Correlation of postoperative survival and angiogenic growth factors in pancreatic carcinoma.

BACKGROUND/AIMS: VEGF (vascular endothelial growth factor) and EGF (epidermal growth factor) are promoters of angiogenesis. It was the aim of this study to investigate a possible coexpression of both growth factors in tumor samples of pancreatic cancer patients in relation to survival after resection of the tumor. METHODOLOGY: We investigated the expression of VEGF165 and EGF in tumor specimen from 19 patients that underwent pancreaticoduodenectomy. Growth factor expression was determined using immunohistochemical methods. RESULTS: Coexpression of VEGF165 and EGF was observed in tumor samples of 9 (47%) patients. VEGF165 and EGF expression in the same tumor correlates significantly (P < 0.05, Fisher-test). UICC stage III pancreatic carcinoma patients with VEGF165 negative tumor cells had a significantly better outcome after surgery compared to UICC stage III patients with VEGF165-positive tumor cells (median survival time 19 months vs. 9 months respectively; P < 0.05, Wilcoxon-test). CONCLUSIONS: Antiangiogenic therapy after surgery for pancreatic cancer may be beneficial, especially for UICC III patients.

Neoadjuvant radio-chemotherapy of adenocarcinoma of the oesophagogastric junction.

BACKGROUND: Recently, neoadjuvant radio-chemotherapy has been demonstrated to induce tumour remission and to prolong survival of patients with locally advanced adenocarcinoma of the oesophagogastric junction.The present study was performed to re-evaluate these data. PATIENTS AND METHOD: A non-randomised trial of multimodal treatment was conducted in order to investigate histopathologic response and survival of patients with adenocarcinoma of the oesophagogastric junction. Treatment consisted of 2 courses of combined chemotherapy with 15 mg/kg 5-fluorouracil on days 1-5 and 75 mg/m(2) cisplatin on day 8 and simultaneous radiation (40 Gy), and a second course starting on day 36, followed by surgery. Abdomino-thoracic oesophagectomy and systematic 2-field lymphadenectomy were performed in patients with Barrett's carcinoma. D2-gastrectomy was performed in patients with type 2 or 3 cancer of the oesophagogastric junction according to the Siewert classification. Probability of survival was estimated using the Kaplan-Meier method. RESULTS: 16 patients with a mean age of 57 years were enrolled in this study. Surgery was performed in 14 of these patients. Response to treatment was evident in 10 patients, but none of these patients had complete histopathologic response. Toxicity related to radiochemotherapy was mild to moderate (37.5%). Perioperative complications, both medical and surgical, occurred in 71.4% of patients. 2 patients had fatal complications. 30-day mortality was 25.4%. The probability of survival at 2 years after surgery was 61.2%. CONCLUSION: Neoadjuvant radio-chemotherapy followed by surgery for cancer of the oesophagogastric junction is associated with a considerable rate of complications. Histopathologic response to radio-chemotherapy is poor. In consequence of these preliminary results, the present study was terminated and the protocol of a future study was modified.

Action of pure ethanol and some alcoholic beverages on the gastric mucosa in healthy humans: a descriptive endoscopic study.

BACKGROUND AND STUDY AIMS: The action of ethanol and alcoholic beverages on the gastric mucosa in healthy humans is largely unknown. This study was designed to compare the effects of beer, white wine, whisky, and the comparable pure ethanol solutions on the gastric and duodenal mucosa in a controlled, randomized, double-blind endoscopic investigation. MATERIALS AND METHODS: In 47 healthy human volunteers, 100 ml of beer, or white wine, or whisky, or a comparable pure ethanol solution (4%, 10%, 40% vol/vol), or isotonic saline as a control, were sprayed on the antral mucosa. The endoscopic appearance of the gastric and duodenal mucosa was assessed before, immediately after, and 30, 60, 240 minutes and 24 hours after instillation. The lesions were scored using an endoscopic grading system (0-5; 0 = normal mucosa and 5 = ten or more hemorrhagic lesions). RESULTS: Pure ethanol damaged the gastric mucosa in a dose-dependent fashion. The lesions occurred within 30 minutes, and reached a maximum after 60 minutes (antral score for 4% = 1.3; 10% = 1.8; 40% 3.8; control = 1.5). Beer, wine and whisky also induced gastric mucosal injury, but to a lesser extent than the comparable ethanol solutions. The 24-hour integrated endoscopic scores for beer and wine were significantly lower (P < 0.05) than the corresponding ethanol content. In the case of pure ethanol > 10% and whisky, the lesions were still present 24 hours later (antral score for 10% = 1.5; 40% = 2.0; whisky = 2.3; control = 0). No lesions were observed in the duodenum. None of the volunteers reported any abdominal pain during the whole investigation. CONCLUSIONS: Intragastric application of 4%, 10%, and 40% vol/vol pure ethanol induces gastric, but not duodenal, mucosal lesions in a dose-dependent fashion. Beer, white wine, and whisky induce gastric mucosal lesions to a lesser degree than the corresponding ethanol content. Lesions induced by higher ethanol concentrations (> 10%) and whisky take more than 24 hours to heal. The lesser damage caused by alcoholic beverages may be due to the protective action of unknown nonalcoholic ingredients.

[Hormone inactive neuroendocrine tumors of the pancreas]. / Hormoninaktive neuroendokrine Tumoren des Pankreas.

During the past 10 years (1987-1996), 842 laparotomies were performed for pancreatic or periampullary neoplasms; in 25 patients (2.9%) a neuroendocrine tumor was diagnosed. In 19 of these 25 patients (76%) a non-functioning endocrine tumor and in 6 patients (24%) a hormone-active tumor (four insulinoma, one gastrinoma, one VIPoma) was found. Of 19 non-functioning neuroendocrine tumors, 14 were malignant. The resection rate of these malignant tumors was 78.6% (11 of 14; 3 resections were palliative); in comparison, the resection rate of ductal pancreatic carcinoma in our hospital was 28.1%. The probability of 5-year survival amounts to 73% after surgical resection in malignant endocrine tumors and to 19% in ductal pancreatic carcinoma (including palliative resections). As it is not always clear whether non-functioning endocrine tumors are benign or malignant, oncological resection is recommended. Adjuvant chemotherapy seems not to be necessary.

HLA class II expression in well differentiated thyroid carcinoma: correlation with clinicopathological features.

Lymphocytic infiltration and aberrant expression of HLA class II antigens on malignant thyroid epithelial cells are assumed to play a relevant role in the immune response against thyroid cancer. Aberrant expression of the HLA class II alpha and beta chains as well as number and distribution of tumor infiltrating lymphocytes were investigated in primary tumors (n = 54) and metastases (n = 4) of well differentiated thyroid carcinomas (follicular carcinoma: n = 26, papillary carcinoma: n = 28). The immunohistochemical findings were correlated with clinicopathological features. An aberrant HLA class II beta chain expression was detected in 9 (28%) papillary carcinomas and 4 (15%) follicular carcinomas. Three HLA class II beta chain positive papillary carcinomas and all follicular carcinomas were negative for the HLA class II alpha chain. All lymph node and distant metastases were negative for both HLA class II alpha and beta chain. Number and distribution of CD45R0+ lymphocytes significantly (p < 0.05, Fisher test) correlated with the aberrant HLA II antigen expression on tumor cells. There was also a significant correlation (p < 0.05, Fisher test) between an aberrant HLA II antigen expression and invasion of the vessels. No correlation was found between aberrant HLA class II expression and the occurrence of lymph nodes or distant metastases. Our findings indicate that the expression of HLA class II antigens on thyroid carcinoma cells is high in the step of invasive growth and that the local immune response towards the HLA class II antigens appears to prevent metastatic spread of HLA II positive tumor cells. There is evidence of different expression of HLA class II chains in follicular and in papillary thyroid carcinomas, which could be a further indicator that in these two subgroups of thyroid carcinomas different changes in the regulatory mechanisms of HLA class II antigen expression occur.

Immunologic findings in tissue of thyroid carcinoma.

We studied the occurrence of DR-antigen (DR-Ag) positive thyroid epithelial cells (TEC), lymphocyte (Ly)-subsets, and antigen-presenting cells (APC) in thyroid carcinoma and the influence of thyroid-stimulating hormone (TSH) on immunologic behavior. Tissue slices from various thyroid carcinomas (n = 14) and endemic goiters (n = 12) were investigated by immunohistochemical methods (PAP/APAAP/FITC) using monoclonal antibodies (MoAbs) against DR-Ag, dendritic cells (APC), endothelial cells, CD-3 Ly, CD-4 Ly, and CD-8 Ly. Monolayers of TEC were cultured in the presence or absence of TSH (0.01 mU/ml) and/or PHA (0.1 mg/ml) over 24 h and screened for DR-Ag expression. Various ranges of DR-Ag expression were detectable in 13 thyroid carcinomas. One thyroid carcinoma and all endemic goiters were DR-Ag-. The amount of APC and local infiltrating Ly correlated very well with the presence and intensity of DR-Ag+ TEC. The lymphocytic CD-4/CD-8 ratio varied in a wide range. No prevalence of Ly-distribution for any type of carcinoma was found. PHA induced DR-Ag expression in all thyroid carcinomas and endemic goiters. This effect was enhanced significantly by TSH. DR-Ag expression on thyroid carcinoma cells may be considered as an immune activating factor. These "neoantigens" may be induced by lymphokines released by the local immune competent cells. The distribution of Ly and DR-Ag+ TEC in thyroid carcinoma seems to represent the individual immunologic response against the tumor. Whether TSH acts as an immune modulator directly or indirectly, as described elsewhere, cannot be concluded from these results.