Stylianos Katsaragakis

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.

Effect of perioperative immuno-enhanced enteral nutrition on inflammatory response, nutritional status, and outcomes in head and neck cancer patients undergoing major surgery.

Administration of imunno-enhanced nutritional support may decrease postoperative morbidity, mortality, and infectious complications in cancer patients. The aim of this study was to verify that perioperative enteral diet, enriched with the nutrients arginine, ribonucleic acid (RNA), and ω-3 fatty acids improves outcomes of head and neck cancer patients undergoing major surgery. Forty patients with squamous cell carcinoma of the head and neck were studied. Group 1 received no preoperative nutritional support, whereas Group 2 received an oral formula with nutrients arginine, RNA, and ω-3 fatty acids. After surgery, Group 1 received a standard enteral formula, whereas Group 2 received an enriched enteral formula. Albumin (g/dl), prealbumin, fibrinogen, CRP, Il-6, and TNFa were measured 5 days before and 8 days after surgery. No statistically significant difference was observed for all the evaluated markers between postoperative and preoperative levels for both groups. The rate of complications was significantly reduced in the total number of patients receiving immunonutrition and in the particular subgroup of well-nourished patients receiving an immuno-enhanced diet. Perioperative enteral immuno-enhanced feeding in head and neck cancer patients undergoing major surgery may influence the postoperative outcomes by reducing the frequency rate of infections and wound complications.

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.

The Effects of Vasopressors on Perfusion of Gastric Graft after Esophagectomy. An Experimental Study

AimsTo evaluate the impact of the perioperative administration of norepinephrine on the perfusion of the esophageal graft.MethodsThis is an experimental study. Six swine underwent transhiatal esophagectomy; the stomach was used to replace the resected esophagus. We provoked hemorrhagic shock to the animals and then we administered noradrenaline to restore the blood pressure. We monitored the graft perfusion perioperatively using the technique of microdialysis.ResultsIn all animals, the graft experienced severe hypoperfusion after the administration of noradrenaline that was statistically significant.ConclusionsOur data support the hypothesis that norepinephrine should be used with extreme caution in the perioperative setting after esophagectomy. Further studies, however, will be required to evaluate the clinical significance of this finding.

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.

Advanced Trauma Life Support certified physicians in a non trauma system setting: is it enough?

OBJECTIVE The purpose of this study was to evaluate the impact of ATLS(®) on trauma mortality in a non-trauma system setting. ATLS represents a fundamental element of trauma training in every trauma curriculum. Nevertheless, there are limited studies in the literature as for the impact of ATLS training in trauma mortality, especially outside the US. DESIGN This is a prospective observational study. The primary end point was to investigate factors that affect mortality of trauma patients in our health care system. We performed a multivariate analysis for this purpose and we identified ATLS certification as a predictor of overall mortality. Following this finding we stratified patients according to the severity of injury as expressed by the ISS score and we compared outcome between those treated by an ATLS certified physician and those treated by non-certified ones. MAIN OUTCOME MEASURES Trauma volume and demographics of trauma patients, factors that affect mortality of traumatized patients and mortality between patients treated by ATLS(®) certified and non-certified physicians. RESULTS In total, 8862 trauma patients were included in the analysis. The majority of trauma patients (5988, 67.6%) were treated by a general surgeon, followed by those treated by an orthopedic surgeon (2194, 24.8%). There were 446 deaths in the registry but, 260 arrived dead in the Emergency Department and were excluded from the analysis. Multivariate analysis of the 186 deaths that occurred in the hospital revealed age, high ISS score, low GCS score, urban location of injury, neck injury and ATLS(®) certification as factors predisposing to mortality. Cross tabulation of ATLS(®) certification and ISS of the trauma patients shows that those treated by certified physicians died more often in all subcategories of ISS score (p<0.05). CONCLUSIONS In Greece, with no formal trauma system implementation, ATLS(®) certified physicians achieve worse outcomes than their non-certified colleagues when managing trauma patients. We believe that these findings must be interpreted in the context of the National health care system. There is considerable room for improvement in our country, and further analysis is required.

Transanal polypectomy using single incision laparoscopic instruments.

Transanal excision of rectal polyps with laparoscopic instrumentation and a single incision laparoscopic port is a novel technique that uses technology originally developed for abdominal procedures from the natural orifice of the rectum. Transanal endoscopic microsurgery (TEM) is a well established surgical approach for certain benign or early malignant lesions of the rectum, under specific indications. Our technique is a hybrid technique of transanal surgery, a reasonable method for polyp resection without the need of the sophisticated and expensive instrumentation of TEM which can be applied whenever endoscopic or conventional transanal surgical removal is not feasible.

The eSMART study protocol: a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer

Introduction While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients. Methods and analysis A total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries. Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes). Ethics and dissemination Ethical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval. eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts. Trial registration number NCT02356081.