Evangelos Messaris

Dehydration Is the Most Common Indication for Readmission After Diverting Ileostomy Creation

BACKGROUND: Early readmission after discharge from the hospital is an undesirable outcome. Ileostomies are commonly used to prevent symptomatic anastomotic complications in colorectal resections. OBJECTIVE: The aim of this study was to identify factors predictive of readmission after colectomy/proctectomy and diverting loop ileostomy. DESIGN: This study is a retrospective review. PATIENTS: Patients were included who underwent colon and rectal resections with ileostomy at our institution. Sex, age, type of disease, comorbidities, elective vs urgent procedure, type of ileostomy, operative method, steroid use, ASA score, and the use of diuretics were evaluated as potential factors for readmission. MAIN OUTCOME MEASURES: The primary outcomes measured were the need for readmission and the presence of dehydration (ostomy output ≥1500 mL over 24 hours and a blood urea nitrogen/creatinine level ≥20, or physical findings of dehydration). RESULTS: Six hundred three loop ileostomies were created mostly in white (95.3%), male (55.6%) patients undergoing colon or rectal resections. IBD was the most common indication at 50.9%, with rectal cancer at 16.1%, and other at 31.0%. The 60-day readmission rate was 16.9% (n = 102) with the most common cause dehydration (n = 44, 43.1%). Regression analysis demonstrated that the laparoscopic approach (p = 0.02), lack of epidural anesthesia (p = 0.004), preoperative use of steroids (p = 0.04), and postoperative use of diuretics (p = 0.0001) were highly predictive for readmission. Furthermore, regression analysis for readmission for dehydration identified the use of postoperative diuretics as the sole risk factor (p = 0.0001). LIMITATIONS: This study is limited by the retrospective analysis of data, and it does not capture patients that were treated at home or in clinic. CONCLUSION: Readmission after colon or rectal resection with diverting loop ileostomy was high at 16.9%. Dehydration was the major cause for readmission. Patients receiving diuretics are at increased risk for readmission for dehydration. High-risk patients should be treated more cautiously as inpatients and closely monitored in the outpatient setting to help reduce dehydration and readmission.

Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.

TIC10 is a small molecule that activates Foxo3a through dual inactivation of Akt and ERK, up-regulates the expression of the TRAIL gene, an endogenous tumor suppressor, and effectively improves the therapeutic properties and utility of TRAIL as an anticancer therapy. TIC’ing Up the TRAIL TRAIL is a naturally occurring tumor suppressor: It stimulates cell death pathways in a variety of human cancers and thus has been a popular target for the development of anticancer drugs. Previous TRAIL-targeting strategies include synthesis of the recombinant protein and stimulatory antibodies. All of these agents exhibit some of the typical drawbacks of protein-based therapeutics, such as short half-lives and a need to administer the drugs directly into the bloodstream or even into the tumor. Now, Allen and colleagues have discovered a drug, TIC10, which can stimulate production of TRAIL while avoiding the shortcomings of protein-based therapies. The authors demonstrated that TIC10 can increase TRAIL and stimulate the death of multiple types of human cancer cells both in culture and in mice. The drug was equally effective when given orally or intravenously and effectively penetrated the blood-brain barrier to target glioblastoma, a difficult-to-treat brain tumor. Whereas recombinant TRAIL displayed a short half-life of ~30 min, TIC10 activity persisted in the mice for days, allowing for once-a-week dosing. Toxicity analysis in mice showed no detectable adverse effects from treatment with TIC10. The authors also showed that TIC10 boosts TRAIL function through inactivation of the Akt and MEK signaling proteins, which results in translocation of the transcription factor Foxo3a into the cell nucleus, where it stimulates TRAIL gene expression. Before TIC10 can be used to treat patients, the drug will need to be tested in clinical trials to confirm safety and efficacy results from mouse studies. In addition, further work is needed to determine the mechanism by which TIC10 causes the dephosphorylation and resulting inactivation of Akt and MEK. However, the discovery of TIC10 clears a path to versatile TRAIL-based cancer therapies. Recombinant tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is an antitumor protein that is in clinical trials as a potential anticancer therapy but suffers from drug properties that may limit efficacy such as short serum half-life, stability, cost, and biodistribution, particularly with respect to the brain. To overcome such limitations, we identified TRAIL-inducing compound 10 (TIC10), a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier. TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10. TIC10 inactivates kinases Akt and extracellular signal–regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.

Motor vehicle trauma: analysis of injury profiles by road-user category

Background: Vehicle accidents in Greece are among the leading causes of death and the primary one in young people. The mechanism of injury influences the patterns of injury in victims of vehicle accidents. Objective: Identification and analysis of injury profiles of motor-vehicle trauma patients in a Greek level I trauma centre, by road-user category. Patients and methods: The trauma registry data of Herakleion University Hospital of adult trauma patients admitted to the hospital after a vehicle accident between 1997 and 2000 were retrospectively examined. Patients were grouped based on the mechanism of injury into three road-user categories: car occupants, motorcyclists, and pedestrians. Results: Of 730 consecutive patients, 444 were motorcyclists (60.8%), 209 were car occupants (28.7%), and 77 were pedestrians (10.5%). Young men constituted the majority of injured motorcyclists whereas older patients (p = 0.0001) and women (p = 0.0001) represented a substantial proportion of the injured pedestrians. With regard to the spectrum of injuries in the groups, craniocerebral injuries were significantly more frequent in motorcyclists and pedestrians (p = 0.0001); abdominal (p = 0.009) and spinal cord trauma (p = 0.007) in car occupants; and pelvic injuries (p = 0.0001) in pedestrians. Although the car occupants had the highest Injury Severity Score (ISS) (p = 0.04), the pedestrians had the poorest outcome with substantially higher mortality (p = 0.007) than the other two groups. Conclusions: The results reveal a clear association between different road-user categories and age and sex incidence patterns, as well as outcomes and injury profiles. Recognition of these features would be useful in designing effective prevention strategies and in comprehensive prehospital and inhospital treatment of motor-vehicle trauma patients.

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.

Predictive value of procalcitonin for bowel ischemia and necrosis in bowel obstruction.

BACKGROUND To our knowledge, the predictive value of procalcitonin for bowel strangulation has been evaluated in only 2 experimental studies that had conflicting results. The objective of this study was to evaluate the value of procalcitonin for early diagnosis of intestinal ischemia and necrosis in acute bowel obstruction. METHODS We performed a prospective study of 242 patients with small- or large-bowel obstructions in 2005. A total of 100 patients who underwent operation were divided into groups according to the presence of ischemia (reversible and irreversible) and necrosis, respectively, as follows: ischemia (n = 35) and nonischemia groups (n = 65) and necrosis (n = 22) and nonnecrosis groups (n = 78). Data analyzed included age, sex, vital signs, symptoms, clinical findings, white blood cell count, base deficit, metabolic acidosis, procalcitonin levels on presentation, the time between symptom onset and arrival at the emergency department and the time between arrival and operation, and the cause of the obstruction. RESULTS Procalcitonin levels were greater in the ischemia than the nonischemia group (9.62 vs 0.30 ng/mL; P = .0001) and in the necrosis than the non-necrosis group (14.53 vs 0.32 ng/mL; P = .0001). Multivariate analysis identified procalcitonin as an independent predictor of ischemia (P = .009; odds ratio, 2.252; 95% confidence interval, 1.225-4.140) and necrosis (P = .005; odds ratio, 2.762; 95% confidence interval, 1.356-5.627). Using receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) of procalcitonin for ischemia and necrosis was 0.77 and 0.87, respectively. A high negative predictive value for ischemia and necrosis of procalcitonin levels <0.25 ng/mL (83% and 95%, respectively) and a positive predictive value of procalcitonin >1 ng/mL were identified (95% and 90%, respectively). CONCLUSION Procalcitonin on presentation is very useful for the diagnosis or exclusion of intestinal ischemia and necrosis in acute bowel obstruction and could serve as an additional diagnostic tool to improve clinical decision-making.

Role of Magnetic Resonance Enterography in the Management of Crohn Disease

OBJECTIVE To assess the impact of magnetic resonance enterography (MRE) on therapeutic decision making for patients with Crohn disease. DESIGN Retrospective study. SETTING Tertiary care medical center. PATIENT One hundred twenty patients who had either a history of or high suspicion for Crohn disease with onset of new symptoms underwent MRE over 18 months at our institution. All patients with Crohn disease were classified according to the Montreal system. INTERVENTIONS Magnetic resonance enterography and medical vs surgical therapy. MAIN OUTCOME MEASURE Changes in management after MRE findings. RESULTS Magnetic resonance enterography demonstrated active Crohn disease in 57.5% of patients, chronic changes of Crohn disease without active inflammation (eg, stricture, fistula, or abscess) in 12.5% of cases, and no evidence of Crohn disease in 30% of cases. After MRE, 37 (31%) had no change in medical therapy, 64 (53%) had additional medical management for active inflammation, and 19 (16%) underwent an operation for complicated Crohn disease or medical intractability. In all surgical patients, the intraoperative findings were consistent with the MRE diagnosis. The mean (SD) MRE score was 1.6 (0.5) for patients who had no change in their treatment plans, 5.8 (1) for patients who underwent surgery, and 8 (0.4) for patients who had their drug regimen changed (P < .001). The MRE score independently correlated with need for intervention (P = .001). CONCLUSIONS Magnetic resonance enterography shows promising ability to characterize the presence of active Crohn disease as well as chronic complications (eg, differentiate between stricture due to edema vs fibrotic scarring). Magnetic resonance enterography is fast becoming a useful adjunct in the management algorithm of patients with Crohn disease.

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.

Administration of human protein C improves survival in an experimental model of sepsis

Objective:Study the effect of human protein C (PC) concentrate administration on organ damage and survival in septic rats. Design:Animal study. Setting:University laboratory. Subjects:Male Wistar rats. Interventions:Cecal ligation and puncture (CLP) was performed in 210 rats. Rats were randomly assigned to receive either human protein C (PC) IV 1, 7, and 13 hrs after CLP (CLP+PC) or placebo (CLP). Septic animals were again randomized in a survival group (CLP: n = 50 and CLP+PC: n = 40) that was monitored for 60 hrs and time groups (CLP: n = 60 and CLP+PC: n = 60) that were killed at 6, 12, 24, 36, 48, and 60 hrs after CLP. Brain, heart, lung, liver, kidney, gastric, and colon tissue were removed and postfixed in paraffin sections. Measurements and Main Results:PC infusion increased PC serum levels in early sepsis (median 7.25) compared with late sepsis (median 2, p = .001). Activated protein C/a1-antitrypsin complex levels in the CLP+PC group were significantly increased in late sepsis (60 hrs after CLP) compared with early sepsis (6, 12, and 24 hrs after CLP, p = .009, p = .004, and p = .008, respectively) and to late septic CLP and normal rats (p = .005 and p = .007, respectively). Their IL-6 and tumor necrosis factor a plasma levels were decreased (by 27% and 25%, respectively) at 6 hrs compared with placebo (p = .008 and p = .016). Their serum PC levels were also decreased in CLP+PC survivors compared with nonsurvivors of the same group (median = 1.5 vs. median = 7, p = .001). Apoptosis was reduced in brain (10% vs. 77.8%, p < .001), stomach (66.7% vs. 100%, p < .002) and intestine (33.3% vs. 85.2%, p < .001) compared with placebo. Finally, the survival of septic rats treated with human PC was significantly increased compared with placebo (75% vs. 54%, p = .033). Conclusions:Human Protein C administration increased survival in septic rats, decreased plasma inflammatory cytokines levels and tissue injury in vital organs.

Total Extraperitoneal Laparoscopic Inguinal Hernia Repair Without Mesh Fixation Prospective Study With 1-Year Follow-up Results

OBJECTIVE To determine the outcomes of patients undergoing total extraperitoneal inguinal hernia repair without fixation of the mesh. DESIGN Prospective cohort. SETTING Community teaching hospital. PATIENTS A total of 274 consecutive patients were included in the study group. INTERVENTIONS All operations were performed by the same surgeon with the patients under general anesthesia in an outpatient setting. A preformed polyester mesh (Parietex; Covidien, Mansfield, Massachusetts) was used in all cases without any fixation. MAIN OUTCOME MEASURES All patients were prospectively followed up at 2 weeks, 1 month, and 1 year after surgery. Operative morbidity, chronic pain, and hernia recurrence were recorded. RESULTS Two hundred seventy-four consecutive patients underwent 311 total extraperitoneal inguinal hernia repairs. No conversions were made to open hernia repairs. No recurrences were found at the 12-month follow-up visit. There were 19 inguinal seromas (6.1%) identified at 2 weeks, but only 7 (1.9%) remained at 1 month, and none at 1 year. No wound infections, scrotal hematomas, or other perioperative complications were reported. Two hundred thirty-six patients used fewer than the 30 prescribed tablets for pain control, while 23 patients requested a refill, 12 of whom had seromas (P < .01). At 12 months, no patient was taking pain relief medication; however, 8 patients reported occasional discomfort in the groin, and 1 patient reported occasional umbilical discomfort. CONCLUSION This single general surgeon experience supports total extraperitoneal inguinal hernia repair without mesh fixation as a safe, effective procedure with low morbidity and no evidence of recurrence at the 1-year follow-up visit.