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Biomedical subjects

P Cottu

Publications and source records attributed to P Cottu.

17 recordsLinked to original sources
PubMed2002

Phase II study of oxaliplatin and fluorouracil in taxane- and anthracycline-pretreated breast cancer patients.

PURPOSE: Phase II study evaluating efficacy and safety of combined oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic breast cancer (ABC) patients. PATIENTS AND METHODS: Sixty-four taxane- and anthracycline-pretreated (within 6 months of study entry) women were treated with oxaliplatin 130 mg/m(2) (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m(2)/d (continuous IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median patient age was 51 years (range, 34 to 71 years), with a median of two involved organs (range, one to six organs), and metastases in the liver (70%), bone (47%), and lung (34%). Patients had a median of two prior chemotherapy regimens (range, one to six regimens), and 78% had previous hormonal therapy, with clinical taxane and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles were administered, with a median of six cycles/patient (range, one to 15 cycles). Sixty patients were assessable for response (World Health Organization criteria): 17 partial response, 26 stable disease, and 17 disease progression, giving an overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26% and 36% in taxane- and anthracycline-resistant populations, respectively, all responders having metastatic liver disease. Median time to progression was 4.8 months, and median overall survival was 11.9 months. Four treatment-related serious adverse events occurred, seven patients withdrew because of treatment-related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4 neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients, respectively, and a single episode of febrile neutropenia. One third of patients developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with grade 3 in only 8%. CONCLUSION: This oxaliplatin/5-FU combination is effective with an excellent safety profile in anthracycline/taxane-pretreated ABC patients, showing encouraging activity in patients with anthracycline/taxane-resistance or visceral disease.

Adult↗
PubMed2001

(99)mTc-tetrofosmin SPET in the detection of both primary breast cancer and axillary lymph node metastasis.

The aim of this study was to evaluate the usefulness of (99m)Tc-tetrofosmin single-photon emission tomography (SPET) in the detection of both primary breast cancer and axillary lymph node metastasis. We studied 192 consecutive patients in whom primary breast cancer was suspected on the basis of mammography and/or physical examination. After intravenous injection of 740 MBq (99m)Tc-tetrofosmin, both planar and SPET scintimammography was performed in all patients using a rectangular dual-head gamma camera equipped with low-energy, high-resolution, parallel-hole collimators. In 175 patients with breast cancer at histology, the per-lesion overall sensitivity of SPET and planar imaging for the detection of breast cancer was 95.8% and 75.9% (P<0.0005), respectively. The sensitivity of SPET and planar imaging was, respectively, 96.5% and 79.5% in palpable (P<0.0005) and 90% and 45% in non-palpable lesions (P<0.01). With regard to lesion size, the sensitivity of SPET and planar imaging was, respectively, 90.5% and 45.2% in lesions < or =10 mm ( P<0.0005), 95.3% and 81.4% in lesions of 11-20 mm (P<0.005), 100% and 84.6% in lesions of 21-30 mm (P<0.05) and 100% and 95.8% in lesions >30 mm (P>0.05). In the remaining 17 patients with benign mammary lesions at histology, per-lesion overall specificity of SPET and planar imaging was 76.2% and 85.7% (P>0.05), respectively. Neither SPET nor planar imaging showed false-positive results in non-palpable lesions or in those < or =10 mm. In 173 breast cancer patients submitted to axillary lymph node dissection (ALND), per-axilla overall sensitivity of SPET and planar imaging in the detection of axillary lymph node metastasis was 93% and 52.3% ( P<0.0005), respectively. The sensitivity of SPET and planar imaging was, respectively, 100% and 82.6% in palpable nodes (P>0.05), 90.5% and 41.3% in non-palpable nodes (P<0.0005), 92.8% and 35.7% in the presence of < or =3 nodes ( P<0.0005) and 93.2% and 68.2% in the presence of >3 nodes (P<0.005). The specificity of SPET and planar imaging was 91% and 100% (P<0.05), respectively. (99m)Tc-tetrofosmin SPET appears to be a reliable method for the detection of both primary BC and axillary lymph node metastasis, and its diagnostic accuracy exceeds that of (99m)Tc-tetrofosmin planar scintimammography. The use of SPET is particularly important in the identification of small non-palpable primary carcinomas and metastatic axillae with < or =3 non-palpable lymph nodes. More extensive use of SPET appears warranted in the management of breast cancer patients.

Axilla↗
PubMed2001

Extensive characterization of genetic alterations in a series of human colorectal cancer cell lines.

A number of genetic alterations have been described in colorectal cancers. They include allelic losses on specific chromosomal arms, mutations of oncogenes, tumor suppressor genes and mismatch repair genes, microsatellite instability in coding repeat sequences of target genes and methylation defects in gene promoters. Since these alterations have been reported by different groups on different tumors and cell lines, the complete repertoire of genetic alterations for any given tumor sample remains unknown. In the present study, we analysed a series of 22 colorectal cancer cell lines for 31 different genetic alterations. We found significant correlations between mutational profiles in these colorectal cell lines associated with differences in mismatch repair status. This panel of colon cancer cell lines is representative of the genetic heterogeneity occurring in sporadic colorectal carcinoma. Our results may prove to be very useful for understanding the different biological pathways involved in the development of colon cancer, and for groups studying cellular biology and pharmacology on the same cell lines.

Base Pair Mismatch↗
PubMed2001

Ecteinascidin-743: a marine-derived compound in advanced, pretreated sarcoma patients--preliminary evidence of activity.

PURPOSE: To report the activity of the chemotherapeutic agent ecteinascidin-743 (ET-743) in advanced pretreated sarcoma patients observed during a phase I study and a named-patient basis, compassionate use program. PATIENTS AND METHODS: Twenty-nine pretreated, advanced soft tissue sarcoma (STS) and bone sarcoma patients consecutively seen in our centers were included, 12 from a phase I trial and 17 from a compassionate use program cohort. Patients were treated every 3 weeks at either 1,200 microg/m(2) (six patients), 1,500 microg/m(2) (the recommended dose, 22 patients), or 1,800 microg/m(2) (the maximum-tolerated dose, one patient), given as a 24-hour infusion every 3 to 4 weeks. RESULTS: Fifteen men and 14 women were treated. The median patient age was 46 years (range, 16 to 71 years), with a median World Health Organization performance status of 1 (range, 0 to 2). Twenty-five patients had STS, three had osteosarcoma, and one had Ewing's sarcoma, and all had progressive disease at accrual. Fifteen patients had bulky disease, and 14 had clinical resistance to anthracyclines. A total of 136 treatment cycles were administered (median per patient, five cycles; range, one to 12 cycles). Transient grade 3 and 4 transaminitis was reported in 24% and 5% of cycles, respectively, grade 3 to 4 neutropenia occurred in 32% of cycles, with concomitant sporadic grade 3 to 4 thrombocytopenia in 5.1% of cycles. Grade 2 to 3 asthenia occurred in 21% of cycles. There were two partial responses (PRs) in STS patients and two PRs in osteosarcoma patients. Two minor responses and 10 disease stabilizations were seen. Median duration of response was 10.5 months (range, 2.8 to 15 months), and mean duration of stabilization was 5.2 months. CONCLUSION: ET-743 has activity in advanced, highly pretreated STS and osteosarcoma patients and warrants further trials to establish the extent of its activity in this setting.

Adolescent↗
PubMed2001

Cytokines and vascular cell adhesion molecule-1 in the blood of patients undergoing HPC mobilization.

BACKGROUND: The mechanism of HPC mobilization in humans is unclear. In this study, the relationship between PBPC mobilization and blood levels of G-CSF, endogenous cytokines (IL-8, SCF, thrombopoietin [TPO]), and the vascular cell adhesion molecule-1 (VCAM-1) was analyzed in patients with malignancy who were undergoing a PBPC mobilization regimen. STUDY DESIGN AND METHODS: Fifty-four patients with multiple myeloma (MM) and 29 with breast cancer (BC) underwent a mobilization regimen combining conventional chemotherapy and G-CSF up to the last day of PBPC collection. The CD34+ cell count was determined on each day when leukapheresis was scheduled. Venous blood samples (n = 117) were drawn before apheresis for CD34+ cell count (flow cytometry) and cytokine (G-CSF, IL-8, SCF, TPO) and VCAM-1 measurements (ELISA). RESULTS: In multiple regression analysis, SCF was a significant determinant of CD34+ cell levels in BC patients (R = 0.50, p = 0.03) and of VCAM-1 levels in MM patients (R = 0.32, p = 0.02). SCF was negatively correlated with CD34+ cell count in patients with BC. SCF and VCAM-1 blood levels were correlated in MM and BC patients. CONCLUSION: SCF and VCAM-1 could play a role in PBPC mobilization in patients and could be useful measures by which to study patients undergoing a mobilization regimen.

Adult↗
PubMed2001

99mTc-Tetrofosmin pinhole-SPECT (P-SPECT) and radioguided sentinel node (SN) biopsy and in breast cancer axillary lymph node staging.

We compared 99mTc-Tetrofosmin P-SPECT with radioguided SN biopsy in 101 T1/T2 BC pts to predict axillary lymph node status. The day before surgery all pts underwent lymphoscintigraphy (LS) to mark the SN, following subdermal injection of 99mTc-colloidal sulphur surrounding the breast lesion. LS was combined with pre and intraoperative gamma probe. Previously, all pts had also undergone P-SPECT. ALND was performed in all cases. The SN(s) was detected in 97/101 cases (96%) by LS and gamma probe; in the 4 missed cases P-SPECT predicted lymph node status. In the 97 comparable cases, radioguided SN biopsy showed a slightly higher accuracy than P-SPECT (94.8% vs 93.8%), but a higher false-negative rate (14.3% vs 8.6%); P-SPECT had a higher NPV (95.2% vs 92.5%). The two procedures when combined achieved 100% accuracy. Radioguided SN biopsy alone had 100% accuracy only in pts with BC < 15 mm. P-SPECT had 3 false negative cases, 2 of which were micrometastatic SNs, and 3 false positives. P-SPECT identified 81.2% of cases with a single node, determined the exact number of nodes in 82.6% of cases with 1 to 3 node and correctly classified 93.7% of pts as having < or = 3 or > 3 metastatic nodes. Radioguided SN biopsy seems indicated in selected, early stage, small BC pts, while P-SPECT shows a high sensitivity independent of primary tumor size, giving additional important preoperative prognostic information. The two procedures combined provided a better axillary lymph node status prediction in T1/T2 carcinomas, and could thus improve ALND pt selection.

Adult↗
PubMed2000

Predictors of short-term mortality in critically ill patients with solid malignancies.

UNLABELLED: Admission of cancer patients with serious medical complications to the ICU remains controversial primarily because of the high short-term mortality rates in these patients. However, the cancer patient population is heterogeneous regarding age, underlying conditions, and curability of their disease, suggesting that large variations may occur in the effectiveness of intensive care within this subgroup of critically ill patients. OBJECTIVES: To identify factors predicting 30-day mortality in patients with solid tumors admitted to a medical ICU. PATIENTS AND METHODS: We conducted a retrospective study in 120 consecutive cancer patients (excluding patients with hematological malignancies) admitted to the medical ICU of a 650-bed university hospital between January 1990 and July 1997. Medical history, physical and laboratory test findings at admission, and therapeutic interventions within the first 24 h in the ICU were recorded. The study endpoint was vital status 30 days after ICU admission. Stepwise logistic regression was used to identify independent prognostic factors. RESULTS: The observed 30-day mortality rate was 58.7 % (n = 68), with most deaths (92 %) occurring in the ICU. Univariate predictors of 30-day mortality were either protective [prior surgery for the cancer (p = 0.01) and complete remission (p = 0.01)] or associated with higher mortality [Knaus scale C or D (p = 0.02), shock (p = 0.04), need for vasopressors (p = 0.0006) or for mechanical ventilation (p = 0.0001), SAPS II score greater than 36 (p = 0.0001), LOD score greater than 6 (p = 0.0001), and ODIN score > 2 (p = 0.0001)]. Three variables were independent predictors: previous surgery for the cancer (OR 0.20, 95 % CI 0.07-0.58), LOD score > 6 (OR 1.26, 95 % CI 1.09-1.44), and need for mechanical ventilation (OR 3.55, 95 % CI; 1.26-6.7). Variables previously thought to be indicative of a poor prognosis (i. e., advanced age, metastatic or progressive disease, neutropenia or bone marrow transplantation) were not predictive of outcome. CONCLUSION: When transfer to an ICU is considered an option by patients and physicians, 30-day mortality is better estimated by an evaluation of acute organ dysfunction than by the characteristics of the underlying malignancy.

APACHE↗
PubMed2000

The role of 99mTc-tetrofosmin Pinhole-SPECT in breast cancer axillary lymph node staging.

The number of metastatic axillary nodes represents one of the most important prognostic factors in preoperative breast cancer patients. 99mTc-Tetrofosmin high resolution Pinhole (P)-SPECT was employed in 112 patients, 100 with breast cancer and 12 with benign mammary lesions, to ascertain axillary lymph node involvement. Axillary P-SPECT images were acquired utilizing specific software connected to a circular high resolution, single-head gamma camera equipped with a pinhole collimator with aperture size of 4.45 mm, rotating 180 degrees around the involved axilla. At the same time, patients also underwent conventional SPECT and planar acquisitions. Per-patient sensitivity and specificity were 100% and 93.6% for P-SPECT, 96.2% and 93.6% for SPECT and 56.6% and 100% for planar imaging, respectively. Moreover, P-SPECT detected more than 51% of lesions ascertained by histology, whereas SPECT and planar detected 32.6% and 20.3%, respectively. Only P-SPECT succeeded in identifying the exact number of metastatic axillary lesions in patients with multiple nodes; this procedure was able to correctly differentiate 88.67% of patients with 3 or less nodes from those with more than 3, thus giving important prognostic information. These data suggest 99mTc-Tetrofosmin P-SPECT is a reliable imaging method both for staging and prognostic purposes in breast cancer, and its routine use is recommended.

Adult↗
PubMed1997

Allelic profiles of mononucleotide repeat microsatellites in control individuals and in colorectal tumors with and without replication errors.

We have recently shown that analysis of BAT-26, was sufficient to establish the Replication Error status of colorectal tumors and cell lines without the need for matching normal DNA. BAT-26, a poly(A) tract in the 5th intron of the hMSH2 gene, does not present significant size variation either between the alleles of one individual or between alleles of different individuals. In colorectal tumors without defects in the replication error system (RER- phenotype), BAT-26 is also quasi-monomorphic. On the contrary, in RER+ colorectal tumors, BAT-26 shows unstable shortened alleles. In order to see whether this behaviour was specific for BAT-26, or was a more general phenomenon for mononucleotide repeat microsatellites, we analysed eight other mononucleotide repeats. In control individuals (72 samples) and in RER- colorectal tumors and cell lines (55 samples), these microsatellites were polymorphic, dimorphic, quasi-monomorphic or monomorphic, indicating that the quasi-monomorphic nature of BAT-26 was not a general rule. All of them showed a tendency to be shorter in RER+ colorectal tumors and cell lines (19 samples), but only quasi-monomorphic and monomorphic mononucleotide repeats could be used to determine the RER status of tumors without matching normal DNA, although with a lower efficiency than BAT-26 due to either a smaller range of shortening in RER+ tumors or to a larger number of false negative cases.

Alleles↗
PubMed1996

A new approach to the problem of surgical wound infections in clean operations.

A study was made of the risk factors causing a high incidence of surgical wound infections in clean operations. Identification of these factors in the preoperative stage allows the patients to be divided into two categories: a high risk (about 10% of patients for surgery) and low risk. By giving antibiotic prophylaxis only to patients at high risk, the incidence of postoperative infections can be reduced, decreasing the number of extra days in hospital and consequently lowering costs. This is a new approach to the problem of surgical wound infections since not only is it based on the usual classification of operations into clean, clean-contaminated, contaminated and dirty, but it also takes into account the defensive capacity of the target of the infection: the patient.

Humans↗
PubMed1995

[Mammary secretion: retrospective study of diagnostic and therapeutic problems].

Nipple secretion is an important clinical symptom in the context of breast pathology second only, in terms of incidence and diagnostic role, to the presence of a mammary nodule. Its importance derives from its possible association with cancer (from 3% to 47%) of which it may be the earliest sign, even if it is most often in relation to a benign pathology. The authors report their experience from 1988 to the present in 60 cases of mammary secretion out of 1200 patients attending the clinic.

Adult↗
PubMed1994

[Chronic pancreatitis: notes on diagnosis and surgical therapy].

The authors analyse their experience of 30 cases of which 25 underwent surgery. In addition to the onset of complications, indications for surgery were based on the presence of severe painful symptoms which did not respond to medical treatment. Over the past few years the latter have represented one of the main indications with a success rate of between 80-90% of cases. The type of surgery must be personalized to the characteristics of each individual patient on the basis of morphological alterations of the gland, which are easily defined during a preoperative study using CPRE, ultrasonography and CT. Of these, CPRE has been found to be the most reliable in diagnostic terms, since it can detect structural alterations at a relatively early phase and is of considerable value in differential diagnosis, which is at times extremely difficult, with pancreatic carcinoma.

Aged↗
PubMedDate not supplied

[Unusual case of benign neoplasm of the breast mimicking a carcinoma: granular cell tumor. Case report].

Granular cell tumors are rare, usually benign neoplasms of soft tissues which most commonly occur in the tongue, skin and subcutaneous tissue. Although the histogenesis is still object of debate, recent immunohistochemical studies and ultrastructural findings support the origin of this neoplasm from the peripheral nervous tissue, most likely from Schwann's cells. Occurrence of this neoplasm in the breast, although uncommon, warrants special attention, since its clinical, mammographic and pathological appearances on frozen sections "may often closely resemble" hose of breast malignancy. The authors analyze and commenton, with special reference to clinical aspects and surgical treatment, a case of benign granular cell tumor of the breast occurring in a 42 year-old woman. The mammographic and clinical findings suggested a breast carcinoma. The correct diagnosis was established by definitive microscopic examination of the paraffin-embedded specimens and the treatment was a simple local excision of the tumour and a small rim of surrounding breast parenchyma. Although the granular cell tumor of the breast is a rare entity, surgeons and pathologists should be aware of its existence in order to avoid inappropriate radical surgery not justified by the benign behavior of the neoplasm.

Adult↗
PubMedDate not supplied

[Our experience in the treatment of superior vena cava syndrome].

In clinical practice SVC syndrome is an important problem, given both the nature of the disease and its fast lethal evolution. Therapy must be instituted as soon as possible because the chances of a positive result are directly related to the staging of the primary illness. Surgery, chemotherapy and high energy therapy can be used. From the literature, although controversial, the superiority of surgical therapy is clear; particularly if up-to-date vascular reconstruction techniques are employed. From March 1980 to March 1988 8 cases of SVC syndrome were observed in which the aetiology was as follows: Hodgkin's disease (2 cases); secondary catheter thrombosis (1 cases); lung carcinoma (5 cases). The 2 cases of Hodgkin's disease were treated by chemotherapy; the secondary thrombosis by open thrombectomy. In the other 5 cases an innominate vein right appendage by-pass was used (3 PTFE, 2 pericardial grafts). The results were encouraging: complete, long-term remission was observed in the Hodgkin and thrombectomy patients. A PTFE graft thrombosis occurred in 2 cases but in the other cases the by-pass is functioning well at a mean 13 months follow-up.

Adult↗