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F Kwiatkowski

Publications and source records attributed to F Kwiatkowski.

At least 19 recordsLinked to original sources
PubMed2006

Correlation between molecular metastases in sentinel lymph nodes of breast cancer patients and St Gallen risk category.

AIMS: To evaluate the clinical significance of tumour metastases detected using real-time reverse transcription-PCR (RT-PCR) in sentinel lymph nodes (SLN) of breast cancer patients. METHODS: Sixty-seven patients with T1-T2 primary breast cancer were included in a prospective study. SLN were analysed for the presence of metastatic tumour cells using standard histopathology staining, immunochemistry (IHC) and multimarker real-time RT-PCR assay for mammaglobin (MMG), carcinoembryonic antigen (CEA) and cytokeratin-19 (CK19) mRNA expression. Correlations between molecular metastases and traditional clinicopathological prognostic factors, including St Gallen risk categories were studied. RESULTS: Of the 67 patients, 15 (22.3%) had one or more pathology-positive SLN. Five (9.6%) pathology-negative SLN were positive by IHC and 19 (36.5%) by RT-PCR. Of note, RT-PCR analysis was also positive in all cases with pathology- or IHC-positive SLN. MMG was the most informative tumour marker in the panel. Molecularly detected metastases were significantly associated with intermediate St Gallen risk category (p=0.023). CONCLUSION: Molecular staging of SLN using real-time RT-PCR for early breast cancer could serve as a useful complement to standard clinicopathological risk factors. Studies with long-term follow-up are necessary to define the impact of molecular metastases on disease free survival and overall survival.

Adult↗
PubMed2006

Does survival increase in metastatic breast cancer with recently available anticancer drugs?

Metastatic breast cancer (MBC) is incurable in most cases. While multiple treatments are available, the median survival is still approximately 2 years. We planned to assess the apparent impact of taxanes and aromatase inhibitors (letrozole, anastrozole, and exemestane) on the survival of 857 MBC patients for more than 30 years. Patients classed into decades by metastatic disease onset date did not survive significantly longer in recent years. This does not exclude some marked improvements with time: 1) in the same period, the disease-free interval for MO patients increased progressively and significantly with time; 2) the overall relapse ratio in MO patients was 20% lower in the 1990-2000 decade compared with 1980-1990; 3) since 1995, treatment for metastasis has been significantly lighter with periods of chemotherapy separated by hormonotherapy or observation in the case of negative receptors. Analyzing individual therapies, availability of taxanes since 1994 did not result in a significant increase of the overall survival. Conversely, receiving hormonotherapy was an important prognostic factor of the overall survival. Three groups were classified according to hormone therapy: group 1--tamoxifen, group 2--aromatase inhibitors, group 3--a combination of tamoxifen then aromatase inhibitors. The combination of tamoxifen then aromatase inhibitors favored a survival improvement from metastasis appearance to death compared with aromatase inhibitors alone and with tamoxifen alone. The sequential treatment of tamoxifen then aromatase inhibitors is presently discussed as a possible standard when used as adjuvant treatment. This sequential effect could also constitute a valuable concept for metastatic patients.

Aged↗
PubMed2005

[Therapeutic potential of melatonin in cancer treatment].

Melatonin is a small lipophile molecule, essentially secreted by pineal gland. The synthesis of this hormone shows a circadian pattern with a peak around 2-3 hours am. Many melatonin receptors are found in the body, which explains its multiple functions as biological rhythms resynchronisation, sleep induction, vasoregulation and even immunomodulation. Many experiments realised in this field have permit to discover different interactions between melatonin and the immune system, and especially the link which exists between melatonin and the fight against cancer via the immune system. Phase II studies reported a decrease of thrombocytopenia, an increase of some cytokines rate and an increase of objective responses in cancer patients. In order to confirm these results and to lead further research, we propose to realise a phase II randomised study melatonin versus placebo in metastatic breast cancer patients after two lines of treatment.

Circadian Rhythm↗
PubMed2005

[Stress, cancer and circadian rhythm of melatonin].

Influence of stress on immunity and pathogenesis relates to corticotropic axis: hypothalamus-hypophysis-surrenals (HHS). Its over-stimulation due to traumas during early childhood or before birth seems to generate brain abnormalities such as reduction of hippocampus volume. More typical of adult age, hypothalamus-pineal gland axis (HP), responsible for melatonin production, may be impaired because of chronic stress, mainly through sleep disturbances or addictive behaviours. Old age has been reported to produce same impairments. Circadian cycle of melatonin is closely related to immune functions and its disturbance seems to induce, among populations undergoing frequent changes of life rhythm, a significant raise of cancer incidence: night shift workers, air pilots... Stress then seems enable to increase cancer risk through its negative impact on HHS and HP axis and therefore on immunity. Immunotherapy, which was an interesting solution considering this, has not yield yet expected results. Upstream, other ways have been successfully investigated in prospective randomised trials, such as psychotherapeutic treatments, with positive effects on cellular immunity and survival. The ability to condition immune responses in animals allows thinking that hypnotherapy could also be used along with standard treatments.

Adult↗
PubMed2005

French multicentre prospective observational study of laparoscopic versus open colectomy for sigmoid diverticular disease.

BACKGROUND: The aim of this study was to compare in-hospital morbidity and mortality rates after elective laparoscopic and open colorectal surgery for sigmoid diverticular disease (SDD). METHODS: This prospective national multicentre observational study included all consecutive patients undergoing open or laparoscopic elective colectomy for SDD in a 4-month period between June and September 2002. Postoperative in-hospital mortality and morbidity in the two groups were compared. RESULTS: Three hundred and thirty-two consecutive patients undergoing either laparoscopic (163 patients) or open (169 patients) colectomy for SDD were analysed. Overall postoperative mortality and morbidity rates were 0.3 and 23.8 per cent respectively. The morbidity rate was significantly higher in the open than in the laparoscopic group (P < 0.001), leading to a significantly longer hospital stay (P < 0.001). The morbidity rate remained significantly higher in the open group when the patients were matched for age (P = 0.015) or American Society of Anesthesiologists score (P = 0.028). An open procedure (relative risk (RR) 2.13 (95 per cent confidence interval (c.i.) 1.29 to 3.45)), age over 70 years (RR 1.62 (95 per cent c.i. 1.14 to 2.30)) and intraperitoneal contamination (RR 2.54 (95 per cent c.i. 1.18 to 5.50)) were identified as independent risk factors for morbidity. CONCLUSION: A laparoscopic approach to elective treatment of SDD may be associated with reduced postoperative morbidity and hospital stay. A randomized study is required to confirm these results.

Aged↗
PubMed2005

[Chronobiology and immunity].

At all times, cycles have focused men's attention and fashioned his life. Today, thanks to genetic, one can find tracks of circadian rhythms programming until cell's DNA, and this in a very amazing and similar manner from amoebas to mammals. A particular rhythm interests the researcher in oncology: the circadian rhythm of melatonin. It stands at the junction of several domains: somatic, immune and psychic, through the many receptors found on leukocytes, through the links between this hormone production and the one of many cytokines but also with activity, life habits and "stress". On an other hand, antioxydant action of melatonin gives a serious argument concerning its possible role in cancer aetiology. As for them, studies on sleep confirm the large ubiquity of biological cycles, for instance thanks to the observation of the impact of particular genetic mutations on advance or delayed sleep syndrome. Because of the great diversity of cyclic phenomena, the study of chronobiology cannot be undertaken today without a wide interdisciplinary collaboration. During the 13th congress of the "Association Francaise de Chronobiologie Medicale", this study has been continued mainly in three different directions of research: fundamental, applied and transverse. Many original experimental results have been presented and new ways of multidisciplinary research specified. The important scientific fecundity of this very convivial annual congress never lacks to satisfy its participants: it continues to favour the onset of new projects, enabling to avoid major shelves thanks to the constructive criticism of each domain specialists.

Chronobiology Phenomena↗
PubMed2004

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.

Adolescent↗
PubMed2004

hTERT expression and prognosis in B-chronic lymphocytic leukemia.

BACKGROUND: In B-chronic lymphocytic leukemia (B-CLL), there is a need for molecular markers to predict the evolution of this heterogeneous disease in individual patients. The level of expression of the human telomerase reverse transcriptase (hTERT) gene has been associated with disease aggressiveness in human cancers. The purpose of the present study was to examine the prognostic significance of hTERT expression in B-CLL. PATIENTS AND METHODS: We used real-time reverse transcription-PCR to quantitate the amount of hTERT transcripts in mononuclear blood cells from 90 B-CLL patients. In addition, samples were analyzed for somatic mutations in the immunoglobulin V (IgV) genes. RESULTS: The expression of hTERT gene was detected in 59% of patients. The level of expression increased with advancing B-CLL stage (P=0.0064). Patients expressing hTERT showed significantly shorter survival than hTERT-negative patients (P=0.000034), irrespective of the disease stage. On average, the level hTERT mRNA expression was seven-fold higher in the poor-prognosis B-CLL group with unmutated IgV than in the Ig-mutated group (P<10(-7)). The level of hTERT expression discriminated the Ig-unmutated from Ig-mutated B-CLL in 89% of cases. CONCLUSION: Our data indicate that hTERT expression in B-CLL may serve as a molecular prognostic marker.

Adult↗
PubMed2003

Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate.

Docetaxel (Taxotere), alone or in combination with other anticancer agents, has proven efficacy in the first- and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II-III primary operable breast cancer. Patients (n=88) were treated with six cycles of docetaxel at 100 mg m(-2) every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1-78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8-28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7-46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P=0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Clinical implications of quantitative real-time RT-PCR analysis of hTERT gene expression in human gliomas.

The presence of telomerase activity in a glioma may be a predictor of its malignant potential. Activation of telomerase is regulated at the transcriptional level of the human telomerase reverse transcriptase (hTERT). Here, we evaluated whether the amount of hTERT mRNA provides a molecular marker of glioma malignancy that would have clinical utility. We used a real-time RT-PCR to assess the number of hTERT transcripts in primary tumour samples derived from 70 glioma patients. Results were standardised by quantifying the number of ABL transcripts as internal control and expressed as hTERT/ABL ratio. The percentage of patients with detectable hTERT mRNA markedly increased with enhanced malignancy: low-grade gliomas expressed hTERT in one out of 14 cases (7.1%), anaplastic gliomas in four out of 13 cases (30.8%) and glioblastoma multiforme (GBM) tumours in 30 out of 43 cases (69.8%). The mean hTERT/ABL ratio was significantly higher in GBMs than in non-GBMs. Subdividing hTERT/ABL ratios as low (< pr = 25%) and high (>25%), we found that the overall survival among hTERT-positive GBMs was significantly worse in high hTERT expressors than in low hTERT expressors (P=0.0082). We conclude that the amount of hTERT mRNA may represent a diagnostic and prognostic indicator for GBM patients.

Adult↗
PubMed2003

[Modeling 5-FU clearance during a chronomodulated infusion].

Drugs pharmacokinetic control is a usual practice in case of flat continuous infusions. It enables among others, to modulate delivered doses when drug concentrations in blood appear too high. With chronotherapy, this possibility becomes more difficult because of sinusoidal outflows of infusion. We propose here a method that enables this follow-up, established through the study of 21 metastatic colorectal cancer patients, treated with a chronomodulated infusion of high dose 5-fluoro-uracil (5-FU) and folinic acid. This pharmacokinetic follow-up permitted the modelisation of 5-FU clearance and the calculation of an index, which was, in our study, correlated to the treatment response and also to main encountered toxicities.

Adenocarcinoma↗
PubMed2003

[Is there a circadian rhythm of interleukin 15 in humans?].

Nine healthy young men were studied under strict conditions for 48 h. The subjects were selected after a clinical examination and exploration of their rest-activity rhythm by actometry. The circadian rhythms of cortisol (peak at 8 AM) and melatonin (peak at 4 AM) were confirmed. The interleukin 15 (IL-15) was detected in the plasma samples with an Elisa kit (R&D System), but no reproducible variation could be observed during day 1 and day 2. In conclusion, in the conditions of our study, no rhythm was observed for IL-15. Our population will be completed with the inclusion of 6 additional subjects. These results will be specified.

Adolescent↗
PubMed2003

High-dose BCNU followed by autologous hematopoietic stem cell transplantation in supratentorial high-grade malignant gliomas: a retrospective analysis of 114 patients.

Conventional treatment of high-grade glioma includes maximal surgical resection followed by external radiation therapy. Despite this treatment, the prognosis for patients is poor. High doses of chemotherapy might be another way to increase the response rate and median survival. Increasing doses of BCNU might be more effective, but also provokes unacceptable myelotoxicity. This dose-limiting toxicity can be circumvented by using autologous blood stem cell rescue. We report our experience of high-dose BCNU followed by transplantation of autologous hematopoietic stem cells in 114 patients with high-grade gliomas. Of the 114 gliomas, 78 were glioblastoma multiforme (GM) (68%), 24 anaplastic astrocytomas (AA) (21%), and 12 anaplastic oligodendrogliomas (OD) (11%). Complete surgical resection was performed for 22 patients (18 GM and 4 AA). The median age was 44 years (range 17-65). A total of 84 patients received autologous hematopoietic stem cells from bone marrow harvest, while 30 patients received granulocyte colony-stimulating factor followed by apheresis and received peripheral blood progenitor cells (PBPC). High dose of BCNU (800 mg/m(2)) was given at least 1 month after neurosurgery. Bone marrow or PBPC was transplanted 48-72 h after chemotherapy. Radiotherapy was started approximately 40 days after transplantation to a total of 60 Gy. Median follow-up was 89 months (19-163). The overall survival (OS) was, respectively, 12 months for GM, 37 months for OD and 81 months for AA. Histological type appeared to be the main discriminating factor, with a worse prognosis for GM. Within the GM population, age, completeness of surgery, and response appeared to be one important prognostic factors. The AA and OD populations were small to reliably assess prognostic factors. On multivariate analysis, the main prognostic factors were histologic type, quality of surgery, and age (P<0.005). Five of 114 patients had lethal complications from the procedure. Four of these patients had a Karnovsky performance score (KPS) of 60%. The protocol thus appears to be feasible but patients should be selected for KPS more than 70%. We observed long-term survivors, although the OS and the time to treatment failure seem to be comparable to that described for other treatment. Additional pilot studies are unlikely to reveal more than a modest benefit from this procedure and therefore a randomized study should be performed.

Adolescent↗
PubMed2003

Intraperitoneal chemohyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures.

BACKGROUND: Peritoneal carcinomatosis has been regarded as a lethal clinical entity. Recently, aggressive treatments combining intraperitoneal chemohyperthermia (IPCH) with cytoreductive surgery have resulted in long-term survival in selected patients. The aim of this trial was to analyze the mortality and morbidity of 216 consecutive treatments of peritoneal carcinomatosis by IPCH by using a closed abdominal procedure combined with cytoreductive surgery. METHODS: Between February 1989 and August 2001, 207 patients who underwent 216 IPCH procedures using a closed abdominal procedure with mitomycin C, cisplatin, or both were prospectively studied. RESULTS: The postoperative mortality and morbidity rates were 3.2% and 24.5%, respectively. The most frequent complications were digestive fistula (6.5%) and hematological toxicity (4.6%). Morbidity was statistically linked with the carcinomatosis stage (P =.016), the duration of surgery (P =.005), and the number of resections and peritonectomy procedures (P =.042). Duration of surgery and carcinomatosis stage were the most common predictors of morbidity. CONCLUSIONS: The frequency of complications after IPCH and cytoreductive surgery was mainly associated with the carcinomatosis stage and the extent of the surgical procedure. The IPCH closed abdominal procedure has shown an acceptable frequency of adverse events.

Adult↗
PubMed2002

Phase II trial of chronomodulated infusion of high-dose fluorouracil and l-folinic acid in previously untreated patients with metastatic colorectal cancer.

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status less-than-or-equal 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 PM to 10:00 AM with peak at 4:00 AM). 5-FU dose was escalated from 900 to 1,100 mg/m(2)/d with fixed dose of l-FA at 150 mg/m(2)/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

Adult↗
PubMed2001

Circadian variation in O6-alkylguanine-DNA alkyltransferase activity in circulating blood mononuclear cells of healthy human subjects.

Cytotoxic agents such as chloroethylnitrosoureas (CENUs) mostly alkylate DNA on the O6-guanine position. This highly mutagenic lesion can be repaired by O6-alkylguanine-DNA alkyltransferase (AGT), which removes the alkyl group by accepting it to the cysteine residue of its active site. AGT activity displayed a circadian rhythm in mouse liver, coincident with that of CENU tolerability. We investigated whether AGT activity displayed a circadian rhythm in human circulating mononuclear cells (MNCs). The study was performed in 12 healthy volunteers aged 19 to 31 years. Circadian synchronization was verified with rest/activity cycle as assessed with wrist actigraphy and plasma cortisol and melatonin rhythms. Subjects were hospitalized for 24 hr and blood samples were obtained at 08:00, 12:00, 16:00, 20:00, 22:00, 00:00, 02:00, 04:00 and 08:00 overnight. MNCs were isolated on Ficoll immediately after blood sampling and frozen at -196 degrees C until AGT activity determination by HPLC. Mean AGT activity (+/- SEM) varied from 821 +/- 67 fmol/mg of total proteins at noon (trough), up to 1,055 +/- 80 fmol/mg at midnight (peak), i.e., by approximately 30%. A circadian rhythm was statistically validated with both analysis of variance (p < 0.009) and cosinor (p < 0.02) for AGT activity in MNCs (acrophase +/- SD at 00:30 +/- 210 min) as well as for MNC circulating count and for plasma cortisol and melatonin concentrations. Despite individual variations in the extent of AGT activity rhythm (more or less pronounced according to subject), AGT activity displayed a circadian rhythm in human MNCs of our healthy study group subjects. The results warrant to further investigate AGT rhythmicity both in circulating MNCs and in target tissues of cancer patients, as a prerequisite for clinical testing of chronotherapy with alkylating agents.

Adult↗
PubMed2000

Quality of life before and after laparoscopic fundoplication.

BACKGROUND: Laparoscopic fundoplication is a well-established surgical option for the treatment of gastroesophageal reflux disease. The aim of this study was to assess the surgical outcomes from the patient's point of view by using a validated quality of life instrument. METHODS: Fifty patients have been prospectively included. All patients underwent a standardized 270-degree posterior fundoplication. Quality of life was measured by the Gastrointestinal Quality of Life Index (GIQLI), a 36-item-questionnaire. The patients received the questionnaire before surgery, and 3 months and 1 year after surgery. RESULTS: Preoperative score was 95.6+/-21 points. The score increased significantly (P <0.0005) at 3 months (103.6+/-16) and 1 year (111.4+/-22) after surgery. This improvement concerned the four domains of the questionnaire (symptoms, social functioning, physical status, and emotions). The score in patients at 1 year remained, however, significantly lower than that in healthy persons (126+/-18). CONCLUSIONS: GIQLI is a sensitive tool to assess surgical outcomes after fundoplication. The quality of life after surgery did not reach the level of healthy population, not because of failure of surgery to treat GERD but probably because of functional dyspepsia that was present prior to surgery and did not change after fundoplication.

Dyspepsia↗