Early prognostic factors in septic shock cancer patients: a prospective study with a proteomic approach.

BACKGROUND: Organ failures are the main prognostic factors in septic shock. The aim was to assess classical clinico-biological parameters evaluating organ dysfunctions at intensive care unit admission, combined with proteomics, on day-30 mortality in critically ill onco-hematology patients admitted to the intensive care unit for septic shock. METHODS: This was a prospective monocenter cohort study. Clinico-biological parameters were collected at admission. Plasma proteomics analyses were performed, including protein profiling using isobaric Tag for Relative and Absolute Quantification (iTRAQ) and subsequent validation by ELISA. RESULTS: Sixty consecutive patients were included. Day-30 mortality was 47%. All required vasopressors, 32% mechanical ventilation, 33% non-invasive ventilation and 13% renal-replacement therapy. iTRAQ-based proteomics identified von Willebrand factor as a protein of interest. Multivariate analysis identified four factors independently associated with day-30 mortality: positive fluid balance in the first 24 h (odds ratio = 1.06, 95% CI = 1.01-1.12, P = 0.02), severe acute respiratory failure (odds ratio = 6.14, 95% CI = 1.04-36.15, P = 0.04), von Willebrand factor plasma level > 439 ng/ml (odds ratio = 9.7, 95% CI = 1.52-61.98, P = 0.02), and bacteremia (odds ratio = 6.98, 95% CI = 1.17-41.6, P = 0.03). CONCLUSION: Endothelial dysfunction, revealed by proteomics, appears as an independent prognostic factor on day-30 mortality, as well as hydric balance, acute respiratory failure and bacteremia, in critically ill cancer patients admitted to the intensive care unit. Endothelial failure is underestimated in clinical practice and represents an innovative therapeutic target.

Severity of Acute Respiratory Distress Syndrome in haematology patients: long-term impact and early predictive factors.

Severe forms of acute respiratory distress syndrome in patients with haematological diseases expose clinicians to specific medical and ethical considerations. We prospectively followed 143 patients with haematological malignancies, and whose lungs were mechanically ventilated for more than 24 h, over a 5-y period. We sought to identify prognostic factors of long-term outcome, and in particular to evaluate the impact of the severity of acute respiratory distress syndrome in these patients. A secondary objective was to identify the early (first 48 h from ICU admission) predictive factors for acute respiratory distress syndrome severity. An evolutive haematological disease (HR 1.71; 95% CI 1.13-2.58), moderate to severe acute respiratory distress syndrome (HR 1.81; 95% CI 1.13-2.69) and need for renal replacement therapy (HR 2.24; 95% CI 1.52-3.31) were associated with long-term mortality. Resolution of neutropaenia during ICU stay (HR 0.63; 95% CI 0.42-0.94) and early microbiological documentation (HR 0.62; 95% CI 0.42-0.91) were associated with survival. The extent of pulmonary infiltration observed on the first chest X-ray and the diagnosis of invasive fungal infection were the most relevant early predictive factors of the severity of acute respiratory distress syndrome.

Early diastolic dysfunction is associated with intensive care unit mortality in cancer patients presenting with septic shock.

BACKGROUND: Cancer patients present a high risk of sepsis and are exposed to cardiotoxic drugs during chemotherapy. Myocardial dysfunction is common during septic shock and can be evaluated at bedside using echocardiography. The aim of this study was to identify early cardiac dysfunctions associated with intensive care unit (ICU) mortality in cancer patients presenting with septic shock. METHODS: Seventy-two cancer patients admitted to the ICU underwent echocardiography within 48 h of developing septic shock. History of malignancies, anticancer treatments, and clinical characteristics were prospectively collected. RESULTS: ICU mortality was 48%. Diastolic dysfunction (e' ≤8 cm s(-1)) was an independent echocardiographic parameter associated with ICU mortality {odds ratio (OR) 7.7 [95% confidence interval (CI), 2.58-23.38]; P<0.001}. Overall, three factors were independently associated with ICU mortality: sepsis-related organ failure assessment score at admission [OR 1.35 ( 95% CI, 1.05-1.74); P=0.017], occurrence of diastolic dysfunction [OR 16.6 (95% CI, 3.28-84.6); P=0.001], and need for conventional mechanical ventilation [OR 16.6 (95% CI, 3.6-77.15); P<0.001]. Diastolic dysfunction was not associated with exposure to cardiotoxic drugs. CONCLUSIONS: Early diastolic dysfunction is a strong and independent predictor of mortality in cancer patients presenting with septic shock. It is not associated with exposure to cardiotoxic drugs. Further studies incorporating monitoring of diastolic function and therapeutic interventions improving cardiac relaxation need to be evaluated in cancer patients presenting with septic shock.

Critically ill cancer patients in the intensive care unit: short-term outcome and 1-year mortality.

BACKGROUND: The short-term survival of critically ill patients with cancer has improved over time. Studies providing long-term outcome for these patients are scarce. METHODS: We prospectively analyzed outcomes and rates of successful discharge of 111 consecutive critically ill cancer patients admitted to intensive care unit (ICU) in 2008 and identified factors influencing these results. RESULTS: ICU mortality was 32% and hospital mortality was 41%. None of the characteristics of the malignancy nor age or neutropenia were significantly different between survivors and others. Two variables were independently associated with ICU mortality: high Logistic Organ Dysfunction score on day 7 and a diagnosis of viral infection and/or reactivation. The 1-year mortality rate for ICU survivors was 58% and was significantly lower in patients with a diagnosis of acute leukemia or multiple myeloma. CONCLUSION: Organ failure scores on day 7 can predict outcome for cancer patients in the ICU. Viral infection and reactivation appear to worsen the prognosis. One-year mortality rate is high and depends on the malignancy.

HLA-DR and B7-2 (CD86) monocyte expressions after major cancer surgery: profile in sepsis.

AIM: HLA-DR monocyte expression may be affected by major surgery. A potential mechanism for monocyte activation is the engagement of costimulatory receptors (B7-2 or CD-86). The aim of the present study was to determine the possible role of monocyte HLA-DR and B7-2 molecules in the occurrence of postoperative sepsis after major cancer surgery. METHODS: This was an observational study in 25 consecutive patients undergoing major elective surgery. Flow cytometry measures were used to determine the expression of HLA-DR and its costimulatory receptors before (day 0) and after surgery (day 1 and day 2). RESULTS: After surgery, the rate of monocytes expressing HLA-DR decreased significantly in all the patients. As compared with day 0, the rate of monocytes expressing B7-2 decreased in all the patients (P<0.03). In the septic group, it remained significantly decreased postoperatively. In the non-septic group, it reached baseline levels at day 2. CONCLUSION: Results suggest a key role for costimulatory molecules in modulating inflammatory response in the context of subsequent postoperative sepsis after major cancer surgery. These molecules may be involved, in association with HLA-DR, in postoperative monocyte dysfunction.

Reduced interleukin-12 release from stimulated monocytes in patients with sepsis after major cancer surgery.

BACKGROUND: Major cancer surgery is a high-risk situation for sepsis in the post-operative period. The aim of this study was to assess the relation between the monocyte production of IL-12 and the development of post-operative sepsis in patients undergoing major cancer surgery. METHODS: In 19 patients undergoing major cancer surgery, the production of cytokines by basal and lipolysaccharide (LPS)-stimulated monocytes was measured before and after (from day 1 to day 3 and day 7) surgery. Seven of them developed a post-operative sepsis. Ten healthy volunteers were used as controls for the assessment of pre-operative values. RESULTS: Before surgery, the production of interleukin (IL)-12 p40 by LPS-stimulated monocytes was similar in the patients and the healthy volunteers. The production of IL-12 p40 by unstimulated monocytes was higher in the patients than in the healthy volunteers. IL-12 production did not differ between the septic and the non-septic patients. After surgery, the production of IL-12 p40 was dramatically reduced in the LPS-stimulated monocytes of the septic patients from day 1 to day 3, as compared with that of the non-septic patients. Before surgery, the production of IL-6, IL-10, and IL-1 receptor antagonist (IL-1ra) in the patients was significantly higher than that of the healthy volunteers for both stimulated and unstimulated monocytes. After surgery, the production of these cytokines by both stimulated and unstimulated monocytes of the septic patients was similar to that of the non-septic patients. Intragroup analysis showed significant changes for IL-6, IL-10, and IL-1ra under all conditions, with the exception of changes in unstimulated monocytes of septic patients that were not significant for IL-10 release. CONCLUSION: After surgery, the septic patients showed drastic failure to up-regulate monocyte LPS-stimulated production of IL-12 p40.

Predictive perioperative factors for developing severe sepsis after major surgery.

BACKGROUND: Early identification of high-risk patients undergoing major surgery can result in an aggressive management affecting the outcome. METHODS: We designed a prospective cohort study of 93 adult patients undergoing major oncological surgery to identify the predictive risk factors for developing postoperative severe sepsis. RESULTS: Nineteen of 93 patients developed a severe sepsis after surgery; seven of the septic patients died in intensive care unit. Multivariate analysis discriminated preoperative and postoperative (first and second day after surgery) predictive risk factors. The postoperative severe sepsis was independently associated with preoperative factors like male gender (OR 4.7, 95% CI between 1.5 and 15.5, P<0.01) and Charlson co-morbidity index (OR 1.3, 95% CI between 1.07 and 1.6, P<0.01). After the surgery, the presence of systemic inflammatory response syndrome (OR 4.0, 95% CI between 1.02 and 15.7, P<0.05) and a logistic organ dysfunction score on day 2 (OR 3.3, 95% CI between 1.9 and 5.7, P<0.001) were found as independent predictive factors. CONCLUSION: We have shown that some of the markers that can be easily collected in the preoperative or postoperative visits can be used to screen the patients at high risk for developing severe sepsis after major surgery.

Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery.

BACKGROUND: Patients who undergo major surgery for cancer are at high risk of postoperative sepsis. Early markers of septic complications would be useful for diagnosis and therapeutic management in patients with postoperative sepsis. The aim of this study was to investigate the association between early (first postoperative day) changes in interleukin 6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) serum concentrations and the occurrence of subsequent septic complications after major surgery. METHODS: Serial blood samples were collected from 50 consecutive patients for determination of IL-6, PCT and CRP serum levels. Blood samples were obtained on the morning of surgery and on the morning of the first postoperative day. RESULTS: Sixteen patients developed septic complications during the first five postoperative days (group 1), and 34 patients developed no septic complications (group 2). On day 1, PCT and IL-6 levels were significantly higher in group 1 (P-values of 0.003 and 0.006, respectively) but CRP levels were similar. An IL-6 cut-off point set at 310 pg ml(-1) yielded a sensitivity of 90% and a specificity of 58% to differentiate group 1 patients from group 2 patients. When associated with the occurrence of SIRS on day 1 these values reached 100% and 79%, respectively. A PCT cut-off point set at 1.1 ng ml(-1) yielded a sensitivity of 81% and a specificity of 72%. When associated with the occurrence of SIRS on day 1, these values reached 100% and 86%, respectively. CONCLUSIONS: PCT and IL-6 appear to be early markers of subsequent postoperative sepsis in patients undergoing major surgery for cancer. These findings could allow identification of postoperative septic complications.

A reappraisal of preoperative chemoradiation for localized pancreatic head ductal adenocarcinoma in a 5-year single-institution experience.

Resection of localized pancreatic head ductal adenocarcinoma (LPHDA) has a limited impact on survival. Mechanisms of improvement provided by preoperative chemoradiation therapy (CRT) remain under debate. This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT. Among 87 patients with LPHDA, 17 had a pancreaticoduodenectomy alone (group I). Thirty-nine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy (group II). Thirty-one with initially unresectable cancers were similarly treated by CRT (group III). Patients in groups II and III were restaged after completion of CRT. In patients with resectable disease, resection was planned. Patients in groups I and II were statistically comparable in terms of age, sex, and pretherapeutic stage. Median survival and 2-year overall survival in group I were 13.7 months and 31%, respectively. In group II, 23 patients (59%) had a pancreaticoduodenectomy (group IIa) and 16 patients (41%) did not have resection (group IIb). Median survival and 2-year overall survival were as follows: group IIa, 26.6 months and 51%; and group IIb, 6.1 months and 0%, respectively. In group IIa, pathologic examination revealed eight major responses (35%) including two sterilized specimens, and none of the patients had locoregional recurrence. In group III, none of the patients had resection, and median survival was 8 months with one 2-year survivor. Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy. However, a high histologic response rate and excellent local control can also be achieved.