High serum CA 19-9 but not tumor size should select patients for staging laparoscopy in radiological resectable pancreas head and peri-ampullary cancer.

BACKGROUND: The objective of this study was to validate current recommendations for the selective use of staging laparoscopy in patients with radiological resectable pancreas head and peri-ampullary tumors. METHODS: Data from a prospectively collected database (2007-2013) of 136 patients with peri-pancreatic head cancer were analyzed. RESULTS: Over a 6 year time period, 136 patients were evaluated, 126 patients were deemed radiological resectable and underwent laparotomy and 10 patients were characterized radiological unresectable. There were 111 patients with pancreas head resection and 15 without resection (8 due to extensive vascular involvement and 3 due to peritoneal/liver metastases). The sensitivity, specificity, PPV and NPV of pre-operative radiological imaging in determining unresectability due to liver/peritoneal metastases were 42%, 100%, 100% and 94.7% respectively. There was a significant difference in CA 19-9 values between metastatic and non-metastatic disease (p = 0.020). ROC curve analysis calculated the optimal CA 19-9 cutoff point for predicting metastasis at 215.37 U/ml with a sensitivity of 72.7%, a specificity of 58.3%, PPV of 15.1% and NPV of 95.5%. Tumor diameter was not a significant factor in predicting resectability. Laparoscopy would have been useful in only 5.3% of patients in the present series. CONCLUSION: High CA 19-9 values (>215 U/ml) and not tumor size should select patients with radiological resectable peri-pancreatic cancer for staging laparoscopy.

Ethical and Practical Challenges in Implementing Informed Consent in HIV/AIDS Clinical Trials in Developing or Resource-Limited Countries

Background/rationale: Ethical issues regarding HIV/AIDS human research in the developing world remain under continuous evaluation; a critical area of concern includes informed consent. This paper reviews several of the most important ethical and practical aspects of informed consent in HIV research in developing countries. Enhancement of overall understanding of such key issues might promote higher ethical standards of future research. Objectives: The major objective was to address informed consent in human research in non-Western societies; and specifically in HIV clinical trials of affected adults. Secondary end-points included the consent complexities in HIV research involving vulnerable patient populations in resource-limited nations; such as children; adolescents and women. Methods: A systematic review of the published literature using MEDLINE and EMBASE from 1998 until December 2008 was performed; using the search terms `HIV/AIDS'; `informed consent'; `clinical trials'; `developing world'. Results: Ethical complexities such as participants' diminished autonomy; coercion or monetary inducement; language difficulties; illiteracy or lack of true understanding of the entire study; cultural barriers mainly due to communitarianism and social diversities were identified in the 44 studies reviewed. Informed consent of vulnerable patient populations must be tailored to their sex and developmental age; while counselling is fundamental. Children and adolescents' assent must be ensured. Local language is to be used; while trusted community leaders and local cultural representatives may convey information. Discussion: Despite the heterogeneity of studies; similarities were identified. Providing adequate and comprehensive information and assessing the true understanding of the research represent fundamental prerequisites. Potential solutions to the critical areas of concern include peer counselling and meetings with local community leaders or local cultural representation. Conclusions: International investigators of HIV human research should bear in mind these ethical issues and their potential solutions; when trying to ensure ethical research conduct; based on a truly informed and culturally relevant consent

Preoperative levosimendan in heart failure patients undergoing noncardiac surgery.

BACKGROUND: Heart failure (HF) is a major cause of perioperative morbidity and mortality in noncardiac surgery. Preoperative optimisation of these patients is, thus, of utmost importance. Levosimendan seems promising for patients undergoing cardiac surgery; however, its safety and efficacy in HF patients undergoing noncardiac surgery have not been evaluated. OBJECTIVE: To evaluate the effects of prophylactic preoperative levosimendan administration on left ventricular function in HF patients undergoing noncardiac surgery. METHODS: HF patients with ejection fraction <30%undergoing elective noncardiac surgery in 2005 were included in this prospective study. Patients were admitted to our surgical intensive care unit one day preoperatively. Under continuous haemodynamic monitoring, the treatment protocol consisted of an initial loading dose (24 microg/kg) for ten minutes followed by a continuous 24-hour infusion (0.1 microg/kg/min) at the end of which patients underwent surgery. Echocardiography was performed before infusion (day 0) and on the 7th postinfusion day (day 7). Measurements included left ventricular ejection fraction (LVEF), velocity time integral(VTI), pre-ejection period (PEP), ejection time (ET),maximum (Pmax) and minimum P(min) transvalvular aortic pressure gradient, and maximum (Vmax) and minimum V(min) aortic velocity. RESULTS: Twelve consecutive patients were enrolled. Levosimendan resulted in a significant increase in LVEF,VTI, P(max), P(min), V(max), and V(min) (p<0.01) and, moreover, a significant reduction in PEP, ET, and PEP/ET (p=0.04) on day 7 compared with day 0 values. No adverse reactions,complications or mortality occurred during 30-day follow-up. CONCLUSION: Prophylactic preoperative levosimendan treatment may be safe and efficient for perioperative optimisation of heart failure patients undergoing noncardiac surgery.

A simplified technique for translaryngeal tracheostomy (TLT). A preliminary report.

OBJECTIVE: In this prospective observational study we present preliminary results of a modification of the translaryngeal tracheostomy technique that was introduced by Fantoni in 1997. The study was conducted in a five-bed surgical intensive care unit of a university teaching hospital. PATIENTS AND METHODS: The study included 14 consecutive surgical patients (8 men, 6 women) who underwent a modified translaryngeal tracheostomy in a 6-month period. In our modification of the technique, we keep the basic principle of the inside-to-outside approach of the Fantoni technique, and combine it with a blind needle insertion, as reported in the classic subcricoid retrograde intubation technique. The technique that we use involves two medical doctors and a nurse. RESULTS: Mean patient age was 68.9 years (range: 31-85 years) and mean APACHE II score was 15.8 (range: 6-31). Mean operative time for the procedure was 15.2 min (range: 11.5-22 min). Eight of the patients died during the postoperative course in the ICU from causes relevant to their surgical pathology. One patient survived to be discharged from the ICU but died of an acute myocardial infraction later in the same hospital stay. Five patients survived to be discharged from the hospital. CONCLUSIONS: The modified translaryngeal tracheostomy seems to be as reliable and safe as the original technique. In addition, the modified technique is faster and can be performed without the use of an endoscope.

Refractory septic shock: efficacy and safety of very high doses of norepinephrine.

The aim of this study was to evaluate the safety, efficacy, and effects of administration of very high doses of norepinephrine (> 4 microg kg(-1) min(-1)) in catecholamine-resistant septic shock. We reviewed the charts of all patients with nonresponding to commonly used norepinephrine doses (< or = 4 microg kg(-1) min(-1)) septic shock from January 1999 to December 2002 in our Surgical Intensive Care Unit. All patients were treated with high norepinephrine doses (> 4 microg kg(-1) min(-1)), after initial resuscitation, so as to achieve a mean arterial pressure higher than or equal to 65 mmHg. During this 4-year period, 12 consecutive patients with catecholamine-resistant septic shock were included in our study. When compared with the values obtained prior to the administration of very high norepinephrine doses, the values of mean arterial pressure (p = 0.003) and systemic vascular resistance (p = 0.002) significantly increased after the administration of such doses, and additionally, lactate concentrations (p = 0.003) decreased. In contrast, no significant changes were observed regarding mean central venous pressure, pulmonary capillary wedge pressure, and pulmonary arterial pressure. Administration of high norepinephrine doses in our patients resulted in a survival rate of 33.4%. Management of catecholamine-resistant septic shock patients poses a challenging problem. Administration of very high norepinephrine doses is safe and effective and may improve survival of these patients with otherwise extremely high mortality rates.

Postresectional pulmonary oxidative stress in lung cancer patients. The role of one-lung ventilation.

OBJECTIVE: The authors conducted a prospective analysis in order to investigate through lipid peroxidation metabolites the generation of oxygen free radicals after one-lung ventilation (OLV). METHODS: From 2001 to 2003, 212 patients were prospectively studied for lung reexpansion/reperfusion injury. They were classified in six groups. Group A, non-OLV lobectomy group; B, OLV pneumonectomy group; C-E, OLV lobectomy of 60, 90, and 120 min duration, respectively; F, normal subjects as baseline group. Preoperative, intraoperative and postoperative strict blood sampling protocol was followed. Malondialdehyde (MDA) plasma levels were measured. The recorded values were analyzed and statistically compared between groups and within each one. RESULTS: Comparison of groups C-E (OLV) to all other documented significant (P<0.001) increase of MDA levels during lung reexpansion and for the following 12h. The magnitude of oxidative stress was related to OLV duration (group E>D>C, all P<0.001). The removal of cancer-associated parenchyma led to MDA level decrease postoperatively (P<0.001) especially after pneumonectomy (A vs. B, P<0.001). CONCLUSIONS: (1) Lung reexpansion provoked severe oxidative stress. (2) The degree of the amount of generated oxygen free radicals was associated to the duration of OLV. (3) Patients with lung cancer had a higher production of oxygen free radicals than normal population. (4)Tumor resection removes a large oxidative burden from the organism. (5) Mechanical ventilation and surgical trauma are weak free radical generators. (6) Manipulated lung tissue is also a source of oxygen free radicals, not only intraoperatively but also for several hours later.

Reconstruction of the pancreatic duct after pancreaticoduodenectomy: a modification of the Whipple procedure.

BACKGROUND AND OBJECTIVES: Pancreaticoduodenectomy is still associated with high morbidity and mortality even though there has been significant progress in the field of pancreatic surgery and postoperative follow-up. The pancreatoenteric anastomosis, regardless of the technique used, is a major cause for both morbidity and mortality after Whipple procedure. To overcome all problems resulting from anastomotic leakage, we used external drainage of the pancreatic duct. METHODS: In 24 patients who underwent pancreaticoduodenectomy in our Department from 1986 to 1995, a modification to the standard Whipple procedure was performed. Instead of pancreaticoenteric anastomosis, external drainage of the pancreatic duct remnant was performed. The pancreatic duct was intubated with a silastic tube, the external end of which was sutured to the skin. All patients received substitution therapy with pancreatic enzymes. RESULTS: Mortality in our group of patients was 4%. No complications due to the external drainage of the pancreatic duct were reported, while no patient developed diabetes mellitus after surgery. CONCLUSIONS: External drainage of the pancreatic duct remnant can be used alternatively to pancreatoenteric anastomosis after pancreatoduodenectomy. The technique is safe and simple to perform and appears to reduce overall operative time. It may be an option for patients with significant comorbidity and/or intraoperative hemodynamic instability which mandates expeditious completion of the operation.

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.

Circulating anti-CEA antibodies in the sera of patients with breast cancer.

AIM: The aim of this study was to detect circulating anti-carcinoembryonic antigen antibodies (anti-CEA) in breast cancer patients and to evaluate their clinical and prognostic significance. METHODS: Fifty-two breast cancer patients and 28 controls were included in this study. Detection of anti-CEA antibodies was performed using a modified enzyme linked immunoassay (ELISA). Sensitivity, specificity and usefulness index of anti-CEA antibodies were compared to those of CEA. The correlation of anti-CEA antibodies with survival and recurrence-free survival was tested with univariate and multivariate analysis. RESULTS: Anti-CEA was present in 57% of breast cancer patients and in 11% of controls. The sensitivity and usefulness index of anti-CEA were significantly better than those of CEA. The specificity of anti-CEA antibodies was less than that of CEA, the difference not being statistically significant. Anti-CEA antibodies were an independent statistically significant, favourable factor in recurrence-free survival. CONCLUSION: Anti-CEA antibodies circulate in breast cancer patients. They could be used as a more sensitive tumour marker than CEA. Their presence is associated with improved recurrence-free survival. These results should be confirmed in a larger series.

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 (> or =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.

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.

Effect of curative versus palliative surgical treatment for stage III pancreatic cancer patients.

UNLABELLED: During the last decade, significant progress has been made in pancreaticoduodenectomy for patients with pancreatic carcinoma. Pancreatic resection performed by surgeons in tertiary referral centres is therefore justified, while the indications for pancreatic resection could be extended in patients with advance stages of disease. The aim of our study is to compare the effect of curative (pancreaticoduodenectomy) versus palliative surgery in patients with stage III pancreatic cancer, during a 20-years period. We retrospectively reviewed the charts of 58 consecutive patients with stage III ductal adenocarcinoma of the head of the pancreas. 23 patients underwent pancreatoduodenectomy with curative intent while the remaining 35 patients had surgery for palliative purposes (combined biliary and gastric bypass was performed in 83%). The hospital mortality rate was similar in both groups (4% vs 6%). 43% of patients undergoing pancreaticoduodenectomy had an uncomplicated post-operative course compared with 49% of patients undergoing palliative bypass. The length of surgical procedure and post-operative hospital stay in pancreaticoduodenectomy group were significant longer compared to those patients undergoing palliative bypass (p = 0.03 and p = 0.02 respectively). The overall actuarial survival was significantly (p < 0.01) longer in the group of patients who underwent pancreaticoduodenectomy compared with the group with palliative intent surgery. CONCLUSION: Pancreaticoduodenectomy with curative intent for stage III pancreatic cancer patients, could improve prognosis with similar peri-operative morbidity and mortality when compared with palliative bypass.

Preventable prehospital trauma deaths in a Hellenic urban health region: an audit of prehospital trauma care.

OBJECTIVE: To identify preventable prehospital deaths, caused by trauma. DESIGN: Analysis of 82 trauma victims who were dead on arrival (DOA) into our hospital. SETTING: General Hospital of Piraeus, Greece. MATERIALS AND METHODS: Evaluation of the autopsy findings of 82 DOAs. MEASUREMENTS: Demographic, autopsy, and toxicology data, ICD9 codes, Abbreviated Injury Score (AIS)-90, Injury Severity Score (ISS)-body regions, central nervous system (CNS) deaths, non-CNS deaths, p values, and opinion of a clinical assessor. MAIN RESULTS: The 29 (35.36%) DOAs had at least one AIS6 injury. Extracranial hemorrhage, airway, and breathing dysfunction were contributing factors of death of 27 "possibly preventable" CNS deaths, and the causes of death for the 20 non-CNS deaths. p value (0.5) indicated that 24 (29.26%) of the DOAs expected to survive. The clinical assessor characterized four (4.87%) as "definitely preventable" and 35 (42.65%) as "possibly preventable" deaths. CONCLUSIONS: Upgrading of the emergency medical care service is required.

Role of early and extensive surgery in the treatment of severe necrotizing soft tissue infection.

Forty-two patients with necrotizing soft tissue infection are reviewed. Bacterial culture revealed between two and seven types of micro-organism in each patient. All patients were treated with radical surgical debridement and a combination of antibiotics. In 30 patients, early diagnosis and treatment resulted in only two deaths. Delayed surgical intervention in 12 patients transferred from outside hospitals was followed by nine deaths. Predisposing factors and site of infection did not affect outcome. Of 26 patients with systemic manifestations of sepsis, 16 survivors responded well to initial surgical debridement.