Interdisziplin?re Leitlinien zur Diagnostik und Therapie der extrazerebralen Amyloidosen

Ohne Zusammenfassung     

Minimal-invasive Chirurgie und Tumorchirurgie – Palliative laparoskopische Techniken

Zusammenfassung. Die Umsetzung radikaler onkologischer Grunds?tze der Tumorchirurgie mit laparoskopischen Operationsmethoden ist zur Zeit nicht gesichert. Minimal-invasive Techniken für die R0-Resektion maligner Tumoren stehen noch in der Phase der kritischen Evaluation. Dagegen sind laparoskopische, palliative Eingriffe zur Minimierung des Operationstraumas durchaus indiziert. Eine Vielzahl von Publikationen belegt die technische Durchführbarkeit bei vertretbarem Operationsrisiko und verkürztem Krankenhausaufenthalt. Trotzdem wird aus verschiedenen Gründen (Voroperationen, unsichere Resektabilit?t, Einsatz interventioneller Methoden etc.) das laparoskopische Vorgehen zur Palliation maligner Tumoren offenbar nur in kleinen Patientenserien realisiert. Am h?ufigsten wird über die palliative Anlage von Gastro- oder Jejunostomien zur enteralen Ern?hrung berichtet. Bei pr?operativ gesicherter Palliativsituation lie?e sich der Anteil laparoskopischer Operationen sehr wahrscheinlich steigern, wenn das minimal-invasive Vorgehen im differentialtherapeutischen Spektrum fester verankert wird. Für den laparoskopisch erfahrenen Chirurgen sind die Methoden in der Regel technisch einfach durchführbar. Der unmittelbare Nutzen für den Patienten nach palliativ-laparoskopischer Resektion tumortragender Abschnitte des Gastrointestinaltrakts ist derzeit noch nicht gesichert. Wenn die Inkurabilit?t w?hrend einer diagnostischen Laparoskopie festgestellt wird, bietet sich die unmittelbar anschlie?ende, laparoskopische Palliation in gleicher Sitzung an.      

Current practice patterns in pancreatic surgery: Results of a multi-institutional analysis of seven large surgical departments in germany with 1454 pancreatic head resections, 1999 to 2004 (german advanced surgical treatment study group)

Despite decreasing mortality rates, morbidity is still high after pancreatic head resection. Comparative data in the United States and Europe show a relationship between hospital volume and mortality. Treatment strategies vary frequently, partially because of the lack of evidence-based data. We performed a multi-institutional analysis in Germany evaluating current numbers, indications, techniques, and complication rates of pancreatic head resection. Questionnaires were completed by seven high-volume surgical departments regarding quantitative and qualitative aspects of pancreatic head resections in the period from 1999 to 2004 (five prospective and two retrospective institutional databases). A total of 1454 pancreatic head resections (944 for malignancy) were reported. Mean annual hospital volume ranged from 14 to 52 (10 to 43 in malignancy). Mortality was between 1.1% and 4.8%, morbidity was between 24% and 46%, and pancreatic leakage was between 9% and 20%. In malignant disease, all centers perform standard lymphadenectomy and regard arterial infiltration as a contraindication for resection. However, the rate of portal vein resection varied from 0% to 28%. No consensus is seen on the type of surgery for malignancy and chronic pancreatitis. After resection for pancreatic cancer less than one fourth of the patients receive adjuvant therapy. The results of our analysis in Germany confirm that pancreatic head resection can be performed with low mortality in specialized units. Variations in indications, operative technique, and perioperative care may demonstrate the lack of evidence-based data and/or personal and institutional experience. The low number of patients receiving adjuvant therapy after resection of pancreatic cancer suggests that more efforts must be made to establish novel adjuvant therapies under randomized study conditions. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

Examining Sedlacek's nontraditional variables of minority student success in a summer enrichment program for health careers

Nontraditional variables associated with minority student success in the health sciences have been identified by Sedlacek and his associates. These eight variables—positive self-concept, realistic self-appraisal, understanding and dealing with racism, long-range goals, availability of a strong support person, leadership, community service and medical interests—are examined with respect to their incorporation into the summer enrichment programs for talented minority students conducted at the University of Tennessee Center for the Health Sciences (UTCHS) during the years 1982-1984. Student comments and illustrations from the summer program''s curriculum are provided for five of Sedlacek''s variables to demonstrate how the UTCHS program is able to further the development of these nontraditional variables as well as to strengthen the cognitive abilities of students in basic science, mathematics, and communication. Evaluations of the summer program have revealed that the students have an increased academic self-concept, a more realistic view of the requirements to become a health professional, and an enhanced awareness of the health care environment.     

In vivo labeling with1251-CRH of human ACTH-producing pituitary adenomas heterotransplanted to nude mice

Tissue from 23 pituitary adenomas causing Cushing’s disease was implanted subcutaneously into 159 NuNu/NMRi mice, resected after 21 or 35 days, and evaluated histologically and immunohistochemically. After 21 days, 74.3% of the grafts survived, 59% having less than 30% necrotic adenoma cells. After 35 days, 45% of the adenoma fragments survived, 37% having less than 30% necrotic adenoma cells. The preservation of the grafts was essentially dependent on the grade of vascularization accomplished by migration of the host’s capillaries. As assessed by adrenal weight and histologically, biological activity of the transplants could not be detected. Histologically, the grafts maintained the features of their primary tumors, and adrenocorticotropic hormone (ACTH) could be visualized immunohistologically.Seventeen mice with subsequently proved preserved adenoma tissue received an intravenous injection of 12.5 μCi¹²⁵l-corticotropin-releasing hormone (CRH) and light microscopy-autoradiography was performed. Specific labeling, as verified by positive and negative controls, was exhibited by 1 1 of 15 transplants originating from 3 highly differentiated ACTH cell adenomas. Four did not label clearly positive. Two grafts of an undifferentiated mucoid cell pituitary adenoma did not show any labeling.The nude mouse model is a useful tool for the study of ACTH-producing pituitary adenomas in vivo. Highly differentiated ACTH cell adenomas can be labeled with radioactive CRH in vivo.     

Recurrent colonization of successively implanted tracheoesophageal vocal prostheses by a member of the Fusarium solani species complex

Tracheoesophageal vocal prostheses (TVP) in laryngectomized patients commonly deteriorate due to overgrowth by yeasts, particularly Candida species. We describe the first case of colonization of such devices by a member of the Fusarium solani species complex in a patient with a history of glottal carcinoma. Three isolates, from three prostheses, were found morphologically consistent with the traditional picture of F. solani. Ribosomal sequence analysis showed that the isolates belonged to a distinct, as yet apparently unnamed phylogenetic species within the F. solani species complex. This species, one of two distinct genetic types (genotype 2) traditionally considered part of the plant-pathogenic subtaxon Fusarium solani f. sp. radicicola, has not previously been identified as an agent of human or animal disease, although it is closely related to a known etiologic agent of mycetoma, an Acremonium-like species recently renamed Fusarium falciforme. Sequence and multisatellite M13 polymorphism analysis revealed no distinctions among the case isolates. Production of cyclosporine was detected for all three case isolates.     

Die Morphologie der paraadenomatösen Adenohypophyse

Zusammenfassung 98 Biopsien der paraadenomatösen Adenohypophyse bei Akromegalie, Akromegalie-Galactorrhoe, isolierter Galactorrhoe, zentralem Cushing-Syndrom, Nelson-Syndrom und endokrin inaktiven Hypophysenadenomen wurden histologisch untersucht, um aus den Zellrelationen und -Strukturen Hinweise auf eine mögliche hyperplasiogene Entstehung der verschiedenen Adenomtypen zu gewinnen.Neben ACTH-Zelltumoren beim Cushing- und Nelson-Syndrom fanden sich hÄufig nodulÄre ACTH-Zellhyperplasien, die vermuten lassen, da\ die Adenome bei diesen Krankheitsbildern hyperplasiogener Natur sind. In der weiteren Entwicklung scheinen diese Adenome autonom zu werden, da bei grö\eren Tumoren die Zahl der paraadenomatösen ACTH-Zellen reduziert ist.Ein Teil der FÄlle mit isolierter Galactorrhoe zeigte Hyperplasien acidophiler und gro\er chromophober Zellen in der paraadenomatösen Adenohypophyse, so da\ angenommen werden kann, da\ die Prolactin-Zelltumoren ebenfalls auf dem Boden von Prolactin-Zellhyperplasien sich entwickelt haben.Die Adenome bei Akromegalie und die inaktiven Tumoren scheinen primÄr autonom zu wachsen, da bei ihnen paraadenomatöse Hyperplasien weitgehend fehlen.Mit Unterstützung durch den Sonderforschungsbereich Endokrinologie (SFB 34) der Deutschen Forschungsgemeinschaft     

Ten novel MSH2 and MLH1 germline mutations in families with HNPCC

Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer-susceptibility syndromes. Germline mutations in mismatch repair genes are associated with the clinical phenotype of HNPCC. We report ten novel germline mutations, three in MSH2 and seven in MLH1. All but one mutation have been found in families fulfilling criteria of the Bethesda guidelines; four of them additionally fulfilled the Amsterdam criteria I or II. Eight mutations were considered pathogenic and predictive diagnostics in healthy family members at risk shall be undertaken; these include five frameshift mutations leading to premature stop codons, in MSH2: c.1672delT (p.S558Xfs) and c.2466_2467delTG (p.C822X) and in MLH1: c.1023delG (p.R341Xfs), c.1127_1128dupAT (p.K377Xfs) and c.1310delC (p.P437Xfs); three mutations leading to splice aberrations, in MSH2: c.1661G>C (r.1511_1661del) and in MLH1: c.677+3A>C (r.589_677del) and c.1990-2A>G predicted to result in a splice site defect. The remaining two mutations are unclassified variants with assumed pathogenicity: one missense mutation in the highly conserved ATPase domain of MLH1 (c.122A>G [p.D41G]) and one in-frame insertion of twelve nucleotides in MLH1 (c.2155_2156insATGTGTTCCACA [p.I719delinsNVFHI]). These two mutations were not found in 102 alleles of healthy control individuals. The corresponding tumors from all patients showed a high level of microsatellite instability (MSI-H). Immunohistochemistry (IHC) revealed complete loss of expression of the affected protein in the tumor cells from all but three patients. The tumors from the patients with the mutations c.1127_1128dupAT and c.1990-2A>G showed a reduction of expression of the MLH1-protein, rather than complete loss. In the tumor from the patient with the missense mutation c.122A>G [p.D41G] a normal expression of the proteins coded by MLH1 and MSH2 was noticed.