Presence Of Systemic Inflammatory Response Research Articles

Circulating levels of the pro-inflammatory monomeric isoform of C-reactive protein (mCRP) correlate with inflammatory markers in patients with stage II-III colon cancer.

e15641 Background: Tumor-promoting inflammation is an established hallmark of cancer. C-reactive protein (CRP) is one of the most studied negative prognostic markers of the systemic inflammatory response (SIR) and known to be implicated in detrimental immune responses. Circulating CRP, as measured in routine practice, is a pentameric structure (pCRP). However, when pCRP binds to activated membranes, the protein dissociates into subunits termed monomeric CRP (mCRP). Pro-inflammatory characteristics of mCRP have been reported to be stronger than for pCRP. While a role for mCRP in cancer has been proposed, the circulating level of mCRP has never been investigated in cancer patients. Our aim was to detect and quantify plasma mCRP of patients diagnosed with stage II-III colon cancer (CC) and investigate possible correlations with other inflammatory markers. Methods: 40 patients treated for stage II-III CC between 2012 and 2015 at Sorlandet Hospital, Norway, were included in the study. 20 patients had pCRP level < 10 mg/L and 20 patients had pCRP > 10 mg/L, the latter interpreted as presence of SIR. Levels of pCRP and albumin were captured at the time of diagnosis. Pre-operative mCRP and the cytokines IL-6, IL-8 and TNFa were all measured using EDTA plasma samples. Pre-operative mCRP levels were measured by a specific ELISA employing reagents kindly provided by Drs. L. Potempa and I. Rajab (Roosevelt University, Schaumburg, IL). Results: Of the 40 patients, 47.5% were female, 57.5% had right-sided primary tumor and 50.0% were stage III. Median values (min-max) were for mCRP 2.55 ng/mL (0.00-10.9), pCRP 9.95 mg/L (0.50-136), IL-6 5.10 pg/mL (2.60-25.1), IL-8 4.95 pg/mL (0.40-32.4), TNFa 5.90 pg/mL (3.10-29.5) and albumin 40 g/L (29.0-46.0). Conclusions: To the authors’ knowledge, this is the first time mCRP has been reported in systemic circulation of cancer patients. Our study shows plasma mCRP to be quantifiable in CC patients, albeit at very low levels. This may be due to its reduced aqueous solubility and supports the notion of mCRP as a circulating particle-bound or tissue-associated isoform. However, despite low circulating mCRP levels and a small number of patients, mCRP still correlated with other well-known SIR markers with proven negative prognostic value in cancer patients, supporting its potential role as a pro-inflammatory player in CC. Further studies correlating SIR with circulating and tissue-bound mCRP are currently being performed. [Table: see text]

The clinical value of C-reactive protein and its association with tumour location in patients undergoing curative surgery for colorectal cancer – a ScotScan collaborative study

Introduction The presence of preoperative systemic inflammatory response (SIR) is an established negative prognostic factor for patients diagnosed with colorectal cancer (CRC). C-reactive protein (CRP) is known to be implicated in detrimental immune responses. The biological differences between right-sided and left-sided CRC are gaining increasing attention. Our aim was to analyse the prognostic value of CRP and explore the association between tumour location and SIR. Material and methods A total of 2059 patients treated for stage I–III CRC, identified from the prospectively sampled ScotScan Collaborative dataset, were included. The clinical and prognostic value of five CRP levels (<10/11–30/31–60/61–100/>100 mg/l) were examined. Additionally, the relationship between SIR and tumour location was explored. Results Increasing levels of CRP were associated with impaired overall and cancer-specific outcome. Presence of SIR was independently associated with right-sided tumour location (p<0.001). However, the impact of SIR on cancer-specific survival (CSS) was greater for left-sided tumour location, even when adjusted for other clinicopathological factors. Conclusions This study confirms CRP as a routinely available, valid, and clinically relevant strong prognostic marker of SIR in CRC patients. Right-sided tumours were more often associated with SIR, but the prognostic impact was stronger in left-sided tumours.

Viability of Chimeric Antigen Receptor T Cell Therapy in Latin America

Introduction: Treatment of diffuse large B cell lymphoma (DLBCL) may be a challenge for Latin American countries. Thus, novel strategies to reduce the economic burden of oncological care are necessary. In Brazil, the DLBCL annual incidence is approximately 6.000 cases, among which 30% will relapse or become refractory (R/R). In this scenario, the limited access to the new therapies reinforce the need to develop new local technologies and improve research initiatives. Here we report the development and clinical application of a Brazilian platform to manufacture genetically modified T-cells to treat patients with R/R leukemia and lymphomas, which may also help reverse the poor prognosis of these patients in low and middle-income countries. Patients and Methods: All patients were referred to our center to consider compassionate use of anti-CD19 CAR-T cell therapy. The treatment was authorized by the local medical ethical committee. Once patients were deemed to be eligible for CAR-T, they were scheduled for lymphopheresis and the cells were processed and cryopreserved. During the manufacturing process and after completion of lymphophersis, all three patients received bridging therapy. Prior to infusion of CAR-T, patients were given lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days. Patients were monitored daily for the occurrence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), which were graduated according to the criteria of the American Society for Transplantation and Cellular Therapy. These treatments were only available because we developed a Brazilian platform to manufacture genetically modified T-cells. Firstly, we developed and validated in vitro and in vivo anti-CD19 CAR T cell expression, expansion, and cytotoxicity. Secondly, in-house lentiviral good-manufacturing practice (GMP) protocols were established for clinical purposes. Thirdly, we upscaled the manufacturing process into the GMP facility originally developed for MSCs and adapted it to genetically modified T-cells. Finally, in-house procedures to deliver anti-CD19 CAR T cells for clinical use were established according to the Brazilian Health Regulatory Agency (ANVISA) policies. Once these steps were implemented, we were able to treat the first three patients of a patient with CAR-T cells produced in Latin America. Results: Two patients presented CAR-T cell expansion after the procedure (Figure 1). Within thirty days after the infusion one patient achieved complete response, one had partial response and one was not evaluated (Table 1). All patients had CRS and only one had ICANS. Two patients died, one from infection and other from intracranial hemorrhage due to domestic accident, — and — days after CAR-T cell infusion, respectively. Discussion: At least two of the reported patients presented improvement of their disease. The other one died before the expected response could have been evaluated. None of the patients died from complications related to manufacturing or infusion procedures, highlighting an acceptable safety profile of the platform. Although these are preliminary results, the CAR-T cell expansion profile, presence of systemic inflammatory response and lack of early disease progression suggest the treatment effectiveness. Conclusion: Apart from all the scientific challenges, this experience highlights the feasibility to implement a viable and efficient CAR-T platform in middle-income countries. Besides, implementation of advanced cellular therapy can also contribute to enhancing the quality of other cellular therapies. [Display omitted] DisclosuresGuerino-Cunha: Novartis: Other: Speaker; BMS: Other: Speaker; Janssen: Other: Speaker. Calado: Instituto Butantan: Consultancy; Alexion Brasil: Consultancy; Team Telomere, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis Brasil: Honoraria; Agios: Membership on an entity's Board of Directors or advisory committees; AA&MDS International Foundation: Research Funding.

Progression of Stage 2 and 3 Acute Kidney Injury in Patients With Decompensated Cirrhosis and Ascites

Progression of stages 2 and 3 acute kidney injury (AKI) in cirrhosis has not been characterized adequately. Patients with higher stages of AKI are believed to have worse outcomes. We assessed outcomes and factors associated with stages 2 and 3 AKI in patients with cirrhosis in the North American Consortium for the Study of End-stage Liver Disease cohort. We collected data from 2297 hospitalized patients with cirrhosis and ascites from December 2011 through February 2017. Our final analysis included 760 patients who developed AKI per the International Ascites Club 2015 definition (419 with maximum stage 1 and 341 with maximum stage 2 or 3; 63% male; mean age, 58 y). We compared demographic features, laboratory values, AKI treatment response, and survival between patients with maximum stage 1 vs patients with stage 2 or 3 AKI. Patients with stage 2 or 3 AKI had higher Model for End-Stage Liver Disease scores (25.9 ± 7.3) than patients with stage 1 AKI (21.9 ± 7.5) (P < .0001). More patients fulfilled systemic inflammatory response syndrome criteria on admission, and more developed a second nosocomial infection (P < .05 for both comparisons). More patients with stage 2 or 3 AKI also had progression of AKI and required dialysis and admission into intensive care units when compared to stage 1 AKI patients (P < .0001 for both). A lower proportion of patients with stage 2 or 3 AKI survived their hospital stay (80% vs 99% with stage 1 AKI; P < .0001), or survived for 30 days without a liver transplant (56% vs 81%; P < .0001). The development of stage 2 or 3 AKI was associated with a higher Model for End-Stage Liver Disease score at the time of admission (P < .0001), presence of systemic inflammatory response on admission (P= .039), and second infection (P < .0001). Based on an analysis of data from the North American Consortium for the Study of End-stage Liver Disease cohort, we found that patients with cirrhosis and more advanced liver disease, as well as a second infection, are more likely to develop stages 2 or 3 AKI, with a progressive course associated with decreased 30-day transplant-free survival. Prevention of AKI progression in patients with cirrhosis and stage 2 or 3 AKI might improve their outcomes.

Assessment and Interpretation of Vitamin and Trace Element Status in Sick Children: A Position Paper From the European Society for Paediatric Gastroenterology Hepatology, and Nutrition Committee on Nutrition.

Assessment of vitamin and trace element status (VTE) is important in the clinical management of the sick child. In this position paper, we present the various assessment methods available to the clinical practitioner, and critically discuss pitfalls with interpretation of their results. There are 4 main approaches to assess the VTE body status of an individual patient including clinical examination, dietary assessment, and measurement of direct and indirect biomarkers of VTE in biological samples. Clinical signs of VTE deficiencies usually present only when body stores are substantially depleted and are often difficult to detect or differentiate from other nonnutrient-related causes. In isolation, dietary assessment of micronutrients can be inaccurate and imprecise, in disease and in individual patient assessment but may be useful to complement findings from other VTE assessment methods. Use of biomarkers is the most common approach to assess VTE status in routine practice but in the presence of systemic inflammatory response and in the absence of appropriate paediatric reference intervals, interpretation of biomarker results might be challenging and potentially mislead clinical practice. The use of a multimodal approach, including clinical examination, dietary assessment, and laboratory biomarkers is proposed as the optimal way to ascertain the VTE status of individual patients. In the presence of acute inflammatory conditions, VTE measurements in plasma should be replaced by biomarkers not affected by systemic inflammatory response or delayed until inflammatory state is resolved.

Mesna Alleviates Cerulein-Induced Acute Pancreatitis by Inhibiting the Inflammatory Response and Oxidative Stress in Experimental Rats.

Acute pancreatitis (AP) is a sudden inflammation of the pancreas that may be life-threatening disease with high mortality rates, particularly in the presence of systemic inflammatory response and multiple organ failure. Oxidative stress has been shown to be involved in the pathophysiology of acute pancreatitis. This study is designed to investigate the possible effect of mesna on an experimental model of cerulein-induced acute pancreatitis. Animals were divided into five groups: Group 1 served as a control group given the saline; group II (mesna group) received mesna at a dose of (100mg/kg per dose, i.p.) four times; group III (acute pancreatitis group) received cerulein at a dose of (20µg/kg/dose, s.c.) four times with 1-h intervals; group VI, cerulein + mesna, was treated with mesna at a dose of (100mg/kg, i.p.) 15min before each cerulein injection. Animals with acute pancreatitis showed elevated serum amylase and lipase levels. Biochemical parameters showed increased pancreatic tumor necrosis factors-α (TNF-α) and interleukin-1β (IL-1β) levels. A disturbance in oxidative stress markers was evident by elevated pancreatic lipid peroxides (TBARS) and decline in pancreatic antioxidants' concentrations including reduced glutathione (GSH); superoxide dismutase (SOD); and glutathione peroxidase (GSH-Px). Histological examination confirmed pancreatic injury. Pre-treatment with mesna was able to abolish the changes in pancreatic enzymes, oxidative stress markers (TBARS, SOD, GSH and GSH-Px), pancreatic inflammatory markers (TNF-α, IL-1β) as well as histological changes. Mesna mitigates AP by alleviating pancreatic oxidative stress damage and inhibiting inflammation.

The relation between Malnutrition Universal Screening Tool (MUST), computed tomography–derived body composition, systemic inflammation, and clinical outcomes in patients undergoing surgery for colorectal cancer

Nutritional status is an important factor affecting a patient's clinical outcomes. Early identification of patients who are at risk of malnutrition is important to improve clinical outcomes and reduce health cost. The Malnutrition Universal Screening Tool (MUST) has been recommended as part of the routine nursing assessment for all patients at hospital admission. The aim of this study was to examine the association between nutritional status (MUST), systemic inflammatory response (SIR), body composition, and clinical outcomes in patients undergoing surgery for colorectal cancer. The malnutrition risk was examined using MUST in patients admitted for surgery for colorectal cancer between March 2013 and June 2016. Preoperative computed tomography scans were used to define the body composition. The presence of SIR was evidenced by the modified Glasgow prognostic score and the neutrophil to lymphocyte ratio. Postoperative complications, severity of complication, length of hospital stay, and mortality were considered as outcome measures. The study included 363 patients (199 males, 164 females); 21% of the patients presented with a medium or high nutritional risk. There were significant associations between MUST and subcutaneous adiposity (P<0.001), visceral obesity (P<0.001), and low skeletal muscle index (P<0.001). No statistically significant association was identified between MUST score and presence of any complication or severity of complication. On multivariate analysis, MUST remained independently associated with the length of hospital stay (OR: 2.17; 95% CI: 1.45, 3.26; P<0.001). Kaplan-Meier survival curves showed an increased number of deaths for patients at medium or high risk of malnutrition (P<0.001). This association was found to be independent of other confounding factors (HR: 1.45; 95% CI: 1.06, 1.99; P=0.020). MUST score is an independent marker of risk in those undergoing surgery for colorectal cancer and should remain a key part of preoperative assessment.

Increased Neutrophil-lymphocyte and Platelet-lymphocyte Ratios in Male Heroin Addicts: A Prospective Controlled Study.

ObjectiveThe neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are markers that can determine the presence of systemic inflammatory response. In this study, we examined the NLR and PLR levels in patients with heroin dependence compared to healthy controls.MethodsThe study sample included 90 male patients with heroin dependence aged 18 to 45 years and 60 healthy subjects who had similar socio-demographic characteristics as the patient group. The diagnoses of heroin dependence and other Axis I psychiatric disorders in the patient and control groups were screened with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID-I). The extent of heroin addiction was assessed with the Addiction Severity Index (ASI).ResultsThe mean NLR and PLR levels of patients with heroin dependence were significantly higher than the control subjects (p=0.031 and p<0.001, respectively). Positive correlations were found between NLR, PLR and duration of the disorder.ConclusionOur results indicate that inflammatory processes may play a role in the pathophysiology of heroin dependence.

How well does qSOFA correspond to underlying systemic inflammatory response?

Need for prompt recognition and management of sepsis recently led to the introduction of qSOFA score. However, its association with underlying host inflammatory response remains unclear, while previous studies have challenged its performance in non – intensive care unit (ICU) patients comparing to previously used systemic inflammatory response syndrome (SIRS) criteria. Between June 2016 and April 2017, we performed a prospective observational study in the medical ward of a tertiary hospital to explore the relation of qSOFA ≥ 2 and <2 to underlying inflammatory response, as this is mirrored in levels of serum pro- and anti-inflammatory mediators i.e. IL-6, IL-10 and TNF-α. A total of 100 consecutive patients were finally included in this study. Comparable levels [(pg/ml) median (IQR)] of IL-6 [200 (53–200) vs 65.1 (17.3–200)], IL-10 [ 7 (2.3–170.6) vs 2.3 (2.3–27.7)], and TNF-α [4 (4–46.1) vs 46.06 (4–227.2)] were noted between group of patients with qSOFA ≥ 2 or <2. Nevertheless, prognosis was worse in patients with qSOFA ≥ 2 showing longer length of stay [10 (7–25) vs 5 (3–7) days, p = .03] and lower recovery rates (41 vs 93%, p < .0001). Our results underline the need for prompt management of critically ill patients in presence of systemic inflammatory response regardless of qSOFA score, partly reflecting its low sensitivity comparing to previously used SIRS criteria.

Handcrafted Vacuum‐Assisted Device for Skin Ulcers Treatment Versus Traditional Therapy, Randomized Controlled Trial

Chronic lower limb ulcers constitute a public health problem, with important socioeconomic implications and high attention cost. This trial evaluates handcrafted vacuum-assisted therapy versus traditional treatment effectiveness for lower limbs ulcers. It was a prospective randomized clinical trial conducted over 144 patients with lower limbs ulcers. Patients were randomized into two groups of 72 patients: Experimental group were treated with debridement, cure and a handcrafted vacuum-assisted device that was changed every 72h. Control group was treated with debridement and cure with soap every 24h. Ulcers were evaluated every 72h and on 10th day. The presence of systemic inflammatory response, pain, granulation tissue and viability for discharge was registered and analyzed . After exclusion of 18 patients, 126 were included, 65.1% were men with an average of 58years. Sole region ulcer by diabetic foot was the more frequent in both groups (73%). Leukocytes count, systemic inflammatory response and pain were significantly lower in experimental group (p<0.05). Discharge criteria and granulation tissue were present earlier in experimental group (p<0.05). Handcrafted vacuum-assisted system is a feasible and safe method to treat chronic ulcers. This system would benefit patients favoring earlier infection control, faster granulation tissue appearance and earlier discharge. Clinical trials registered in https://www.clinicaltrials.gov/ Number NCT02512159.

The Glasgow Prognostic Score (GPS) predicts toxicity and efficacy in platinum-based treated patients with metastatic lung cancer

PurposeLung cancer is the most common cause of cancer death. A cumulative prognostic score based on C-reactive protein and albumin, termed the Glasgow Prognostic Score (GPS), indicates the presence of systemic inflammatory response. GPS has been proposed as a powerful prognostic tool for patients with various types of malignant tumors, including lung cancer. The aim of this study was to assess the predictive value of baseline GPS in terms of toxicity and response in lung cancer patients treated with platinum-based chemotherapy. Patients and methodsPatients referred to our institution for consideration of first-line platinum-based treatment were eligible. Demographics and disease-related characteristics were recorded. Toxicity was graded according to NCI CTCAE version 3.0 throughout first-line therapy. GPS was calculated before the onset of treatment and was related to the development of toxicity. Response to first-line therapy and survival data were also collected. ResultsTotally, 96 lung cancer patients were accrued. GPS was associated with increased mucositis p=0.004), neurotoxicity (p=0.038), neutropenia (p=0.02), dose reductions or/ and need for granulocyte colony-stimulating factor (G-CSF) support (p=0.005), toxicity-related termination of treatment (p=0.001) and chemotherapy-related toxic deaths (p=0.013). GPS was associated with overall survival (p=0.016) and progression-free survival (p=0.016) as well as response to treatment (p=0.05). ConclusionsOur data demonstrate that GPS assessment is predictive of the most important aspects of platinum-related toxicity and this may partly explain its associations with poor clinical outcome in patients with metastatic lung cancer.

A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI)

Background:There is increasing evidence that the presence of an ongoing systemic inflammatory response is a stage-independent predictor of poor outcome in patients with cancer. The aim of this study was to investigate whether an inflammation-based prognostic score, the prognostic nutritional index (PNI), is associated with overall survival (OS) in patients with hepatocellular carcinoma (HCC).Methods:All patients with a new diagnosis of HCC presenting to the Medical Oncology Department, Hammersmith Hospital between 1993 and 2011 (n=112) were included. Demographic and clinical data were collected. Patients in whom the combined albumin (g l−1) × total lymphocyte count × 109 l−1 was ⩾45, at presentation, were allocated a PNI score of 0. Patients in whom this total score was <45 were allocated a score of 1. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with OS. Independent predictors of survival identified on multivariate analysis were validated in an independent, stage-matched cohort of 68 patients.Results:Univariate analyses showed that PNI (P=0.003), intrahepatic spread (P<0.001), the presence of extrahepatic disease (P=0.006), portal vein thrombosis (P=0.02), tumour multifocality (P=0.003), alfa-fetoprotein >400 ng ml−1 (P<0.001) and Barcelona Clinic Liver Cancer score (P<0.01) were all predictors of OS in the training set. Multivariate analysis revealed the PNI (P=0.05), presence of extrahepatic disease (P<0.001) and degree of intrahepatic spread (P<0.001) as independent predictors of worse OS in this population. The PNI retained independent prognostic value in the validation set (P<0.001).Conclusion:The presence of a systemic inflammatory response, as measured by the PNI, is an independent and externally validated predictor of poor OS in patients with HCC.

Systemic inflammatory response to predict clinical outcome in patients with resected pancreatic cancer treated with adjuvant gemcitabine monotherapy.

223 Background: Systemic inflammatory response (SIR) has been shown to associate with poor outcome in either inoperable or operable pancreatic cancer. However, whether the presence of a SIR predicts poor clinical outcome of pancreatic cancer patients in adjuvant setting is unclear. The aim of present study was to determine the relationship between SIR, as evaluated by Modified Glasgow prognostic score (mGPS), and outcome of pancreatic cancer patients treated with adjuvant chemotherapy. Methods: A total of 42 resected pancreatic cancer patients were analyzed for mGPS before adjuvant gemcitabine chemotherapy. The mGPS was constructed as follows: patients with both an elevated C-reactive protein (&gt; 0.3mg/dl) and hypoalbuminaemia (&lt; 3.5mg/dl) were allocated a score of 2. Patients with one or none of these abnormalities were allocated a score of 1or 0, respectively. Results: There were 25 patients assigned to score 0, 12 patients to score 1, and 5 patients to score 2. The median OS in patients with score 0, score 1, and score 2 were 23.9 months, 10.3 months, and 9.9 months, respectively. The DFS in patients with score 0, score 1, and score 2 were 11.0 months, 5.9 months, and 3.6 months, respectively. The OS and DFS after surgery of the patients with SIR (score 1 and 2) were significantly poorer than that of the patients with score 0 (P=0.0278 for OS, P=0.0011 for DFS by log-rank test). Conclusions: The presence of SIR, as evaluated by Modified Glasgow prognostic score (mGPS), predicts poor clinical outcome in resected pancreatic cancer patients treated with adjuvant gemcitabine monotherapy.

Prognostic significance of a systemic inflammatory response in patients receiving first-line palliative chemotherapy for recurred or metastatic gastric cancer

BackgroundThere is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor prognosis in patients with advanced cancers. We evaluated the relationships between clinical status, laboratory factors and progression free survival (PFS), and overall survival (OS) in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy.MethodsWe reviewed 402 patients with advanced gastric adenocarcinoma who received first-line palliative chemotherapy from June 2004 and December 2009. Various chemotherapy regimens were used. Eastern Cooperative Oncology Group performance status (ECOG PS), C-reactive protein (CRP), albumin, Glasgow prognostic score (GPS), and clinical factors were recorded immediately prior to first-line chemotherapy. Patients with both an elevated CRP (>1.0 mg/dL) and hypoalbuminemia (<3.5 mg/dL) were assigned a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were assigned a GPS of 1, and patients with a normal CRP and albumin were assigned a score of 0. To evaluate the factors that affected PFS and OS, univariate and multivariate analyses were performed.ResultsAccording to multivariate analysis, the factors independently associated with PFS were ECOG PS (HR 1.37, 95% CI 1.02-1.84, P = 0.035), bone metastasis (HR 1.74, 95% CI 1.14-2.65, P = 0.009), and CRP elevation (HR 1.64, 95% CI 1.28-2.09, P = 0.001). The factors independently associated with OS were ECOG PS (HR 1.33, 95% CI 1.01-1.76, P = 0.037), bone metastasis (HR 1.61, 95% CI 1.08-2.39, P = 0.017), and GPS ≥ 1 (HR 1.76, 95% CI 1.41-2.19, P = 0.001).ConclusionsThe results of this study showed that the presence of a systemic inflammatory response as evidenced by the CRP, GPS was significantly associated with shorter PFS and OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Bone metastasis and GPS were very useful indicator for survival in patients with recurrent or metastatic gastric cancer receiving palliative chemotherapy.

Effect of pentoxifylline and/or alpha lipoic acid on experimentally induced acute pancreatitis

Acute pancreatitis is a sudden inflammation of the pancreas that may be life threatening disease with high mortality rates; particularly in presence of systemic inflammatory response and multiple organ failure despite of the conventional antibiotic and symptomatic treatment. Oxidative stress has been shown to be involved in the pathophysiology of acute pancreatitis. This study was designed to investigate the possible effect of pentoxifylline and alpha lipoic acid respectively and in combination on rats with L-arginine induced acute pancreatitis. Rats were divided as follow; Group 1: served as control, Group 2 and Group 3: sacrificed after 24 h and 7 days; respectively, from induction of acute pancreatitis by L-arginine 250 mg/100 g, Group 4 and Group 5: rats treated by pentoxifylline (12 mg/kg) and sacrificed after 24 h and7 days; respectively, from induction of acute pancreatitis, Group 6 and Group 7: treated by alpha lipoic acid (1 mg/kg) and sacrificed after 24 h and 7 days; respectively, from induction of acute pancreatitis, Group 8 and Group 9: treated by pentoxifylline and alpha lipoic acid and sacrificed after 24 h and 7 days; respectively, from induction of acute pancreatitis. Serum samples were collected to assay levels of amylase enzyme, C-reactive protein, IL-6, catalase enzyme activity, malondialdehyde and pancreases were excised for histopathological examination and assay of pancreatic myeloperoxidase. L-arginine induced-acute pancreatitis was evident by increased in serum marker enzymes and by histopathological findings compared to control group. Pentoxifylline and alpha lipoic acid respectively provided protection against L-arginine induced acute pancreatitis possibly by their antioxidant and anti-inflammatory effect. Treatment with alpha lipoic acid exhibited pronounced improvement in the course of pancreatitis when compared to treatment with pentoxifylline. Moreover, the combination of pentoxifylline and alpha lipoic acid offered the most evident protection when compared to groups that received monotherapy; pointing to the effectiveness of such combination therapy.

Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study

BackgroundA frequent manifestation of advanced NSCLC is malnutrition, even though there are many studies which relate it with a poor survival, its relation with toxicity has not yet been consistently reported. The aim of this study was to associate malnutrition and albumin serum levels with the occurrence of chemotherapy-induced toxicity in cisplatin plus paclitaxel chemotherapy-treated NSCLC.MethodsWe prospectively evaluated 100 stage IV NSCLC patients treated with paclitaxel (175 mg/m2) and cisplatin (80 mg/m2). Malnutrition was assessed using SGA prior treatment. Neutrophil Lymphocyte Ratio (NLR) and the Platelet Lymphocyte Ratio (PLR) were used to determine the presence of systemic inflammatory response (SIR) and were related to the development of toxicity. Toxicity was graded according to NCI CTCAE version 3.0 after two chemotherapy cycles.ResultsMedian age was 58 ± 10 years, 51% of patients were malnourished, 50% had albumin ≤3.0 mg/mL. NLR ≥ 5 was associated with basal hypoalbuminemia (mean ranks, 55.7 vs. 39 p = 0.006), ECOG = 2 (47.2 vs. 55.4 p = 0.026) and PLR ≥ 150 were significantly related with a basal body mass index ≤20 (56.6 vs. 43.5; p = 0.02) and hypoalbuminemia (58.9 vs. 41.3; p = 0.02). Main toxicities observed after 2 cycles of chemotherapy were alopecia (84%), nausea (49%), neuropathy (46%), anemia (33%), lymphopenia (31%), and leukopenia (30%). Patients malnourished and with hypoalbuminemia developed more chemotherapy-induced toxicity overall when compared with those without malnutrition (31 vs 22; p = 0.02) and normal albumin (mean ranks, 62 vs 43; p = 0.002), respectively. Hypoalbuminemia was associated with anemia (56 vs 47; p = 0.05), fatigue (58 vs 46; p = 0.01), and appetite loss (57.1 vs 46.7; p = 0.004) compared with normal albumin. PLR ≥ 150 was related with the development of toxicity grade III/IV (59.27 vs. 47.03 p = 0.008) and anemia (37.9 vs 53.8 p = 0.004).ConclusionSIR parameters were associated with malnutrition, weight loss and hypoalbuminemia. Chemotherapy-induced toxicity in NSCLC patients treated with paclitaxel and cisplatin was associated with malnutrition and hypoalbuminemia. Early nutritional assessment and support might confer beneficial effects.

Evaluation of an inflammation-based prognostic score in patients with advanced ovarian cancer

Background There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of this study was to validate whether an inflammation-based prognostic score (Glasgow Prognostic Score, GPS) is associated with survival in patients with advanced stage (stage III/IV) ovarian cancer. Patients and methods An audit was conducted of patients with a new diagnosis of stage III or IV ovarian cancer presenting to the West London Gynae-Oncology Centre between October 2003 and June 2006 ( n = 154). The GPS was constructed as follows: Patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminaemia (<35 g/l) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. Results On univariate analysis GPS, histological type, ALP, performance status, primary surgery and ascites were predictors of overall survival. On multivariate a high GPS score, non-serous histology, high ALP and no initial surgery were independent predictors of worse overall survival in this population. Conclusions The presence of a systemic inflammatory response, as measured by the GPS, is an independent predictor of poor overall survival in patients with advanced ovarian cancer independent of treatment received.

The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer

The systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, is a stage-independent prognostic factor in patients undergoing curative nephrectomy for localised renal cancer. However, it is not clear whether the systemic inflammatory response arises from the tumour per se or as a result of an impaired immune cytokine response. The aim of the present study was to examine C-reactive protein, interleukin-6 and interleukin-10 concentrations before and following curative resection of renal cancer. Sixty-four patients with malignant renal disease and 12 with benign disease, undergoing resection were studied. Preoperatively, a blood sample was collected for routine laboratory analysis with a further sample stored before analysis of interleukin-6 and interleukin-10 using an enzyme-linked immunosorbent assay (ELISA) technique. The blood sampling procedure and analyses were repeated at approximately 3 months following resection. Circulating concentrations of both interleukin-6 and interleukin (P⩽0.01) were higher and a greater proportion were elevated (P<0.05) in malignant compared with benign disease. The renal cancer patients were grouped according to whether they had evidence of a systemic inflammatory response. In the inflammatory group T stage was higher (P<0.01), both interleukin-6 and interleukin-10 concentrations were higher (P<0.001) and elevated (P<0.10) compared with the non-inflammatory group. Tumour volume was weakly correlated with C-reactive protein (r2=0.20, P=0.002), interleukin-6 (r2=0.20, P=0.002) and interleukin-10 (r2=0.24, P=0.001). Following nephrectomy the proportion of patients with elevated C-reactive protein, interleukin-6 and interleukin-10 concentrations did not alter significantly. An elevated preoperative C-reactive protein was associated with increased tumour stage, interleukin-6 and interleukin-10 concentrations. However, resection of the primary tumour did not appear to be associated with significant normalisation of circulating concentrations of C-reactive protein, interleukin-6 or interleukin-10. Therefore, the presence of systemic inflammatory response is unlikely to be solely be determined by the tumour itself, but may be as a result of an impaired immune cytokine response in patients with renal cancer.