Manoussos M. Konstadoulakis

Perioperative Erythropoietin Administration in Patients With Gastrointestinal Tract Cancer: Prospective Randomized Double-Blind Study

ObjectiveTo investigate the effect of recombinant human erythropoietin (r-HuEPO) administration on perioperative hemoglobin concentrations and on the number of blood transfusions in patients undergoing surgery for gastrointestinal tract malignancies. Summary Background DataErythropoietin has been shown to improve the yield of autologously predonated blood and to reduce the subsequent requirements for homologous blood transfusions in cancer patients. MethodsIn this double-blind placebo-controlled study, 31 cancer patients received subcutaneous r-HuEPO in a dose of 300 IU/kg body weight plus 100 mg iron intravenously (study group) and 32 patients received placebo medication and iron (control group). All patients received the medications daily for at least 7 days before and 7 days after the operation. ResultsPatients who received erythropoietin received significantly fewer transfusions intraoperatively and postoperatively. Postoperatively, the study group had significantly higher hematocrit, hemoglobin, and reticulocyte count values compared to the control group. The use of erythropoietin was also associated with a reduced number of postoperative complications and improved 1-year survival. ConclusionsPatients with gastrointestinal tract cancer and mild anemia benefit from perioperative erythropoietin administration in terms of stimulated erythropoiesis, reduction in the number of blood transfusions, and a favorable outcome.

Comparison of Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scoring systems in a single Greek intensive care unit

Objective: To evaluate Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II scoring systems in a single intensive care unit (ICU), independent from the ICUs of the developmental sample; and to compare the performance of APACHE II and SAPS II by means of statistical analyses in such a clinical setting. Design: Prospective, cohort study. Setting: A single ICU in a Greek university hospital. Patients: In a time interval of 5 yrs, data for 681 patients admitted to our ICU were collected. The original exclusion criteria of both systems were employed. Patients <17 yrs of age were dropped from the study to keep compatibility with both systems. Eventually, a total of 661 patients were included in the analysis. Interventions: Demographics, clinical parameters essential for the calculation of APACHE II and SAPS II scores, and risk of hospital death were recorded. Patient vital status was followed up to hospital discharge. Measurements and Main Results: Both systems showed poor calibration and underestimated mortality but had good discriminative power, with SAPS II performing better than APACHE II. The evaluation of uniformity of fit in various subgroups for both systems confirmed the pattern of underprediction of mortality from both models and the better performance of APACHE II over our data sample. Conclusions: APACHE II and SAPS II failed to predict mortality in a population sample other than the one used for their development. APACHE II performed better than SAPS II. Validation in such a population is essential. Because there is a great variation in clinical and other patient characteristics among ICUs, it is doubtful that one system can be validated in all types of populations to be used for comparisons among different ICUs.

Prognostic significance of circulating antibodies against carcinoembryonic antigen (anti-CEA) in patients with colon cancer

OBJECTIVE:The discovery of antibodies against carcinoembryonic antigen (CEA) in patients with digestive cancers, in the late 1970s, initiated a number of studies on the role of these antibodies in patients with cancers of the GI tract. Our aim was to determine the prevalence and prognostic significance of the IgG and IgM anti-CEA antibodies in the serum of patients with colon cancer.METHODS:Using an enzyme-linked immunoassay, the sera of 58 colon cancer patients were examined for the presence of carcinoembryonic antigen (CEA) and for circulating antibodies against the CEA (anti-CEA). An inhibition assay was carried out for the determination of the specificity of the IgG and IgM anti-CEA antibodies.RESULTS:The CEA was elevated (≥10 ng/ml) in only 12 patients (20.6%). Anti-CEA IgM and/or IgG antibodies were detected in 46 patients with colon cancer (79.1%). In the control group (n = 28), 10% of the individuals had detectable amounts of IgG and/or IgM anti-CEA antibodies. Patients with detectable amounts of circulating IgM anti-CEA antibodies (n = 14, 30.5%) had a statistically significantly better 2-yr survival compared to the rest of the patients (p = 0.017). The IgM anti-CEA antibodies can also be used as an independent prognostic factor in these patients (p = 0.0323).CONCLUSIONS:In this study, a high number of colon cancer patients have circulating anti-CEA antibodies in their sera. These may be used as diagnostic markers and as independent prognostic factors. In addition, the presence of these antibodies in the patients studied is associated with better prognosis and significantly increased 2-yr survival. It was also found that the anti-CEA antibodies (IgG and IgM) are more sensitive markers than CEA. These findings underline the biological importance of the anti-CEA antibodies and provide additional information on their potential use as markers of the immune status in patients with colon cancer.

Risk of Basal Cell and Squamous Cell Carcinoma in Persons with Prior Cutaneous Melanoma

Background. Melanoma has been associated with an overall increase in actinic tumors, including actinic keratoses, as well as with noncutaneous malignancies. Objective. Determine the risk of developing basal cell and squamous cell skin cancer in patients with prior cutaneous melanoma (actinic keratoses not encountered). Methods. This retrospective study included 1396 white patients with prior cutaneous melanoma followed at the Roswell Park Cancer Institute in the period 1977–1978. The control group was the white population of the Detroit area in the same period (1977–1978). Results. A total of 25 patients (18 males, 7 females) developed 35 basal cell and/or squamous cell carcinomas: 18 developed basal cell carcinomas, 2 squamous cell carcinomas, and 5 both. The calculated odds ratio was 3.49 (males 3.67, females 2.86, 95% confidence interval 1.52–8.00). No correlations were found with age, type, anatomic site, and length of follow‐up of cutaneous melanoma. Conclusion. A history of cutaneous melanoma significantly increases the risk of basal cell and squamous cell skin cancer.

The presence of anti-carcinoembryonic antigen (CEA) antibodies in the sera of patients with gastrointestinal malignancies

Using an enzyme-linked immunoassay we tested the sera of 71 patients with digestive system cancer, 35 patients with various nonmalignant disorders, and 28 normal individuals for anti-CEA activity. Antibodies were found in the sera of 51% of the patients. Most of the patients positive for the antibodies (70%) had no evidence of metastatic disease. Fewer than 10% of the sera from control groups had anti-CEA activity. The authors concluded that the patients suffering from cancer of the GI system are capable of producing tumor-specific antibodies. These antibodies could be used as a tumor marker and/or as a possible index for the function of the immune system. The presence of a large tumor mass could lead to the removal of these antibodies from the circulation.

Protein Expression of bax, bcl-2, and p53 in Patients with Non-Hodgkin's Gastric Lymphoma: Prognostic Significance

Abstract. The biologic significance of bcl-2, bax, and p53 gene expression in patients with non-Hodgkins gastric lymphoma is unknown. We examined the prognostic value of these genes in 36 patients with gastric lymphoma treated in our clinic between 1990 and 1995. Paraffin-embedded specimens from 36 patients who underwent primary resection of the stomach for gastric lymphoma were analyzed immunohistochemically for p53, bax, and bcl-2 gene expression. Expression of bax was seen in 24 of 36 patients (66.7%), p53 expression was found in 8 of 36 tumors (22.2%), and bcl-2 cytoplasmic staining was detected in 6 of 36 patients (16.7%). We performed a univariate analysis to examine the possible correlation between the expression of these genes and the survival of our patients. Expression of bax protein proved to be a statistically significant prognostic factor (p= 0.049). Protein expression of p53 and bcl-2 did not statistically correlate with survival. In the bcl-2-negative (−) patient group (30 patients), those who were bax-positive had a statistically significant better survival than those who were bax-negative (63.3% vs. 36.7%, p= 0.03). There was also a statistically significant correlation between p53 expression and the grade of the tumor (p= 0.0014). P53 protein expression increased along with the grade. Expression of bax is a significant prognostic factor in patients with gastric lymphoma. Its prognostic value increases significantly when studied in bcl-2-negative patients; but expression of bax failed to be an independent prognostic factor. Expression of bcl-2 and p53 has no prognostic significance. Expression of p53 seems to represent a marker for loss of differentiation.

Common prognostic factors for stage III melanoma patients and for stage I and II melanoma patients with recurrence to their regional lymph nodes.

This study was undertaken in order to identify the prognostic factors for stage III malignant melanoma patients. In addition we compared the survival data of these patients with data from patients presenting with stage I and II disease who subsequently developed a regional nodal recurrence, in order to identify common prognostic factors and to compare the biological behaviour of the two groups. We retrospectively examined two groups of patients. The first consisted of 116 patients with stage III malignant melanoma and the second consisted of 57 patients with stage I and II malignant melanoma that were found to have regional lymph node metastases diagnosed at least 6 months after surgical treatment of their primary lesion. The age of the patients, the number of disease-involved lymph nodes, the site of the primary lesion and the presence or not of palpable lymph nodes proved to be significant prognostic factors of the first group. We also analysed the survival data of the second group and compared it with data from the stage III patients. The 5 year survival starting from the time after diagnosis of the primary lesion was 47.37% compared with 25.86% in stage III patients; however, this difference was not statistically significant. Patients who present with stage III malignant melanoma seem to have a more aggressive phenotype than stage I and II malignant melanoma patients who present with recurrent disease in their regional lymph nodes. Disease behaviour is dictated by the number of disease-involved lymph nodes, the site of the primary lesion and the type of surgical procedure performed (elective or therapeutic lymph node dissection).

Evaluation of the autoimmune response in leprosy.

Immunological responses to a panel of antigens were evaluated in 27 patients with lepromatous and 20 patients with tuberculoid leprosy and compared with 24 pulmonary tuberculosis patients, 25 systemic lupus erythematosus patients and 41 healthy blood donors. Some autoantibody specificities were extensively studied for the first time in mycobacterial infections. Striking immunoserological abnormalities were found in patients with lepromatous leprosy, particularly in those presenting with relapse. Inhibition assays were performed, providing a tool for further analysis of the binding range of specific anti-N.D.O. BSA antibodies and strengthening the suggestion of molecular mimicry reactions between cytoskeletal proteins, host stress proteins and Mycobacterium leprae antigens or stress proteins. A significant serological overlap between lepromatous leprosy and autoimmune diseases is indicated.

EXTENDED CYTOPROTECTIVE EFFECT OF AUTOPHAGY IN THE LATE STAGES OF SEPSIS AND FLUCTUATIONS IN SIGNAL TRANSDUCTION PATHWAYS IN A RAT EXPERIMENTAL MODEL OF KIDNEY INJURY.

ABSTRACT The impact of a potential autophagy (LC3a/b) deregulation in hyper and in hypo stages during sepsis-induced kidney injury and the temporal profile of phosphorylated extracellular signal-related kinase, P38 (pP38), Akt (pAKT), and 13-3-3&bgr; protein were investigated in the current study, using a rat cecal ligation and puncture (CLP) model, by means of flow cytometry and immunohistochemistry. Cell viability was assessed by protein C zymogen concentrate (PC), 7-aminoactinomycin D (7-AAD) staining and inflammation by S100 protein immunostaining. The impact of reduced kidney inflammation in autophagy was assessed by PC administration, an anti-inflammatory and cytoprotective substance. Sepsis induction increased LC3a/b expression, which presented two peaks at 6 and 36 h after CLP, both in the percentage of positive cells (P = 0.024, P = 0.025, respectively) and in fluorescence intensity. At 6 h when inflammation was already apparent, LC3a/b increase was escorted by phosphorylated extracellular signal-related kinase stimulation and high cell viability (65%), designating autophagy as a cytoprotective mechanism against microbial infection. The phosphorylation of P38 was delayed to 12 h after CLP, when autophagy was reduced. pAkt and 14-3-3&bgr; expression was stimulated between 6 and 36 h after CLP, although a slight inhibition of pAkt within each cell was detected (lower MnIX value). During the second peak, inflammation was intensified, necrosis was significantly increased with LC3a/b+/7-AAD + cells to present a 1.5-fold increase. Protein C zymogen concentrate administration declined autophagy at 6 and 36 h after CLP and reduced necrosis, whereas double positive LC3a/b and 7-AAD cells were increased by 1.68 and 2.78-fold, respectively. These data open new prospectives in sepsis treatment, since they further support that autophagy represents a cytoprotective mechanism triggered by stress conditions, rather than an alternative cell death pathway.