George Androulakis

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.

Time-dependent mitochondrial-mediated programmed neuronal cell death prolongs survival in sepsis.

Objective:To investigate whether apoptosis is a possible mechanism of brain dysfunction occurring in septic syndrome. Design:Experimental prospective study. Setting:Laboratory of Surgical Research at the University of Athens. Subjects:Male pathogen-free Wistar rats. Interventions:Rats (n = 112) were subjected to sepsis by cecal ligation and puncture. Sham-operated animals (n = 40) underwent the same procedure but without ligation or puncture. Septic animals were either randomly divided (n = 62) in six groups and studied at 6, 12, 24, 36, 48, and 60 hrs after the operation or monitored (n = 50) for 48 hrs as a survival study group. Sham-operated animals were killed at 6, 12, 24, 36, 48, and 60 hrs after the procedure. Brain and cecum were then removed and postfixed in paraffin sections. Apoptosis was evaluated by light microscopy in hematoxylin and eosin-stained specimens and by transmission electron microscopy. In paraffin-embedded sections, immunostaining for bax, bcl-2, cytochrome c, and caspase-8 was done. Measurements and Main Results:In septic rats, increased apoptosis was detected in neurons of the CA1 region of the hippocampus, in choroid plexus, and in Purkinje cells of the cerebellum. Bax immunopositivity was found decreased after the septic insult (p = .03). Bax immunoreactivity was altered as the septic syndrome evolved; it was up-regulated in the early stages (6–12 hrs) and progressively decreased in the late phases (p = .001). Cytochrome c presented a similar regional pattern of expression and was found to be the sole gene marker carrying an independent prognostic role (p = .03). Both bcl-2 and caspase-8 expression remained at constant levels at all times evaluated. Conclusions:There is evidence that more neurons undergo apoptosis during sepsis than in normal brain tissue in certain sites where the blood-brain barrier is compromised. In this phenomenon, mitochondrial gene regulators such as bax and products such as cytochrome c seem to play important regulating and prognostic roles, respectively.

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.

Implantation of microballoons in the management of fecal incontinence.

PURPOSE: The implantation of expandable microballoons has proved successful for the treatment of stress urinary incontinence. This led us to test its effectiveness in the treatment of severe fecal incontinence. METHODS: Six patients (four male), of average age of 43 (range, 29–60) years, with severe fecal incontinence, underwent implantation of expandable microballoons in the submucosa of the anal canal. The implantation was performed under intravenous sedation as an outpatient procedure. Anal manometry, endosonography, and incontinence assessment with a scoring system were performed before and after the implantation. RESULTS: With a mean follow-up of 8.6 (range, 7–12) months, the incontinence scores improved in all patients from an average of 16.16 (standard deviation: ± 1.6) before the implantation to an average of 5 (standard deviation: ± 1.26) after the procedure. The anal pressure at rest was not improved in any patient (mean: 50.16 before treatment to a mean of 53 after treatment). No significant adverse events were associated with the procedure, and no serious postim-plantation complications were noted. DISCUSSION: Anal implantation of expandable microballoons seems to be a simple, safe, and effective method that restores the fecal continence without hindering normal defecation.

Helicobacter pylori infection in hospital workers over a 5-year period : correlation with demographic and clinical parameters

Background: We aimed to determine whether any of various groups of medical and nonmedical staff in a large acute care hospital were at increased risk of acquiring Helicobacter pylori infection over a 5-year period, and we also aimed to identify risk factors or symptoms related to H. pylori positivity and seroconversion. Methods: A total number of 437 subjects, aged 36.8 ± 7.7 years (range, 23–60 years)—employees of our hospital—were tested by immunoassay for serum IgG antibodies against H. pylori. Subjects were assigned to four main groups: (I) nursing staff (n = 249; aged 34.7 ± 7 years); (II) administrative and technical staff (n = 127; aged 39.2 ± 8.1 years); (III) medical staff (n = 31; aged 42.4 ± 4.9 years); and (IV) paramedical staff (blood donor department) (n = 30; aged 37.6 ± 8.5 years). Differences in age and educational level between these four groups were statistically highly significant (P < 0.0001). Each subject completed a questionnaire containing several clinical and demographic parameters. The same cohort of individuals was tested 5 years later. Results: The overall seroprevalence of H. pylori infection was 45.5%, and in each group (I, II, III, and IV) being 48.6%, 44.1%, 41.9%, and 30% respectively. Logistic regression analysis revealed that the risk of infection by H. pylori was significantly higher in group I compared with group II (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.04–3.52; P = 0.037). The H. pylori positivity increased with age: 40.6% for those aged 23–40 years and 57.5% for those aged 41–60 years (P = 0.001). The level of education was inversely associated with H. pylori infection (P = 0.001). During the 5-year observation, 59 of 238 (24.8%) subjects initially negative for H. pylori infection became positive, thus giving an annual seroconversion rate of 4.95%. Logistic regression analysis revealed that the seroconversion rate was significantly higher in group I compared with group II (28.1% vs 21.1%; OR, 2.34; 95% CI, 1.08–5.07; P = 0.03). The rate of seroconversion was higher in subjects aged 35–55 years compared with subjects aged 23–34 years (32% vs 17.5%; P = 0.009). Subjects who were positive for H. pylori infection in both examinations had a higher percentage of heartburn (P = 0.029), regurgitation (P = 0.023), and nausea (P = 0.037) compared with those who were negative in both examinations. Differences between those who were continuously negative for H. pylori infection and those who seroconverted during the observation period were not significant. Conclusions: In this longitudinal study of workers in a large acute care hospital in Greece it was found that nursing staff had a significantly higher risk of infection compared with administrative and technical staff. Age was significantly positively related both to H. pylori infection and to seroconversion. The level of education was strongly related to the prevalence, but not to the incidence of H. pylori infection. The presence of infection over the time was associated with a higher percentage of heartburn, regurgitation, and nausea compared with subjects who were continuously negative for H. pylori infection.

Apoptosis in cells of bronchoalveolar lavage: a cellular reaction in patients who die with sepsis and respiratory failure.

Objective Apoptosis represents a physiologic clearance mechanism in human tissues. The role of apoptosis has not been examined in lung cell populations, such as alveolar macrophages of septic patients, an organ frequently insulted in these patients. This study was designed to examine the effect of sepsis on the apoptosis of alveolar macrophages. Design Prospective study. Setting Intensive care unit and surgical intensive care and trauma unit of a large university hospital in Athens, Greece. Patients Bronchoalveolar lavage was obtained from 20 consecutive patients who met the criteria for sepsis, admitted to two intensive care units. Bronchoalveolar lavage was obtained from nine volunteers without lung disease who served as controls. Interventions None. Measurements and Main Results The specimens were analyzed by using annexin V binding, terminal deoxynucleotidyl transfer-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL), DNA laddering, light microscopy, and immunohistochemistry. Spontaneous apoptosis of bronchoalveolar lavage cells and particularly of alveolar macrophages was significantly decreased in septic patients compared with nonseptic controls. This finding was confirmed by using morphologic criteria and the TUNEL method. Furthermore, gel electrophoresis of DNA obtained from bronchoalveolar cells revealed that DNA fragmentation was not necessarily associated with apoptotic cell death. The bcl-2 gene was minimally expressed in the control group. An inverse correlation was found between the percentage of apoptotic alveolar macrophages and the severity of sepsis. Conclusions The prolonged survival of lung cells in septic patients and especially of alveolar macrophages may be attributable to the inhibition of apoptosis. This seems to represent an initial attempt of the host to increase the defense capacity to kill the invading microorganism, resulting in an unbalanced tissue load of cells and an uncontrolled release of toxic metabolites. Furthermore, the inhibition of apoptosis in septic patients may explain why lung function is impaired, leading to sepsis-induced acute respiratory distress syndrome and death.

Laparoscopic or open cholecystectomy in patients with sickle cell disease: which approach is superior?

OBJECTIVE To compare laparoscopic with open cholecystectomy in patients with sickle cell disease. DESIGN Retrospective clinical study. SETTING University hospital, Greece. SUBJECTS 41 patients (22 men and 19 women) with sickle cell disease had laparoscopic cholecystectomy between September 1991 and June 1998. Each patient was matched for age, sex, year of operation, and number of preoperative transfusions with control patients with sickle cell disease who had open cholecystectomy. MAIN OUTCOME MEASURES Duration of operation, postoperative stay in hospital, incidence of complications, and conversion to open operation. RESULTS The mean operation time was 81.4 min (range 55-125) for open cholecystectomy and 64.2 min (range 45-90) for laparoscopic cholecystectomy (p < 0.01). Complications occurred in 5% (2/41) of the patients in the laparoscopic group and in 20% (8/41) of the patients in the open group (p = 0.04). The mean length of stay in hospital was 5.6 days (range 3-9) in the open group and 2.7 days (range 2-5) in the laparoscopic group (p < 0.01). Conversion to open operation was necessary in 2 (5%) patients. CONCLUSIONS Laparoscopic cholecystectomy resulted in a shorter hospital stay with fewer postoperative complications than open operation in patients with sickle cell disease and may be the procedure of choice in the treatment of cholelithiasis in such patients.

Relationship of smoking and coffee and alcohol consumption with seroconversion to Helicobacter pylori: A longitudinal study in hospital workers

Background and Aim:  There are few data concerning the relationship between Helicobacter pylori seroconversion, and smoking habits and coffee and alcohol consumption. The aim of the present study was to investigate the relationship between smoking habits, coffee and alcohol consumption, and H. pylori seroconversion.

Prognostic variables for patients with stage III malignant melanoma

OBJECTIVE To evaluate the prognostic factors for patients with stage III malignant melanoma and to identify patients at high risk of developing recurrent disease who may benefit from adjuvant therapy. DESIGN Retrospective study. SETTING Specialist hospital, USA. SUBJECTS 130 patients with stage III malignant melanoma (according to the TNM classification), treated at the Roswell Park Cancer Institute between 1970 and 1992. MAIN OUTCOME MEASURES Survival and prognostic factors on multivariate analysis. RESULTS Four factors were independent prognostic indicators for patients with stage III malignant melanoma: age >51 years (p = 0.008), >3 involved lymph nodes, (p = 0.03), the site of the primary tumour on head or trunk, (p = 0.007), and the presence of palpable lymph nodes (p = 0.004). CONCLUSION These prognostic factors help us to stratify patients into low and high-risk groups. High-risk patients may benefit from more aggressive adjuvant therapy in future trials of treatment of melanoma.