High-dose sequential chemotherapy with recombinant granulocyte colony-stimulating factor and repeated stem-cell support for inflammatory breast cancer patients: does impact on quality of life jeopardize feasibility and acceptability of treatment?

PURPOSE: This study was designed to investigate the quality of life (QOL) of patients enrolled onto the High-Dose Chemotherapy for Breast Cancer Study Group trial (PEGASE 02), a French pilot multicenter trial of the treatment of inflammatory breast cancer (IBC) aimed at evaluating (1) toxicity and feasibility of sequential high-dose chemotherapy (HDC) with recombinant human granulocyte colony-stimulating factor (filgrastim) and stem-cell support and (2) response to HDC in terms of pathologic response and survival. PATIENTS AND METHODS: QOL measures were performed at inclusion and four times subsequently up to 1 year using an ad hoc side-effect questionnaire (19 physical symptoms) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30). RESULTS: Of the 95 patients entered, the overall QOL questionnaire completion compliance was 75.6%. During cycle 3 of HDC, the number of symptoms was high (mean +/- SD QOL score, 10 +/- 3), with fatigue, hair loss, appetite loss, nausea, change in taste, vomiting, fever, and weight loss reported by more than 60% of patients. Toxicity and distress associated with HDC were reflected in the decline of four EORTC QLQ-C30 scores: global QOL (P =.001), and physical, role, and social functioning (P <.001 for all statistics). However, QOL deterioration disappeared after treatment completion, except for physical functioning (P =.025). One year after inclusion, most QOL scores returned to baseline, and both emotional functioning and global QOL scores were even higher than baseline (P =.030 and P =.009, respectively). CONCLUSION: If it is confirmed that improvements in pathologic response rates with HDC effectively translate into increased probabilities of survival for IBC patients, adoption of such treatment as PEGASE 02 will not involve crucial choices between length of life and QOL and should not be delayed for QOL arguments.

Healthy sibling donor anxiety and pain during bone marrow or peripheral blood stem cell harvesting for allogeneic transplantation: results of a randomised study.

This study reports the first comparison of healthy donor subjective well-being during two alternative procedures of hematopoietic stem cells harvesting for allogeneic transplantation. Among the 105 donors included between September 1996 and October 1998 in the SFGM French randomised trial aiming to compare allogeneic bone marrow (BM) transplantation and blood cell (BC) transplantation, 64 donors (33 in BC and 31 in BM groups) were relevant for the analysis. They had received a set of self-administered questionnaires to complete during the collection process, aiming to measure anxiety (assessed using the Spielberger's State-Trait Anxiety Inventory) and pain induced by the procedure (evaluated using a visual analogical scale). Results showed that no harvest procedure is free from pain even if none was more painful than the other. Levels of anxiety before the collection procedure were high in both groups and significantly so for BC donors. Although BC collection induces at least similar levels of pain and anxiety as does BM collection, they were of a different kind, and the short-term impact of G-CSF stimulation on the well-being of BC donors has to be taken into account in improving quality of care in the allogeneic setting.

Comparison of anxiety, pain and discomfort in two procedures of hematopoietic stem cell collection: leukacytapheresis and bone marrow harvest.

The aim of this study was to compare anxiety, pain and discomfort of cancer patients submitted to either peripheral blood progenitor cell collection (PBPCC) or bone marrow harvest (BMH). Patients, randomized (7/1993-2/1994), in view of autograft, to receive the first procedure or the second one, completed self-administered questionnaires. Anxiety was assessed by the State Trait Anxiety Inventory and pain using visual analogical scale (VAS) and McGill Pain questionnaire. Before the procedure, BMH patients (n = 25) experienced more anxiety (P < 0.01) and more trouble or inconvenience for having to come and stay at the hospital (P < 0.0001) than PBPCC patients (n = 40). Pain due to BMH is significantly higher than pain induced by PBPCC (P < 0.001 for VAS and total McGill score). However, patients submitted to PBPCC with a femoral catheter (n = 19) had significantly higher total McGill scores and sensory sub-scores than patients without it (n = 21). At discharge from the hospital, PBPCC patients expressed more positive judgements towards the collection procedure than BMH patients. These results suggest that a better patient acceptability of high-dose chemotherapy followed by autograft may be obtained by substituting PBPCC for BMH for stem cell collection.

[Assessment of the quality of life in the surgery of cancer of the esophagus: critical review of the literature]. / Mesure de la qualité de vie dans la chirurgie du cancer de l'oesophage: revue critique de la littérature.

The surgery of the oesophageal carcinoma is subjected today to a renewed interest. In the objective to draw recommendations for the clinicians wishing to include quality of life measures in clinical trials, it seemed pertinent to us to critically review existing studies. The review of the literature, presented here, is based on a bibliographic research using Medline database (January 1986-December 1996). A precise methodology was adopted to read the eighteen articles retained and the psychometric instruments used in each study were listed and classified. Nine studies considered the issue of quality of life but failed to measure the outcome or used not validated psychometric instruments and 4 others used only indicators of physical performance. Only five studies assessed quality of life using instruments with known psychometric properties (Quality of Life Index of Spitzer, Rotterdam Symptom Checklist and EORTC QLQ-C30 questionnaire) more often associated to ad hoc dysphagia scales. This review of literature shows that the inclusion of validated quality of life measures in the surgery of oesophageal carcinoma is very recent and that it presents some difficulties inherent to the lack of specific tools. The EORTC QLQ-OES24, specific of oesophageal cancer, being not yet validated in french, the authors recommend the use of the EORTC QLQ-C30 jointly with ad hoc dysphagia scales.

[Adjuvant chemotherapy with mitoxantrone, cyclophosphamide and 5-fluorouracil in breast neoplasms: therapeutic life]. / Chimiothérapie adjuvant par mitoxantrone, cyclophosphamide et 5 fluro-uracile dans les cancers du sein: vécu thérapeutique.

The chemotherapy side-effects are insufficiently documented while they strongly condition patients' quality of life. The aim of the study was to assess by means of a self-administered questionnaire the somatic symptoms experienced by breast cancer patients during their NCF (mitoxantrone + cyclophosphamide + 5-fluorouracil) chemotherapy and to demonstrate the interest of this self-report by comparing the frequency of side-effects assessed by the patients to that noted by the physicians in medical records. The study was carried out among 44 patients receiving their chemotherapy + radiotherapy at the Paoli-Calmettes Institute (marseille) between July 1994 and May 1995. The questionnaire comprized of 17 symptoms evaluated in terms of frequency, duration/severity and distress. The most frequent symptoms are: hair loss and nausea (75%), hot flush (57%), lack of appetite and headache (46%) associated with distress in 67 to 100% of cases. Their frequency was underestimated by the physicians in medical records. This study showed a large discordance patient-physician in the assessment of chemotherapy side-effects. The type of tool presented in this study could complement the usual scales of toxicity that do not provide an estimation of true patients' experience.

[Comparison of anxiety and pain in two procedures of hematopoietic stem cell collection: cytapheresis and bone marrow collection]. / Comparaison de l'anxiété et de la douleur au cours de deux procédures de recueil des cellules-souches hématopoïétiques: la cytaphérèse et le prélèvement de moelle osseuse.

The aim of this study was to compare anxiety, pain and discomfort of cancer patients submitted to two procedures of hematopoietic stem cells collection: peripheral blood stem cells collection (PBSCC) or bone marrow collection (BMC). Patients, randomized (July 1993-February 1994), in view of autograft, to receive the first procedure or the second one, completed self-administered questionnaires before, during and after the procedure. Anxiety was evaluated by State-Trait Anxiety Inventory. Pain was assessed using visual analogical scale (VAS) and McGill Pain questionnaire. Before the procedure, in comparison with PBSCC patients (n = 40), BMC patients (n = 25) experienced more State-anxiety due to the procedure approach (p < 0.01) and more trouble or inconvenience for having to come and stay at the hospital (p < 0.0001). During the procedure, pain related to BMC, as assessed by VAS, is significatively higher than pain induced by PBSCC, whichever the access used (p < 0.001). The McGill total score is twice as high for BMC patients than for patients submitted to PBSCC with femoral catheter (n = 19). The latter patients significatively reported more pain than patients without femoral catheter (n = 21). At the discharge from hospital, 32% of BMC patients judged the procedure quite difficult vs 5% of PBSCC patients (p < 0.05). These results explain a higher acceptability of the peripheral blood stem cells collection.

[Sensitivity of obstetrical ultrasonography in the prenatal diagnosis of major fetal anomalies]. / Sensibilité de l'échographie obstétricale dans le diagnostic anténatal des anomalies foetales majeures.

With the aim of evaluating the sensitivity of obstetrical ultrasonography for prenatal screening of major birth defects, a retrospective study was conducted on 164 pregnancies which ended in the birth of an affected baby. The 164 cases had been reported to the Birth Defects Monitoring System of the Bouches du Rhône area by 5 maternity Hospitals between January 1, 1985 and December 31, 1987. Among these 164 cases, 50 were live births, 19 died after birth, 21 were stillbirths and 74 were terminations of pregnancy after prenatal diagnosis. Data from ultrasound reports were cross-checked with data from clinical examination at birth for live births, or from systematic protocol applied to every stillbirth or termination of pregnancy. The 164 notified cases had 196 major fetal anomalies. The results showed that the overall sensitivity of ultrasonography for detection of major fetal anomalies was 75%. The detection rate was assessed for each anomaly. The advised timing for morphological examination of the fetus by ultrasound in France is 20-22 and 30-32 weeks' gestation. Among the major fetal anomalies which were ultimately detected in utero, only 28% were screened before 22 or by 22 weeks' gestation and 14% were not by 32 weeks' gestation. This study underlines the effectiveness of this technique in prenatal diagnosis of major birth defects but also its limits, mainly linked to the lateness of many diagnoses.

[QALYS or not QALYS: that is the question?]. / QALYS or not QALYS: that is the question?

The article discusses the proposal of some health economists to use the "cost per QALY (quality-adjusted-life year)" ratio as an universal indicator for economic assessment of medical interventions, in the so-called "cost-utility" analyses. Authors argue that QALYs are not a straightforward application of expected utility theory, which is the standard economic model of individual behaviours toward risk and uncertainty. Indeed, QALYs are compatible with economic utility theory only if individuals' preferences regarding health states satisfy certain very restrictive properties: utility independence between length of life and quality of life, constancy of the proportional trade-off between quality of life and length of life, risk neutrality towards health states, constancy through time of the utility associated with each health state. Aggregation of individual QALYs to obtain an indicator for patient groups at the societal level also raises complex equity problems. Last but not least, from the epistemological point of view, QALYs are based on the hypothesis that health interventions only affect the health of the individual and not any other aspects of his well-being. The authors conclude that the "cost per QALY" approach should be abandoned in order to avoid ambiguities that could impede the development of health economics in the medical field.

[Evaluation of the effects of a support campaign on exclusive breast feeding at 1 month]. / Evaluation des effets d'une campagne de soutien à l'allaitement exclusif au sein à un mois.

The aim of this study was to evaluate the effects of a support campaign on exclusive breast-feeding at one month postpartum among women having chosen breast-feeding. The study population consisted of all women (n = 657) having delivered in the Maternity Hospital in Pertuis (Area of Vaucluse-France) between January 1, 1987 and December 31, 1988. The first 151 women belonged to the control group not submitted to interventions while the following 506 composed the groups submitted to interventions. Interventions mainly aimed at providing information to women, supporting them after delivery, raising the awareness of their environment and educating Health professionals. Mothers were interviewed at the maternity and at their home one month later. Results showed that interventions significantly increased the number of women breast-feeding at one month (66% vs 52%-p less than 0.01) and reduced physical and medical problems related to breast-feeding (51% vs 60%-NS). To resolve these problems, Health professional education particularly appeared efficacious. The mothers' planned duration of breast-feeding was not significantly changed showing that actions were well conducted, as we wished, in the sense that the choice of mothers was respected. The greatest benefit was seen among the lowest social class (p less than 0.05), the less educated (p less than 0.01), and Maghrebin women (p less than 0.01).

[Comparative study of the costs for two hematopoietic cell specimen collections: cytapheresis and bone marrow collection]. / Etude comparative des coûts de deux procédures de recueil des cellules souches hématopoïétiques : la cytaphérèse et le prélèvement de moelle osseuse.

The aim of this study, carried out at the Institut Paoli-Calmettes (Marseille-France), was to compare, in terms of monetary and non monetary costs, alternate procedures for hematopoietic stem cells collection i.e. peripheral blood stem cells collection (PBSCC) and bone marrow collection (BMC) used in cancer therapies. Monetary costs have been evaluated by calculating the direct costs of the two types of procedures and non monetary costs by comparing anxiety, discomfort and pain of cancer patients submitted to PBSCC or BMC. Patients, randomized (7/1993-2/1994), in view of autologous transplantation, to receive the first procedure or the second one received three self-administered questionnaires to complete before, during and after the procedure. Pain was assessed using visual analogical scale and McGill Pain questionnaire. Anxiety was evaluated by means of State-Trait Anxiety Inventory. Results showed that, under some conditions, presently realized in the current practice, direct costs of PBSCC (10,140 to 13,780 FF) were lower than BMC ones (16,509 FF) and that anxiety and pain experienced by patients submitted to PBSCC, with or without femoral catheter, were significantly less severe than in other group patients (State anxiety, before procedure : p < 0.01 ; pain related to the procedure assessed on VAS : p < 0.001 and total McGill score : p < 0.00001). These findings justify the substitution of bone marrow transplantation by peripheral blood stem cells transplantation, provided there is a demonstration of similar medical efficacy for cancer therapy.

[Prenatal diagnosis: perceptions of women concerning their pregnancies]. / Diagnostic prénatal: connaissances des femmes à l'issue de leur grossesse.

After a pregnancy with a normal outcome what are women's perception and knowledge of prenatal tests performances? A survey was carried out during 1990, in the Bouches-du-Rhône area, on a representative sample of French speaking women who had just delivered a normal liveborn. The participation rate was 80% and the mean maternal age was 28.9. On average, 5 (4.7-5.1) prenatal ultrasound scans were carried out per pregnancy and 93% of the women thought that the main interest of this exam performed during the 4-5th month of pregnancy was to confirm that the foetus was normal; only 9% answered that when the scan was normal one could be sure that the fetus was normal. Among those responding, 87% were informed about the existence and the goal of amniocentesis: media were the first source of information about the test in 42%. The level of education was the major determinant of women's knowledge and this factor should be taken into account by the practitioner during the prenatal surveillance.

[Antenatal surveillance and risks of prematurity and fetal growth retardation]. / Surveillance anténatale et risques de prématurité et d'hypotrophie foetale.

The essential aim of this work was to investigate the relationship between antenatal care and preterm delivery or low birth weight. This study has been done by means of a case-control survey carried out among 435 women who delivered in 4 Maternity Hospitals in Aix-en-Provence-Pertuis area, between November 20th, 1987 and September 30th, 1988. Cases consisted of 124 women having delivered single livebirths before 37 weeks' gestation and 69 women having delivered, at term, single livebirths weighting less than 2,500 g. Controls were 242 women who delivered normal single livebirths. Results showed that, within the geographic area of the study, low birth weight and preterm delivery rates were respectively 6% and 5.4%. Antenatal care was generally according to medical profession recommendations: average number of visits: 7.9; first visit achieved, for 98.8% of women, within first trimester; intervention of a specialist in 97.1% of pregnancies; average number of ultrasound examinations: 3.5. Only mothers of low birthweight infants had more often an inadequate antenatal care (OR = 2.63, 95% confidence interval: 1.22-5.70). The risk factors for low birth weight were: previous history of preterm and/or low birth weight delivery, single marital status, low lever father's education, smoking during pregnancy, no contact with maternity team and for preterm delivery: previous history of preterm and/or low birth weight delivery, complications during the penultimate pregnancy, hypertension, metrorragies. These results suggest that it seems unlikely, in the future, to decrease unfavorable pregnancy outcomes by increasing antenatal care.

Vertical transmission of HIV--a rediscussion of testing.

It is worthwhile reconsidering the debate on mandatory or voluntary testing for HIV antibody among women of childbearing age, in the light of recent virological and therapeutic discoveries that have altered the parameters of the issue. The therapeutic possibilities of reducing the risk of transmission for women confirmed as seropositive are an incontestable benefit for anyone who is aware of her serological status; the fact of being able to detect real infection at birth could mean that causing unnecessary distress to the antibody positive but uninfected newborn infant is avoided. Medical professionals now have convincing arguments to persuade women at risk to accept the test when it is offered. But, in any case, the voluntary nature of the decision for testing must be respected.

Cancer and polyps of the colorectum and lifetime consumption of beer and other alcoholic beverages.

Two parallel case-control studies were conducted in the Marseilles metropolitan area of France from 1979 to 1985 on cancers and adenomatous polyps of the colorectum. All cases of cancer (n = 389) and polyps (n = 252) were incident and histologically confirmed. Controls (n = 641) matched for sex and age were selected among patients undergoing functional reeducation for injury or trauma in one of five hospital centers. Intake of alcoholic beverages was investigated by questions on daily or weekly intake of wine, beer, apéritifs, and distillates during different life periods. Questions on alcoholic beverages were integrated in a detailed diet history interview questionnaire. The risk of rectal cancer was elevated in male beer drinkers (relative risk = 1.73, 95% confidence interval 1.01-2.95) and in men and women combined (relative risk = 1.71), while beer consumption was not associated with colon cancer. Total ethanol intake and consumption of wine and distillates were not associated with the risk of cancer of the colon or rectum, nor with risk of polyps. Adjustment in the statistical analysis for energy intake and for other dietary variables (fiber from fruits and fiber from vegetables), which were found to be risk factors in the study, did not substantially change the results found for beer and other alcoholic beverages. Etiologic hypotheses related to nitrosamine content of beer are discussed in the light of growing epidemiologic evidence that beer consumption specifically increases the risk of rectal cancer.

Jaundice and chronic pancreatitis.

A study was conducted on a group of 48 patients presenting with jaundice during the course of chronic pancreatitis. Two different patterns of symptoms could be opposed: (1) Short-lasting cholestatic jaundice which is accompanied by pain, but free from pruritus and fever, is linked to a medium consumption of alcohol, occurs in the course of advanced chronic pancreatitis and seems to be the consequence of a stricture of the main bile duct due to pancreatic lesions. (2) Protracted, intense jaundice which is linked to a high alcohol consumption, is encountered among less-advanced cases of chronic pancreatitis, the main bile duct being generally normal. In such a case, direct toxic effect of alcohol on the liver must be questioned.

Functional evaluation of the transplanted lung after long-term preservation.

In dogs the immediate value of transplanted lungs was tested after preservation in Collins 3 solution and administration of aprotinin. 15 animals received a left or right homograft, which had been preserved for 24 h. In 3 cases preservation time was prolonged to 48 h, and in another 2 dogs both of the lungs were replaced by 24-hour preserved organs in a one-stage operation. The value of the transplants was tested by several physiological, morphological and clinical phenomena. (1) A positive O2 uptake of the transplant after a temporary occlusion of the opposite pulmonary artery documented its capacity for gaseous exchange. (2) Scintigraphic visualization of perfusion and ventilation in 3 dogs demonstrated satisfactory results. (3) A positive response to acetylcholine of the bronchial muscular system was observed in all transplants. (4) Normal light microscopy showed a lack of obvious morphological change. (5) Only slight alterations in electron microscopy were found when compared to those found before preservation. (6) The absence of acute bronchial edema excludes the possibility of irreversible altertions of the alveolocapillary wall. The results demonstrate that preservation of the lung is possible up to a period of 48 h.

Case-control study on colorectal cancer and diet in Marseilles.

A case-control study of cancer of the colon and rectum was conducted in the Marseilles region of southern France. Cases (399) and a corresponding number of controls, matched for age and sex, were included, the controls being selected from patients undergoing functional re-education for injuries or trauma which reduced their mobility. A dietary history questionnaire was used to determine the usual eating habits during the year preceding diagnosis for cases, or preceding interview for controls. The cases reported lower consumption of vegetables and oil than controls, but no differences were seen in the consumption of meat, bread, eggs or butter. The intake of several nutrients, particularly vitamins B2, B6, C, potassium, iron, magnesium and vegetable fibre, was lower among cases. However, when all these nutrients were analysed jointly and adjusted one for the other, only potassium retained a significant effect. This may be due to the high degree of colinearity between the estimated intake of many nutrients. No association was seen with fat or fibres from cereals.

Colorectal polyps and diet: a case-control study in Marseilles.

This study investigates the differences in usual past diet between 252 subjects with newly diagnosed adenomatous or villous polyps of the colon and rectum and a group of 238 hospital controls. Cases and controls were interviewed in hospital by 3 nutritionists using a dietary history questionnaire focused on the diet during the preceding year. Nutrient intake was estimated by means of ad hoc food tables adapted from French and British tables. Out of 16 food groups considered in the analyses, the cases reported lower consumption of oil and potatoes and higher consumption of sugar added to food and drink. Among nutrients, we found that cases had a lower consumption of carbohydrates (not taking into account added sugar), potassium, magnesium and vitamin B6. We found a slightly lower intake of fibre and a slightly higher intake of saturated fat among cases, though neither was statistically significant. Intake values for fibre and for carbohydrates were highly intercorrelated and, due to measurement errors, the effect of one may be masked by the other and vice versa. The hypothesis that some components of carbohydrates (starches, fibre and natural sugars but not added sugar) play a protective role in relation to the biology of tumours of the intestinal tract is considered in further multivariate analyses and in the "Discussion".