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Ziel: Ziel der Arbeit war eine Erfassung der Raten an Gesamt-, Fruh- und Spatkomplikationen aller zentralvenosen Portsystemimplantationen zwischen 1998 und 2008 an der Chirurgischen Universitatsklinik Rostock. Zusatzlich wurden verschiedene Implantationstechniken bez. Erfolgsrate, Komplikationsrate und OP-Dauer verglichen. Die Ergebnisse wurden in Abhangigkeit des Ausbildungsstands des Operateurs und in Bezug auf verwendete OP-Technik, OP-Dauer, Konversionshaufigkeit und Komplikationen aufgearbeitet. Material und Methoden: Es wurden 1423 Portsystemimplantationen in den Jahren 1998 bis 2008 retrospektiv analysiert. Ergebnisse: Die Rate der Gesamtkomplikationen betrug 13,8 %. Unter den 4,7 % Fruhkomplikationen stellte der Pneumothorax die haufigste Komplikation dar. Die Rate an Spatkomplikationen betrug 9,1 %. Hierbei stellte die Infektion mit 4,9 % die allgemeine Hauptkomplikation. Die Katheterdysfunktion war mit 3,5 % die zweithaufigste Komplikation. Insgesamt wurden 1322 Punktionsverfahren und 101 Venae sectiones angewandt. Die OP-Zeiten der Venae sectio im Vergleich zur Punktion sind signifikant langer (46,5 min vs. 38,7 min, p = 0,005). Beim Punktionsverfahren gibt es signifikant mehr Spat- (9,6 % vs. 2 %, p = 0,01) und Gesamtkomplikationen (14,5 % vs. 4 %, p = 0,005). Die primare Erfolgsrate bei der Venae sectio lag bei 100 %, beim Punktionsverfahren bei 96,8 %. Die Rate an Komplikationen war unabhangig vom Ausbildungsstand der Operateure, jedoch sinkt die Rate an Gesamt- und Spatkomplikationen mit steigender Operationsfrequenz signifikant. Schlussfolgerung: Die Portanlage ist ein einfacher operativer Eingriff trotz vorhandener Komplikationsmoglichkeiten. Die Venae sectio ist hierbei das Verfahren mit den geringsten Komplikationen. Die Rate an Komplikationen ist unabhangig vom Ausbildungsstand des Operateurs. Die Rate an Komplikationen sinkt mit der Operationsfrequenz des Operateurs. Somit ist die Portanlage und insbesondere die Venae sectio im Rahmen einer strukturierten chirurgischen Ausbildung ein idealer Ausbildungseingriff.

In 4 Studien (EVAR-1, DREAM, OVER, ACE) zur Behandlung des asymptomatischen infrarenalen Bauchaortenaneurysmas wurde zwischen endovaskularer und operativer Behandlung randomisiert. Patienten wurden eingeschlossen bei einer Aneurysmagrose von 5 cm oder mehr, korperlicher Fitness und anatomischer Eignung fur eine endovaskulare Aortenreparatur (EVAR). EVAR zeigte eine geringere perioperative Mortalitat, barg aber in der Folgezeit ein erhohtes Risiko fur kardiale und aneurysmabezogene Komplikationen. Dadurch kam es bereits nach wenigen Jahren zur Angleichung der Uberlebenskurven nach EVAR und offener Aortenreparatur (OAR). Wahrend die kardialen Komplikationen bei OAR verstarkt periprozedural auftraten, zeigte EVAR in der Nachfolgezeit eine erhohte kardiale Mortalitat. Beide Behandlungsverfahren konnen daher als gleichwertig angesehen und dem zu behandelnden Patienten angeboten werden. Die operative Behandlung sollte dann vorgezogen werden, wenn EVAR technisch nicht geeignet erscheint oder der Patient sich fur ein lebenslanges Uberwachungsprogramm nicht qualifiziert. Lebensqualitat, sexuelle Dysfunktionen und Kosten der Behandlung sind Parameter, die bei beiden Verfahren ohne erkennbaren Unterschied in Erscheinung treten.

Graft pancreatitis is induced by ischemia/reperfusion injury in which neutrophil infiltration is believed to be a crucial early event. This observation suggests the presence of adhesion molecules already at the time of reperfusion. Therefore, this study was performed to evaluate the pattern of ICAM-1 and P-Selectin expression on human pancreas allografts following cold ischemia and reperfusion.We performed an analysis of pancreas biopsy specimens taken from 13 patients undergoing pancreas transplantation compared with pancreas specimens from 10 patients following resection. Cryostat sections were stained with monoclonal antibodies against CD11b, a neutrophil marker, and the adhesion molecules ICAM-1 and P-Selectin.Extensive infiltration of CD11b-positive cells was detected in venules and capillaries of pancreas allografts after reperfusion (18.38 +/- 0.87) compared with controls (T1 4.22 +/- 0.55) or with tissue specimens at about 10 hours of cold ischemia (2.60 +/- 0.35; P.001). Similarly, the pattern of P-Selectin showed a moderate expression before organ harvest (1.54 +/- 0.21) and in samples during cold ischemia (1.46 +/- 0.24) followed by a significantly greater number of P-Selectin-positive cells after reperfusion (2.54 +/- 0.18; P = .005). ICAM-1 was only weakly expressed on the surface of the venular endothelium in all controls (0.77 +/- 0.12). In contrast to P-Selectin, ICAM-1 showed prominent up-regulation during cold ischemia (2.23 +/- 0.23; P.001) with no further increase after reperfusion (2.23 +/- 0.17).The data suggested that ICAM-1 was already up-regulated during cold ischemia, possibly representing the mechanism of early neutrophil infiltration observed in human pancreatic ischemia/reperfusion injury.

We analyzed the immunologic impact of adeno-associated virus type 2 (AAV-2), a small single-stranded parvovirus with tumorsuppressive properties, on DSL6A pancreatic carcinoma in syngeneic rats. Established tumors of animals treated with AAV-2 or mock infected were resected (Ro), and DSL6A cells were rechallenged on the different site. Eleven (92%) of 12 mock-infected animals but only 3 (25%) of 12 AAV-2-treated animals redeveloped tumors. Adeno-associated virus type 2 infection provoked systemic raises in monocytes and neutrophils numbers and in levels of the proinflammatory monocyte chemoattractant protein 1 and interleukin 10. Adeno-associated virus type 2-treated tumors were infiltrated with monocytes, macrophages, natural killer cells, CD4+ T cells, and especially CD8+ T cells. In cytotoxicity assays, AAV-2-infected DSL6A tumor cells were recognized by lymphocytes from AAV-2-treated animals and from controls. Yet, uninfected DSL6A cells were exclusively killed by lymphocytes from AAV-2-treated animals. Additionally, those lymphocytes displayed high natural killer cell activity but failed to attack unrelated tumor targets. Taken together, these results suggest that the antiviral response toward AAV-2 cross-activates the immune system toward simultaneously present tumor disease. This and the known potential to significantly reduce toxic side effects of chemotherapy make nonpathogenic viruses such as AAV-2 as "1-agent combination therapy" to an interesting treatment option of residual tumor disease.

Background: Experimental gene transfer can make tumors more immunogenic, leading to local regression and inducing immunological memory sufficient to permit resistance to a tumor rechallenge. However, this rarely had any significant impact on large established tumors. Methods: To analyze potential immunological effects, we used weakly immunogenic pancreatic carcinomas in syngeneic, immunocompetent Lewis rats and performed in situ adenoviral mediated cytosine deaminase (CD) gene transfer followed by administration of the prodrug, 5-fluorocytosine (5FC). In order to reflect the clinical situation, such treated tumors were surgically resected and animals were rechallenged with parental DSL6A pancreatic tumor cells. Tumor growth and cytotoxic activity of immune cells were determined. Results: CD/5FC treatment of the DSL6A cells revealed significant induction of apoptosis in vitro and slowed down tumor progression in syngeneic hosts. Furthermore, we observed neither significant change in tumor growth nor protective immunity in the rechallenged animals. Analysis of T lymphocytes showed no specific cytotoxic activity against DSL6A cells. There was only a trend towards a minor NK cell activation. Conclusions: Albeit the present study failed to induce protective antitumor immunity, the initial finding of reduced tumor growth argues for the development of multimodal therapeutic options to overcome negative impacts of advanced malignant disease or chemotherapy-related anergy and immunosuppression.

Background and aims: Conflicting results exist about the presence of Mycobacterium avium subspecies paratuberculosis (MAP) specific IS 900 DNA in Crohn’s disease (CD) tissues. Therefore, we examined IS 900 in a large number of gut samples from patients with CD (n = 100) and ulcerative colitis (UC, n = 100), and in non-inflamed control tissues (nIBD, n = 100). We hypothesised that IS 900 DNA detection might be associated with distinct clinical phenotypic characteristics in CD. Methods: The prevalence of MAP DNA in surgically resected tissues was examined using a mechanical-enzymatic disruption technique and nested IS 900 specific polymerase chain reaction (PCR). CD patients were stratified according to the criteria of the Vienna classification and other clinical characteristics. Results: IS 900 PCR detection rate was significantly higher in CD tissue samples (52%) than in UC (2%) or nIBD (5%) specimens (p 900 DNA was detected in samples from both diseased small bowel (47%) as well as from the colon (61%). No firm association between MAP specific IS 900 detection rates and clinical phenotypic characteristics in CD could be established. However, corticosteroid medication constituted a factor which tended to have a negative influence on IS 900 DNA detection rates in CD (p Conclusions: The presence of MAP specific IS 900 DNA is a predominant feature of CD. Therapeutic intervention against MAP might represent a potential target for disease mitigation in Crohn’s disease.

Peptide presentation by HLA class I and II antigens regulates specific antigen recognition by T cells. The present study aimed to investigate T cell infiltration and its relation to HLA antigen expression in pancreatic neuroendocrine tumors. Fresh tissue samples were collected from five insulinomas and six other neuroendocrine tumors (one gastrinoma, one glucagonoma, two carcinoid, and two neuroendocrine carcinomas). Normal pancreatic and splenic tissue samples were used as controls. Investigation of infiltrating lymphocyte populations, as well as staining of HLA class I and II antigens, were performed by standard immunohistochemistry. The majority of investigated tumors demonstrated an intratumoral infiltration by CD3 + , CD4 + and CD8 + T cells that was significantly higher than in normal pancreatic islets. Only a minority of tumor-infiltrating T cells showed the CD45RO + phenotype. The expression of HLA class I antigen was altered in 10 of 11 tumors. A loss of beta-2microglobulin represented the most frequent type of alteration to HLA class I expression, although the total loss of HLA class I was found in only one case of neuroendocrine carcinoma. HLA class II molecules were expressed by endothelial and lymphoid cells and not by tumor cells. In conclusion most neuroendocrine pancreatic tumors induce a T cell mediated immune response resulting in an intratumoral infiltration with CD3 + , CD4 + and CD8 + T cells. Loss of beta-2microglobulin is a frequent alteration in these tumors, which may influence the normal function of the HLA class I antigen complex. In contrast to malignant tumors of the exocrine pancreas, expression of HLA class II was absent in neuendocrine pancreatic tumor cells.

Emergency Cases in Crohn’s Disease: When to Operate? Emergency operations in Crohn’s disease become necessary due to typical complications: mechanical obstruction, bleeding, or sep

The aim of this study was the analysis of total, early and late complications following venous access port implantation between 1998 and 2008 at the Department of Surgery of the University of Rostock, Germany. A comparison between different implantation techniques addressing success rate, complication rate and duration of operation was performed. These results were further analysed in regard to the level of training of the participating surgeons.A retrospective analysis of 1423 venous access port implantations between 1998 and 2008 was performed.The rate of total complications was 13.8%. Among 4.7% early complications pneumothorax was the most common. The rate of late complications was 9.1%. Most common were infection (4.9%) followed by dysfunction of the catheter (3.5%). 1322 venous access port implantations were performed using puncture of the subclavian vein and Seldinger's technique. 101 operations were performed by direct access through dissection of the cephalic vein and open introduction of the catheter. Operation time in the open group was significantly longer than in the puncture group (46.5 min vs. 38.7 min, p = 0.005). There were significantly more late complications (9.6% vs. 2%, p = 0.01) and total complications (14.5% vs. 4%, p = 0.005) in the puncture group vs. the open access group. Primary success rates of open access vs. puncture were 100% and 96.8%, respectively. The rate of complications was independent of the experience status of the surgeon. However, the rate of total and late complications significantly decreases with number of performed operations.Venous port implantation is a relatively simple procedure despite its possible complications. An open access technique is safer than puncture. The rate of complications significantly decreases with increasing number of performed operations. Therefore venous port implantation and especially the open access method is an ideal teaching operation in a structured surgical training programme.

Einleitung: Etwa 10 % aller Insulinome – dem haufigsten endokrinen Pankreastumor – sind multiple Tumoren des Pankreas (z. B. multiple endokrine Neoplasie Typ I) oder prasentieren sich selten als Inselzellhyperplasie. In weiteren ca. 10–15 % der Falle sind die Tumoren bei der Diagnosestellung maligne. Fur diese speziellen Patientengruppen und Patienten mit einer Reoperation ist eine praoperative Lokalisationsdiagnostik aufgrund moglicher Schwierigkeiten bei der intraoperativen Lokalisation der Tumoren anzustreben. Die bildgebenden Verfahren, wie die Computertomographie (CT), Kernspintomographie (MRT), Ultraschall und Octreotidszintigraphie, sind in der Lokalisation oft unzureichend. Methoden: Diese Studie zeigt unsere Erfahrungen mit dem intraarteriellen Calciumstimulationstest (ASVS) zur regionalen Lokalisierung und dem operativen Management des Insulinoms bei Patienten mit einem Reeingriff aufgrund eines Rezidivs bzw. einer persistierenden Erkrankung oder eines malignen Insulinoms bzw. Patienten mit einer abdominellen Voroperation. Ergebnisse: Fur alle 3 Patienten konnte der funktionelle ASVS die richtige praoperative Regionalisierung des Insulinoms diagnostizieren und war damit der praoperativen bildgebenden Diagnostik uberlegen. Schlusfolgerung: In Ubereinstimmung mit der aktuellen Literatur ist der ASVS eine sehr sensitive ( > 90 %) und wenig invasive Methode zur praoperativen Regionalisierung von Insulinomen. Fur Patienten mit einem Reeingriff sollte dem ASVS der Vorzug gegenuber den verschiedenen, in der Summe kostenintensiven praoperativen Diagnostikverfahren gegeben werden.

Die Therapie der pigmentierten villonodularen Synovitis (PVNS), insbesondere der diffusen Form, wird weiterhin unterschiedlich beurteilt aufgrund der geringen Incidenz dieser Erkrankung. Die wichtigsten operativen Verfahren stellen die arthroskopische oder offene Synovektomie dar. Zur Vermeidung von Gelenkdestruktionen und funktionellen Einschrankungen ist die fruhe Erkennung der PVNS entscheidend. In den Jahren 1994 und 1995 haben wir 4 Falle operativ behandelt und in einem Zeitraum von mehr als 12 Monaten nachuntersucht. In 2 Fallen wurde die komplette Synovektomie, in einem Fall die partielle Resektion der Synovia und in einem weiteren Fall die Gelenkresektion und Arthrodese als offene Verfahren durchgefuhrt. Anhand unserer Ergebnisse lies sich zeigen, das das MRT unverzichtbar in der Diagnostik und der operativen Therapieplanung ist. Liegt ein lokaler Befall der Synovia vor, so scheint die partielle Synovektomie ausreichend. Bestehen aber Zweifel in der Einschatzung oder zeigt sich klar das Bild eines diffusen Befalls, sollte die komplette Synovektomie, aufgrund der hohen Rezidivrate der diffusen PVNS, bevorzugt werden. Es zeigte sich weiterhin, das bei allen unseren Patienten sekundare ossare Lasionen auftraten bis hin zur Gelenkdestruktion bei einem Patienten. Daher ist die fruhzeitige operative Therapie als z. Z. einzig kausale Behandlung zu empfehlen. Inwieweit arthroskopisch oder als offenes Verfahren vorgegangen werden kann, ist abhangig von der Form der PVNS, dem Ausmas des Tumorbefalls und sekundaren Gelenkveranderungen.

Discussion of the volume-outcome relationship in pancreatic surgery has gained increasing interest. Currently, no data describe the situation in Germany. Pursuant to a recent legislative reform, a threshold of 10 operations per year was introduced for pancreatic surgery in 2006. This study describes the situation in Germany and the effect of the legislative reform between 2006 and 2009.In 2007 and 2010, anonymous questionnaires were sent to leading surgeons in the German Society of General and Gastrointestinal Surgery asking for the numbers of pancreatic operations, methods of operation, and mortality for the years 2006, 2008, and 2009. Volume categories were defined by dividing hospitals into quartiles according to their annual volume of operations.The return rate was about 48%. In the years 2006, 2008, and 2009, overall mortality in all hospitals was 2.85%, 3.98%, and 2.58%. High volume was defined as ≥ 32 pancreatic operations (2006) and ≥ 34 pancreatic operations (2008, 2009). Although mortality decreased with increasing volume, mortality between each volume category was not statistically different in any year. In the years 2006, 2008, and 2009, the number of operations increased in university hospitals (38.4%, 51.2%, and 50.4%, P.001) and decreased in teaching hospitals (51.8%, 41.3%, and 41.2%, P.001). The number of hospitals that did not perform pancreatic operations increased from 15.6% to 32.5% and 31% (P.001).In pancreatic surgery, a centralization effect occurred after a legislative reform in Germany. Overall mortality after pancreatic resection in German hospitals is good. Although mortality decreases with greater volume, there were no differences compared to other volume categories. Also, low-volume hospitals can produce good results; however, the difference in quality is considerable among these institutions. Our data suggest that the German threshold agreement in pancreatic surgery might have a positive effect with regard to reproducible quality and outcome.

The Vogelstein Lab demonstrated in pionier work that spores of Clostridium novyi NT are efficient in eradicating established solid tumors in combination with standard chemotherapy [1]. Despite progress of oncologic and surgical therapy pancreatic cancer still has an outstanding poor prognosis. Therefore, we investigated the effectiveness of attenuated Clostridium novyi spores (C. novyi-NT) for treatment of established subcutaneous Panc02 tumors in the syngeneic, immunocompetent C57BI/6 model. After corresponding growth of tumor c. novyi NT Spores (75 Mio) were applied intravenously. These experiments demonstrated, that (I) small tumors ( 500 mm3) responded with substantial necrosis followed by shrinkage accompanied with disastrous lethality due to tumor lysis syndrome (n=3), (III) an optimal treatment window exists for tumors of approximately 300 mm3 (n=20).

Colorectal cancer is caused by genetic instability of somatic cells. Two different molecular pathways generate either chromosomal or high level microsatellite instability (MSI-H). The latter is induced by defects of the DNA mismatch repair system and results in insertion or deletion of single nucleotides at short repetitive DNA sequences. About 15% of sporadic and more than 90% of hereditary nonpolyposis colorectal cancers display MSI-H. Mutation of microsatellites located within coding regions results in a shift of the reading frame and translation of novel frameshift peptides (FSPs) at the carboxy terminus of the respective gene products. On the one hand, functional tumor promoting relevance has been demonstrated for a growing number of genes frequently hit by this mutational mechanism. On the other hand, it is likely, that immune reactions against FSPs are involved in the immune surveillance of MSI-H cancers. In the present study we provide conclusive data that the (−1) frame of the MSI-H target gene U79260(FTO) encodes and HLA-A0201-restricted cytotoxic T cell epitope (FSP11; TLSPGWSAV). T cells specific for FSP11 efficiently recognized HLA-A0201 (pos) tumor cells harboring the mutated reading frame. Considering the exceptionally high mutation rate of U79260(FTO) in MSI-H colorectal carcinoma (81.8%) these data recommed FSP11 as a component for vaccines against MSI-H cancers.

Klinisch zeigte sich eine deutliche Weichteilschwellung am linken Ellenbogen. Die periphere Durchblutung und Motorik waren unauffallig, die Sensibilitat war lediglich an D IV und D V leicht eingeschrankt Zur weiteren diagnostischen Abklarung wurde eine konventionelle Rontgenaufnahme des linken Ellenbogens in zwei Ebenen angefertigt (Abb. 1a und b). In der AP-Aufnahme sieht man bei noch offenen Epiphysenfugen des Epicondylus ulnaris und radialis humeri eine erhohte Transparenz des distalen Humerus radialseitig. Die Ausenkontur des distalen Humerus erscheint intakt, jedoch erkennt man eine zweite Kontur proximal des hemero-radialen Gelenks. In der Seitenaufnahme sieht man eine halbmondformige Struktur ventral in der Ellenbeuge sowie eine Verlagerung der Fettlamelle ventral und dorsal als Hinweis auf einen Gelenkergus. Ihre Diagnose ?

The success of cancer gene therapy is likely to require the targeting of multiple antitumor mechanisms. In this study we demonstrate that infection of Lewis rats bearing pancreatic tumors with the Adenoassociated Virus type 2 (AAV-2) induces a systemic anti-tumor response and protects these animals from a subsequent tumor rechallenge.

Peptide presentation by HLA class I and II antigens regulates specific antigen recognition by T cells. The present study aimed to investigate T cell infiltration and its relation to HLA antigen expression in pancreatic neuroendocrine tumors. Fresh tissue samples were collected from five insulinomas and six other neuroendocrine tumors (one gastrinoma, one glucagonoma, two carcinoid, and two neuroendocrine carcinomas). Normal pancreatic and splenic tissue samples were used as controls. Investigation of infiltrating lymphocyte populations, as well as staining of HLA class I and II antigens, were performed by standard immunohistochemistry. The majority of investigated tumors demonstrated an intratumoral infiltration by CD3+, CD4+ and CD8+ T cells that was significantly higher than in normal pancreatic islets. Only a minority of tumor-infiltrating T cells showed the CD45RO+ phenotype. The expression of HLA class I antigen was altered in 10 of 11 tumors. A loss of beta-2microglobulin represented the most frequent type of alteration to HLA class I expression, although the total loss of HLA class I was found in only one case of neuroendocrine carcinoma. HLA class II molecules were expressed by endothelial and lymphoid cells and not by tumor cells. In conclusion most neuroendocrine pancreatic tumors induce a T cell mediated immune response resulting in an intratumoral infiltration with CD3+, CD4+ and CD8+ T cells. Loss of beta-2microglobulin is a frequent alteration in these tumors, which may influence the normal function of the HLA class I antigen complex. In contrast to malignant tumors of the exocrine pancreas, expression of HLA class II was absent in neuendocrine pancreatic tumor cells.

Background: In preclinical models adenovirus-mediated p53 gene transfer (Ad-p53) demonstrated therapeutic efficacy against a wide range of human tumor types containing nonfunctional p53, both in vitro and in vivo. Alterations in the p53 function are present in 50% – 75% of pancreatic cancer patients. The traditional therapeutic approach for advanced pancreatic cancer is still chemotherapy. Before starting clinical trails it is important to study possible interactions between Ad-p53 gene transfer and chemotherapeutic drugs. Methods: Transfection of two human (DANG, Capan-1) and one murine (DSL6A) pancreatic cancer cell lines with a replication-deficient adenoviral vector expressing wt p53 (Ad-p53) were performed in vitro. Determination of the p53 status of pancreatic cancer cell lines and Ad-p53 gene transfer were evaluated by Western blot analysis and immunofluorescence. Proliferation of tumor cells and apoptosis were quantitated after incubation with different ratios of Ad-p53 particles and cell numbers (multiplicities of infection, MOI 1–100) in combination with various 5-FU doses by cell proliferation assay (WST-1) and FACS (PI staining). In vivo 1 x 106 DSL6A syngenic pancreatic tumor cells were inoculated subcutanously in Lewis rats and 8 weeks later treatment started. The animals were separated into the following groups: (1) Control, no treatment, n = 8; (2) 5-fluorouracil (5 mg/kg/BW i.p.), n = 8; (3) Ad-p53 (1 x 108 infectious particles i.t.), n = 8; and (4) Ad- P53 + 5-FU, n = 8. The treatment was performed twice a week for 1 month. Our evaluation included tumor size, weight and survival of the animals. Results: Capan-1, DANG and DSL6A were very efficiently transduced at MOI of 1–10 by Ad-p53 and revealed a significant inhibitory effect on tumor growth. The pancreatic tumor cell lines Capan-1, DANG and DSL6A were sensitive to the cytotoxic action of 5-FU. The combined application of Ad-p53 and 5-FU chemotherapy resulted in a more reduced number of viable tumor cells (40% vs. 70%) and higher apoptotic rate (30% vs. 10%) compared with Ad-p53 or 5-FU therapy alone. In vivo experiments showed the most potential tumor regression in animals treated with Ad-p53+5-FU (p < 0.05) and prolonged survival time. In contrast, 5-FU single therapy had no effect on tumor growth and survival rate. Ad-p53 gene therapy alone inhibited tumor progression for the first 2 weeks of treatment, but then tumor growth started again rapidly. Conclusions: Our results demonstrated a greater anticancer efficacy of the combination Ad-p53 plus 5-FU chemotherapy and support this approach for advanced pancreatic cancer patients in clinical trails.

Approximately 10% of all insulinomas--the most common neuroendocrine pancreatic tumor--occur in multiple sites of the pancreas (e.g., multiple endocrine neoplasia type I) and rarely as islet cell hyperplasia. Malignant insulinomas appear in 10% to 15% of cases. For these special groups and for patients with a reoperation preoperative localization of the tumour is advisable. With current imaging technology, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and somatostatin receptor scintigraphy (SRS), localization of insulinomas is often inadequate.In this study we report our results using intra-arterial calcium-stimulated venous blood sampling (ASVS) to localize and guide the management of insulinomas for patients with a reoperation because of recurrent insulinomas or persistent hyperinsulinism, for patients with malignant neoplasm and for patients with a previous abdominal operation.For all three cases the insulinomas were correctly localized by the ASVS in contrast to the preoperative imaging studies.Our experience and a review of the current literature demonstrate that ASVS is a highly accurate (sensitivity90%) and a safe method for preoperative localization of insulinomas. For patients with a reoperation ASVS is recommended and the extensive use of other costly preoperative methods should be avoided.

Because this disease is so rare the optimum treatment of pigmented villonodular synovitis (PVNS), in particular the diffuse form differs in the literature. The most important surgical procedures are arthroscopic and open synovectomy. The prevention of disease progression, as well as joint destruction and dysfunction, depends upon the early diagnosis of PVNS. During 1994 and 1995, we treated four cases of PVNS surgically and followed the patients for a time period of more than 12 months. Two patients were treated with complete synovectomy, one patient underwent partial synovial resection, and in the final case an arthrodesis was performed. Our results indicate that an MRI is essential for diagnosis and treatment planning. For the localized form of PVNS, it appears that a partial synovectomy is appropriate. However, in the event of diagnostic uncertainty or obvious diffuse involvement of the synovium, a total synovectomy is indicated because of the high recurrence rate. In our study, all four patients had disease involving secondary bony lesions and, in one case, joint destruction. Based on our findings, it is clear that early surgical therapy is the only recommended curative intervention. The decision regarding the surgical approach, arthroscopic versus open, depends on the form of PVNS, the extent of the disease and secondary changes of the joint.

The aim of the present study was to prove the effect of successful percutaneous transluminal coronary angioplasty (PTCA) on the occurrence of symptomatic and silent myocardial ischemia recorded during 24-h ECG, considering the number of diseased coronary arteries, a history of myocardial infarction, and the interval between myocardial infarction and PTCA. Before PTCA, 28 of 56 patients (50%) had ischemic ST-segment alterations, 3-8 days thereafter, there were only 13 patients (23%) with signs of myocardial ischemia (p0.01). The number of episodes of ischemia (IE) was reduced 44% (p0.05), their duration (ID) 51% (p0.01). In symptomatic patients, the decrease was 67% (p0.05) and 83% (p0.05), in patients with silent myocardial ischemia 20% (n.s.) and 29% (n.s.). Patients with one-vessel disease exhibited a 73% reduction of IE (p0.01) and a 85% reduction of ID (p0.01). In patients with two-vessel disease, the decrease was 47% (p0.05) and 26% (p0.05), whereas in those with three-vessel disease, there was no significant change. Patients without stenosis (50%) after PTCA had--irrespective of primary findings--a decrease of IE of 78% (p0.05) and of ID of 85% (p0.05), while patients with persisting coronary artery stenosis exhibited no significant decrease (20% and 35%, n.s.). In patients without history of myocardial infarction, the reduction of IE was 79% (p0.01) and that of ID 85% (p0.05); in patients with recent myocardial infarction (3 months) the decrease was 59% (p0.05) and 70% (p0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Results of investigations about the pattern of livestock in the five new countries of the Federal Republic are described in this paper. Groupings about the distribution of enterprises with cattle-, pig- and sheep-keeping and their animals to classes of size set priorities. The problem of mass-animal keeping is shown in a survey about large equipment. Calculations of manure units per hectare agricultural area show, that with the maintaining of necessary organisation principles the permissible yield guidelines of manure and liquid manure should not be exceeded.

Aims: Although the majority of patients undergoing renal transplantation currently receive kidneys from cadaveric donors, living donors continue to be an important source of transplanted kidneys. Recipients of living donor kidneys demonstrate improved graft survival. We have reviewed our living donor nephrectomy experience over 35 years to analyze the donor and recipient morbidity and mortality rate. Methods: The operative complications and the long-term outcome of 219 living donated of all 1915 kidney transplantations before and after introduction of cyclosporine A were evaluated. Donor and graft complications as well as recipient complications and survival rate were investigated. Additionally, the findings of 16 laparoscopically operated living donors were compared to a group of 20 patients that underwent a conventional operation. Results: The overall recipient 3and 5-year survival rates in the cyclosporine A era were 95% and 94%, respectively. Prior to the introduction of cyclosporine A, the overall recipient survival rates at 3 and 5 years were 84% and 84%, respectively. The overall graft survival rates were 92% and 85% for the cyclosporine A era compared to 68% and 60% before introduction of cyclosporine A, at 3 and 5 years, respectively. The patient and graft survival rate in the cyclosporine group were significantly higher than in the pre-cyclosporine group (log-rank: p 0.0107 and p 0.0003, respectively). Donor complications included pain at the incision site (35%), mild hypertension (27%), proteinuria (19%), urinary tract infection (11%), pneumothorax (5%), blood transfusion (3.5%), and wound infection (3%), with no mortalities. Our results showed longer operation, warm ischemia, and cold ischemia time in laparoscopically operated living donors than the conventional approach. There was no statistically significant difference in complications between both techniques. However, the hospitalization days and usage of analgesic medication in laparoscopy donors were lower than in the conventional approach. Conclusions: The results of the present analysis confirm an increase in patient and graft survival rates in the cyclosporine era compared to before its usage. Living donor nephrectomy, done through a conventional or laparoscopic approach, remains a valuable source of kidneys for transplantation with low complication rates.

There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU). Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status.Human pancreatic cancer cell lines Capan-1(p53mut), Capan-2(p53wt), FAMPAC(p53mut), PANC1(p53mut), and rat pancreatic cancer cell lines AS(p53wt) and DSL6A(p53null) were used for in vitro studies. Following infection with different ratios of Ad-p53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining). In addition, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies. Tumor size, apoptosis (TUNEL) and survival were determined.Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53. In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU. Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU.Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.

Background Multidrug resistance (MDR) is a clinically, highly relevant phenomenon. Under chemotherapy many tumors show an increasing resistance towards the applied substance(s) and to a certain extent also towards other agents. An important molecular cause of this phenomenon is an increased expression of transporter proteins. The functional relationship between high expression levels and chemotherapy resistance makes these MDR and MRP (MDR related protein) proteins to interesting therapeutic targets. We here wanted to systematically analyze, whether these proteins are tumor specific antigens which could be targeted immunologically. Results Using the reverse immunology approach, 30 HLA-A2.1 restricted MDR and MRP derived peptides (MDP) were selected. Stimulated T cell lines grew well and mainly contained activated CD8+ cells. Peptide specificity and HLA-A2.1 restriction were proven in IFN-γ-ELISpot analyses and in cytotoxicity tests against MDP loaded target cells for a total of twelve peptides derived from MDR-1, MDR-3, MRP-1, MRP-2, MRP-3 and MRP-5. Of note, two of these epitopes are shared between MDR-1 and MDR-3 as well as MRP-2 and MRP-3. However, comparably weak cytotoxic activities were additionally observed against HLA-A2.1+ tumor cells even after upregulation of MDR protein expression by in vitro chemotherapy. Conclusions Taken together, these data demonstrate that human T cells can be sensitised towards MDPs and hence, there is no absolute immunological tolerance. However, our data also hint towards rather low endogenous tumor cell processing and presentation of MDPs in the context of HLA-A2.1 molecules. Consequently, we conclude that MDR and MRP proteins must be considered as weak tumor specific antigens-at least for colorectal carcinoma. Their direct contribution to therapy-failure implies however, that it is worth to further pursue this approach.