[Recurrent bleeding of a duodenal ulcer in a 55-year-old man after heart transplantation]. / Rezidivierende Blutungen aus einem Ulcus duodeni bei einem 55-jährigen Patienten nach Herztransplantation.

Duodenal ulcers are most often caused by Helicobacter pylori (HP) infection, followed by nonsteroidal anti-inflammatory drugs and hypoperfusion. Posttransplant lymphoproliferative disorder (PTLD) occurs in about 1-6.3% of patients with a heart transplant under immunosuppression therapy. Up to 25% of cases of PTLD have gastrointestinal involvement. Due to a wide spectrum of clinical symptoms and pathological entities, the diagnosis can be challenging. We report the case of a 55-year-old man 12 years after receiving a heart transplant being treated with immunosuppressive agents (tacrolimus) who presented with recurrent bleeding from peptic duodeni. Immunohistochemistry revealed a rare Epstein-Barr-virus-associated polymorphic PTLD. Rarely, PTLD can manifest only with isolated lesions of the duodenal bulb. The course was progressive, going from an incidental finding requiring transfusion anemia to a perforation within 1 month. Repeated endoscopic interventions were unsuccessful. After a surgical intervention the patient died in the course of multiple organ failure. Retrospectively, a reduction of immunosuppression in polymorphic PTLD would have been a treatment option.

[A very rare submucosal tumour of the rectum - primary endometrioid adenocarcinoma of the rectum wall]. / Ein sehr seltener submuköser Tumor des Rektums - primäres endometrioides Adenokarzinom der Rektumwand.

A 56-year-old female, with a past history of hysterectomy 13 years previously due to uterine myomata, presented with complaints of pain around the anus of a few months duration. Three years previously she underwent a colonoscopy, which was found to be unremarkable. A high suspicion of a submucosal tumour of the rectum in endoscopic examinations was confirmed by endoscopic ultrasound. The biopsy could not specify the tumour characteristics. Based on the diagnosis of a 4 cm submucosal tumour with infiltration of bowel wall and regional lymph nodes the affected segment was resected. Histolopathology revealed an adenocarcinoma involving tissue from the outer bowel wall to the submucosa. However, immunohistochemistry revealed an endometrioid adenocarcinoma, suspicious for primary endometrioid adenocarcinoma of the ovary with rectum metastasis in the absence of a uterus. But this assumption could not be confirmed in the excised ovary. The tumour cells were immunopositive for cytokeratin 7, CA 12 - 5, vimentin and oestrogen receptor, but negative for cytokeratin 20 and CDX-2. Ultimately, we report a very rare case of primary endometrioid adenocarcinoma arising in endometriosis in the rectum wall and presenting as a submucosal tumour.

[Endoscopic resection of a rare gastric adenoma (pyloric gland adenoma) with transition into a well-differentiated adenocarcinoma]. / Endoskopische Resektion eines seltenen Magenadenoms (Pyloric-gland-Adenom) mit Übergang in ein gut differenziertes Adenokarzinom.

We present the case of a 76-year-old lady in whom the work-up for iron-deficiency anaemia resulted in the finding of a giant gastric polyp. The polyp could be completely removed endoscopically. The final histology showed the rare entity of a pyloric gland adenoma with focal transition into a well-differentiated adenocarcinoma. The patient is well after a follow-up of 12 months. Pyloric gland adenoma was first described in 1990. In spite of its benign histological appearance, a transition into adenocarcinoma has been reported in up to 30 % of the cases. Thus, although relatively rare, the gastroenterologist/endoscopist, as well as the pathologist should be aware of the entity of pyloric gland adenoma.

Urokinase plasminogen activator receptor (CD87) expression of tumor-associated macrophages in ductal carcinoma in situ, breast cancer, and resident macrophages of normal breast tissue.

UNLABELLED: Macrophages concentrate urokinase-type plasminogen activator (uPA) at the cell surface by expressing urokinase receptors (uPAR) in order to focus the pericellular space plasminogen-dependent proteolysis important in matrix remodeling and cell movement. This study examines the uPAR levels of tumor-associated macrophages (TAM) of invasive breast carcinomas, of TAMs from ductal carcinoma in situ (DCIS) and of macrophages derived from normal (non-tumor) breast tissue. TAMs from invasive breast carcinomas (n = 30), from DCIS (n = 12), and macrophages from normal breast tissue (n = 30) were cultured and immunocytochemically phenotyped by using a panel of antibodies. Urokinase receptor levels were determined by Western blot analysis and in cell-free supernatants by enzyme-linked immunosorbent assay. Urokinase receptor cell surface fluorescence intensity was determined by FACS and by confocal laser scan microscopy. Urokinase-receptor mRNA was detected by in situ hybridization. TAMs of invasive breast carcinomas and of DCIS possess significantly elevated uPAR levels compared with macrophages derived from normal breast tissue. CONCLUSIONS: activated macrophages with elevated uPAR levels belong to inflammatory areas in close vicinity of infiltrating and non-infiltrating (DCIS) tumor cells. Blood monocytes that possess elevated uPAR-levels may be selectively recruited from the bloodstream to inflammatory sites close to carcinoma cells, and/or breast cancer and precursor lesions may induce elevated uPAR-levels in TAMs by paracrine interactions.

Labour-associated expression of intercellular adhesion molecule-1 (ICAM-1) in placental endothelial cells indicates participation of immunological processes in parturition.

Inflammatory cytokines induce or upregulate de novo expression of cell adhesion molecules on endothelial and epithelial cells. In order to demonstrate inflammatory reactions within placental tissues in association with normal term as well as non-infection-induced preterm labour, the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) was examined by immunohistochemical methods in both trophoblastic villi (n=123) and umbilical cord (n=61). As a result, ICAM-1 immunoreactivity was exclusively localized in the endothelial cells of the fetal vascular system, while VCAM-1 and ELAM-1 were not detected. Whereas ICAM-1 was not expressed in early pregnancy (9-12 weeks of gestation), it could be weakly detected at the end of pregnancy in cases of elective caesarean delivery in the absence of labour, and was significantly more strongly expressed in cases of vaginal delivery after spontaneous onset of normal term labour. Significantly increased immunoreactivity of ICAM-1 within umbilical cord tissues was also found in association with uncontrollable preterm labour in the absence of intrauterine infection which was excluded after histological examination of fetal membranes, umbilical cord and chorionic plate. We conclude that ICAM-1 expression in the endothelium of the fetal vascular system is associated with the presence of labour and reflects participation of immune-inflammatory reactions in labour-promoting mechanisms.

Identification of placental cytokine-producing cells in term and preterm labor.

OBJECTIVE: To determine if the production of proinflammatory cytokines by placentally derived macrophages changes with term and preterm labor and to examine if changes in antigen expression of these cytokines can be detected by immunohistologic methods. METHODS: Enzymatically dispersed placental cell suspensions of the trophoblastic villi, obtained from 16 women with spontaneous term delivery, 16 women with elective cesarean delivery without any labor, and 22 preterm delivering women with labor unresponsive to tocolysis, were fractionated by magnetic-associated-cell-sorting, on the basis of CD11b-antigen expression. Positively and negatively sorted cell fractions were cultured and concentrations of interleukin-6, interleukin-1beta, and tumor-necrosis-factor-alpha were measured in the culture supernatants. Immunohistologic staining was used for identification of cytokine-producing cells within placental tissues. RESULTS: Positively sorted cells obtained from term (median 2027 pg/mL, P = .037) and preterm (median 3628 pg/mL, P = .001) laboring women produced significantly elevated amounts of tumor-necrosis-factor-alpha compared with nonlaboring (median 1088 pg/mL) women at term. Negatively sorted cell fractions obtained from term (median interleukin-1beta 162 pg/mL, P = .031, median interleukin-6 3134 pg/mL, P = .004) and preterm (median interleukin-1beta 934 pg/mL, P = .003, median interleukin-6 5695 pg/mL, P = .001) laboring women produced significantly elevated amounts of interleukin-1beta and interleukin-6 compared with nonlaboring (median interleukin-1beta 29 pg/mL, median interleukin-6 135 pg/mL) women at term. Immunohistologic staining revealed that tumor-necrosis-factor-alpha activity was localized in isolated stromal cells, whereas interleukin-1beta and interleukin-6 were predominantly found in endothelial cells within placental villi. CONCLUSION: The source of labor-associated release of tumor-necrosis-factor-alpha from placental tissues are macrophages, whereas interleukin-1beta and interleukin-6 are released from placental endothelial cells.

Urokinase plasminogen activator induces angiogenesis and tumor vessel invasion in breast cancer.

Urokinase plasminogen activator (uPA) is a proteolytic enzyme implicated in cancer invasion and tumor progression. Urokinase PA and its inhibitor (PAI-1) appear to be new and independent prognostic markers in breast cancer. To investigate how uPA- and PAI-1-levels correlate with angiogenesis and tumor vessel invasion, we counted microvessels and their tumor invasion and determined the uPA- and PAI-1 levels in 42 primary invasive breast carcinomas. 20 Patients had no lymph node metastasis at the time of surgery, while 22 patients had positive nodes. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for CD31 and Factor VIII. After gaining tumor tissue extracts, we determined the uPA- and PAI-1-levels by ELISA. A positive correlation between microvessel density, angioinvasion and uPA- and PAI-1-levels was found. We speculate that high uPA levels may induce tumor neovascularisation, angioinvasion and may cause tumor progression and metastasis. The degradation of the vessel wall by uPA causes a leak. This wall defect may, on the one hand, be the stimulus for endothelial cell proliferation and formation of new blood vessels and, on the other hand, it may be the place of tumor cell entry.

Polo-like kinase: a novel marker of proliferation: correlation with estrogen-receptor expression in human breast cancer.

Previous data have shown that the mRNA-expression of the serin/threonine-kinase polo-like kinase (PLK) is closely correlated with the survival of patients suffering from a subset of malignant tumors. PLK-mRNA and protein-expression are restricted to cells in the cell cycle. PLK-mRNA-transcripts are highly abundant in proliferating cells; no gene expression is found in G0-phase cells. Here we investigated the mRNA- and protein-expression of PLK- and estrogen-receptor (ER) in human breast-carcinoma by northern-blotting, RT-PCR and immunohistochemistry. The expression of MIB-I was determined on serial sections. Analysis of the immunohistochemical data revealed a close correlation between the ER and PLK-expression (r = 0.677; p = 0.001, n = 30). No relationship between the mRNA-expression of ER and PLK was found. Furthermore, no correlation for the protein expression of PLK and MIB-I exists. The influence of estrogen (ES) is known to have proliferative potential. The expression of ER correlates with the ES-plasma-level. In addition, the hormone cycle of premenopausal women undergoes rapid vacillations with varying effects on the proliferating tumor cells, e.g., growth induction. Our results therefore show that ER-expression is not only of therapeutic value for the clinician, but it may also be a tool for determining the tumor proliferation index more precisely by integrating the hormone-mediated proliferation stimulus.

[Experiences with a modified nephrostomy instrument kit in ultrasound-guided kidney fistulization]. / Erfahrungen mit einem modifizierten Nephrostomiebesteck bei ultraschallgeführter Nierenfistelung.

During a period of 24 months, ultrasound-guided percutaneous nephrostomies were performed in 51 patients in the Hospital at Köln-Merheim. The procedure was carried out with a modified nephrostomy instrument manufactured by Angiomed, Ettlingen, according to our own design. The procedure was successful in 49 patients. In one case it had to be abandoned because of lack of patient co-operation. In one patient a pyonephrosis was found and the patient was treated surgically.

Captopril in acute myocardial infarction: beneficial effects on infarct size and arrhythmias.

It is known from experiments that angiotensin-converting enzyme inhibitors can limit infarct size. In a prospective, randomized, placebo-controlled double-blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 and 18 h from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With the exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV, p < 0.05). The number of ventricular premature beats at 24 h from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred seven times in the placebo group, but did not occur in the captopril group. The creatine kinase infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). Mean arterial pressure was reduced by 12 mmHg with captopril treatment. The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.

[Large Brunner adenoma in the duodenal bulb--a case report]. / Grosses Brunner-Adenom im Bulbus duodeni--ein Fallbeispiel.

Benign, proliferative changes of the Brunner's gland are very rare and account for about 10% of duodenal bulb neoplasias. The authors present a case of Brunner's gland adenoma of unusual dimensions (12 x 5 x 2.5 cm). The patient presented with vague epigastric discomfort as isolated symptoms. In this case we performed surgical treatment, including a duodenotomy and polypectomy. Because they are localized in the submucosa small, superficial endoscopic biopsies may fail to confirm the diagnosis. Malignancy seems to occur only very rarely, with only 14 cases reported in the literature. As the majority of Brunner's adenomas are quite small, endoscopic polypectomy will confirm the diagnosis and cure the condition in most cases. Large symptomatic adenomas may require surgical resection.

Captopril in acute myocardial infarction. Beneficial effects on infarct size and arrhythmias.

OBJECTIVE: It is known from experiments that angiotensin converting enzyme (ACE) inhibitors can limit infarct size. We examined the effect in patients. METHODS: In a prospective, randomized, placebo-controlled double blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 hours and 18 hours from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. RESULTS: The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV) (p < 0.05). The number of ventricular premature beats at 24 hours from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred 7 times in the placebo group, but did not occur in the captopril group. The creatine kinase (CK) infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). The mean arterial pressure was reduced by 12 mmHg with captopril treatment. CONCLUSIONS: The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.

[Nuclear localization of heterochromatic regions varies in hyperplastic and preneoplastic lesions of the breast]. / Unterschiedliche intranukleäre Lokalisation von Heterochromatinregionen in hyperplastischen und neoplastischen Läsionen der Mamma.

Previous molecular cytogenetic studies in breast cancer revealed numerous chromosomal changes and identified alterations involving the chromosomes 1 and 16 as early incidents in mammary carcinogenesis. Since both chromosomes reveal pericentromeric heterochromatic areas, these chromosomal alterations might result from instable heterochromatin caused by DNA hypomethylation. In the present study, we investigated whether hyperplastic and neoplastic lesions of the breast differ regarding the distance between the heterochromatic areas of chromosomes 1 and 16 within the nuclei. We hybridized differently fluorescence-labeled DNA samples specific for the heterochromatic regions of chromosomes 1 and 16 to formalin-fixed tissue sections. Histological classification of the lesions was supported by immunohistochemical staining using cytokeratin-specific antibodies. The methylation state of the heterochromatic regions was tested by staining with an antibody specific for methylated cytidin. Our results revealed an increased frequency of paired intranuclear signals specific for chromosomes 1 and 16 in neoplastic lesions (atypical ductal hyperplasia, ductal carcinoma in situ) compared to ductal hyperplasia and normal glandular epithelium. Staining with the methylation-specific antibody reavealed a weaker staining in neoplastic lesions compared to hyperplastic lesions and normal cells. We conclude that atypic ductal hyperplasia represents the histomorphological equivalent for the beginning of tumor genome evolution that progresses in ductal carcinoma in situ and infiltrating carcinoma.

Lack of clinical efficacy of imatinib in metastatic melanoma.

This two-centre phase-II trial aimed at investigating the efficacy of imatinib in metastasised melanoma patients in correlation to the tumour expression profile of the imatinib targets c-kit and platelet-derived growth factor receptor (PDGF-R). The primary study end point was objective response according to RECIST, secondary end points were safety, overall and progression-free survival. In all, 18 patients with treatment-refractory advanced melanoma received imatinib 800 mg day(-1). In 16 evaluable patients no objective responses could be observed. The median overall survival was 3.9 months, the median time to progression was 1.9 months. Tumour biopsy specimens were obtained from 12 patients prior to imatinib therapy and analysed for c-kit, PDGF-Ralpha and -Rbeta expression by immunohistochemistry. In four cases, cell lines established from these tumour specimens were tested for the antiproliferative effects of imatinib and for functional mutations of genes encoding the imatinib target molecules. The tumour specimens stained positive for CD117/c-kit in nine out of 12 cases (75%), for PDGF-Ralpha in seven out of 12 cases (58%) and for PDGF-Rbeta in eight out of 12 cases (67%). The melanoma cell lines showed a heterogenous expression of the imatinib target molecules without functional mutations in the corresponding amino-acid sequences. In vitro imatinib treatment of the cell lines showed no antiproliferative effect. In conclusion, this study did not reveal an efficacy of imatinib in advanced metastatic melanoma, regardless of the expression pattern of the imatinib target molecules c-kit and PDGF-R.

Protein and mRNA expression of uPAR and PAI-1 in myoepithelial cells of early breast cancer lesions and normal breast tissue.

Myoepithelial cells (MEs), which surround ducts and acini of the breast glands, exhibit an anti-invasive phenotype and form a natural border separating proliferating tumour cells of ductal carcinoma in situ (DCIS) from basement membrane (bm) and underlying stroma. Invasion requires penetration of these host cellular and extracellular matrix barriers. This destruction is caused by proteolytic activity of tumour cells and host bystander cells. There is substantial evidence that high concentrations of the urokinase plasminogen-activating system are conducive to tumour cell spread and metastasis. Prompted by the conspicuous absence of studies examining the role of the ME in breast cancer progression, we studied the expression of the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor type-1 (PAI-1) in MEs of 60 DCIS samples. Our results show that nearly all MEs of DCIS and normal breast glands exhibit the uPAR antigen, whereas the PAI-1 antigen was mainly expressed in MEs of high-grade DCIS. In one intermediate DCIS numerous ducts showed an incomplete myoepithelial layer expressing uPAR and PAI-1. We conclude that uPAR in MEs may be necessary to attach them to the bm by uPAR/vitronectin (Vn) interaction. The strong expression of PAI-1, which is known to resolve the uPAR/Vn binding, may be involved in the detachment of MEs of DCIS. Although the role of PAI-1 acting as cell detachment factor could not be demonstrated in our study, we speculate that the loss of the anti-invasive ME layer in DCIS may be triggered by PAI-1 and could be an early sign of subsequent tumour cell infiltration.

[Monstrous, retroperitoneal liposarcoma--a case report]. / Monströses, retroperitoneales Liposarkom--eine Fallbeschreibung.

Liposarcomas comprise about 20% of soft tissue sarcomas and occur in 14% in the retroperitoneal space originating in one third from the perirenal fat. The case of a patient with an extraordinary huge, resectable, well-differentiated retroperitoneal liposarcoma is reported. The presenting symptoms were abdominal pain and distension as well as weight gain. Magneticresonance imaging revealed a huge retroperitoneal tumor suspected of well-differentiated liposarcoma. Curative resection of the tumor could be obtained. Only 50% of all tumors are excised without residual tumor and recurrence, occurring in 90% after 10 years, is the main therapeutic challenge. Since neoadjuvant and adjuvant therapy as well as intraoperative radiotherapy failed to prove prognostic value, curative resection remains the main treatment for primary and recurrent liposarcomas.

[Captopril in acute myocardial infarct: its effect on infarct size and arrhythmias]. / Captopril bei akutem Herzinfarkt: Einfluss auf Infarktgrösse und Rhythmusstörungen.

The effect of captopril on infarct size and arrhythmias was determined in a prospective, randomized, placebo-controlled double-blind study of 46 patients (9 women, 37 men; mean age 61 [38-86] years). Within 2-18 hours of entry into the study these patients received either a slow intravenous bolus injection of 2.5 or 5.0 mg captopril followed by a continuous infusion of 1.5-2.0 mg/h for a period of 48 hours (n = 22), or of a placebo by the same mode of administration (n = 24). The two groups were comparable as to age, infarct site and time of intervention. All patients, except one in each group, also received nitroglycerin (1.2-6.0 mg/h intravenously). QRS complexes were measured to provide a necrosis index. Q-wave amplitudes decreased under captopril (-0.08 +/- 0.04 mV) while increasing under placebo (+0.15 +/- 0.04 mV; P less than 0.05). The number of ventricular extrasystoles in the first 24 hours after onset of treatment or on placebo was 25/h and 9/h, respectively (P less than 0.02). Ventricular fibrillation occurred in 7 patients of the placebo group, in none of the captopril group. Creatine-kinase infarct weight was 59 and 45 gram-equivalents, respectively (placebo vs treated group: not significant). The mean arterial blood pressure fell by 14 mm Hg during the first hour in the captopril group, but by only 3 mm Hg on placebo (P less than 0.01). These results indicate that captopril has a favourable influence on infarct size and electrical stability which is additional to that provided by standard nitroglycerin treatment.

Urokinase and macrophages in tumour angiogenesis.

Recent studies have shown that elevated levels of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) in breast cancer correlate with an increased risk of a reduced relapse-free survival time and shortened overall survival times. Urokinase PA and PAI-1 are independent prognostic indicators for breast cancer. The fact that plasminogen activators are indispensable for tube formation of microvascular cells and that they may induce angiogenesis in vitro strongly suggests a role for uPA and PAI-1 in tumour neovascularisation. Because macrophages and tumour cells produce uPA, we postulate a close collaboration between tumour cells and tumour-associated macrophages in angiogenesis. To investigate how uPA levels and macrophage counts in tumour tissue correlate with angiogenesis, we counted microvessels and determined uPA levels and macrophage content in 42 primary invasive breast carcinomas. Using light microscopy, we highlighted the vessels by staining their endothelium cells immunocytochemically for CD31 and factor VIII and the macrophages for CD68. After obtaining tumour tissue extracts, we determined the uPA and PAI-1 levels by ELISA. A positive correlation between microvessel density, vascular invasion, uPA level, macrophage content and proliferation rate was found.

Angiogenesis and cathepsin expression are prognostic factors in pancreatic adenocarcinoma after curative resection.

BACKGROUND: Curative resection of pancreatic adenocarcinoma is the only clinical parameter related to a favorable prognosis while other clinicopathological parameters fail. To evaluate whether angiogenesis, vascular endothelial growth factor (VEGF) or certain tumor proteases, e.g., cathepsin B (CTSB) and L (CTSL), are factors of prognostic relevance, we investigated their expression in patients with long- and short-term survival after curative resection (RO) because of pancreatic adenocarcinoma. METHODS: Twenty-nine tissue samples from patients with adenocarcinoma of the pancreas were examined. The patients were selected in a long-term survival group with a survival > or = 24 mo (n = 18) and a shortterm survival group of patients, who died within 8 mo after surgery because of their malignancy (n = 11). The microvessel quantification was performed immunohistochemically using a monoclonal anti-CD34 antibody. VEGF, CTSB, and CTSL expressions was studied using polyclonal antibodies (PAbs). RESULTS: The median microvessel density (MVD) was 75 (range 39-182). MVD correlated significantly with the survival time after surgery (p = 0.0132) but not with clinicopathological parameters. In cancer cells, VEGF was positive in 82.8% and showed significant correlation with the MVD (p = 0.0002) and survival time (p = 0.0395). Positive immunoreactivity could be obtained for 96.5% for CTSB and 84.2% for CTSL. Expression of both proteases correlated significantly with the survival time after surgery (CTSB p = 0.0002, CTSL p = 0.0001). Furthermore, CTSB expression correlated with invasion of the perineural space. Thus, a short postoperative survival correlated with a high MVD, and highly expressed VEGF, CTSB, and CTSL. No significant correlation between MVD, VEGF, as well as CTSL and clinicopathological parameters was found. For routinely assessed markers (e.g., TNM-stage, UICC-stage, and so on) no significant correlation with survival time was found in this small group of patients. CONCLUSION: These findings indicate that the MVD, VEGF, CTSB, and CTSL are prognostic factors after curative resection, whereas other parameters (TNM, UICC, and so on) failed to show prognostic relevance in our group of patients. Furthermore, the correlation between MVD and VEGF underlines the importance of this growth factor for angiogenesis and tumor growth. The correlation between CTSB and perineural invasion demonstrates the involvement of cathepsins in local tumor invasion.