Blood gas analysis in patients with hyperleucocytosis: validity of repeated measures on same sampling without ice?
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Blood Gas Analysis↗
Biomedical subjects
B Escudier
Publications and source records attributed to B Escudier.
Immunotherapy with interleukin-2 (IL2) and lymphokine-activated natural killer cells: improvement of clinical responses in metastatic renal cell carcinoma patients previously treated with IL2.
Treatment with interleukin-2 (IL2) induces clinical responses in 15-30% of metastatic renal cell carcinoma (MRCC) patients, with mainly partial responses. In order to improve clinical response, we decided to treat partial response patients from a previous IL2 treatment with a second course of IL2 associated with lymphokine-activated natural killer (LANAK) cells. 10 patients who underwent PR after an IL2 protocol (24 x 10(6) U/m2/day, 2 days a week for 5 weeks, either alone or with interferon-gamma) subsequently received a combination of high-dose IL2 (16-20 x 10(6) U/m2/day, 2 days a week) and LANAK cell infusions. Four complete responses were obtained, and 2 additional patients whose tumour mass was further reduced achieved complete response following surgery. These results support the view that initial responses obtained with primary IL2 courses can be improved by complementary treatments. The potential role of cellular immunotherapy and, more particularly, of LANAK cells as an effective procedure to further reduce tumour burden in patients responsive to IL2 will have to be assessed in randomised studies.
Adult↗
Recombinant interferon-alpha efficacy in relapsed adult nephroblastoma: a case report.
We report on a 37-year-old woman with progressive lung and pleural metastases from a right nephroblastoma, who achieved partial remission with recombinant interferon-alpha. The drug was given subcutaneously at a dose of 5 mu. 3 times per week. The response was documented after 3 months of treatment and was maintained for at least 9 months. Although such a response has not been reported in the literature, this case suggests promising activity of recombinant interferon-alpha in relapsed nephroblastoma.
Adult↗
Do bacteriuria and candiduria have predictive value in the diagnosis of postlaparotomy peritonitis?
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Aged↗
T-cell receptor repertoire in colorectal adenocarcinoma patients with hepatic metastases and its changes induced by preoperative adjuvant interleukin-2 therapy.
The liver is the primary site for colorectal metastases and hepatic resection often fails to cure these patients. Little is known about T-cell immune response in these patients or its changes after interleukin-2 (IL-2) infusion. Using polymerase chain reaction methodology, we investigated T-cell receptor (TCR) V alpha and V beta gene segment subfamily usage in tumor, hepatic tissue, and blood of six patients undergoing hepatic resection and, in addition, in six patients receiving preoperative adjuvant IL-2 therapy (randomized phase I trial). The objectives were (a) to analyze the TCR repertoire in patients undergoing hepatic resection (without IL-2), (b) to analyze the TCR repertoire in patients undergoing hepatic resection after IL-2 therapy, (c) to analyze the effects of preoperative IL-2 infusion on the tumor-infiltrating lymphocyte (TIL) TCR repertoire by comparing TCR V gene segment usage in IL-2-treated versus nontreated patients, and (d) to analyze the effect of IL-2 infusion on the peripheral blood mononuclear cell (PBMC) TCR repertoire by comparing TCR V gene segment expression in pre- versus posttreatment PBMC of IL-2-treated patients. With regard to the first objective, we observed an unrestricted use of V alpha and V beta gene segment subfamily specificities in tumor hepatic tissue and blood of patients undergoing hepatic resection. In addition, we found that some V alpha and V beta specificities were overexpressed in tumor compared with hepatic tissue and blood, suggesting that the corresponding T-cell subpopulations were expanded at the tumor site. In IL-2-treated patients, in whom the tumor and liver were heavily infiltrated by T lymphocytes, the TIL TCR repertoire was also highly diverse and roughly similar to that detected in hepatic tissue and blood, except for a few overexpressions. To analyze the effect of IL-2 on TIL, we next compared the data obtained in IL-2-treated versus nontreated patients. No significant difference between the two groups was observed. Finally, no major changes in the PBMC TCR repertoire were found after IL-2 infusion. Further studies are needed to identify discrete T-cell subpopulations in these patients that may participate in either tumor immune surveillance or active immunotherapy mechanisms triggered by systemic IL-2 infusion.
Adenocarcinoma↗
High-dose interleukin-2 two days a week for metastatic renal cell carcinoma: a FNCLCC multicenter study.
The purpose of this study was to determine the efficacy and safety of a new high-dose interleukin (IL)-2 regimen, given two days a week, for renal cell carcinoma. One hundred and four patients received IL-2 as a continuous i.v. infusion for 48 h at a daily dose of 24 x 10(6) IU/m2/day for 5 consecutive weeks. Patients were assessed for efficacy 4 and 8 weeks after the end of therapy, and patients who stabilized or responded received maintenance therapy with the same regimen. An objective clinical response was observed in 20 patients (complete in four, partial in 16). The dose of infused IL2 was significantly higher in the responders than in the nonresponders (p < 0.05). Clinical responses were significantly associated with a sedimentation rate of < 20 (p = 0.02), but no other prognostic factor was identified. Mean survival was 13 months. Grade 3 and 4 toxicities were rare, except for hypotension (58% of patients), the main dose-limiting toxic effect. Overall, 83% of the planned dose of IL-2 was given. IL-2 given 2 days a week is active in metastatic renal cell carcinoma and well tolerated.
Adult↗
Influence of interleukin-2 administration on the expression of T-cell receptor V gene segments in patients with renal-cell carcinoma.
Tumor regression induced by IL-2 in a fraction of patients with metastatic renal-cell carcinoma (MRCC) could not be predicted by immunological monitoring. In addition, the general mechanisms leading to tumor regression or even the distinct cell subsets (e.g., T vs. NK cells) involved are poorly identified. To evaluate the influence of IL-2 administration on circulating T-cell subpopulations, TCR V alpha and V beta gene segment usage was analysed by PCR in 7 MRCC patients using a panel of V gene segment subfamily-specific oligonucleotide primers (V alpha I-w29/V beta I-w24). Three samples were examined in each patient: (i) peripheral blood cells (PBMCs) before therapy (day I); (ii) PBMC 2 days after the interruption of IL-2, at day 36 (i.e., at the lymphocytic rebound), (iii) the CD25-enriched cell fraction at day 36. Virtually all V alpha and V beta subfamily specificities were found in pre- as well as in post-treatment PBMCs and CD25+ cell fractions. These results support the view that circulating T-cell subpopulations are highly polyclonal after IL-2 therapy without any major alteration in the TCR V alpha and V beta repertoire. In addition, the results of quantificative densitometric analysis of V alpha and V beta amplified products suggest that a unique V beta 18-expressing T-cell subpopulation may be expanded in the CD25+ cell fraction after IL-2 therapy. Further characterization of these T cells may contribute to a better understanding of in vivo effects of IL-2 on renal-cell carcinoma metastases.
Adolescent↗
Analysis of T-cell-receptor variable gene segment usage in peripheral-blood lymphocytes of advanced cancer patients.
Advanced cancer patients generally display impaired T-cell immune functions. The underlying mechanisms are not well understood. The aim of this study was to analyze whether major alterations of TCR variable gene segment usage could be detected in the blood of these patients. Seventeen individuals with various malignancies were tested using PCR and a panel of V-gene-segment-sub-family-specific (V alpha 1-w29/V beta 1-w24) oligonucleotide primers. The results indicate that these cancer patient lymphocytes expressed most V alpha and V beta sub-family specificities, similarly to the lymphocytes of healthy donors (n = 10). This suggests that immunodepression in advanced cancer patients is not related to major deletions in their T-cell repertoires. We also compared the mean relative expression of each V-sub-family specificity of patients and healthy donors by quantitative densitometric analysis. We found significant differences in 4 V beta specificities (and no V alpha). Our analysis identified unique T-cell sub-sets putatively involved in the mechanisms leading to immunodepression in advanced cancer patients. Alternatively, the observed differences in terms of V beta specificity expression may reflect the host response against the tumor.
Adolescent↗
[Cytokines and solid tumors].
Various cytokines can be used in the treatment of solid tumours. They are factors of proliferation and/or differentiation of haematopoiesis or immunopoiesis, and they stimulate the effector cells of anti-tumoral response. The various steps in the preclinical and clinical development of a cytokine in the field of oncology are detailed, taking IL-2 as an example. The results of the clinical trials reported (essentially with INF and IL-2) are presented and discussed.
Cytokines↗
Combination of interleukin-2 and gamma interferon in metastatic renal cell carcinoma.
The use of high-dose interleukin-2 (IL2), alone or in association with lymphokine activated killer cells in patients with metastatic renal cell carcinoma (MRCC) results in a 20-25% response rate. However, the toxicity of IL2 is substantial and despite many clinical trials, response rates initially reported have not been improved. The aim of this study was to evaluate a combination of IL2 and gamma interferon (IFN) in MRCC with respect to both efficacy and tolerance. IL2 was given by continuous intravenous infusion at a daily dose of 24 x 10(6) U/m2 for 2 consecutive days during 5 consecutive weeks. Gamma IFN was given subcutaneously at a daily dose of 5 x 10(6) U/m2 on the same days as IL2. 33 patients with MRCC entered the study. Clinical responses were comparable with other published series: 7 patients (21%) achieved partial response, 13 (39%) were stable and 13 had progression, despite therapy. Immunological profile observed with this regimen showed a major increase in natural killer cells which became the predominant lymphocyte population at the end of the therapy. Tolerance was good with 92.5% of the planned doses actually received by the patients. This was reflected by an early discharge from the hospital in 95% of the cycles, increasing acceptability of the regimen by the patients.
Adult↗
[Cancer immunotherapy: immunologic bases, reality and hopes].
The use of the immune system for the treatment of cancer is still debated. Recent advances in antigen presentation and recognition mechanisms, and the characterization of tumor-specific antigens generating a T cell response are crucial steps for the stimulation of research in this direction. These advances should allow the development of selective immunotherapy, either passive (infusion of lymphocytes with specific recognition of autologous tumor) or active (vaccination), and the evaluation of this new approach in cancer treatment strategies.
Antigens, Neoplasm↗
[A multivariate prospective study of prognostic factors in 200 operated epidermoid cancers of the esophagus. Definition of patients for whom surgical resection was of benefit].
From 1982 to 1991, 200 patients with squamous-cell esophageal cancers underwent operation. Sixteen prognostic parameters were prospectively collected and analyzed. The main aim of this study was to define the best preoperative criteria for selection for curative surgery and which patients would benefit most from radical resection. Squamous-cell head and neck carcinoma was associated in 43.5% of cases. Of these, 24% preceded the esophageal carcinoma while 19.5% were synchronous. Resection was curative (i.e. grossly complete) in 144 cases, palliative (leaving gross tumor behind) in 25 cases, and judged impossible in 31 cases. Twenty-one patients died during their hospitalization. Five-year survival, according to the Kaplan-Meier method, was 18 +/- 3.6% for all patients, and 27 +/- 4.8% for patients undergoing curative resection (including postoperative mortality). Palliative resections or invasion of adjacent organs, but not resection with positive lymph nodes, was thought to be synonymous with incurability. Multivariate analysis showed that the two principal statistically significant characteristics were the stage as determined by roentgenological and endoscopic evaluation (P = 0.003) (clearly assessable during initial work-up) and type of resection (complete or not) (P = 0.04). Tumor diameter, as determined on CT-scan (< or > than 30 mm), was at the limit of statistical significance (P = 0.09). A second multivariate analysis of prognostic factors was conducted in 128 patients undergoing resection with curative intent and who survived the initial postoperative period. Roentgenologic/endoscopic staging alone emerged as being statistically significant (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms.
The diagnostic value of elevated human chorionic gonadotropin (hCG) and its free alpha (hCG alpha) and beta (hCG beta) subunit serum levels as specific tumor markers for nongonadal malignancies is controversial. In the present report, different monoclonal based immunoradiometric assays specific for hCG and its free hCG alpha and hCG beta subunits have been used to reevaluate the presence of these molecules in the serum of patients with a wide variety of tumors. Serum samples from patients with newly diagnosed, persistent, or recurrent malignancies of either known (n = 717) or unknown (n = 32) primary site, healthy blood donors (n = 309), and nonmalignant disease controls (n = 86) were studied using four highly specific and sensitive monoclonal based immunoradiometric assays to hCG and its free subunits. Low level hCG elevations (less than 1000 pg/ml) were found to be common in cancer patients, normal subjects, and disease controls. However, serum levels greater than 1000 pg/ml were highly diagnostic of gonadal tumors and specifically identified nonseminomatous testicular tumors. Significant serum elevations of free hCG alpha subunit (as high as 3000 pg/ml) were found in approximately 96% of cancer patients, normal individuals, and disease controls. In contrast, free hCG beta subunit levels (greater than or equal to 100 pg/ml) were detected in 70 and 50% of patients with nonseminomatous and seminomatous testicular cancers, respectively, and in 47% of bladder, 32% of pancreatic, and 30% of cervical carcinomas. All normal subjects and disease controls had free hCG beta levels less than 100 pg/ml. Thus, the detection of the free hCG beta subunit in serum of nonpregnant subjects was highly diagnostic of malignancy in general and specifically defines a subgroup of aggressive nongonadal malignancies.
Adult↗
[Therapeutic strategy in metastatic renal cancer].
Prognostic factors have been described in metastatic renal cell cancer: performance status, weight loss, elevated erythrocyte sedimentation rate, presence of liver metastases. The treatment for a patient with good prognosis consists of: surgical exeresis of solitary metastasis, immunotherapy by either interferon or interleukin 2. Treatment in case of a rom prognosis is a combination of supportive care, orthopedic surgery for pathologic fracture or medullar compression, antalgic radiotherapy, embolization, nephrectomy for hematuria, and analgesic treatments.
Blood Sedimentation↗
Studies on NK cell purification by negative selection in human peripheral blood.
We have attempted to improve negative selection procedures for the large scale purification of human CD-3 CD56+ NK cells. In a series of experiments, purifications of NK cells from 10(8) PBMC were performed by T cell depletion using either direct or indirect anti-CD3 labeling and the Magnetic Activated Cell Separation (MACS) procedure. Contaminating CD3+ cells were still present using either one of these two different T cell depletion protocols as shown by phenotyping IL-2 supplemented cell cultures on day 12. A second cycle of purification was therefore added. When MACS and Dynabeads were compared as complementary procedures to the first MACS cycle starting with 10(8) cells, the Dynabeads method was found to be superior to the MACS with regard to the elimination of residual T cells. Starting from 10(9) PBMC, we showed that this MACS+Dynabeads procedure gave similar satisfactory results when compared to the scaling-up of a previously established two steps procedure using Dynabeads. These two approaches (MACS+Dynabeads and 2 cycles of Dynabeads) have been also tested in a clinical setting to purify NK cells from cancer patients prior to in vitro expansion. The results indicate that the two methods are equivalent with respect to purity and recovery rate; a slight advantage in terms of feasibility was found in favor of 2 cycles of Dynabeads.
Animals↗
Esophageal squamous cell carcinoma: the specific limited place of surgery defined by a prospective multivariate study of prognostic factors after surgical approach.
From 1982 to 1990, 181 patients underwent surgery for esophageal squamous cell carcinoma, for which 14 prognostic parameters were prospectively recorded in order to perform a multivariate study. A squamous cell head and neck cancer was associated with the esophageal tumor in 40% of the cases (synchronous 18% and metachronous 22%). Resection was curative (i.e. macroscopically complete) in 128 cases, palliative (i.e. with residual tumor) in 24 cases and not possible in 29 cases. There were 21 deaths in hospital (hospital mortality was 11.7%). One hundred and twenty-two patients received preoperative chemotherapy and 77 received postoperative radiotherapy according to different phase II prospective studies. The 5-year survival rate according to the Kaplan-Meier method was 15.8% (+/- 3.4) for all patients and 23.5% (+/- 4.8) for the patients who had a curative resection. A palliative resection or the invasion of a neighbouring organ was synonymous with incurability, but positive lymph nodes were not considered proof of incurability. The multifactorial study concerning all the patients highlighted two main prognostic parameters: the histological staging according to the Japanese classification (P = 0.0006) and the type of resection (curative or not) (P = 0.006). An objective response to preoperative chemotherapy was the third and last parameter revealed by Cox's model. The multivariate study, which was limited to the 112 patients who were alive after a curative resection, showed that only the stage was an important prognostic factor (P = 0.003), with stages 2 and 3 carrying a worse prognosis. We propose a therapeutic scheme, based on these prognostic data and on the usual pre-therapeutic workup with three additional exams: CT scan measurement of tumor diameter, ultrasound examination +/- fine needle aspiration cytology of supra-clavicular lymph nodes and echo-endoscopy. The aim of this scheme is to limit surgery to the subgroup of patients for whom this modality is really beneficial.
Adult↗
Wegener's granulomatosis presenting as diffuse pulmonary hemorrhage.
A 35-year-old woman experienced diffuse intraalveolar haemorrhage with respiratory distress and acute renal failure. Renal histology and evolution confirmed Wegener's granulomatosis. Early use of immunosuppressive drugs allowed weaning from mechanical ventilation and temporary improvement of the renal failure. A review of the literature emphasizes the rarity of alveolar hemorrhage as an initial symptom of Wegener's granulomatosis and the necessity of aggressive management.
Adult↗
Heat and moisture exchanger vs heated humidifier during long-term mechanical ventilation. A prospective randomized study.
Adequate humidification of inspired gases with HMEs during long-term MV remains controversial. In this study, a comparison is made between tracheal secretions during long-term MV either with HME or conventional HH. Both the HME and HH groups were similar with respect to age, sex, diagnosis, duration of MV, SAPS and mortality. Temperature of gases in the tracheal tube was lower and the amount of tracheal instillations was greater in the HME group than in the HH group. Tracheal secretions became thicker between day 1 (control) and day 5, in the HME group than in the HH group. Four and two tube occlusions occurred in HME and HH groups, respectively. Tracheal bacterial colonization was similar in the two groups. Given the advantages of HME (reduced nurses' work and financial cost), HME could be routinely used under cautious surveillance and replaced by HH if difficulty in suctioning occurs.
Female↗