Attempts for identifying targeted therapy strategies in metastatic gastric and gastroesopheal junction cancer (upper-GI) revealed that the inhibition of human epidermal growth factor receptor-2 ...(HER2) by monoclonal antibody trastuzumab improves survival of these patients. Hence, adding trastuzumab to doublet chemotherapy has become the standard treatment in this setting. Although the patient survival is extended among clinical trials, the knowledge on the real-time setting is limited. With this retrospective, single center analysis of the patient data of the Medical University of Vienna, we sought to investigate the clinical characteristics and outcome of patients, who received trastuzumab-based chemotherapy for metastatic upper-GI tumor. All patients, who received trastzumab at least once were included to the analysis. Clinical and pathological data were recorded. This search revealed 33 patients. The demographic data was comparable with that of the previous clinical trials. Progression free survival (PFS) was 11 months, whereas overall survival (OS) was 21 months. OS was significantly associated with initially favorable response to treatment. Thirteen patients (39%) received trastuzumab as maintenance treatment with a median cycle number of 6. Toxicity profile was acceptable with only one patient detected to have cardiotoxicity. Taken together, trastuzumab based treatment induced a considerable PFS and OS in metastatic or advanced upper-GI tumors with acceptable toxicity profile. The maintenance therapy with trastuzumab was safe and effective in patients who had initially a favorable response to chemotherapy. The optimal duration of the maintenance therapy should be tested in future clinical trials.
The ability of malignant tumors to metastasize presents a severe challenge in cancer treatment. Lymphatic vessels provide one of the main routes for tumor-metastasis on the way to regional lymph ...nodes. Increasing evidence suggests that inflammatory cells play an important role in tumor-associated angiogenesis and lymphangiogenesis. Recent data show that a specialized sub fraction of tumor-associated macrophages (TAMs) expressing the lymphoangiogenic growth factors vascular endothelial growth factor-C and -D (VEGF-C/D) at the tumor site, is related to lymphangiogenesis, lymphovascular invasion, and lymph node metastasis. Aim of this study was to clear the role of VEGF-C/D expressing TAMs in invasive breast cancer.
One hundred-seven cases of lymph node positive invasive breast cancer were included into the study. Lymphatic microvessel density (LMVD), lymphovascular invasion (LVI), peritumoral inflammatory reaction (PI), and VEGF-C expression in tumors (VEGF-C
T) and TAMs (VEGF-C
C) were evaluated by immunohistochemistry and in situ hybridization.
Significant associations were seen between LMVD and LVI, LMVD and VEGF-C
T, and between VEGF-C
T and VEGF-C
C. Further significant correlations were evaluated between VEGF-C
C/VEGF-C
T and PI as well as between PI and LVI. LVI remained an independent prognostic factor for disease-free survival and overall survival.
Our data provide evidence that the peritumoral inflammatory reaction and VEGF-C expressing TAMs may play an important role in tumor lymphangiogenesis and lymphovascular invasion in invasive breast cancer, implying new potential anti-tumor targets.
Background: Measuring platelet activation in patients has become a potent method to investigate pathophysiological processes. However, the commonly applied markers are sensitive to detrimental ...influences by in vitro platelet activation during blood analysis.
Objectives: Protein isoforms of platelet‐derived thrombospondin‐1 (TSP‐1) were investigated for their potential to identify in vitro platelet activation when monitoring in vivo processes.
Methods: TSP‐1 was determined in plasma, serum or supernatant of purified platelets by ELISA and immunoblotting and was compared with standard markers of platelet activation. A collective of 20 healthy individuals and 30 cancer patients was analyzed.
Results: While in vitro platelet degranulation led to a selective increase in the 200‐kDa full‐length molecule, an in vivo process involving platelet activation such as wound healing resulted in the predominant rise of the 140‐kDa TSP‐1 protein. The physiological ratio of circulating TSP‐1 variants was determined and a cut‐off level at 1.0 was defined to identify plasma samples with artificial in vitro platelet activation exceeding the cut‐off level. In contrast, cancer patients known to frequently exhibit increased in vivo activation of platelets presented with a significantly decreased ratio of TSP‐1 variants as compared with healthy volunteers.
Conclusions: In comparison to standard platelet markers, TSP‐1 constitutes a sensitive and stable parameter suited to monitor in vitro platelet activation. The analysis of TSP‐1 protein isoforms further offers a valuable tool to reliably discriminate between in vitro and in vivo effects, to exclude variability introduced during blood processing and improve clinical monitoring.
Summary
Esophageal stenting with self‐expanding plastic or covered metal stents is believed to be safe and effective. As data on the outcome of patients with long‐term stenting are not available, ...this study was conducted to evaluate the safety and efficacy of long‐term esophageal stenting. From 2002 to 2008, 70 patients with long‐term esophageal stenting for various indications from a prospective database were included into further analysis. The median stent period was 297 (124–1980) days during a mean follow‐up time of 55 ± 52.4 months. Overall complication rate was 30% with a primary success rate of 97.2%. The stent‐related total reintervention rate was 17.1%. There were no correlations between stent characteristics and the risk of complication or migration. No stent‐related death was observed. Our data provide evidence that long‐period esophageal stenting is safe and effective for various indications.
Few data on the influence of lymphatic microvessel density (LMVD) on survival in patients with melanoma are available. The aim of this study was to assess LMVD and blood microvessel density (MVD) in ...tissue samples from 120 patients with melanoma. LMVD was stained with an antibody staining for podoplanin, and blood MVD was assessed by CD31 (PECAM-1)-immunostaining. Survival was determined using univariate and multivariate analysis. A significant association between a high CD31 MVD (but not LMVD) and the presence of lymph node metastases (P=0.007) was observed. Patients with a high LMVD had a significant shorter overall (OS) (P=0.0436) and disease-free survival (DFS) (P=0.0249) in univariate analysis. The survival analysis showed CD31 MVD was a strong prognostic factor for OS and DFS in both uni-and multivariate analyses. Our results demonstrate LMVD as a prognostic factor in malignant melanoma, although its prognostic relevance is much smaller compared with blood MVD.
Inhibitor of differentiation/DNA binding (Id) proteins are transcription factors, involved in cell cycle regulation and neoangiogenesis. Using immunohistochemistry, we investigated the prognostic ...influence of Id-1, Id-2, and Id-3 expression in 89 patients with cervical cancer stage pT(1b). In univariate and multivariate analysis, patients with strong or moderate expression of Id-1 had a significant shorter overall survival time (P = 0.0144, log-rank test) and disease-free survival time (P = 0.0107, log-rank test) compared with those with low or absent Id-1 expression. Id-1 expression is an independent prognostic marker in early-stage cervical cancer.
The goal of this study was to estimate the incidence of temporary and permanent unilateral recurrent laryngeal nerve paralysis (URLNP) after esophagectomies with cervical anastomosis and to determine ...the impact of surgical technique, tumor type, tumor localization and age on the incidence of URLNP. From March 2002 to November 2009, 84 patients underwent a laryngoscopical evaluation before and after esophagectomy with cervical anastomosis prospectively. If the postoperative URLNP recovered within 6 months, the paresis was classified as transient; if not, it was defined as permanent. The results indicate that the overall incidence of postoperative URLNP was 50% (42/84). Twenty-four of the 84 patients (28.6%) showed a transient URLNP. A permanent URLNP was observed in 9 of the 84 patients (10.7%). The remaining 9 of the 84 patients (10.7%) were categorized as paresis with unknown clinical outcome due to missing follow-up. There were significantly more postoperative URLNPs in the group operated by transthoracic esophagectomy than by transhiatal esophagectomy (
p
< 0.001). Multifocal tumors and those localized suprabifurcational showed a higher incidence of postoperative URLNP than unifocal lesions with infrabifurcational localization (
p
= 0.046). Histological type of tumor and patients’ age had no impact on URLNP. The high incidence of URLNP in our study underlines the high risk of URLNP after esophagectomy with cervical anastomosis, and consequently the importance of routine laryngoscopic pre- and postoperative evaluation of the vocal fold motility.
Gastroesophageal adenocarcinoma is a major contributor to global disease burden with poor prognosis even in resectable, regionally limited stages. Feasible prognostic tools are crucial to improve ...patient management, yet scarce.
Disease-related symptoms, patient, tumour, treatment as well as laboratory parameters at initial diagnosis and overall survival (OS) of patients with stage II and III gastroesophageal adenocarcinoma, who were treated between 1990 and 2020 at the Medical University of Vienna, were evaluated in a cross-validation model to develop a feasible risk prediction score.
In total, 628 patients were included in this single-centre analysis. The final score ranked from 0 to 10 and included the factors sex (female +1), age, years (30-59 +1, >60 +2), underweight classified by body mass index (+2), location of the tumour (stomach +1), stage (III +2), stenosis in endoscopy (+1) and weight loss (+1). The score was grouped into low- (0-3), medium- (4-6) and high-risk (7+) subgroups. The median OS were 70.3 95% confidence interval (CI) 51.2-111.8, 23.4 (95% CI 21.2-26.7) and 12.6 (7.0-16.1) months, respectively. The 1-year survival probabilities were 0.88 (95% CI 0.83-0.93), 0.75 (95% CI 0.70-0.79) and 0.54 (95% CI 0.39-0.74), whereas the 5-year survival probabilities were 0.57 (95% CI 0.49-0.66), 0.24 (95% CI 0.20-0.28) and 0.09 (95% CI 0.03-0.28), respectively.
The VIennese risk prediction score for Oesophagogastric Localized Adenocarcinoma (VIOLA) risk prediction score poses a feasible tool for the estimation of OS in patients with regionally limited gastroesophageal adenocarcinoma and, thus, may improve patient management in clinical routine. Prospective analyses should be carried out to confirm our findings.
•Feasible prognostic tools for resectable gastroesophageal cancer are highly needed.•Alarm symptoms, patient and tumour characteristics are associated with prognosis.•The VIOLA risk prediction score is based on these three prognostic categories.•Sex, age, body mass index, location of the tumour, stage, stenosis and weight loss are included.•It is a feasible tool to help clinicians and patients with treatment decisions.
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