Infliximab as therapeutic option in steroid-refractory ulcerative colitis after kidney transplantation: case report.

In inflammatory bowel disease refractory to established therapies, treatment with biological agents such as monoclonal tumor necrosis factor-α antibodies is an established therapeutic option. However, application in renal allograft recipients is either not licensed or has not yet been systematically examined. Herein, we present 2 case reports of renal allograft recipients who had steroid-refractory ulcerative colitis who demonstrated improvement of symptoms after treatment with infliximab, without signs of effect on transplant function. In both patients, stool frequency decreased significantly. Colonoscopy controls and histologic examination after initiation of treatment revealed a state of remission. Renal function parameters and drug concentrations remained constant.

[Multilayer analysis of signal transduction and cell cycle control in GIST. Identifying new interaction partners with differential regulation]. / Multilayer-Analyse der Signaltransduktion und Zellzykluskontrolle in GIST. Identifizierung neuer Interaktionspartner mit differenzieller Regulation.

To identify new interactions as well as diagnostically, prognostically and therapeutically relevant differences in the regulation of gene expression in gastrointestinal stromal tumors (GISTs), we analyzed the methylation status, mRNA expression, microRNA expression, protein expression and protein phosphorylation in parallel in identical tumor tissue samples. The data were analyzed in a multilayer approach and were correlated to each other and to clinico-pathological parameters. Differentially regulated genes were mapped to signal transduction pathways which are already known to play a major role in GISTs. A functionally orientated overview of the different data layers was constructed, which enabled new insights into gene regulation in GISTs.

Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer.

BACKGROUND: Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis. However, targeting tumour angiogenesis in clinical trials showed only modest efficacy. We therefore scrutinised the concept of tumour angiogenesis and lymphangiogenesis by analysing the expression of crucial markers involved in these processes in primary breast cancer. METHODS: We analysed the expression of angiogenic, lymphangiogenic or antiangiogenic factors, their respective receptors and specific markers for endothelial and lymphendothelial cells by quantitative real-time RT-PCR in primary breast cancer and compared the expression profiles to non-cancerous, tumour-adjacent tissues and breast tissues from healthy women. RESULTS: We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated. Concomitantly, angiogenic and lymphangiogenic receptors were downregulated in breast tumours. This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers. CONCLUSION: Primary breast tumours are not a site of highly active angiogenesis and lymphangiogenesis. Selection for tumour cells that survive with minimal vascular supply may account for this observation in clinical apparent tumours.

Increased KIT signalling with up-regulation of cyclin D correlates to accelerated proliferation and shorter disease-free survival in gastrointestinal stromal tumours (GISTs) with KIT exon 11 deletions.

Gastrointestinal stromal tumours (GISTs) with deletions in KIT exon 11 are characterized by higher proliferation rates and shorter disease-free survival times, compared to GISTs with KIT exon 11 point mutations. Up-regulation of cyclin D is a crucial event for entry into the G1 phase of the cell cycle, and links mitogenic signalling to cell proliferation. Signalling from activated KIT to cyclin D is directed through the RAS/RAF/ERK, PI3K/AKT/mTOR/EIF4E, and JAK/STATs cascades. ERK and STATs initiate mRNA transcription of cyclin D, whereas EIF4E activation leads to increased translation efficiency and reduced degradation of cyclin D protein. The aim of the current study was to analyse the mRNA and protein expression as well as protein phosphorylation of central hubs of these signalling cascades in primary GISTs, to evaluate whether tumours with KIT exon 11 deletions and point mutations differently utilize these pathways. GISTs with KIT exon 11 deletions had significantly higher mitotic counts, higher proliferation rates, and shorter disease-free survival times. In line with this, they had significantly higher expression of cyclin D on the mRNA and protein level. Furthermore, there was a significantly higher amount of phosphorylated ERK1/2, and a higher protein amount of STAT3, mTOR, and EIF4E. PI3K and phosphorylated AKT were also up-regulated, but this was not significant. Ultimately, GISTs with KIT exon 11 deletions had significantly higher phosphorylation of the central negative cell-cycle regulator RB. Phosphorylation of RB is accomplished by activated cyclin D/CDK4/6 complex, and marks a central event in the release of the cell cycle. Altogether, these observations suggest increased KIT signalling with up-regulation of cyclin D as the basis for the unfavourable clinical course in GISTs with KIT exon 11 deletions.

Loss of 9p leads to p16INK4A down-regulation and enables RB/E2F1-dependent cell cycle promotion in gastrointestinal stromal tumours (GISTs).

Loss of chromosome 9p is a reliable predictor of malignant behaviour in gastrointestinal stromal tumours (GISTs). p16INK4A located at 9p21 inhibits the CDK4/6/cyclin D complex from phosphorylating RB. Phosphorylation of RB through CDK4/6/cyclin D in early G(1) phase frees the transcription factor E2F1 from RB and enables mRNA transcription of genes essential for G(1)/S phase transition. This study aims to determine the impact of 9p loss on mRNA and protein expression of p16INK4A and further key cell cycle regulators in the different phases of the cell cycle. Sixty primary GISTs previously characterized for 9p loss by comparative genomic hybridization were analysed for mRNA expression of p16INK4A, p15INK4B, CDK4, CDK6, cyclin D, p21CIP1p27KIP1, CDK2, cyclin E, cyclin B, RB and E2F1, using quantitative RT-PCR. The protein expression of CDK6, CDK2, p21CIP1, p27KIP1 and phosphorylated RB (S807/S811) was evaluated using protein arrays as a novel and highly sensitive platform for profiling of protein abundance and protein phosphorylation. In parallel, the nuclear percentages of immunohistochemical staining for p16INK4A, cyclin D, E2F1 and RB were quantified on a tissue microarray. GISTs with 9p loss had significantly higher proliferation rates, higher metastatic behaviour and shorter disease-free survival. On the molecular level, GISTs with 9p loss had a significantly reduced mRNA as well as nuclear protein expression of p16INK4A. RB was significantly more phosphorylated in these tumours, together with increased mRNA expression and nuclear staining for E2F1. Furthermore, GISTs with 9p loss had up-regulation of the late G1/S phase promoters CDK2 and cyclin E. We conclude that loss of 9p accompanied by early G1 phase inhibitor p16(INK4A) down-regulation in GISTs facilitates phosphorylation of RB, enabling E2F1-dependent transcription of genes essential for late G1/S phase transition. This study provides a possible basis for the accelerated proliferation and particularly malignant behaviour in GISTs with 9p loss.

Characterization of a newly established uterine carcinosarcoma cell line featuring the sarcomatous phenotype of the tumor in vitro.

We describe the newly established cell line CS-99 derived from a uterine carcinosarcoma retaining features of the sarcomatous phenotype in vitro. CS-99 cells exhibit a mesenchymal morphology with predominantly spindle-shaped cells at nonconfluence turning to pleomorphic appearance at confluence. The mesenchymal phenotype was evidenced immunohistochemically by strong vimentin and moderate SM-actin, which was similar to the sarcomatous component of the primary tumor. P53 was overexpressed in a subset of CS-99 cells. Epithelial membrane antigen was moderately expressed whereas other markers including pan CK, CK 5/6, CK 34, epidermal growth factor receptor, desmin, carcinoembryonic antigen, S100, KIT, ERBB2, and the hormone receptors, estrogen receptor and progesterone receptor revealed either weak or no specific staining in CS-99 cells. High self-renewal capacity corresponded to the population doubling time of 23 h in high passage. CS-99 cells were able to develop three-dimensional tumor spheroids in vitro. Cytogenetic analysis and multicolor fluorescence in situ hybridization of CS-99 demonstrated an almost stable karyotype including numerical changes +8, +18, and +20 and translocations, amongst others der(1)t(1;2), der(1)t(1;7), der(2)t(2;19), der(5)t(5;8), and der(5)t(5;14). Taken together, the cell line CS-99 exhibits strong growths dynamics and a complex but stable karyotype in higher passages, and can be further a useful in vitro model system for studying tumor biology of carcinosarcomas.

Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells.

Vacuole membrane protein 1 (Vmp1) is described as a cancer-relevant cell cycle modulator, but the function of this protein and its mode of action in tumor progression are still unknown. In this study, we show that the VMP1 mRNA level is significantly reduced in kidney cancer metastases as compared to primary tumors. Further, VMP1 expression is also decreased in the invasive breast cancer cell lines HCC1954 and MDA-MB-231 as compared to the non-invasive cell lines MCF-12A, T-47D and MCF-7. We show for the first time that Vmp1 is a plasma membrane protein and an essential component of initial cell-cell contacts and tight junction formation. It interacts with the tight junction protein Zonula Occludens-1 and colocalizes in spots between neighboring HEK293 cells. Downregulation of VMP1 by RNAi results in loss of cell adherence, and increases the invasion capacity of the non-invasive kidney cancer cell line Caki-2. In conclusion, our findings establish Vmp1 to be a novel cell-cell adhesion protein and that its expression level determines the invasion and metastatic potential of cancer cells.

Morphological and immunohistochemical characterization of isolated tumor cells by p53 status in gastrointestinal tumors.

BACKGROUND AND AIMS: Isolated tumor cells (ITCs) in cancer patients are retrieved mostly using immunohistochemistry with antibodies directed against antiepithelial antigens (for example Ber-EP4), which are supposed not to be present in metastatic-free tissue. To date, there has been ongoing controversy whether those cells have biologic significance and are linked with tumor progression and impaired patient's prognosis. Therefore, the aim of this study was to further characterize Ber-EP4-positive cells in various tissues, with special emphasis on their tumorigenic origin. MATERIALS AND METHODS: The frequency and prognostic impact of ITCs in lymph nodes displayed by means of monoclonal antibody Ber-EP4 were evaluated in retrospective (n = 292) and prospective (n = 100) collectives of various gastrointestinal carcinomas free of metastatic disease in conventional histopathology (pN0). Furthermore, the frequency of ITCs in the peritoneal cavity and bone marrow was analyzed in case of absence of overt distant metastasis (pM0) in the prospective collective. Ber-EP4-immunoreactive cells were further characterized for tumorigenic origin using morphological criteria and immunohistochemical double staining for Ber-EP4 and p53. RESULTS: Ber-EP4-positive cells could be revealed in lymph nodes in 44.3% of pN0-gastrointestinal carcinomas, in the peritoneal cavity in 19%, and in the bone marrow in 10%. In lymph nodes, BerEP4-immunoreactive cells exhibited a metastatic-atypical morphology in 59%; however, it was always typical for true tumor cells in the peritoneal cavity or bone marrow. The cumulative 5-year survival rate was adversely affected by Ber-EP4-immunoreactive cells in uni- and multivariate analysis, irrespective of the underlying cell morphology (68% for Ber-EP4 negative, 41% for Ber-EP4 positive with atypical and typical morphology each). In the case of a p53-positive primary tumor, 70% of the corresponding ITCs also overexpressed p53, while the remainder was deemed p53 negative (p = 0.002). CONCLUSION: ITCs detected by the antiepithelial antibody Ber-EP4 are present in a substantial proportion of apparently tumor-free lymph nodes. These cells impair patients' prognoses, irrespective of the underlying cell morphology. As approximately one third of Ber-EP4-positive cells in p53-positive primary tumors do not overexpress p53; their true tumorigenic origin needs to be further investigated.

An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cytogenetic evolution with prognostic implications.

To model the cytogenetic evolution in gastrointestinal stromal tumour (GIST), an oncogenetic tree model was reconstructed using comparative genomic hybridization data from 203 primary GISTs (116 gastric and 87 intestinal GISTs, including 151 newly analysed cases), with follow-up available in 173 cases (mean 40 months; maximum 133 months). The oncogenetic tree model identified three major cytogenetic pathways: one initiated by -14q, one by -1p, and another by -22q. The -14q pathway mainly characterized gastric tumours with predominantly stable karyotypes and more favourable clinical course. On the other hand, the -1p pathway was more characteristic of intestinal GISTs, with an increased capacity for cytogenetic complexity and more aggressive clinical course. Loss of 22q, more closely associated with -1p than -14q, appeared to initiate the critical transition to an unfavourable cytogenetic subpathway. This -22q pathway included accumulation of +8q, -9p, and -9q, which could all predict disease-free survival in addition to tumour site. Thus, insights into the cytogenetic evolution obtained from oncogenetic tree models may eventually help to gain a better understanding of the heterogeneous site-dependent biological behaviour of GISTs.

Parvovirus B19 detected in Rosai-Dorfman disease in nodal and extranodal manifestations.

Sinus histiocytosis with massive lymphadenopathy (SHML), also designated as Rosai-Dorfman disease (RDD), is a rare benign reactive lymphoproliferative disorder. It is defined by a characteristic histopathology with sinus histiocytosis and haemophagocytosis known as emperipolesis. In histiocytes S100 is strongly expressed, whereas CD1a staining typically is negative. The disease mainly manifests at a single lymph node; however, multilocular and extranodal affection can occur. Causative infectious agents, and virus infections in particular, have repeatedly been suspected, although until now the origin of the disease has been unclear. Four cases of RDD (two nodal sites and two extranodal upper respiratory tract sites) were analysed for parvovirus B19 (B19) infection by immunohistochemistry to detect B19 capsid proteins VP1/VP2. In all the four cases, huge numbers of B19-positive cells were partly detected. The positive cells were identified either as lymphocytes or, in one extranodal case, also as respiratory epithelial cells. This is the first report of B19 infection in RDD tissue, indicating that B19 may be associated with the pathogenesis of SHML.

Histomorphological tumor regression grading of esophageal carcinoma after neoadjuvant radiochemotherapy: which score to use?

Histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer after neoadjuvant radiochemotherapy (RCT). The system introduced by Mandard to group TRG (Cancer 1994;73:2680-2686) has been used to analyse and discuss its prognostic significance on survival in a single institution retrospective analysis: TRG 1 (complete regression) - TRG 5 (absence of regressive changes). Sixty patients with locally advanced (T3/4 or N1) adenocarcinoma or squamous cell carcinoma received cisplatin-based RCT. Three to four weeks later operation for curative intent was performed. Median follow-up was 17.7 months. Histopathological tumor stages were stage 0 in 17%, stage I in 10%, stage II in 60%, stage III in 12% and stage IVA in 1%. The 5-year overall survival (OS) rate was 35%. In univariate analysis, ypN-status and TRG correlated significantly with OS (P = 0.004, P = 0.0008, respectively). While OS of TRG 1 differed significantly from all other groups, no differences in OS between the other TRG groups were seen. Patients with complete tumor regression after neoadjuvant RCT showed a much better survival than patients with tumors that responded less to induction therapy. Further qualitative subdivision of tumor regression could not identify patient groups with significant differences in prognosis. After comparing our data with the literature, it is reasonable to consider classifying all patients into 'Complete tumor regression' and 'Incomplete tumor regression'.

[Significance of occult lymphatic tumor spread in pancreatic cancer]. / Okkulte lymphatische Tumorzelldisseminierung beim Pankreaskarzinom.

PURPOSE: The aim of this study was to determine the frequency and effect on prognosis of occult tumor cells in regional lymph nodes judged to be tumor-free in conventional histopathology of pancreatic cancer patients. PATIENTS AND METHODS: Among 115 patients who underwent pancreatic resection for pancreatic (n=84) or distal common bile duct malignancy (n=12) or carcinoma of the papilla (n=19), 48 (42%) were staged pN0. Archival paraffin blocks of 271 resected regional lymph nodes of 41 pN0 patients were reevaluated for occult tumor cells using monoclonal antibody Ber-EP4. Cases with or without isolated tumor cells were compared regarding the distribution of various clinicopathological factors. RESULTS: Of 41 pN0 patients, 16 (39%) exhibited single Ber-Ep4 immunoreactive cells or small cell clusters in at least one lymph node. The occurrence of occult tumor cells was not dependent on other clinicopathological factors such as pT stage, grading, or curative resection. However, those cells were encountered more frequently in common bile duct carcinomas (100%) than in pancreatic (36%) or papilla (20%) carcinomas (P=0.009). Occult tumor cells impaired prognosis significantly in uni- and multivariate analyses (estimated 5-year survival 53% for pN0((i-)) vs 10% for pN0((i+)) and 9% for pN1/N2; P=0.0047). CONCLUSION: Occult tumor cells are frequent in apparently tumor-free lymph nodes of pancreatic cancer patients and often overlooked in conventional histopathology. They are encountered even in limited stages of disease and they impair prognosis, which is comparable to that of patients with true lymphatic metastases. Occult tumor cells in lymph nodes of pancreatic cancer patients could be used to stratify adjuvant therapy.

Expression of the sodium iodide symporter in differentiated thyroid cancer: clinical evidence.

AIM: Molecular analysis of the expression of the sodium iodide symporter (NIS) in 32 patients with differentiated thyroid cancer (DTC) and correlation with scintigraphic findings ((131)I,(123)I) in 19 (59.4%) of them. PATIENTS, METHODS: NIS expression of 27 primary tumours, 13 lymphnodes and 18 distant metastases was determined by immunostaining using a murine monoclonal anti-NIS-antibody. NIS expression and radionuclide uptake of metastases were analysed by a semiquantitative visual score. Patients were divided into two subgroups: Group 1 (n = 8 patients): indirect correlation of radioiodine uptake (RIU) of subsequent metastases with NIS expression of 7 primary tumours and 3 metastases; Group 2 (n=11 patients): direct correlation of radionuclide uptake with NIS expression of 19 metastases which were excised after imaging. RESULTS: 49 of 58 specimens (84.5%) were NIS-positive. A preserved NIS-expression was found in 12 primary tumours and 8 of 10 (80%) synchrone and 6 of 7 (85.7%) metachrone metastases. Group 1 revealed a 100% positive predictive value (PPV) of a preserved NIS expression in the primary tumour regarding radioiodine uptake in metastases while a lack of NIS expression in the primary tumor did not reliable predict a loss of the metastases' ability to concentrate radioiodine. In group 2, only 11 of 19 (57.9%) specimens showed a concordant NIS expression and RIU whereas in the remaining 8 cases without visible RIU NIS expression was still present. CONCLUSIONS: NIS expression of the primary tumour and metastases in DTC is usually well preserved. We found a positive correlation between NIS expression of the primary and metastatic tissue but could not identify such well correspondence between NIS expression and the RIU of subsequent metastases.

[In-vitro study of the cellular response of human fibroblasts cultured on alloplastic hernia meshes. Influence of mesh material and structure]. / Hernienchirurgie: Wachstumsverhalten humaner Fibroblasten auf alloplastischen Kunststoffnetzen. In-vitro-Studie zum Einfluss des Materials und der Oberflächenstruktur.

BACKGROUND: The biocompatibility of meshes in hernia surgery seems to be influenced markedly by the amount of the selected material and its structure. Fibroblasts play a major key role during the process of mesh incorporation. This study was performed to investigate differences in cell morphology and proliferation of human fibroblasts cultured on different polypropylene meshes. METHODS: In the present in vitro study the cellular response of human fibroblasts was investigated by scanning electron microscopy (SEM), comparing three different polypropylene meshes: a newly constructed low-weight and microporous mesh (NK1), a low-weight and macroporous mesh with absorbable polyglactin filaments (Vypro), and a heavy-weight and microporous mesh (BiomeshP1). Human fibroblasts (1,5.10(5) cells) were incubated with the meshes (each 12 mm(2)) for 6 hours, 5 days, 2, 4, 6, and 12 weeks. Computer-assisted morphometry of the fibroblast/mesh surface ratio served to reflect the biological cell response. RESULTS: The Vypro mesh showed the significantly highest fibroblast density during the first 6 weeks, but cell growth was nearly exclusively limited to the polyglactin filaments. At 3 months, after reabsorption of the polyglactin, the fibroblast-coated polypropylene mesh surface was only 50% compared to NK1 and BiomeshP1. The morphologic aspect of the fibroblasts on the BiomeshP1 mesh was much more degenerative and unphysiological, compared to NK1 and Vypro, with isolated, single cells instead of a broad, connective growth. The BiomeshP1 showed a significantly higher fibroblast proliferation around the nodes of the mesh compared to the straight filaments. On the NK1 mesh fibroblasts exclusively proliferated on the filaments but not on the pressed mesh surface. CONCLUSIONS: The polymer surface and structure appears to be of major importance for the biocompatibility of meshes: human fibroblasts preferably grow on low-weight meshes, thin filaments, and mesh nodes. Heavy-weight meshes induce degenerative cell reactions. Polyglactin seems to further improve cell proliferation whereas a pressed mesh surface without pores hinders fibroblast growth.

Gastrointestinal stromal tumor (GIST) -- single center experience of prolonged treatment with imatinib.

BACKGROUND: The tyrosine kinase inhibitor imatinib has been introduced into the treatment of gastrointestinal stromal tumors (GIST). Here we report our results of prolonged treatment in comparison to a similar group of GIST patients who had died before imatinib became available. METHODS: Fourteen patients with recurrent or metastatic GIST were treated with imatinib. Clinical data and tumor samples of ten patients from the pre-imatinib era were available for comparison. Comparative genomic hybridisation (CGH) was performed on tumors to identify changes that may predict response to treatment. RESULTS: Fourteen patients were treated, mean treatment time 22.3 months (1 non-response, 2 progression after initial response, 2 stable diseases, 8 partial responses, 1 complete response). Adverse side effects were mild in general. Survival was higher in the treated group (41.1 months vs. 34.8 months in the historical group). Eleven treated patients are alive. CGH analysis showed comparable numbers of chromosomal aberations in both groups. CONCLUSION: Prolonged treatment with imatinib is safe and effective in patients with recurrent or metastatic GIST.

Simultaneous tumour-like, atypical basal cell hyperplasia and acinar adenocarcinoma of the prostate: a comparative morphological and genetic approach.

Basal cell tumours of the prostatic gland are rare, and the classification is difficult. In the present case report, a large, tumour-like proliferation of atypical basaloid cells was found incidentally in a prostatectomy specimen that otherwise contained a conventional acinar adenocarcinoma. The basaloid cells displayed a solid or adenoid-cystic growth pattern and strongly expressed high-molecular-weight cytokeratins and bcl-2. A high Ki-67 index was recorded within the atypical basaloid cells, by far exceeding the one counted in the conventional adenocarcinoma. However, there were no definite criteria for a malignant behaviour of the basal cell tumour. Comparative genomic hybridisation from microdissected tumour cells yielded losses at the short arms of chromosomes 8 and 12 in the conventional adenocarcinoma and a normal karyotype in the basal cell tumour. The pathological findings favoured the diagnosis of an atypical basal cell hyperplasia.

Prognosis factors in incisional hernia surgery: 25 years of experience.

BACKGROUND: Incisional hernia underwent a change from conventional techniques to mesh implantation. The relevance of different factors, like operative technique, mesh material, and patient-related parameters concerning the outcome following mesh repair, are still under debate. METHODS: In a comparative retrospective study of 421 incisional hernia operations on 348 patients, we investigated 241 Mayo procedures and 180 mesh repairs over a 25-year period. In addition to the quality of life following mesh implantation, the prognostic relevance of demographic, preoperative and intraoperative parameters, surgical technique, mesh material, and the surgeon's experience were analysed, both in a univariate and multivariate manner. RESULTS: With a mean follow-up of 9.7+/-8.8 years, the total recurrence rate following Mayo overlap was 37%, in contrast to 15% after mesh implantation (P=0.001). Mesh size was the only significant prognostic factor concerning quality of life following mesh implantation, and 86% of the patients with mesh repair were satisfied. The complication rate was determined significantly by patients' risk factors, size of hernia, operative technique, and the surgeon's experience, whereas the rate of recurrences was significantly influenced by the parameters obesity (BMI>25), size of hernia, and surgical experience. The recurrence rate decreased significantly with surgeon's experience-a minimum of 16 mesh repairs led to a recurrence rate of less than 10%. CONCLUSIONS: Only the mesh repair revealed acceptable recurrence rates with high patient comfort. From a surgical point of view, the most important prognostic factor following mesh repair is the surgeon's experience.

Impact of vasoactive intestinal polypeptide and gastrin-releasing peptide on small bowel microcirculation and mucosal injury after hepatic ischemia/reperfusion in rats.

BACKGROUND AND AIMS: Alterations in microvascular perfusion of the intestine after hepatic ischemia/reperfusion have been suggested as an important cause of postoperative septic complications. We therefore investigated small bowel microcirculation and mucosal injury after liver ischemia/reperfusion in a rat model. Furthermore, we analyzed the effects of the regulatory peptides vasoactive intestinal polypeptide and gastrin-releasing peptide for their splanchnic vasoactivity. METHODS: Hepatic ischemia was induced by clamping of the left hepatic artery and vein for 40 min, followed by 60 min of reperfusion. The control group was treated similarly, but without clamping of the liver vessels. Ten minutes after clamping of the hepatic vessels, vasoactive intestinal polypeptide or gastrin-releasing peptide, respectively, were continuously infused intravenously in the experimental groups. Small bowel microcirculation and mucosal injury were assessed using intravital microscopy and the Chiu-score, respectively. RESULTS: The functional capillary density of the small intestine following ischemia and reperfusion of the left hepatic lobe significantly decreased compared to normal controls in both the mucosa and the smooth intestinal muscle. Red blood cell velocity decreased, whereas leukocyte-endothelium adherence, stasis index and the mucosal injury score increased. Administration of vasoactive intestinal polypeptide resulted in an increase of functional capillary density in the mucosa and of the red blood cell velocity and a decrease in the stasis index. The mucosal injury score was significantly higher in reperfused animals without treatment. The application of gastrin-releasing peptide resulted in an isolated increase of the red blood cell velocity. Leukocyte adherences could not be altered by the regulatory peptides. CONCLUSION: We conclude that hepatic ischemia/reperfusion injury leads to significant alterations of small bowel microcirculation and mucosal injury. Vasoactive intestinal polypeptide and gastrin-releasing peptide attenuate the damage in a different manner.

Bilateral thoracic extraadrenal myelolipoma.

Myelolipoma commonly occurs in the adrenal gland and is composed of both adipose tissue and normal hematopoietic elements. Extraadrenal myelolipoma may occur in the retroperitoneum, stomach, liver, lung, and in 3% of cases even in the mediastinum. We present a 65-year-old female patient with unspecific clinical symptoms. Routine chest roentgenograms revealed bilateral widening of the posterior mediastinum. Computed tomography showed bilateral, paravertebral lesions of 4.5 and 6.5 cm in diameter, respectively. After surgical removal, bilateral thoracic myelolipoma was pathomorphologically diagnosed. The imaging differential diagnosis of bilateral solid lesions in the posterior mediastinum including lymph node metastases, lymphomas, neurogenic tumors and extramedullary hematopoietic tumors is discussed.