Biomedical subjects

F Kwiatkowski

Publications and source records attributed to F Kwiatkowski.

53 records · Page 3Linked to original sources

PubMed1997

Adjuvant chemotherapy with doxorubicin-containing regimen for 326 stage II breast cancers: 15-year results.

Between 1975 and 1986, 326 patients with stage II breast cancer were treated with an adjuvant combination of doxorubicin, vincristine, cyclophosphamide, and 5-fluorouracil (AVCF) following regional therapy (232 modified radical mastectomy, 94 lumpectomies, 304 irradiations). The AVCF regimen consisted of 4-week cycles of doxorubicin (30 mg/m2 day 1, modified radical mastectomy), vincristine (1 mg/m2 day 2), 5-fluorouracil 400 (mg/m2), and cyclophosphamide (300 mg/m2) days 3-6. Two hundred twenty-four patients (pts) had six cycles and 102 pts 12 cycles; 90 pts also received 30 mg daily tamoxifen for 1 year after chemotherapy. As of March 1994, the median follow-up was 130 months (range 86-221). One hundred eighteen pts developed recurrences (7 local, 19 controlateral, 92 metastatic) and 104 died. Estimated disease-free survival (DFS) was 5 years, 76 +/- 5%; 10 years, 64 +/- 5%; 15 years, 54 +/- 9%. Overall survival (OS) was 5 years, 85 +/- 4%; 10 years, 70 +/- 5%; 15 years, 58 +/- 10%. Survival was affected by the number of involved lymph nodes (258 pts were N+), menopausal status (OS at 15 years: 53% for MP+ and 65% for MP-) and Scarff-Bloom-Richardson grading, but not by hormonal receptors, number of courses, or associated hormonotherapy. Minimal cardiac toxicity was induced by doxorubicin either during or subsequent to treatment completion.

Adult↗

PubMed1997

Analysis of randomized controlled trials in laparoscopic surgery.

BACKGROUND: Randomized controlled studies of surgical procedures are difficult, but can be done to acceptable standards. There are few published objective assessments of such trials. METHODS: The original articles that involved a randomized controlled trial including at least one laparoscopic procedure were reviewed and evaluated with special interest in their methodology. An assessment form containing 11 generic questions and three additional criteria (assessment of quality of life, cost analysis and laparoscopic experience required) was used. Forty trials were retrieved including 12 on cholecystectomy, 12 on hernia repair and 12 on appendicectomy. Each trial was scored by two assessors. RESULTS: The agreement among the two independent assessors was very good. Six of the trials were well conducted but 22 had a poor score. The trials on cholecystectomy were scored the best in contrast to those on hernia repair or appendicectomy. Few trials provided an adequate prospective calculation of the sample size, an unbiased assessment of endpoints, evaluation of the quality of life and a study of the economic aspects. CONCLUSION: Readers should be cautious when interpreting the results of some of these trials and their impact on daily surgical practice.

Humans↗

PubMed1996

Circadian rhythm in toxic effects of cystemustine in mice: relevance for chronomodulated delivery.

Cystemustine is a new nitrosourea with high anti-tumor activity and a short plasma half-life in mice. The influence of circadian dosing time upon its toxicities was first investigated in a total of 368 synchronized male B6D2F1 mice. Late survival rate varied from 4% in mice receiving a single dose of cystemustine (conventional lethal dose 50%) at 7 hours after light onset (HALO) up to 88% in mice treated at 15 or at 19 HALO. Target organ toxicities (bone marrow, circulating blood cells, spleen, colon and duodenum) were studied following a single slightly lower dose of cystemustine. Leukopenia was the major hematologic effect encountered. Leukocyte count nadir occurred 7 days after injection and was lowest following cystemustine at 7 HALO as compared to 13 or 19 HALO. Recovery was faster after cystemustine at 19 HALO as compared to other dosing times. Bone-marrow necrotic lesions were more pronounced 1 day after cystemustine at 7 HALO than after cystemustine at 19 HALO. Thus, a large-amplitude circadian rhythm characterized the toxicity of this nitrosourea in mice. The lowest cystemustine toxicity was found near the middle of the active span of the rest-activity circadian cycle of mice.

Animals↗

PubMed1996

Circadian variation in O6-methylguanine-DNA methyltransferase activity in mouse liver.

Bifunctional chloroethylating cytostatic agents produce lethal DNA lesions, as a result of the formation of O6-alkylguanines. These lesions can be repaired by O6-methylguanine-DNA methyltransferase (MGMT). This ubiquitous nuclear and cytosolic enzyme removes the alkyl group by accepting it to the cysteine residue of its active site, thus preventing the formation of DNA interstrand cross-links. The role of the circadian organization in cellular protection against such DNA insults was examined in male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (LD12:12). MGMT activity was determined in liver of mice obtained at eight different circadian times, located 3 h apart. MGMT activity varied 5-fold along the 24 h time-scale, from 7 +/- 1 pmol/g of tissue at 7 h after light onset (HALO), during the rest span, up to 32 +/- 9 pmol/g at 19 HALO (second mid to late activity span). This large amplitude circadian rhythm in MGMT activity may be an important determinant of the susceptibility rhythms to alkylating agents. The greatest DNA repair activity occurred at night when mice were active, eat and drink, and thus are at a higher risk of being exposed to chemical insults.

Animals↗

PubMed1994

Low grade supratentorial astrocytomas. Management and prognostic factors.

BACKGROUND: The authors examined the principal prognostic factors for supratentorial low grade astrocytomas and the effects of treatment on survival time. METHODS: Fifty-eight patients, 32 males and 26 females, treated from January 1970 through December 1990 are reported. Thirty-five patients underwent surgery, of whom three died. Among the survivors there were 7 gross total resections, 13 subtotal resections, and 12 partial resections. Of the 23 remaining patients, diagnosis was obtained by stereotactic biopsy. Twenty-five patients were irradiated and eight received chemotherapy. The histologic material, originally graded 1 or 2 according to Kernohan's system, was reviewed using the St. Anne-Mayo Clinic system, with which there were 18 Grade 3 tumors. RESULTS: Six patients had pilocytic astrocytomas (mean age, 18 years), of which three astrocytomas could be removed, and the patients were well 128, 152, and 254 months, respectively, after diagnosis. Among the other three patients, one with a hypothalamic localization refused any form of treatment and died rapidly. The remaining two patients also had deep-seated tumors and were irradiated: one died 17 months later, and the other remained relapse free 56 months after diagnosis. The 49 patients with ordinary astrocytomas who survived surgery (mean age, 37 years) had a median survival time of 64 months and 5- and 10-year survival rates of 54.6% and 34.1%, respectively. Patients with Grade 1 or 2 tumors had a median survival time of 108.6 months, compared with 39.4 months for patients with Grade 3 tumors. Gross total and subtotal resections were significantly associated with longer survival time only in patients with Grade 1 and 2 tumors: in this group, the 5- and 10-year survival rates were 87.5% and 68.2%, respectively, when tumor was completely resected, instead of 57% and 31.2% in patients with incomplete or no surgical resection. There was a trend suggesting that antimitotic drugs and X-ray therapy could benefit patients with Grade 3 tumors. CONCLUSION: The importance of an accurate histologic grading system and a gross total resection of Grade 1 and 2 astrocytomas is emphasized.

Actuarial Analysis↗

PubMed1994

The hematopoietic stem cell transplantation in Hodgkin's disease: questions and controversies.

Most patients with Hodgkin's disease (HD) are cured with chemotherapy and/or radiotherapy. However, half of those with advanced stage disease (IIIB, IV) do not respond adequately to treatment or relapse. Salvage therapy used in such cases gives from 10% to 50% complete remission but only 10% long term survival. The results of bone marrow transplantation reported in acute leukemia and non-Hodgkin's lymphoma encouraged some authors to develop this new therapeutic strategy in Hodgkin's disease. In the early 1980's promising results were achieved when refractory and relapsed patients were selected to receive myeloablative therapy followed by bone marrow transplantation. Today, high dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is used more and more often in poor prognosis Hodgkin's disease. After a review of the literature concerning the results of transplantation in Hodgkin's disease, we develop the numerous problems associated with this procedure which remain to be solved such as: the optimal indication, the timing of HSCT, the type of graft, the conditioning regimen, the place of radiotherapy and the optimal use of hematopoietic growth factors. We conclude with future prospects.

Age Factors↗

PubMed1994

[PS2 as a prognostic factor in 1065 cases of human breast cancer. A multicenter study].

pS2 protein assay was performed with Elsa-pS2 kit (CIS-Biointernational) on a group of 1,065 patients with operable breast cancer who underwent breast surgery in the years 1982 through 1990. The median follow-up was 57 months. This group included exclusively infiltrating ductal carcinoma with primary surgery. Age mean was 58 yr; T0-T1, 33.6%; T2-T4, 66.4%; Differentiation grade I, 29%; node negative, 53%; estrogen receptor (ER) positive, 62.4%; progesterone receptor (PR) positive, 55.2%; mean tumor size, 2.4 cm; local recurrence, 5.2%; metastasis, 17.5%. pS2 values varied from 0.1 to 707 ng/mg of cytosol protein (median, 5.6; mean 24.5; 95th percentile 112 ng/mg p). There was no significant relationship between the mean level of pS2 and age, tumor size, nodal status, whereas pS2 was related to histological grade (P < 10(-3)), ER (P < 10(-5)), and PR (P < 10(-5)). By using 2 ng/mg p as pS2 cutoff, 77/391 (19.7%) of ER+PR+ tumors were pS2-, and 122/345 (35.4%) of ER-PR-tumors were pS2+; with this cutoff, a strong relationship existed between pS2 and overall survival, but not between pS2 and relapse-free survival. With Cox multivariate analysis, pS2 protein was classified after lymph node status, histological size, ER, differentiation grade, age, clinical stage, PR. In patients with axillary lymph node involvement (N+), pS2 status could discriminate between good and bad prognosis, specially for patients with small tumors (< 2 cm) and with less than seven invaded nodes. This study showed that pS2 protein was a poor prognostic factor in comparison with classical factors.

Breast Neoplasms↗

PubMed1994

[Prognostic value of beta-2-microglobulin in Hodgkin disease in young adults].

From 1977 to 1989, we measured serum beta-2-microglobulin (beta 2-MG) levels from 64 unselected and untreated patients, between 18 to 50-year-old, affected by Hodgkin's disease. Serum beta 2-MG level was measured by radioimmunoassay (Phadebas beta 2 microtest). Then, all patients received a chemotherapy such as MOPP or alternating MOPP/ABVD followed or not by radiotherapy. Elevated serum beta 2-MG level (> 2.4 mg/l) is associated with advanced stage disease (stage III-IV), presence of systemic symptoms and bulky tumor. Nevertheless, a multivariate analysis shows that the serum beta 2-MG level is the most significant prognostic indicator for disease free survival. The prognostic value of serum beta 2-MG is demonstrated for myeloma and non Hodgkin's lymphoma. A few authors have evaluated the prognostic impact of serum beta 2-MG in Hodgkin's disease. This study requires confirmation by multicentric and prospective trial.

Adolescent↗

PubMed1993

Treatment results, survival and prognostic factors in 109 inflammatory breast cancers: univariate and multivariate analysis.

Between 1978 and 1987, 109 patients without metastatic disease were treated by induction chemotherapy for inflammatory breast cancer (IBC) or "neglected" locally advanced breast cancer (LABC): 62 patients had a clinical history of rapidly growing tumours (doubling time < or = 4 months) and inflammatory signs; conversely, the 47 neglected patients had local inflammation with a longer history of LABC. 103 patients were fully evaluable. All patients received the same induction chemotherapy with doxorubicin, vincristine, cyclophosphamide and 5-fluorouracil. After six cycles, locoregional treatment was by radiotherapy if a complete or nearly complete response had been obtained, and total mastectomy, with pre or postoperative radiotherapy, in other cases. The chemotherapy after local treatment comprised of six cycles for LABC and 12 cycles for IBC (six without doxorubicin). With a median follow-up of 120 months, the median overall survival (OS) time was 70 months as against 45 months for disease-free survival (DFS). No difference was observed for OS and DFS between LABC and IBC. The regional recurrence rate was 24% (15% for radiotherapy alone). 20 factors of potential prognostic significance were evaluated by univariate and multivariate analysis. For DFS and OS, univariate analysis suggested a worse prognostic significance for "peau d'orange" appearance of the skin, clinical evidence of node involvement and poor response to chemotherapy after three cycles, on mammographic criteria. The cumulative dose of doxorubicin after three cycles seemed to have a significant effect on OS (P < 0.03) but was too closely correlated with age to draw definite conclusions. In the multivariate analysis, "peau d'orange", menopausal status and clinical node involvement predicted DFS. "Peau d'orange" and clinical node involvement also predicted OS. Our results indicate that IBC and LABC do not behave differently when treated with our procedure.

Age Factors↗

PubMed1993

[Chromosomal analysis of bladder tumors. Technical aspects, anatomoclinical correlations and perspectives. Report of 18 cases].

The course of bladder tumours is difficult to predict. The most reliable prognostic factor at the present time is histological grade. Cytogenetic subclasses of bladder tumours can be distinguished on the basis of the demonstration of karyotype anomalies in bladder tumour cells. Eighteen patients underwent cytogenetic examination of their bladder tumour and were followed for an average of 35 months. Multivariate analysis of the clinical and laboratory parameters studied revealed the importance of age and the absence of trisomy 7 in the tumour on patient survival. The presence of trisomy 7 in a bladder tumour may therefore constitute a factor of poor prognosis. This hypothesis needs to be confirmed by further studies in larger populations. The search for this anomaly can be performed by fluorescent in situ chromosomal hybridisation, a technique which transforms cytogenetics from an experimental procedure into a routine complementary investigation. These techniques can be performed on urine samples, suggesting the possibility of their application to screening or follow-up of bladder tumours.

Adult↗

PubMed1992

Neoadjuvant chemotherapy in 126 operable breast cancers.

126 patients with non-inflammatory operable breast cancer, who otherwise would have undergone modified radical mastectomy (MRM), were treated by induction chemotherapy. Before treatment, every patient had a local and general assessment, and pathological or cytological evidence of malignancy. Patients received, every 3 weeks, the same treatment with doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil (AVCF); methotrexate was added in 80 cases (AVCFM). Tumour shrinkage greater than 50% was documented in 105 (83%) of the 126 women. A higher objective response rate was obtained in aneuploid or high S phase tumours, especially in the patients treated with methotrexate. After chemotherapy, 41 patients were then treated by radiotherapy alone after complete or sub-complete response; 64 had a residual tumour that could be treated by conservative surgery and radiotherapy. Only 19 had MRM and radiotherapy. Histopathological complete remission was documented in 1 case; isolated residual tumour cells were found in 5 patients. Thus primary chemotherapy enhanced the possibility of breast conservation in up to 83% of the cases in a series in which most would have been otherwise subjected to a MRM because of tumour size.

Adjuvants, Pharmaceutic↗

PubMed1991

Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma.

In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index). The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation. The end point was defined as either local/regional recurrence or metastasis. Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02). Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1989

Comparison between 180 degrees and 360 degrees data collection in technetium-99m MIBI SPECT of the myocardium.

In a series of 12 patients presenting with a single-vessel coronary artery disease and who were injected with 370 MBq of 99mTc-2-methoxyisobutylisonitrile at peak exercise, two consecutive single photon emission computed tomography (SPECT) data collections, i.e., 32 views of 30 sec during a 180 degrees rotation and 64 views of 15 sec during a 360 degrees rotation, were performed 1 hr later. In both cases, transverse sections were reconstructed using (a) a backprojection method with a ramp filter, (b) a correction for downscatter, (c) a correction for depth attenuation by the Chang method, or (d) both corrections. Each reconstructed myocardium was then divided into four short-axis sections which were radially divided into nine sectors. Sectors with an activity below 80% of the maximum were considered as abnormal. Sensitivity and specificity were calculated relative to a sector-by-sector theoretical anatomic distribution of the perfusion abnormalities. Results demonstrate that, of all situations, the best balance between sensitivity and specificity was achieved with the 180 degrees data collection and no correction at reconstruction. Using the 360 degrees data sampling technique mainly lowered the sensitivity in the patients with a circumflex or right coronary artery disease. It is concluded that there does not seem to be any definite advantage in performing a 360 degrees rather than a 180 degrees data collection in 99mTc myocardial SPECT.

Adult↗

PubMedDate not supplied

Early CYFRA 21-1 variation predicts tumor response to chemotherapy and survival in locally advanced non-small cell lung cancer patients.

We have evaluated CYFRA 21-1 serum level variations as an indicator of tumor response and survival in 44 consecutive patients with locally advanced non-small cell lung cancer (NSCLC) treated with induction chemotherapy (IC). Irrespective of the initial CYFRA 21-1 serum concentration, a more than 65% decrease in the serum level after the first chemotherapy course was significantly predictive of an objective tumor response (p = 0.0022). In addition, a more than 80% decrease in this level significantly predicted a better disease-free survival (p = 0.039). In patients with initial CYFRA 21-1 serum levels > 3.3 ng/mL (n = 29), a more than 80% decrease after the first IC course was the most significant predictor of overall survival (p = 0.025) in a Cox analysis including initial staging, tumor response and surgery. We conclude that early monitoring of CYFRA 21-1 serum levels may be a useful prognostic tool for tumor response and survival in stage III NSCLC patients treated by induction chemotherapy.

Adult↗

PubMedDate not supplied

Loss of heterozygosity at the ATM locus in colorectal carcinoma.

Patients homozygous for mutation of the ATM gene exhibit constitutional genetic instability and have a high risk of cancer. A-T heterozygotes also have an increased tendency to develop adenocarcinomas. Colorectal cancer (CRC) is the second most common cancer in western populations, and tumors of the right colon are typically highly genetically unstable. The DNA mismatch repair genes mutated in most familial and some sporadic CRCs account for one route by which cells acquire additional oncogenic mutations during the progression of malignancy. Mismatch repair defects, however, do not seem to account for the majority of CRCs. Because of its role in maintaining genomic stability, and the high risk of cancer to homozygotes, ATM is a candidate gene for inactivation in the evolution of chromosomal instability in tumor cells. We have examined 114 CRC patients for loss of heterozygosity (LOH) using six microsatellite markers tightly linked to the ATM locus. Our data suggest that LOH of this region is not associated with cancer of the proximal colon. In the distal colon, LOH was found in 23-31% of cases, which is moderately elevated above the non-specific LOH reported in tumors of this tissue. No correlations were found with regard to clinicopathological variables aside from tumor location.

Adult↗

PubMedDate not supplied

Allelic imbalance at NBS1 is frequent in both proximal and distal colorectal carcinoma.

Nijmegen breakage syndrome (NBS) is a hereditary disorder involving chromosomal instability, cancer risk and radiosensitivity. NBS carriers have an increased risk of cancer, though the significance of mutations in the NBS1 gene in sporadic cancer has not yet been investigated. Because the loss of NBS1 is associated with increased chromosomal re-arrangements, and tumors of the colon are particularly prone to chromosomal anomalies, we have begun to study the NBS1 locus in colorectal cancer (CRC). DNA was isolated from 99 microdissected colorectal tumors, and microsatellite markers flanking the NBS1 locus at 8q21.3 as well as elsewhere on 8q were analyzed. Normal lymphocyte DNA from each patient served to normalize the amplification of each allele, and a reduction of at least 35% in the intensity of one allele was taken as evidence of allelic imbalance (AI). In proximal and distal CRCs we found 25.9 and 36.2% with AI at 8q21.3, respectively. AI in proximal CRC tended not to extend to marker D8S555 at 8q24.1, whereas in distal CRC the region of AI frequently included all the informative markers. AI of 8q21.3 was not associated with any clinical variable. These results suggest that 8q21.3 contains a tumor suppressor gene involved in proximal CRC, possibly NBS1. The large regions of AI make it difficult to determine the importance of AI at the NBS1 locus in distal CRC.

Alleles↗

PubMedDate not supplied

Association between H-ras minisatellite and colorectal cancer risk.

BACKGROUND: The H-ras locus has been suggested to play an important role in susceptibility to cancer. However, the results remain controversial. METHODS: In order to elucidate the potential role of the H-ras locus in colorectal carcinogenesis, 142 colorectal tumors with matched normal samples were studied for genomic instability and loss of heterozygosity (LOH), and 143 healthy samples of white blood cell DNA were examined by PCR, for H-ras allelic polymorphism. RESULTS: Nine percent of colorectal cancer patients constitutionally presented at least one rare allele versus 1.4% of healthy individuals (P = 0.0034). The risk of developing colorectal cancer increased significantly with the presence of rare H-ras alleles (odds ratio = 7.10 and 95% confidence interval = 1.92-26.35). The genotype associating one common allele and one rare allele was overrepresented in cancer patients (P < 0.01). No associations were observed between the rare alleles and tumor site or with the aggressiveness of cancer. Low frequencies of LOH (5%) and genetic instability (0.7%) at the H-ras locus were found in our colorectal cancer set. CONCLUSIONS: Consequently, the presence of uncommon alleles at the H-ras locus appeared to be an informative genetic marker.

Adenocarcinoma↗