Expression of insulin-like growth factor receptor type 1 correlate with lymphatic metastases in human gastric cancer.

Most patients with gastric cancer are diagnosed at advanced clinical stages with a high frequency of lymph node metastasis. It is very important to find novel factors for the early diagnostic and prognostic evaluation of gastric cancer. It has been shown that IGF-1R activates mitotic division and inhibits apoptosis of cancer cells through the activation of signaling MAP/ERK and PI3K/Akt-1 pathways. IGF-1R plays a role in cell transformation and maintenance of the phenotype in modified cells. Moreover, an IGF-1 receptor effect influences the processes of adhesion, migration, invasion and metastasis of tumor cells. The aim of the study was to assess the expression of IGF-1R in gastric carcinoma in correlation with selected anatomo-clinical parameters. The study enrolled a group of 49 patients treated surgically for gastric cancer. 28 patients had no lymph node metastases. The expression of the studied proteins was assessed using the immunohistochemical method. We found that the expression of IGF-1R in gastric cancer is associated with lymph node metastasis (p < 0.001), is correlated with worse prognosis and high histological malignancy grade, and is an independent predictor of survival in patients with gastric cancer (p < 0.001). IGF-1R may play an important role in tumor growth and metastasis via the lymphatic pathway.

Platelet activation in patients with advanced gastric cancer.

The aim of this study was to evaluate platelet activation in gastric cancer patients with regard to histopathological classification and the presence of distant metastases, by using platelet morphological parameters: MPV, L-PLT, MPC, as well as quantitative evaluation of surface receptor expression: CD41a, CD61, CD42b, CD62P, by flow cytometry at the resting state and after TRAP activation. In gastric cancer patients higher values of MPV and LP, as well as decreased MPC values were determined. Quantitative evaluation of surface antigen expression also revealed higher number of CD41a, CD61 and CD62P molecules, as compared with the platelets in the control group. Significant decrease of CD42b molecules' number after TRAP incubation, and the increased CD41a, CD61 and CD62P expression also point to the retained reactivation capacity of platelets. Good correlation between morphological parameters and the number of CD62P molecules indicates the usefulness of routine tests in evaluation of platelet activation.

Serum erythropoietin and angiogenetic factors in human colorectal cancer.

AIMS AND BACKGROUND: Erythropoietin, VEGF, VE-cadherin are involved in angiogenesis. Besides that erythropoietin stimulates erythropoiesis and increases haemoglobin and hematocrit levels as well. Moreover, erythropoietin could directly stimulate colorectal cancer cell growth due to the presence of both erythropoietin receptor and erythropoietin production in malignant cells of this neoplasm. Therefore we aimed at measurement and comparison of serum erythropoietin with VEGF, VE-cadherin levels, blood haemoglobin and hematocrit in colorectal cancer patients of different clinicopathological profiles. METHODS: We applied ELISA kits to evaluate preoperative serum levels of endogenous erythropoietin, VEGF and VE-cadherin in samples from 92 colorectal cancer patients and control group of 16 healthy volunteers. RESULTS: Endogenous erythropoietin was significantly elevated in preoperative sera in colorectal cancer patients (p = 0.013) compared with healthy volunteers, however, erythropoietin levels were not significantly higher with the advancement of colorectal cancer. There were significantly higher levels of erythropoietin in the group of anaemic men in comparison to men with normal haemoglobin levels (p < 0.0001). VEGF and VE-cadherin did not correlate with erythropoietin. Erythropoietin levels negatively correlated with haemoglobin and hematocrit levels in all cancer patients; particularly in node positive cancers (N+), moderately differentiated tumours (G2) and deeply invading neoplasms (pT3+pT4). CONCLUSIONS: Erythropoietin levels increase in colorectal cancer but circulating erythropoietin does not associate with progression of the disease. Thus, the use of recombinant erythropoietin seems to be safe. Our results suggest that negative feedback regulation persists between haemoglobin and erythropoietin in colorectal cancer. Production of erythropoietin remains therefore anaemia-associated, hypoxia-dependent and doesn't seem to be autonomic despite abundant expression of erythropoietin by colorectal cancers.

P53 correlates positively with VEGF in preoperative sera of colorectal cancer patients.

Diversity of P53 impact on tumor angiogenesis is due to the fact that wild-type P53 decreases expression of vascular endothelial growth factor (VEGF), but mutant P53 upregulates it. Therefore, we aimed at uncovering relations between preoperative serum levels of VEGF and P53 in colorectal cancer (CRC) patients. Preoperative blood samples of 125 CRC patients and 16 control healthy volunteers were examined with an ELISA-kit for serum P53 levels and VEGF. P53 did not correlate with VEGF in the whole group of CRC patients. However, P53 associated with VEGF in case of colorectal cancer patients, whose serum values of VEGF were higher than in controls (VEGF{H} >5.9333 pg/ml) (r=0.274, p<0.009). We revealed a positive correlation between P53 and VEGF{H} in subsets of poorly differentiated (G3) cancers (p<0.02), lymph node positive (p<0.007), pT3 or pT4 patients (p<0.004) without analogous relation in moderately differentiated (G2) tumors, node negative patients or pT1 or pT2 patients. P53 and IGF-I negatively correlated in all CRC patients (p<0.04) and VEGF{H} individuals of pT3 or pT4 (p<0.05) without any significant linkage in tumors of pT1 or pT2. The positive correlation between serum P53 and VEGF points at mutation of P53 and is a highly probable sign of poor prognosis in colorectal cancer. For now it can not be excluded that the binary analysis of serum P53 and VEGF could help select CRC patients endangered by rapid growth and lymph node metastases.

Poly-C specific ribonuclease activity correlates with increased concentrations of IL-6, IL-8 and sTNFR55/sTNFR75 in plasma of patients with acute pancreatitis.

Plasma pancreatic-type Poly-C specific ribonuclease (P-RNase)-enzyme activity increases in patients with acute pancreatitis (AP) who develop pancreatic necrosis and severe disease course. It is considered as a marker of pancreatic tissue destruction. The aim of this study was to estimate interrelations between major inflammatory cytokines such as: interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor soluble receptors: sTNFR55 and sTNFR75 output, and plasma P-RNase activity. The study was carried out in a group of 56 patients with AP, where 20 developed pancreatic necrosis. It was found that serum P-RNase concentration and levels of all studied inflammatory cytokines significantly increase already in the first day from diagnose of the disease (2.5 folds for P-RNase, 20 for IL-8, about 200 for IL-6 and 1.5 for receptors, respectively). In the first day from admission to hospital, P-RNase activity significantly correlated with plasma concentration of studied inflammatory cytokines. The most pronounced correlation was found for P-RNase and IL-6 in days 1-4 from diagnose, manifested by Pearson correlation r coefficients amounting to 0.86, 0.79, 0.60 and 0.57 respectively (p<0.001). Dividing the studied AP patients into two groups, varying in severity of disease a significant differences in P-RNase and IL-6, IL-8 and sTNFR55/sTNFR75 were found. In patients with acute necrotizing pancreatitis P-RNase significantly correlate with levels of major inflammatory cytokines. Carried out studies suggest that activity of P-RNase reflects severity of inflammatory reaction, which is dependent on development of pancreatic injury and tissue necrosis in AP.

Morphological parameters of the angiogenic response in pancreatic ductal adenocarcinoma--correlation with histological grading and clinical data.

The aim of this study was to evaluate angiogenesis in tissue of the pancreatic ductal adenocarcinoma and to correlate it with histopathological data such as tumour differentiation, tumour size, lymph node metastasis and patients survival. Tumour samples obtained during surgery from 36 patients were immunostained for the presence of blood vessels with monoclonal antibody against the CD31 molecule. Evaluation of microvasculature was perfomed by counting the microvessel density (MVD) in selected areas under light microscope as well as by computer assisted image analysis (CAIA). In the latter, the following parameters were used for assessment of microvessels: mean number/field, mean area of the vessels, total area/field and total perimeter/field. MVD values obtained under optical microscope and with CAIA were highly correlated. All parameters characterising microvasculature in CAIA also revealed a significant correlation with the histological grading of tumours; generally the less differentiated tumours manifested more extensive vascular network. No significant relationship was found between the tumour size and any of the CAIA parameters. The area of vessels (both total and mean values) revealed a significant, inverse correlation with the incidence of lymph node metastases. The same type of correlation was also found between the mean vessel area and the postoperative survival period. The results show that CAIA of microvessels offers new parameters with some predictive value for the outcome of patients with pancreatic cancer.

Prognostic factors of long-term survival after resective procedures for pancreatic cancer.

BACKGROUND/AIMS: Five-year survival rates following surgical resection of pancreatic cancer reported by the leading medical centers do not exceed 25%. It necessitates further extensive research in this area. The aim of the study was to determine prognostic factors of long-term survival after surgical treatment for pancreatic cancer. METHODOLOGY: From 1980 to 1999, 212 patients underwent surgical resection for pancreatic carcinoma. Statistical analysis of prognostic factors of long-term survival after pancreatic cancer surgery estimated by Kaplan-Meier method was carried out using multiple regression model. RESULTS: A group of 212 patients underwent surgery, where 98 had Whipple's resection, 50 Traverso, 35 total pancreatic resections, 25 left subtotal resections, and the remaining 4 segmental pancreatic body resections. Perioperative mortality was below 8%, 5-year survival approximately 15%, increasing to 65% in patients with early cancer. It was observed, that the following prognostic factors influenced the long-term survival rate: tumor size, localization, histopathologic type, and metastases to lymph nodes. The type and extent of surgery was of significance in the case of small neoplasms. CONCLUSIONS: Based on the analysis carried out, the authors conclude that the main prognostic factors for long-term survival after pancreatic cancer surgery are related to the tumor itself and show associations with the natural development biology.

Hypertrophic gastritis, primary diffuse G-cell hyperplasia and pancreatic metaplasia of the gastric mucosa (pseudo-Zollinger-Ellison syndrome)--case report.

We report a case of pseudo-Zollinger-Ellison syndrome in a 17-year-old man presenting with gastrin levels exceeding 2000 pmol/l and BAO 24 mEq/hr. Histologically, apart from hypertrophic gastritis with the thickening of mucosal folds and diffuse G-cell hyperplasia, gastric mucosa was found to contain foci of pancreatic metaplasia.

Mixed (ductulo-endocrine, amphocrine) carcinoma of the pancreas. Report of a case and some remarks on the histogenesis of pancreatic neoplasms.

We report a case of a 42-year-old woman undergoing surgery due to mixed ductulo-endocrine carcinoma of the pancreas, and in this context we make some remarks on the histogenesis of pancreatic neoplasms.

Does extended lymphadenectomy improve survival of pancreatic cancer patients?

PURPOSE: Aim of the study was to assess the value of extended lymphadenectomy for pancreatic cancer. MATERIALS AND METHODS: A retrospective analysis of 201 patients with pancreatic and ampullary cancer who underwent pancreatectomy with standard or extended lymph node dissection were analysed in order to compare the rate of perioperative complications and 5-year survival. RESULTS: Of 201 patients treated, 65 (32%) underwent standard (group I) and 136 (68%) extended (group II) lymphadenectomy. These two groups were similar with regard to age, gender, tumour location, advancement and radicality of performed resection. The mean operating time in the extended lymphadenectomy group was longer (383 +/- 81 min) compared to the standard group (357 +/- 64 min) but observed difference was insignificant. Similarly, there were no significant differences with respect to transfused blood and plasma units. The mean number of resected lymph nodes was significantly (p < 0.001) higher in group II (29.0 +/- 17.7) compared to group I (13.0 +/- 7.4). The overall morbidity and mortality rates were 43% and 6.9%, respectively without significant differences between both groups. The overall 5-year survival for pancreatic and ampullary cancer was 16.7% and 67.6% respectively, and was similar regardless the type of performed lymphadenectomy. Patients with node-negative pancreatic cancer following extended lymphadenectomy had significantly higher (p < 0.01) 5-year survival (48%) compared to the standard resection (22%). CONCLUSIONS: Extended lymphadenectomy can be performed with similar morbidity and mortality rates compared to the standard resection. Benefits of 5-year survival can be achieved only in a limited group of patients with non-advanced pancreatic cancer.

[A case of isolated gallbladder rupture after blunt abdominal trauma]. / Przypadek izolowanego pekniecia pecherzyka zólciowego w nastepstwie tepego urazu jamy brzusznej.

Isolated injury of gall bladder as a result of blunt abdominal trauma is very rare. We report a case of 39 year old man, who was admitted to our Clinic during emergency. He presented upper right quadrant abdominal pain, increasing on palpation and guarding. Ultrasound examination showed fluid under liver. Disruption of the neck of the gall bladder was found during laparotomy. Cholecystectomy was performed. Patient was discharged from hospital five days after the operation.

Long-term results of pancreatic cancer surgery.

Despite of growing incidence of pancreatic cancer and dynamic development of modern diagnostic methods, long-term treatment results are still unsatisfying. The aim of the study is the assessment of long-term outcome of pancreatic cancer surgery. Group of 621 patients hospitalized between 1972-1999 was analyzed. Pancreatic resection was performed in 34.1% (n = 212) patients, and in 65.9% (n = 409) cases a palliative bypass procedure was carried out. Increased number of resective procedures (from 6.2% to 40.1%) in the recent years was observed with lower perioperative mortality rates (from 20% to below 5%). The analysis of the long-term results of surgical treatment for pancreatic cancer showed significant improvement of the overall 5-year survival from 4.2% to 17.1% in the recent years. Based on the carried out analysis the authors conclude, that pancreatic cancer surgery performed by the experienced surgeon improves long-term results lowering to minimum the rates of complications.

[Abrikosov's tumor of the esophagus]. / Guz abrikosowa przelyku.

The authors are reporting a case of Abrikosov's tumor of the oesophagus (myoblastoma granulocellulare, granular cell tumor, GCT). Due to the rare incidence of these lesions, they are also presenting general state of knowledge on these particular tumors based on the literature, diagnostic methods and treatment.

[Hormonal islet cell tumors. Proposition of a diagnostic-therapeutic model]. / Guzy hormonalnie czynne trzustki. Propozycja modelu diagnostyczno-terapeutycznego.

Islet cell tumors make a serious therapeutic problem due to their specific clinical presentation and the necessity of applying a variety of multidisciplinary diagnostic and therapeutic methods. The authors present their own algorithm for diagnosing and treatment of islet-cell tumors worked out basing on many-year experience.

Effects of perioperative immunostimulating nutritional therapy on the phagocytic activity of blood platelets in patients with various clinical stages of gastric cancer.

PURPOSE: The aim of this study was to evaluate the total blood platelets count, fraction of phagocytizing thrombocytes (PhT%), and phagocytic index of thrombocytes (PhIT) in gastric cancer considering the stage of the disease, and perioperative immunonutrition support. METHODS: Our study included 44 patients operated for gastric cancer divided into 2 groups depending on the clinical stage, and 40 healthy volunteers -a control group. Group I included 18 patients with stage I-III locoregional malignancies and Group II included 26 patients with stage IV peritoneal dissemination. All patients received immunonutrition during the perioperative period. The phagocytic activity of blood platelets was assessed by measuring PhT% and PhIT prior to and after nutritional therapy. RESULTS: In Group I, the pre-treatment PhT% and PhIT amounted to 1.08 and 0.99, respectively, and 1.26, and 1.1 after the therapy (p<0.01). In Group II, pre-treatment PhT% and PhIT were 1.12 and 0.97, after 1.18 and 1.06, respectively (p<0.05). In the controls, PhT% and PhIT were 2.26 and 1.83, respectively, significantly higher comparing to gastric cancer patients (p<0.01). CONCLUSION: Severe impairment of the thrombocyte phagocytic activity in gastric cancer patients has been found. Phagocytic activity of blood platelets was partially improved as a result of perioperative immunonutrition both in locoregional disease and in peritoneal dissemination.

Parenteral nutrition and preOp preparation in prevention of post-operative insulin resistance in gastrointestinal carcinoma.

PURPOSE: The aim was to compare preventive effect of total parenteral nutrition (TPN) and oral nutrition (preOp) on the perioperative insulin resistance prevention in surgical gastrointestinal cancer patients. MATERIAL/METHODS: The study was conducted in a group of 75 elective gastric and large intestine cancer patients. Patients were randomly divided into 3 study groups, 25 patients each: group I (NIL) - no preparations influencing tissue sensitivity to insulin, group II (TPN) - total parenteral nutrition in its preoperative stage and group III (TPN + preOp) parenteral nutrition and preOp in the preoperative phase. RESULTS: Immediately after the surgery, no statistically significant differences in insulin resistance level between groups were observed. During the first 6 postoperative hours, a statistically significant decrease of insulin resistance level in the TPN+ preOp group in comparison to others, was observed. During the first 24 postoperative hours, the NIL group was the only one to keep the insulin resistance level the same as in the preoperative phase. CONCLUSIONS: Application of TPN in the preoperative phase leads to shortening of perioperative insulin resistance time. Combining TPN with oral application of carbohydrate before surgical procedure is an effective and the best method in postoperative insulin resistance syndrome prevention.

Matrix metalloproteinase 2 (MMP-2) and their tissue inhibitor 2 (TIMP-2) in gastric cancer patients.

BACKGROUND: Matrix metalloproteinase 2 (MMP-2) is able to degrade type IV collagen and its activity is mostly regulated by tissue inhibitor of matrix metalloproteinase 2 (TIMP-2). These proteins might play a role in tumor progression, including gastric cancer (GC). METHODS: The study included 108 individuals, GC patients and healthy subjects. Serum levels of all analyzed markers were evaluated by the immunological methods, while immunohistochemistry was used to assess the expression of these proteins in GC, interstitial inflammatory cells and normal tissues. RESULTS: The percentage of positive reactions of MMP-2 and TIMP-2 was higher in GC and inflammatory cells compared to normal tissue, while serum levels of these proteins were statistically lower in GC patients in comparison to healthy subjects. There was a significant positive correlation between TIMP-2 immunoreactivity in inflammatory cells and the presence of lymph node metastasis. Area under ROC curve (AUC) for TIMP-2 was higher than MMP-2, while serum MMP-2 was an independent prognostic factor of GC patients' survival. CONCLUSION: Our findings suggest that TIMP-2 seems to be a predictor of tumor progression, especially for nodal involvement, whereas serum MMP-2 might be useful as an independent prognostic factor of patients' survival.

Immunohistochemical assessment of apoptosis-associated proteins: p53, Bcl-xL, Bax and Bak in gastric cancer cells in correlation with clinical and pathomorphological factors.

PURPOSE: The p53 protein as well as Bcl-2 family proteins such as Bax, Bak and Bcl-xL regulate apoptosis. The study objective was to analyze the expression of p53, Bak, Bcl-xL and Bax in gastric cancer and in healthy gastric mucosa. MATERIAL AND METHODS: The study group consisted of 66 patients with gastric cancer, treated surgically in II Department of General and Gastroenterological Surgery, Medical University of Bialystok. The expression of the studied proteins was assessed using the immunohistochemical method. RESULTS: Significant differences were found in the expressions of the studied proteins as compared to healthy gastric mucosa. The expressions of p53 and Bax were significantly higher (70% vs 13% and 50% vs 13%), whereas those of Bak and Bcl-xL significantly lower (18% vs 83% and 74% vs 97%) in cancer cells than in normal mucosa (p<0.001). Significant differences were also noted in the expressions of Bax and Bcl-xL in relation to histological type. In the intestinal type (Lauren I), the expressions of Bax and Bcl-xL were higher as compared to the diffuse type (Lauren II) (93% vs 43% and 91% vs 43%). Simultaneously, correlations were noted between changes in the expression of Bax vs Bcl-xL and Bak. High expression of Bax showed a positive correlation with reduced Bak and Bcl-xL (p<0.05). Moreover, positive expression of p53 caused poorer distant survival of patients (p<0.05). CONCLUSION: Our study concluded that disturbances in the expression of p53, Bax, Bcl-xL and Bak proteins are associated with their involvement in the process of carcinogenesis in the stomach. It is suggesting that they might appeared in the early phase of carcinogenesis.