Showing papers by "J. R. Siewert published in 2005"

Prognostic relevance of systematic lymph node dissection in gastric carcinoma

Abstract: In a prospective multicentre study of 2394 patients with gastric carcinoma the prognostic relevance of systematic lymph node dissection was evaluated Of 1654 patients undergoing resection, 558 had a standard lymph node dissection, defined as fewer than 26 nodes in the specimen, and 1096 underwent radical lymphadenectomy, ie 26 or more nodes in the specimen Radical dissection signficantly improved the survival rate in patients with Union Internacional Contra la Cancrum (UICC) stages II and IIIA tumours Multivariate analysis identified radical dissection as an independent prognostic factor in the subgroups of patients with UICC tumour stages II and IIIA Radical dissection conferred no survival advantage in patients with pN2 tumours There was no significant difference in morbidity and mortality rates between radical and standard lymph node dissection Radical lymphadenectomy improves survival in patients with UICC gastric cancer stages II and IIIA, and should be the recommended treatment for such patients

Ratio of invaded to removed lymph nodes as a predictor of survival in squamous cell carcinoma of the oesophagus

Abstract: Prognostic factors that may alter the indications for primary surgical resection or that can be influenced by the extent of the procedure were analysed in a homogeneous group of 186 patients with squamous cell carcinoma of the oesophagus. All patients underwent standardized en bloc oesophagectomy and lymph node dissection with prospective documentation of the histopathological findings; follow-up was complete. Multivariate analysis identified the Union Internacional Contra la Cancrum R category (i.e. the presence of residual tumour after resection) as the most important independent prognostic factor (P< 0.001) followed by the ratio of invaded to removed lymph nodes (P< 0.001). These data suggest that only patients in whom R0 resection can be anticipated based on preoperative assessment should undergo primary resection for oesophageal cancer. Extended lymphadenectomy may improve survival in patients with a limited number of invaded mediastinal nodes.

Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases

Abstract: A retrospective immunohistological analysis of 100 patients with pT1-3 N0 and pT1-3 N1 gastric adenocarcinoma demonstrated a high frequency of micro-involvement in the removed lymph nodes. The presence of three or more tumour cells in more than 10 per cent of the lymph nodes was of significant prognostic value in the pN0 cases. Multivariate analysis identified micro-involvement as an independent prognostic factor. The results explain why patients benefit from lymphadenectomy even if the removed lymph nodes are not involved by tumour (pN0) in routine histological examination. The frequent occurrence of micro-involvement is a strong argument favouring routine D2 lymph node dissection in gastric cancer surgery in patients with lymph node metastasis.

Preoperative chemotherapy for stage III–IV gastric carcinoma: Feasibility, response and outcome after complete resection

Abstract: Despite extensive resection and systematic lymphadenectomy the prognosis of patients with locally advanced gastric carcinoma remains poor. The effect of preoperative outpatient chemotherapy with etoposide, doxorubicin and cisplatin was evaluated prospectively in 30 patients who had been shown by preoperative staging (including endosonography and surgical laparoscopy) to have gastric carcinoma stages IIIA, IIIB or IV. Haematological side-effects were common and necessitated hospitalization in 13 of 30 patients. Complete clinical response to neoadjuvant therapy was observed in eight of 27 evaluable patients. Resection was performed in 27 of 30 patients, with complete macroscopic and microscopic tumour removal in 24. There were no deaths and no major morbidity following operation. On multivariate analysis complete clinical response (P<0.01) and complete tumour resection (P<0.01) were the major independent predictors of long-term survival after neoadjuvant chemotherapy. Actuarial survival after complete tumour removal was superior with neoadjuvant therapy compared with results in an age-, sex- and tumour stage-matched control population who had primary resection (P=0.07). Recurrence occurred in 17 of 23 evaluable patients who had complete tumour removal, with relapse in the tumour bed or area of lymphatic drainage in 11. These data show that neoadjuvant therapy in patients with locally advanced gastric carcinoma is feasible and appears to increase the rate of complete tumour removal. More powerful and less toxic regimens are, however, required to improve the response rate and to delay or avoid recurrence after neoadjuvant chemotherapy.

Preoperative assessment of lymph node metastases in patients with gastric cancer: evaluation of the Maruyama computer program.

Abstract: The probability of survival of patients with gastric cancer depends upon depth of wall penetration by the primary tumour and metastatic lymph node burden. Radical lymphadenectomy may lead to prolonged survival but with increased morbidity. A computer program from Maruyama, National Cancer Centre, Tokyo enables evaluation of individual survival time and infiltration of lymph nodes, This analysis was applied to a German population. Computer-aided predictions were determined retrospectively using the prognostic factors of sex, age, Borrmann classification, histology, depth of wall penetration, location and diameter of the tumour. Data were collected from 222 patients at the Technical University of Munich (median age 66 years, sex ratio (M:F) 2:1), who had been operated on (72 per cent total gastrectomy, 28 per cent subtotal gastrectomy) for gastric cancer. The predicted results were compared with the postoperative pathological findings. The prediction of node metastases was highly accurate (lymph nodes 13–16, 96 per cent; 7–12, 89 per cent; 1–6, 82 per cent). These computer predictions may provide perioperative information of therapeutic value.

Number of lymph node metastases is significantly associated with survival in patients with radically resected carcinoma of the ampulla of Vater

Abstract: Between 1983 and 1994, 66 patients with cancer of the ampulla of Vater were studied to identify prognostic factors and determine who might benefit from radical resection. Three patients (4.5 per cent) died after operation. Radical resection including lymphadenectomy resulted in potentially curative (R0) resection in 92 per cent. The rate of nodal positivity increased with tumour diameter. Patients with up to two positive lymph nodes had a more favourable prognosis than other patients (P < 0.001). Median survival time for all patients was 41 months; the 5-year survival rate was 35 per cent. Radical resection and lymphadenectomy should therefore be the treatment of choice for patients with tumours of the ampulla of Vater.

Anterior versus posterior reconstruction after transhiatal oesophagectomy: A randomized controlled trial

Abstract: In a prospective randomized trial the clinical results after transhiatal oesophagectomy with reconstruction in the anterior mediastinum (51 patients) or posterior mediastinum (45 patients) were compared. There were no differences in age, preoperative risk factors, tumour stage and local (surgical) complications between the two groups. However, reconstruction in the posterior mediastinum was associated with significantly fewer days spent in the intensive therapy unit (9 versus 14), fewer cardiopulmonary complications (13 versus 25 per cent) and lower mortality (30-day mortality rate 2 versus 6 per cent; hospital mortality rate 4 versus 10 per cent). These data show superiority of reconstruction in the posterior mediastinum after transhiatal oesophagectomy. This route is strongly recommended, particularly for patients with cardiopulmonary risk factors.

Association of pretherapeutic expression of chemotherapy-related genes with response to neoadjuvant chemotherapy in Barrett carcinoma.

Abstract: Purpose: We analyzed pretherapeutic gene expression patterns of patients with locally advanced adenocarcinomas of the esophagus with regard to response to neoadjuvant chemotherapy. Experimental Design: Pretherapeutic, paraffin-embedded, formalin-fixed endoscopic esophageal tumor biopsies of 38 patients with locally advanced esophageal adenocarcinomas (Barrett adenocarcinoma) were included. All patients underwent two cycles of cisplatin and 5-fluorouracil (5-FU) therapy with or without additional paclitaxel followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU metabolism-associated genes thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, MAP7 , and ELF3 , of platinum- and taxane-related genes caldesmon, ERCC1, ERCC4, HER-2/neu , and GADD45 , and of multidrug resistance gene MRP1 were determined using real-time reverse transcriptase-PCR. Expression levels were correlated with response to chemotherapy, histopathologically assessed in surgically resected specimens. Results: Responding patients showed significantly higher pretherapeutic expression levels of MTHFR ( P = 0.012), caldesmon ( P = 0.016), and MRP1 ( P = 0.007). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery ( P = 0.013 and P = 0.015, respectively). Additionally, investigation of intratumoral heterogeneity of gene expression of relevant genes ( MTHFR, caldesmon, HER-2/neu, ERCC4 , and MRP1 ), verified in nine untreated Barrett adenocarcinomas by examination of five distinct tumor areas, revealed no significant heterogeneity in gene expression indicating that expression profiles obtained from biopsy material may yield a representative genetic expression profile of total tumor tissue. Conclusions: Our results indicate that determination of mRNA levels of few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced Barrett adenocarcinoma.

COX2 expression, angiogenesis, proliferation and survival in Barrett's cancer.

Abstract: Objectives To examine COX2 expression and its relation to angiogenesis, Ki67 and Bcl2 expression in Barrett's cancer. Methods Specimens from 48 R0-resected Barrett's adenocarcinoma were immunostained for cyclooxygenase 2 (COX2), CD 31 and α-sm actin to discriminate between mature and immature vessels, Mib-1 and Bcl2. COX2 staining, angiogenesis, Ki67 expression and Bcl2 expression were also measured. Results COX2 expression was increased in 25 of 48 cases. There was no significant correlation between COX2 expression and age, sex and tumor differentiation. A significant association was found between lymph node positive cases and elevated COX2 expression ( p =0.008). The percentage of Ki67 positive cancer cells was 43.8% (range 15.4–67.5%) in the low COX2 group and 57.8% (range 12.0–84.6%) in the high COX2 group. The difference was statistically significant ( p =0.046). The median neovascularisation coefficient in the low COX2 group was 11.68 (range 8.22–43.64) and 25.47 (range 8–38.3) in the high COX2 group. The difference was statistically significant ( p =0.012). A significant difference in survival was observed between patients in the COX2 low category when compared with the COX2 high category (log-rank test p =0.013). Conclusions Elevated COX2 expression is associated with lymph-node metastases and reduced survival in Barrett's cancer. This appears to be related to the induction of angiogenesis and proliferation.

The modified AFP score: an attempt to make the results of anti-reflux surgery comparable.

Abstract: Comparison of different strategies in anti-reflux therapy is complicated by wide variations in patient selection and in the criteria employed to assess outcome. A modification of the classification system originally developed by Bancewicz et al. was used to grade a series of 57 patients before and after fundoplication (primary reflux group). An additional group of 39 patients with an unsatisfactory result after previous Nissen fundoplication (failed Nissen group) were assessed before and after reoperation. The classification system used comprises three elements: the A element depicts gastro-oesophageal anatomy based on the findings at endoscopy: the F element codes the amount of acid reflux by means of 24-h intra-oesophageal pH monitoring; and the P element describes mucosal abnormalities. The overall severity was quantified by means of a score on a scale from 0 to 10. The mean preoperative score in the primary reflux group was 5.45 and in the failed Nissen group 7.3. After fundoplication, this was reduced to 1.07 and 1.30, respectively. In general, there was good correlation between the results of the three elements under consideration, pointing to a potential pathophysiological inter-relationship. Marked individual variation did occasionally occur. The AFP system enabled a detailed description of the preoperative and postoperative condition of the patient, and proved easy to use in clinical practice. Its employment is recommended as an objective means of comparing the value of different treatment strategies.

Current and future concepts of abdominal sepsis.

Abstract: Abdominal sepsis, intraabdominal infection, and peritonitis are often used synonymously. Some authors, however, differentiate between peritonitis as the localized equivalent of the systemic inflammatory response syndrome (SIRS) and intraabdominal infection as the localized equivalent of systemic sepsis [1, 2, 3, 4]. Peritonitis denotes intraabdominal infection caused by microbial pathogens or their products [4]. The clinical differentiation of these definitions is difficult in practice and consequently not particularly important for further diagnostic or therapeutic steps. It is important, however, to distinguish whether a patient is suffering from a local intraabdominal infection or an intraabdominal infection with a systemic reaction (abdominal sepsis). Many efforts have been made to classify peritonitis and, as a result, a variety of pathologic conditions have been described that range in severity from local problems to systemic complications [3, 5, 6, 7]. Complex classifications, however, lack transparency and lead to an imprecise gradation of peritonitis. Wittmann et al. presented a simplified scheme that is depicted in Table 1. It differentiates the relatively rare forms of primary and tertiary peritonitis from the more common secondary peritonitis for which surgical intervention is mandatory [4]. Clinical management of sepsis and peritonitis has been the subject of several recent reviews [4, 8, 9, 10, 11, 12, 13]. Table 1 Management of peritonitis. Kind of therapy Focal point Type of analysis References Conservative therapy Antiinflammatory Risk/efficacy of antiinflammatory agents Retrospective 8 Secondary peritonitis Review 4 ICU management Review 9 New concepts Immunology, standard + additive therapy Review 10 Operative therapy Laparotomy/relaparotomy open-abdomen management Secondary peritonitis Review 4 Operative management in ICU Review 9 Relaparotomy for secondary peritonitis Meta-analysis 11 Relaparotomy Report 12 Open-abdomen management Report 13 ICU: intensive care unit.

Esophagectomy as therapeutic principle for squamous cell esophageal cancer

Abstract: The fatalistic approach towards surgical therapy of esophageal squamous cell cancer has been replaced in recent years by a more differentiated view. This was triggered by the establishment of individualized therapeutic modalities based on tumor stage, tumor location, general patient status, and comorbidity. Despite advances in nonsurgical therapy of squamous cell esophageal cancer, esophagectomy remains the central therapeutic modality. Primary subtotal en-bloc esophagectomy with lymphadenectomy is the only curative option with a high likelihood of success for resectable tumors (uT1-3 categories) located below the level of the tracheal bifurcation and for early more proximal tumors. In patients with locally advanced tumors at or above the level of the tracheal bifurcation, surgical resection can still cure those who respond to neoadjuvant radiochemotherapy. Preoperative "conditioning" of risk patients, surgical safety strategies in risk situations, and standardization of both the operative procedure and the perioperative management have resulted in a marked reduction of the previously substantial postoperative mortality to below 3% in experienced centers. In our own experience of 900 esophagectomies for squamous cell esophageal cancer, the 5-year survival rate rose from about 20% to more than 50% in the last two decades. Esophagectomy thus has become a safe operation and remains the only therapeutic option offering cure for a substantial proportion of patients with squamous cell cancer of the esophagus.

Abdomino-rechts-thorakale Ösophagusresektion mit intrathorakaler Anastomose beim Barrett-Karzinom

Abstract: Die abdomino-rechts-thorakale Osophagektomie (Lewis-Tanner-Zugang) gewinnt in modifizierter Technik zunehmend an Popularitat als operativer Eingriff der Wahl beim resektablen Adenokarzinom des distalen Osophagus (sog. Barrett-Karzinom). Die technischen Details der abdomino-rechts-thorakalen Osophagusresektion und Wiederherstellung der Intestinalpassage durch Magenschlauch mit hoher intrathorakaler Anastomosierung, so wie sie sich in unserer Klinik in den letzten Jahren bewahrt hat, wird im Detail dargestellt.

Individualized indication for neoadjuvant treatment based on metabolic response Assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in adenocarcinoma of the esophago-gastric junction (AEG)

Abstract: 4041 Background: FGD-PET was found to be a valuable tool for the prediction of response during neoadjuvant chemotherapy (CTx) in locally advanced AEG. Histological responses were seen in 53% of met...

Barrett-Ösophagus

Abstract: Einleitung Es wird allgemein anerkannt, dass lange Segmente einer Barrett-Mukosa durch eine gastroosophageale Refluxkrankheit (GERD) im Endstadium verursacht werden. Jedoch ist noch wenig bekannt uber die Korrelation der Schwere der Refluxkrankheit und dem Ausmas einer intestinalen Metaplasie.

Reoperation for thyroid cancer

Abstract: Reoperation for thyroid cancer needs to consider patient-, tumor- and therapy-related aspects as well as present diagnostic results. Reoperation because of thyroid remnants, persistence of the primary tumor and lymph node metastasis (completion surgery) has to be distinguished from reoperation due to locoregional recurrence (primary tumor, lymph nodes). The primary surgical strategy should avoid the need for reoperation. The extent of reoperation is related to the extent of primary surgery, stage, and distant metastasis. The timing and indication of reoperation for differentiated thyroid carcinoma in an interdisciplinary multimodal treatment setting depends on diagnostic radioiodine scans and radioiodine therapy. Long-term, recurrence-free survival is achieved by sufficiently radical surgery with acceptable morbidity, including all additive or adjuvant treatment options.

Prophylaktische Chirurgie des Magens

Abstract: Prophylaktische Eingriffe am Magen setzen den Nachweis molekularer oder histopathologischer pramaligner Veranderungen mit einem hohen Magenkarzinomrisiko voraus. Der Nachweis einer E-Cadherin-Keimbahnmutation geht mit einem 70–80%igen Lebenszeitrisiko fur ein diffuses Magenkarzinom, der Nachweis einer hochgradigen intraepithelialen Neoplasie mit einem 60–70%igem Magenkarzinomrisiko einher. Andere pramaligne Veranderungen wie das HNPCC-Syndrom (Magenkarzinome mit 5% an 3. Stelle) sowie eine geringgradige intraepitheliale Neoplasie (ca. 10%iges Magenkarzinomrisiko) stellen moderate Risikofaktoren fur die Magenkarzinomentstehung dar. Sie rechtfertigen keine prophylaktisch-chirurgischen wohl aber Fruherkennungsmasnahmen und bei Nachweis einer hochgradigen intraepithelialen Neoplasie bzw. eines Fruhkarzinoms die Option einer erweiterten Radikalitat im Sinne einer totalen Gastrektomie anstelle einer subtotalen Resektion. Eine positive Magenkarzinomfamilienanamnese sowie eine fruhe Magenkarzinommanifestation stellen Risikofaktoren dar, die bei der Indikationsstellung einer prophylaktischen Gastrektomie oder erweiterten Radikalitat berucksichtigt werden sollten.

Microarray-Genexpressionsanalyse zur Prädiktion der Response einer neoadjuvanten Radiochemotherapie bei lokal fortgeschrittenen Rektumkarzinomen

Abstract: Introduction: Neoadjuvant radiochemotherapy has become a standard treatment for locally advanced rectal cancer. Unfortunately, only app. 30%–50% of the patients shows histopathological response. Pretherapeutic response prediction would be of significant clinical relevance, but is currently not available. Patients and methods: During a phase II trial of neoadjuvant radiochemotherapy for patients with locally advanced rectal cancer pretherapeutic biopsies of 33 patients were available for microarray analyses. After RNA extraction and amplification gene chip analysis was done with the Human Genom U133 chip (Affymetrix). Results: Histopathological evaluation of response prediction showed a regression grade I or II (responder) in 39% (13/33) of the cases, in 43% (14/33) of the cases a regression grade III (partial responder) was found, and in 18% (6/33) a regression grade IV or V (non-responder). Statistical analysis based on 24 differentially expressed genes distinguished clearly between responders and partial or non- responders. Furthermore, a significant different gene expression profile consisting of 99 genes was found comparing responders and non-responders. Conclusion: Microarray based analyses of pretherapeutic biopsies identified responders and non-responders of neoadjuvant radiochemotherapy. This way of response prediction could help to individualize cancer therapy in the future.

Präoperativer Nachweis freier peritonealer Tumorzellen in kurativ resezierten Magenkarzinomen UICC Stadium I

Abstract: Introduction: The dissemination of free peritoneal tumor cells (FPTC) in the process of metastasis is understood as an event, which occurs by continous tumor progression of an serosa invading, invasive carcinoma. We examined, if free peritoneal tumor cells were detectable in patients with gastric carcinoma UICC stage I and if these cells have prognostic impact. Methods: Peritoneal lavage was performed in 164 patients with gastric carcinoma stage I during 1987 and 2001. Immunocytochemical staining with the antibody directed against Ber-Ep4 after centrifugation of the peritoneal fluid was used for the evaluation of free peritoneal tumour cells. The median follow-up time was 70 months. Results: Fourteen patients (9%) had immunocytochemical detected, free peritoneal tumor cells (FPTC) in the examined peritoneal lavage. Seven patients (7%) with early stage gastric carcinoma (pT1) had FPTC. The 10-year overall survival of patients with FPTC was 89% ± 3% and significantly worse than the survival of patients without detection of FPTC (58% ± 17%) (p < 0,01). Patients with gastric carcinoma at stage I or stage II had in combination with the detcetion of FPTC almost identical 10 year overall survival rates of 58% and 59%, respectively. Multivariate analysis identified the lymph node status (pN), the depth of tumor infitration (pT) and the detection of free peritoneal tumor cells as independent prognostic factors with a relative risk of 10.5 (confidence intervall 79.0–1.4), 8,5 (CI 37.7–1.9) und 4.6 (CI 15.4–1.4). Conclusion: Free peritoneal tumor cells are detectable in gastric carcinoma stage UICC I and have prognostic impact. There is evidence that tumour infiltration of blood and lymph vessels located in the submucosa layer lead to peritoneal tumour spread.

IL-12 und IL-18 als perioperative Risikoanalyse einer letalen Sepsis

Abstract: Postoperative sepsis after major visceral surgery is a severe complication with high mortality. The aim of the study was to find indicators which allow for a detection of high risk patients for septic compli-cations and early predictive parameters for a severe course of abdominal sepsis. The function of monocytes prior to surgery and its significance for postoperative sepsis was examined in 1113 patients. Monocytes from patients developing lethal postoperative sepsis exhibited an impaired secre-tion of IL-12 p70 and IL-12 p40. Preoperative monocyte IL-12 production was identified as a predic-tive factor for lethal outcome.

IL-12 Messung im Vollblutassay als präoperativer Indikator für den letalen Verlauf einer postoperativen Sepsis

Abstract: Aim: A selective preoperative defect in monocyte IL-12 production has been identified as a predictive factor for the lethal outcome of postoperative sepsis. In order to simplify the investigation and to better match the in vivo situation whole-blood was chosen as specimen. In the present study the value of preoperative IL-12 whole-blood levels in predicting the outcome of postoperative sepsis was evaluated. Material and methods: Preoperative blood samples of 1441 patients before major abdomi-nal surgery were collected. Whole-blood was incubated with Escherichia coli lipopolysaccharide (LPS) and IL-12 production assessed in supernatants by IL-12 p40 Enzyme Linked Immunosorbant Assay (ELISA). Results: There was no significant correlation between preoperative IL-12 synthesizing capa-bility and sepsis occurence (p = 0.274). However, in a multivariate analysis IL-12 was the only factor associated with lethal outcome of postoperative sepsis (p = 0.004), while neoadjuvant or immunosuppressive pre-treatment (p = 0.671), underlying malignant disease (p = 0.939), type of operation (p = 0.235) and age (p = 0.407) were not significantly associated with death due to sepsis. IL-12 synthesizing capability in patients surviving a postoperative sepsis was significantly higher compared to patients with lethal sepsis (p = 0.006). Summary: IL-12 production after LPS — stimulation of whole blood seems to be a suitable tool for preoperative risk-assessment in the math of elective procedures associated with a high incidence of septic complications.

Regulation angiogener Wachstumsfaktoren (VEGF-A und C) durch Cyclooxygenasen (COX-1 und 2) beim Barrett-Karzinom: Implikationen für Chemopräventionskonzepte

Abstract: Background: Prevention of esophageal adenocarcinomas within the precancerous Barrett’s esophagus by inhibition of the enzyme cyclooxygenase (COX) is recognized as a promising strategy. Regulation of angiogenesis is regarded as one major effect of COX. Materials and Methods: Expression of COX-1 and 2, as well as VEGF-A- and C mRNA was determined in 97 primary resected Barrett’s cancer cases, using RT-PCR. COX protein expression was analyzed using immunhistochemistry. Cell culture experiments using selective inhibitors of COX-1 (SC-560), COX-2 (rofecoxib) or non-selective COX-inhibitors (diclofenac) were assigned to substantiate a potential regulatory relationship between COX and angiogenesis. Results: All carcinomas were positive for COX-1 and COX-2 protein. mRNA expression levels varied between tumor tissues of different patients. The expression levels of both COX-isoforms were strongly correlated with each other as well as with VEGF-A and C. Exposition of esophageal cancer cell lines OE-33 and OSC-1 with COX-inhibiting drugs lead to a significantly reduced expression of VEGF-A and VEGF-C. Conclusions: The variable expression of both COX-isoforms and the strong significant correlation with the proangiogenetic factors VEGF-A and C suggests a pathogenetic role in Barrett’s carcinogenesis, via an effect on angiogenesis and lymphangiogenesis. The functional relationship was substantiated by cell cultural inhibition experiments. Thus, chemoprevention by COX-inhibition may be — at least in part — antiangiogenetic in nature.