An Intravenous 100-mL Lipid Emulsion Infusion Dramatically Improves Myocardial Glucose Metabolism Extinction in Cardiac FDG PET Clinical Practice.

PURPOSE: Physiological myocardial accumulation of FDG impairs the diagnosis of inflammatory/infectious or tumoral myocardial detection by FDG PET/CT. We prospectively evaluated the addition, 3 hours before imaging, of an intravenous 100-mL lipid emulsion infusion (Intralipid) to a high-fat, low-carbohydrate diet (HFLCD) for at least 2 meals followed by a fast of at least 6 to 12 hours in patients referred for the diagnosis of myocardial inflammation, endocarditis, cardiac or paracardiac masses, intracardiac device, or prosthetic valve infections. METHODS: Data of 58 patients consecutively included (28 Intralipid patients, 30 controls with HFLCD alone) were compared. FDG uptake in normal myocardium was scored from 0 (complete myocardial suppression) to 3 (high diffuse uptake). Myocardial maximal, peak, and mean SUV and the rate of interpretable images according to the clinical indication were measured. RESULTS: Compared with controls, Intralipid infusion significantly improved the rate of score 0 (89% vs 63%, P = 0.021), of interpretable images according to the clinical indication (100% vs 72%, P = 0.0047) and decreased all myocardial SUV values (eg, SUVmax median, 1.9 [interquartile range, 1.7-2.5] vs 3.1 [interquartile range, 2.3-4.1]; P < 0.001). CONCLUSIONS: A lipid emulsion infusion in addition to HFLCD better suppresses cardiac glucose metabolism than HFLCD alone.

Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma.

Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18-25 year old controls and 50-80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.

Incremental value of normal adenosine perfusion cardiac magnetic resonance: Long-term outcome.

BACKGROUND: The purpose of the study was to determine the long-term prognostic value of normal adenosine stress cardiac magnetic resonance imaging (CMR) in patients referred for evaluation of myocardial ischemia. METHODS: We reviewed 300 consecutive patients (age 65 ± 11 years, 74% male) with suspected or known coronary disease and normal wall motion who had undergone adenosine stress CMR negative for ischemia and scar. Most patients were at intermediate risk of coronary artery disease. The end points studied were all causes of mortality and major adverse cardiac events, including cardiac death, myocardial infarction, revascularization, and hospitalization for unstable angina. RESULTS: During a mean follow-up of 5.5 years (mean = 5.4 ± 1.1), 16 patients died because of various causes (cardiac death in 5 patients). Three patients had a nonfatal myocardial infarction, 7 patients were hospitalized for revascularization, and 11 were medically treated for unstable angina. The annual cardiac event rate was 1.3% (0.78% in the first 3 years and 1.9% between the fourth and sixth years). The predictors of major adverse cardiac events in a multivariate analysis model were as follows: advanced age (hazard ratio [HR] 1.15, 95% confidence interval [95% CI] 1.02-1.30), diabetes (HR 17.5, 95% CI 2.2-140), and the habit of smoking (HR 5.9, 95% CI 1.0-35.5). For all causes of mortality, the only predictor was diabetes (HR 11.4, 95% CI 1.76-74.2). Patients with normal stress CMR had an excellent outcome during the 3 years after the study. The cardiac event rate was higher between the fourth and sixth years. CONCLUSION: Over a 5.5-year period, a low event rate and excellent prognosis occurred in patients with normal adenosine stress CMR. Low- to intermediate-risk patients with a normal CMR are at low risk for subsequent cardiac events.

Relative impact of iodine supplementation and maternal smoking on cord blood thyroglobulin in pregnant women with normal thyroid function.

OBJECTIVE: To assess the impact on cord blood (CB) thyroglobulin (Tg) of early iodine supplementation during pregnancy. METHODS: A total of 111 healthy pregnant women with normal thyroid function were included in a prospective randomized study and divided into two groups with (150 µg/day) or without iodine supplementation started during the first trimester. Maternal smoking was assessed qualitatively by self-reported statements and quantitatively by cotininuria. Exhaustive thyroid tests were performed at delivery in the mother and in CB. RESULTS: Third-trimester ioduria documented compliance with iodine supplementation (160 vs. 76 µg/l in controls). CB Tg was not different between the iodine and control groups (median 77 vs. 79.5 ng/ml, respectively) and did not correlate with maternal ioduria. CB Tg was higher in newborns from smoking mothers (114 vs. 64.7 ng/ml) and correlated with self-reported smoking status more than with maternal cotininuria. Nonsmokers had no difference in CB Tg whether they took iodine supplementation or not, as opposed to smokers, who tended to benefit from supplementation. CONCLUSIONS: Iodine supplementation does not significantly impact CB Tg in healthy nonsmoker pregnant women selected for normal thyroid function, as opposed to maternal smoking. CB Tg appears to be a marker of in utero tobacco exposure. In areas of mild iodine deficiency, iodine supplementation could especially benefit the fetuses of smokers.

[Assessment of an immature platelet fraction (IFP%) in the diagnosis of thrombocytopenia]. / Valeur du pourcentage de plaquettes réticulées dans le diagnostic étiologique d'une thrombopénie.

Reticulated platelets are young platelets containing mRNA. They reflect the rate of thrombopoesis. The aim of this study was to evaluate the reliability of the percentage of reticulated platelets (IPF%) as a diagnostic test for thrombocytopenia pathogenesis. IPF% was measured using XE 2100 Sysmex. An IPF% reference range in 52 healthy individuals was established as 1-4.5% with a median 2.2%. In all the 13 patients with idiopathic thrombocytopenic purpura IPF% was increased (median 11.8, range 5.3-54.3%). Only 7 out of 18 patients with disseminated intravascular coagulation had high IPF% (median 5.4%, range 2.9-14.1%). Surprisingly, IPF% was increased in 17 out of 22 patients with acute leukaemia (median 9.7%, range 0.9-41.9%). In CIVD, IPF% values correlated with the severity of the illness. Increased values in acute leukaemia could not be explained by non specific staining but by delayed maturation of reticulated platelets. A high IPF% does not substantiate hyperdestructive thrombocytopenia but a diagnosis of idiopathic thrombocytopenic purpura should be questioned if IPF% is not raised.

Relationship between impulse oscillometry and spirometric indices in cystic fibrosis children.

BACKGROUND: The aim of our retrospective study was to determine the relationship between impulse oscillometry (IOS) data and spirometric tests in cystic fibrosis (CF) children. methods: Thirty CF children aged 4-19 years have performed lung function tests (LFT). A subset of 15 patients repeated LFT on five separate occasions. IOS parameters were respiratory resistance (Rrs), reactance (Xrs) and impedance at 5 Hz (R5, X5, Zr) and the resonant frequency (Fres). Spirometry indices (SI) included forced expiratory volume in 1 sec (FEV(1)), forced expiratory flow during the middle half of FVC (FEF(25-75)) and forced vital capacity (FVC). RESULTS: An inverse relationship was observed between raw values of R5, Zr, Fres and SI respectively, and X5 correlated positively with SI. Although significant, these correlations were poor. Receiver operating characteristic curves (ROC) were constructed to identify cutoff points for IOS parameters to discriminate between children according to predefined FEV(1) thresholds (percent predicted), generally used to categorize the level of lung function impairment. No acceptable cutoff points can be found for IOS parameters. Trends analyses in the subgroup of 15 patients showed a significant decline of FEV(1) between the first and the fifth evaluation. None of the IOS indices demonstrated a consistent tendency, apart from a slight decrease of Fres. CONCLUSION: IOS measurements presented an insufficient sensitivity to detect and follow bronchial obstruction in CF patients.

NF-kappaB inhibition triggers death of imatinib-sensitive and imatinib-resistant chronic myeloid leukemia cells including T315I Bcr-Abl mutants.

The Bcr-Abl inhibitor imatinib is the current first-line therapy for all newly diagnosed chronic myeloid leukemia (CML). Nevertheless, resistance to imatinib emerges as CML progresses to an acute deadly phase implying that physiopathologically relevant cellular targets should be validated to develop alternative therapeutic strategies. The NF-kappaB transcription factor that exerts pro-survival actions is found abnormally active in numerous hematologic malignancies. In the present study, using Bcr-Abl-transfected BaF murine cells, LAMA84 human CML cell line and primary CML, we show that NF-kappaB is active downstream of Bcr-Abl. Pharmacological blockade of NF-kappaB by the IKK2 inhibitor AS602868 prevented survival of BaF cells expressing either wild-type, M351T or T315I imatinib-resistant mutant forms of Bcr-Abl both in vitro and in vivo using a mouse xenograft model. AS602868 also affected the survival of LAMA84 cells and of an imatinib-resistant variant. Importantly, the IKK2 inhibitor strongly decreased in vitro survival and ability to form hematopoietic colonies of primary imatinib resistant CML cells including T315I cells. Our data strongly support the targeting of NF-kappaB as a promising new therapeutic opportunity for the treatment of imatinib resistant CML patients in particular in the case of T315I patients. The T315I mutation escapes all currently used Bcr-Abl inhibitors and is likely to become a major clinical problem as it is associated with a poor clinical outcome.

Cancer risk and impact of disease-modifying treatments in patients with multiple sclerosis.

BACKGROUND: Prior to the era of immunomodulating or immunosuppressive (IS) treatments Multiple Sclerosis (MS) was linked to reduced rates of cancer. Method A descriptive study of MS patients with a documented oncological event was performed. From 1 January 1995 to 30 June 2006, we collected and studied the profile of 7,418 MS patients gathered from nine French MS centers. We evaluated the incidence of cancer in a Cancer Risk In MS Cohort. RESULTS: Thirty one patients (1.75%) with confirmed MS had a history of cancer: mean age at MS diagnosis of 37.9 years and a mean age at cancer diagnosis of 46.4 years. The most frequent cancers were breast (34.5%), gynecological (12.5%), skin (10.2%), acute leukemia and lymphoma (5.9%), digestive (8.8%), kidney and bladder (5.1%), lung (3.4%) and central nervous system (3%). Calculated standardized incidence rates were 0.29 (0.17-0.45) for men and 0.53 (0.42-0.66) for women. The incidence of cancer in this MS population was lower than that expected for the general population. Matched to age, gender and histology, cancers in MS were associated with a young age and exposure to IS treatments. When considering all patients, treated patients had a 3-fold higher risk of developing cancer, if they had a history of IS (P = 0.0035). For treated patients, the cancer sites were more likely the breast, the urinary tract, the digestive system and the skin. CONCLUSION: Our data suggest that MS patients do not have an increased risk of cancer. Rather for several types of cancer a significantly reduced risk was observed, except for breast cancer in women treated with IS. The relative increased risk of breast cancer in MS women under IS treatment warrants further attention.

Sarcomatoid lung cancer (spindle/giant cells): an aggressive disease?

OBJECTIVE: We investigated the clinical, surgical, and pathologic features of sarcomatoid lung carcinomas with spindle/giant cells, giving special attention to the prognostic behavior of these rare tumors. METHODS: Surgical specimens from 39 patients (29 men and 10 women; mean age, 61 years) were examined by means of light microscopy. Preoperative and postoperative data were collected, and survival was calculated by using the Kaplan-Meier method. RESULTS: Nineteen patients were diagnosed with cancer preoperatively. Only one sarcomatoid tumor had been diagnosed. Presenting symptoms were noted in 85% of patients, and complete resection was achieved in 37 tumors. Postoperative pTNM staging: T2/T3/T4, 22/15/2; N0/N1/N2, 28/8/3; 15 stage IB, 14 stage IIB, 7 stage IIIA, 2 stage IIIB, and 1 stage IV. Histopathologic analysis revealed necrosis in 90% of the tumors (34 pleomorphic, 3 spindle cell, and 2 giant cell carcinomas). During follow-up (median, 24 months), 21 patients died of disease recurrence, and 3 died of postoperative complications. The 5-year survival rate (33%; median, 11 months) was negatively influenced by large tumors (7.5% survival for > or =7 cm vs 56% for <7 cm, P = .0026). The disease-free interval was significant for patients who relapsed (0% for disease-free interval <6 months vs 33% for disease-free interval > or =6 months, P = .0019). CONCLUSIONS: A highly heterogeneous group, spindle/giant cell lung carcinomas tend to be symptomatic, peripheral, and necrotic. Preoperative diagnosis is difficult. Most patients in our study relapsed and died the first year after surgical intervention. Surgical intervention can permit long-term survival, but adjuvant therapy warrants consideration because of the aggressive nature of these tumors.

Prophylactic use of noninvasive ventilation in patients undergoing lung resectional surgery.

QUESTION OF THE STUDY: We studied whether prophylactic use of noninvasive pressure support ventilation (NIPSV) administered pre- and postoperatively may reduce the postoperative pulmonary function impairment. PATIENTS AND METHODS: Prospective randomized clinical trial. Thirty-nine patients with a preoperative FEV(1) <70% of the predicted value scheduled for elective lobectomy related to lung cancer were enrolled. Seven patients were excluded after enrollment. Patients were required to follow standard treatment without (control group, n=18) or with NIPSV (study group, n=14) during 7 days at home before surgery, and during 3 days postoperatively. Primary outcome variable was the changes on arterial blood gases on room air. RESULTS: Two hours after surgery, PaO(2), FVC and FEV(1) values were significantly better in the NIPSV group. On day 1, 2 and 3, PaO(2) was significantly improved in the NIPSV group. Also on day 1, FVC and FEV(1) improved significantly in the NIPSV group. The hospital stay was significantly longer in the control group than in the study group (p=0.04). The incidence of major atelectasis was 14.2% in the NIPSV group and 38.9% in the no-NIPSV group (p=0.15). ANSWER TO THE QUESTION: Prophylactic use of NIPSV in a pre- and postoperative manner significantly reduces pulmonary dysfunction after lung resection. As a result, recovery of preoperative respiratory function is accelerated.

Long-term survival of patients downstaged by oxaliplatin and 5-fluorouracil combination followed by rescue surgery for unresectable colorectal liver metastases.

OBJECTIVES: To evaluate long-term survival of patients resected for primarily unresectable colorectal liver metastases downstaged by systemic chemotherapy. METHODS: Among a group of 82 patients with advanced colorectal cancer, 39 had unresectable liver metastases. After treatment with systemic 3-weekly 5FU/folinic acid/oxaliplatin chemotherapy, the outcome of 11 patients made resectable thanks to chemotherapy was compared to that of 28 patients who were not. Criteria for non-resectability consisted of diffuse bilobar invasion with inability to achieve complete resection, unilobar or bilobar invasion plus vascular extension (invasion of inferior vena cava or 2 supra-hepatic veins plus continuity with the 3rd) or involvment of hepatic pedicle. Before and after surgery, CT scan evaluation was performed every 2 months. Progression free survival was defined as the time between starting chemotherapy and recurrence of the disease. We used Kaplan-Meier survival curves and log-rank test for comparisons, P values were two-sided and considered significant if<0.05. RESULTS: Progression free survival times were 14 and 6 months, median overall survival were 60 and 18.5 months, respectively, in favour of secondary resected subjects. CONCLUSION: Considering the magnitude of the survival benefit, one may question the need and feasibility for trials to assess more formally the impact of surgery in that setting.

Gemcitabine combined with oxaliplatin is safe and effective in patients with previously untreated advanced pancreatic adenocarcinoma.

AIM: The aim of this study was to determine the safety and the efficacy of a gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients with metastatic or unresectable locally-advanced pancreatic cancer. PATIENTS AND METHODS: Patients received gemcitabine 1000 mg/m2 as a 10-mg/m2/min infusion on day 1 followed on day 2 by oxaliplatin 100 mg/m2 as a 2-hour infusion, each cycle being given every 2 weeks. All patients had measurable disease and histological diagnosis before inclusion. Patients were treated until progression or for 12 cycles in the absence of progression. Tumor lesions were assessed by computed tomography scan every 4 cycles. RESULTS: Between January 2001 and January 2003, 32 patients were eligible for the study. The objective response rate (OR) was 28.1% with a 12.5% complete response rate (CR). Median progression-free survival and median overall survival were 7 and 9 months, respectively. Median overall survival for patients with metastatic disease and locally-advanced disease were 7 and 25 months, respectively (P < 0.0007). Eleven patients were alive at 1 year (34.4%), six at 2 years (18.8%) and two at 3 years (6%). Fourteen (43.8%) of 32 patients experienced a clinical benefit response. CONCLUSION: These results support the safety, the antitumor activity and the possibility of durable responses of the GEMOX regimen in patients with locally-advanced disease.