriconazole, demonstrated stable activity against most of these strains and may offer an option in the treatment of refractory fungal infections.

Antifungal Agents↗
PubMed2002

[Primary operative gastrostomy or percutaneous endoscopic gastrostomy (PEG) in progressive oesophageal carcinomas? A case report on abdominal wall metastases following PEG].

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a safe and easy procedure used to provide enteric nourishment in patients with non-operable, constricting, malignant tumors of the oropharynx or esophagus. However, as a late complication, the development of abdominal wall metastases have been described, the mechanism of which is controversially. PATIENTS AND METHODS: We describe two cases in which abdominal wall metastases developed 9 and 14 months, respectively, following PEG. Both patients suffered from an advanced esophageal carcinoma. One patient had to undergo surgery because of the size of the metastasis. This was followed by several weeks of hospital treatment. The second patient was already in a prefinal condition so that no surgical procedure was performed. Reviewing the current literature, we discuss the question of whether, in certain cases, an operative gastrostomy should be preferred to a PEG. RESULTS: As in our opinion the reason for abdominal wall metastases is direct tumor seeding, we suggest that in certain cases, in order to avoid a possible metastasis resection, an operative gastrostomy should be discussed. This is particularly relevant if the tumor is constricting with a high risk of losing tumor cells. If possible, a minimal-invasive method is to be preferred.

Abdominal Neoplasms↗
PubMed2002

[Therapeutic results after papilloduodenal injuries following ERCP].

INTRODUCTION: Our goal was to compare operative vs. conservative therapeutic strategies after injuries following ERCP. METHODS: Eight patients with ERCP-induced injuries were surveyed retrospectively. Four of them were treated operatively, four conservatively. Criteria for an operative therapy were clinical and radiological findings and laboratory data. RESULTS: The four patients that were treated conservatively had an uncomplicated course whereas three of four patients treated operatively had long and complicated stays. In these patients the operation was performed more than 24 hours after injury. All of them showed advanced biliary peritonitis. One patient was operated on within 24 hours. He was discharged after a short stay without complications. All injuries were located in the retroperitoneum. Five patients showed anatomical abnormality of either duodenum, papilla or common bile duct. In five cases the duodenum was involved in the injury. CONCLUSIONS: The course of disease of the operated patients was longer and more complicated compared to those treated conservatively. According to our data the timing of the operation seems to be an important criterion with respect to the prognosis. Due to the small number of patients, whether conservative therapy should be preferred cannot be determined. The role of the location of injury is also not clarified.

Adult↗
PubMed2002

[Does intraoperative nerve monitoring reduce the rate of recurrent nerve palsies during thyroid surgery?].

Two different aspects of the influence of neuromonitoring on the possible reduction of post-operative recurrent laryngeal nerve palsies require critical examination: the nerve identification and the monitoring of it's functions. Due to the additional information from the EMG signals, neuromonitoring is the best method for identifying the nerves as compared to visual identification alone. There are still no randomized studies available that compare the visual and electrophysiological recurrent laryngeal nerve detection in thyroid operations with respect to the postoperative nerve palsies. Nevertheless, comparisons with historical collectives show that a constant low nerve-palsy-rate was achieved with electrophysiological detection in comparison to visual detection. The rate of nerve identification is normally very high and amounts to 99 % in our own patients. The data obtained during the "Quality assurance of benign and malignant Goiter" study show that in hemithyreoidectomy and subtotal resection, lower nerve-palsy-rates are achieved with neuromonitoring as compared to solely visual detection. Following subtotal resection, this discrepancy becomes even statistically significant. While monitoring the nerve functions with the presently used neuromonitoring technique, it is possible to observe the EMG-signal remaining constant or decreasing in volume. Assuming that a constant neuromonitoring signal represents a normal vocal cord, our evaluation shows that there is a small percentage of false negative and positive results. Looking at the permanent recurrent nerve palsy rates, this method has a specificity of 98 %, a sensitivity of 100 %, a positive prognostic value of 10 %, and a negative prognostic value of 100 %. Although an altered neuromonitoring signal can be taken as a clear indication of eventual nerve damage, an absolutely reliable statement about the postoperative vocal cord function is presently not possible with intraoperative neuromonitoring.

Electromyography↗
PubMed2001

Calcitonin kinetics in the early postoperative period of medullary thyroid carcinoma.

INTRODUCTION: Calcitonin is a sensitive marker for medullary thyroid carcinoma. Normalisation of calcitonin levels following resection of medullary thyroid carcinoma has been described after a few hours; however, it may be observed more than 4 weeks after surgery. The aim of this study was to correlate the postoperative calcitonin kinetics with preoperative calcitonin levels and tumour stage. Furthermore, we wanted to test the prognostic impact of the calcitonin kinetics. Therefore, only patients with postoperative normalisation of calcitonin levels (biochemical cure) were included in this study. METHODS: Fourteen biochemically cured patients were analysed, including measurement of postoperative basal and pentagastrin-stimulated calcitonin concentration. With respect to the time of postoperative basal calcitonin normalisation, patients were classified into two groups: (A) patients with normalisation of basal calcitonin levels within 24 h and (B) patients with normalisation of basal calcitonin levels later than 24 h postoperatively. RESULTS: Eight patients were found to have normalisation of basal calcitonin levels within 24 h (group A). In the remaining six patients (group B), the period to normalisation of basal calcitonin levels varied from 6 days to 14 days and longer. There were no differences between the two groups with regard to tumour size, number and pattern of lymph node metastases and tumour stage. However, preoperative basal calcitonin levels were significantly different (258 ng/ml vs 955 ng/ml, P<0.01). In the group with slow-decreasing calcitonin levels, no strong correlation between the preoperative level and the postoperative time to normalisation of basal calcitonin levels could be established, which may be due to the small number of patients. After a median follow-up of 21 months, no patient developed tumour recurrence. However, an increased basal calcitonin level was observed in one patient from group B. All other patients had normal basal and peak calcitonin levels. CONCLUSION: Using a highly sensitive calcitonin assay, we demonstrated that normalisation of basal calcitonin levels may be delayed in patients suffering from medullary thyroid carcinoma. The lack of correlation of preoperative levels and the time to normalisation of the basal calcitonin levels, as well as the positive pentagastrin test in some of the patients, argues that this phenomenon is not simply due to prolonged biochemical calcitonin elimination. Nevertheless, a prognostic influence could not be shown in this study due to the short follow up-period. Further investigations and a longer follow-up are necessary to determine the nature and the prognostic impact of delayed normalisation of calcitonin levels.

Adult↗
PubMed2001

Antibiotic therapy in intra-abdominal infections--a review on randomised clinical trials.

There have been 79 randomised antibiotic studies in intra-abdominal infections retrieved. The overall success rate of the studied antibiotics ranges from 70-100%. Unfortunately only about one fourth of the studies have used a disease severity classification, e.g., APACHE II score, despite clear recommendations by the Surgical Infections Society of North America. The mortality rate in the published antibiotic studies is still rather low (approximately 4%) and does not correspond to the average mortality in peritonitis (30-40%). Failure analysis is not uniform and only performed in about 1/5 of retrieved studies. Failure analysis included data on diagnosis, type of operation, pathogen isolated at first operation, susceptibility and persistence of pathogen, re-operation or change of antibiotic regimen, and follow-up (ICU duration, death or survival, hospitalisation). Only one study has performed an analysis of the adequacy of the surgical treatment (source control). The clinical success rate of the antibiotics studied in a larger population is comparable for gentamicin + clindamycin (80%), tobramycin + clindamycin (83%), meropenem (89%), imipenem (85%), aztreonam + clindamycin (89%), cefoxitin (88%), cefotetan (92%), moxalactam (83%), cefotaxime + metronidazole (87%), ampicillin/sulbactam (87%). Piperacillin/tazobactam has in most studies a success rate of approximately 90%. The aggregated data on adverse events and clinical failure rate do not show a major advantage for any of these antibiotics. It is striking that the adverse event rate reported for ticarcillin/clavulanic acid is low when compared to all other antibiotics, which is in contrast to severe adverse events reported for clavulanic acid. The data of quinolone studies in intra-abdominal infections do not yet allow a recommendation, even when it is acknowledged that two studies were performed with good results and a good study plan. In conclusion, the comparability of antibiotic studies in intra-abdominal infections is limited due to a lack of disease severity stratification and a relatively small study population for most antibiotics. The clinical success rate of the best-studied antibiotics is similar and the choice which antibiotic is used depends on the expected pathogens and the resistance rate in a clinical setting.

APACHE↗
PubMed2001

Nuclear factor-kappaB is constitutively active in C-cell carcinoma and required for RET-induced transformation.

Specific point mutations of the RET proto-oncogene have been demonstrated to be responsible for multiple endocrine neoplasia (MEN) types 2A and 2B, for familial medullary thyroid carcinoma (MTC) syndromes, as well as for sporadic MTC. Here we show that nuclear factor (NF)-kappaB is activated in RET-associated C-cell carcinoma specimens. TT cells, a human MTC cell line expressing MEN 2A type RET, display transcriptionally active RelA(p65) in the nucleus. NF-kappaB activity in these cells is attributable to constitutive IkappaB kinase (IKK) activity and high turn over of IkappaBalpha. RET harboring the mutations C634R (MEN 2A) or M918T (MEN 2B), in contrast to wild-type RET, activates a NF-kappaB-dependent reporter construct upon transient transfection in HeLa cells. We show that the prototype RET mutation C634R enhances phosphorylation of IkappaBalpha by IKKbeta but not by IKKalpha. RET-induced NF-kappaB and IKKbeta activity requires Ras function but does neither involve the classical mitogen-activated protein kinase kinase/extracellular signal-regulated kinase nor the phosphoinositide 3-kinase/Akt pathways. In contrast, RET-induced NF-kappaB activity is dependent on Raf and MEKK1. Inhibition of constitutive NF-kappaB activity results in cell death of TT cells and blocks focus formation induced by oncogenic forms of RET in NIH 3T3 cells. These results suggest that RET-mediated carcinogenesis critically depends on IKK activity and subsequent NF-kappaB activation.

3T3 Cells↗
PubMed2001

Paradigm change in 30 years peritonitis treatment -- a review on source control.

Peritonitis remains a hot spot for surgeons despite advancements in surgical technique and intensive care treatment. There is an ongoing interest to improve the survival rate by analyzing the pathogenesis and pathophysiology of this threatening disease. - The significance of source control, e.g., eradication of a focus of infection, elimination of microbial contamination and restoration of local environment, is well recognized since the beginning of the last century. Recently the term "source control" has gained new interest with regard to guidelines for clinical studies. It appears that despite stratification in most clinical peritonitis studies there is still a lack of comparability of those studies with regard to source control. A medline search on peritonitis and source control was performed and 90 studies were evaluated for information on source control evaluation. In summary, there is no uniform definition of source control available. Most studies in peritonitis treatment are according to evidence based medicine level 3-5 evidence. Lack of hard scientific evidence how to measure the success of source control had to be substituted by surgical experience. Re-operation or relaparotomy may be considered as acknowledgment that source control failed. Controversy exists about primary anastomosis in the inflammed peritoneum. Despite all efforts and more patients enrolled in studies to improve surgical treatment of peritonitis in thirty years it is obvious that the mortality rate has decreased only marginally from 40% to 30%. Commonly accepted principles for source control documentation and evaluation should be established and confirmed in multi-center studies before further studies with new compounds are started.

Communicable Disease Control↗
PubMed2001

Over-representation of a germline variant in the gene encoding RET co-receptor GFRalpha-1 but not GFRalpha-2 or GFRalpha-3 in cases with sporadic medullary thyroid carcinoma.

In contrast to the hereditary form of medullary thyroid carcinoma (MTC), little is known about the etiology of sporadic MTC. Somatic gain-of-function mutations in the RET proto-oncogene, encoding a receptor tyrosine kinase, are found in an average of 40% of sporadic MTC. We analysed 31 sporadic MTC for somatic and germline variants in GFRA1, GFRA2 and GFRA3 which encode the co-receptors of RET. Although there were no somatic mutations in any of the three genes, a sequence variant (-193C>G) in the 5'-UTR of GFRA1 was found in 15% of cases. Three patients were heterozygous (het); another three patients homozygous (hom) for the G variant. The G allele was not observed in 31 race-matched normal controls. Hence, the relative frequency of this variant in sporadic MTC cases and controls differed significantly (P<0.05). Since this variant lies in the 5' UTR, likely at the transcriptional start site, we analysed for differential expression of GFRalpha-1 at the transcript and protein levels. At the mRNA level, GFRA1 was over-expressed in tumors harboring the rare variant (P=0.06). The presence of the G polymorphic allele seemed to be associated with increased expression by immunostaining for GFRalpha-1. Interestingly, cytoplasmic staining was stronger in intensity for het patients and nuclear staining predominant in hom cases. In conclusion, mutation analysis of GFRA1, GFRA2 and GFRA3 revealed over-representation of a rare variant in GFRA1 (-193C>G) in the germline of sporadic MTC cases. Our data suggest that the mechanism is related to over-expression of GFRalpha-1 and differential subcellular compartmentalization but the precise mechanism as to how it acts as a low penetrance susceptibility allele for the development of sporadic MTC remains to be elucidated.

Carcinoma, Medullary↗