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Biomedical subjects

P Lothaire

Publications and source records attributed to P Lothaire.

At least 19 recordsLinked to original sources
PubMed2005

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis.

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16-1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26-2.02) and in studies using PCR (HR 1.40; 95% CI 1.18-1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86-1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Survival improvement in resectable non-small cell lung cancer with (neo)adjuvant chemotherapy: results of a meta-analysis of the literature.

The recent publication of many randomised trials about (neo)adjuvant chemotherapy in resectable non-small cell lung cancer (NSCLC) has prompted our group to update a prior meta-analysis of the literature. Randomised studies published in French and English between 1965 and June 2004 were included in this analysis. A qualitative assessment of each trial was first performed using the European lung cancer working party (ELCWP) and the Chalmers' scales. In absence of statistically significant quality difference between positive and negative trials, a quantitative aggregation (meta-analysis) of the individual results was performed. Two trials for which data were available on ASCO virtual meeting website were also included in the meta-analysis. Twenty-five studies eligible for this analysis assessed chemotherapy as induction (n = 6) or adjuvant to surgery (n = 19). No quality difference was detected between positive and negative trials according to the two scores, whatever all trials were combined or only adjuvant chemotherapy studies were considered. The overall meta-analysis showed that the hazard ratio (HR) of the combined results was 0.66 (95% CI 0.48-0.93) in favour of the addition of induction chemotherapy to a standard surgical procedure and 0.84 (95% CI 0.78-0.89) in favour of adjuvant chemotherapy. The effect was significant for adjuvant chemotherapy in stages I and II with a HR of 0.88 (95% CI 0.83-0.94). It was not statistically significant in stage III although the trend was in favour of chemotherapy whatever adjuvant (HR = 0.85; 95% CI 0.69-1.04) or (neo)adjuvant (HR = 0.65; 95% CI 0.41-1.04) chemotherapy was tested. In conclusion, our meta-analysis shows the efficacy of adjuvant chemotherapy in stages I and II resected NSCLC. More data are needed to confirm such a role for induction chemotherapy. Further trials should separate stage III disease from earlier stages.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Skin metastases from a head and neck carcinoma: a prognostic factor?

BACKGROUND: Distant metastases in head and neck cancer are often to the lung, and rarely to the skin sites. METHOD: To ascertain that a skin metastasis indicates a poor prognosis, a review was conducted of patients with head and neck cancer. RESULTS: Three out of seven patients had evidence of local recurrence at the time of development of the skin metastases, and three out of seven had evidence of distant metastases. The average survival time was 1 month after the development of skin metastases. CONCLUSION: Skin metastases may represent the first clinical evidence of impending recurrence or distant metastasis. The development of skin metastasis is associated with a poor prognosis. Current treatment options are limited in their efficacity.

Aged↗
PubMed2004

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis.

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

Biomarkers, Tumor↗
PubMed2004

[Surgical resection for gastrointestinal metastatic melanoma].

AIM: Metastases of melanoma are frequent. On the gastro-intestinal tract, commonest localizations are small bowel, stomach and colon. Surgical treatment of digestive metastases from melanoma is not well known and its value is still debated. PATIENTS AND METHODS: Medical records of 10 patients (six female and four male) operated for metastatic melanoma to gastro-intestinal tract were reviewed to determine results of surgery. RESULTS: Gastro-intestinal metastases were symptomatic in eight patients (abdominal pain in three, bowel obstruction in three, abdominal mass and obstructive jaundice in one each). Two patients had anemia. Diagnosis has been suggested by imaging in seven patients and endoscopy in three. All patients were operated on by laparotomy for resection of metastases located on small bowel in four patients, gallbladder in two, stomach in two and colon in two. Complete resection suppressed symptoms in nine cases. In one patient, resection was incomplete but provided satisfying symptomatic relief. One patient died at day 3; in other patients, median survival was 18 months (range: 3-120). CONCLUSION: In a patient with previous history of melanoma, digestive symptoms indicate morphological explorations due to suspicion of metastases to gastro-intestinal tract. Surgical treatment of these metastases is usually palliative but, in some cases, allows long-term survival.

Abdominal Pain↗
PubMed2004

Survival is better predicted with a new classification of stage III unresectable non-small cell lung carcinoma treated by chemotherapy and radiotherapy.

UNLABELLED: The 1997 International staging system (ISS) classification separated stage III non-small cell lung cancer (NSCLC) into stages IIIA and IIIB. In a previous study including unresectable NSCLC initially treated with chemotherapy, we analysed survival according to tumour (T) and node (N) stages and derived a classification into stages IIIbeta (T3-4N3) and IIIalpha (other TN stage III) that had a better discrimination on survival distribution. The aim of this study was to validate these results in a further set of patients. Patients with unresectable stage III NSCLC included in a phase III trial assessing the role of increased dose chemotherapy (SuperMIP: mitomycin 6 mg/m2, ifosfamide 4.5 g/m2, cisplatin 60 mg/m2, carboplatin 200 mg/m2) in comparison to standard chemotherapy MIP (mitomycin 6 mg/m2, ifosfamide 3 g/m2, cisplatin 50 mg/m2), before thoracic irradiation (60 Gy in 30 fractions over 6 weeks) were the subject of this study. Survival distributions were assessed by the method of Kaplan-Meier. Survival comparisons were made by the log-rank test. Multivariate analyses using Cox regression models, included all potential prognostic factors for survival with a P-value <0.2 in univariate analysis. According to the 1997 International staging system classification, 328 eligible patients were included in the study. There was no imbalance between the two arms. Five parameters were significantly associated (P < or = 0.05) with survival in univariate analysis: European lung cancer working party (ELCWP) staging (IIIalpha[n = 294 pts] versus IIIbeta [n = 46]), Karnofsky index, weight loss, platelet count and haemoglobin level. These variables as well as the 1997 ISS staging, white blood cell (WBC) count, LDH and sodium levels were included in a multivariate analysis. Two models were constructed, including either the ELCWP or the 1997 ISS. In model 1 (ISS included), Karnofsky index (HR 0.69; 95% confidence interval (CI) 0.47-1.00; P = 0.05) and haemoglobin (HR 1.49; 95% CI 1.11-1.99; P = 0.007) were found significant. In model 2, including ELCWP staging, two variables were associated with survival: ELCWP staging (HR 1.68; 95% CI 1.20-2.35; P = 0.002) and haemoglobin (HR 1.54; 95% CI 1.15-2.07; P = 0.01). CONCLUSION: In initially unresectable stage III NSCLC treated by chemotherapy and radiotherapy, we validated the results of our previous study. The classification into stages IIIbeta (T3-4N3M0) and IIIalpha (other TN stage III) better discriminates the patients in term of survival than the 1997 ISS classification.

Aged↗
PubMed2004

[Metastatic prostate carcinoma mimicking a parotid tumor: a case report].

We report a case of prostate carcinoma metastatic to the mandible that had been initially suspected as being a primary tumor of the parotid. The initial symptom was hard swelling in the left parotid region. No pathologic fracture was diagnosed. The metastatic lesion was diagnosed 4 years after diagnosis of the carcinoma of the prostate. This is a very interesting event because of its unusual localization.

Adenocarcinoma↗
PubMed2004

[Tracheotomy].

INTRODUCTION: Tracheotomy was initially described as a means to relieve acute upper airway obstruction. Indications for its use have changed and developed over time. STATE OF THE ART: During the 1960's, tracheotomy was promoted as a treatment for ventilator-dependent patients but the complications reported in the 1970's and early 1980's both reduced its accepted indications and led to it being proposed later. During the last 20 years advances in intensive care medicine and a reduction in the rate of complications associated with the procedure have encouraged intensivists again to propose tracheotomy at an earlier stage. PERSPECTIVES: Over the last 10 years, a new technique, percutaneous dilatational tracheotomy has gained widespread acceptance because of its simplicity of execution, its low cost and the low rate of postoperative complications that has been observed. CONCLUSIONS: Although the ideal time to perform a tracheotomy has not yet been established, the benefits of this approach compared to prolonged laryngeal intubation, the low morbidity associated with modern surgical tracheotomy and the development of percutaneous techniques support the use of this procedure in the management of patients requiring prolonged ventilatory support.

Humans↗
PubMed2004

A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer.

PURPOSE: The aim of this study was to determine the role of chemotherapy dose intensity in patients with initially unresectable non-metastatic non-small-cell lung cancer (NSCLC), with survival as primary end point, by testing two different regimens as induction chemotherapy followed by thoracic irradiation. PATIENTS AND METHODS: Patients had pathologically proven NSCLC, an initially unresectable non-metastatic tumour without homolateral malignant pleural effusion, no prior history of malignancy and had received no prior therapy. Treatment was randomised for chemotherapy between three courses of MIP (mitomycin C 6 mg/m2; ifosfamide 3 g/m2; cisplatin 50 mg/m2) or SuperMIP (mitomycin C 6 mg/m2; ifosfamide 4.5 g/m2; cisplatin 60 mg/m2, carboplatine 200 mg/m2), followed by chest irradiation (60 Gy; five times per week, for 6 weeks). If the tumour became resectable after chemotherapy, surgery was performed, followed by mediastinal irradiation. RESULTS: A total of 351 patients were eligible: 176 in the MIP arm and 175 in the SuperMIP arm, with 43% and 51% stages IIIA and IIIB, respectively. There was a significantly higher objective response rate with SuperMIP (46%) compared with MIP (35%) (P=0.03) [95% confidence interval (CI) for the difference between the response rates, 1% to 22%]. After induction chemotherapy, surgery was performed in 54 (15%) patients (27 per arm) and chest irradiation in 203 (57%) patients (102 in the MIP arm and 101 in the SuperMIP). In terms of survival, there was no statistically significant difference between the two study arms (P=0.16), with median survival times of, for MIP and SuperMIP, respectively, 12.5 (95% CI 10.1-14.9) and 11.2 (95% CI 9.7-12.8) months. Haematological toxicity and dosage reductions were higher with SuperMIP, which was nevertheless associated with a significantly increased absolute dose intensity. CONCLUSIONS: High dose-intensity induction chemotherapy does not improve survival in initially unresectable non metastatic NSCLC.

Adult↗
PubMed2004

Molecular profiling of head and neck tumors.

PURPOSE OF REVIEW: Head and neck squamous cell carcinoma is the fifth most common cancer worldwide. Unfortunately, patients with the same diagnostic and prognostic profile can have markedly different clinical outcomes. This most likely results from the fact that the current taxonomy of head and neck squamous cell carcinoma groups molecularly different diseases with distinct clinical phenotypes into classifications based mainly on morphology. A combination of circumstances, including the advent of array-based technology and progress in the human genome initiative, now provides an ideal opportunity to begin performing comprehensive molecular and genetic profiling of head and neck squamous cell carcinoma. This article reviews recently reported studies that have used such approaches. RECENT FINDINGS: Comparison of gene expression profiles between head and neck squamous cell carcinoma and normal tissues showed altered expression levels of genes involved in the control of cell growth and differentiation, angiogenesis, apoptosis, cell cycle, and signaling, most of which have not been previously described in head and neck squamous cell carcinoma. Additionally, they revealed the implication of different signaling and metabolic pathways such wnt and noch, highlighting the potential role of these pathways in oral cancer development. Their results provide new insights into the carcinogenesis of head and neck squamous cell carcinoma as well as a source of potential prognostic and predictive markers and targets for its prevention and therapeutics. SUMMARY: Although the sample sizes of these studies were small and their findings therefore require further validation in larger trials, such preliminary results provide important clues to the understanding of the various gene networks implicated in oral carcinogenesis and may contribute to the selection of target genes for possible molecular diagnosis and therapy in the future.

Carcinoma, Squamous Cell↗
PubMed2003

[EGF-R expression correlation between biopsy and surgical specimens of lung carcinoma].

INTRODUCTION: Most of the time, biological parameters are evaluated on tissues obtained on surgical samples of the primary tumour. New approaches in non small cell lung cancer (NSCLC) treatment consist to administer neoadjuvant chemotherapy or anti-EGF-R (epidermal growth factor receptor) drug. METHODS: We assessed the expression of EGF-R by immunohistochemistry on biopsy samples and on the paired resected tumours in 27 patients. RESULTS: The mean percentage of EGF-R positive neoplastic cells was 11% in surgical specimens compared to 28% in biopsy specimens (p=0.02) although a good correlation (R=0.67; p=0.0001) between biopsies and surgical specimens was observed. Furthermore, the positivity (cut-off > 1% cells) rate was not statistically different between biopsies (55%) and tumours (48%) (p=0.63). In term of positivity rate, we found 85% concordant results between biopsies and resected tumours, 4% false negative and 11% false positive on biopsies in comparison with the resected tumours. The positive and negative predictive value of the biopsies were respectively 80% and 92%. CONCLUSIONS: The evaluation of EGF-R by immunohistochemistry on biopsies may provide reliable information about non small cell lung cancer EGF-R status.

Adenocarcinoma↗
PubMed2001

Subcutaneous lymphoid hyperplasia arising at site of ethnic scarifications and mimicking subcutaneous panniculitis-like T-cell lymphoma.

The case of a 40-year-old black man, who developed a very unusual tumour-like lymphoid hyperplasia involving primarily the subcutaneous tissue, is reported. The lesion, which arose at a site of tribal scarifications, displayed a deceptive morphology that closely resembled subcutaneous panniculitis-like T-cell lymphoma (SPTCL). An accurate diagnosis could only be made following detailed immunohistochemical and molecular studies. Although SPTCL has been thought to represent a very specific clinicopathologic entity, the present case illustrates that its histological appearance can, however, be closely mimicked by reactive and benign conditions.

Adult↗
PubMed2001

[Isolated pelvic metastasis of thyroid cancer].

Thyroid cancer rarely metastasizes to the pelvis. We report a case where the metastasis was found two years before the thyroid cancer. Treatment included initial surgery with resection of the metastatic tumor and reconstruction of the acetabulum with bone cement, and secondly total thyroidectomy, node dissection and I131. Surgical treatment of locoregional recurrence had no influence on the clinical course leading to the patient's death. Early diagnosis of unique metastasis of a thyroid cancer is important in terms of prognosis and quality of life. This case is exceptional due to the unique bone metastasis and treatment options for acetabular metastases. Therapeutic options should be adapted according to algorithms reported in the literature.

Acetabulum↗
PubMed2001

[Prognostic factors in epidermoid carcinoma of the mobile tongue classified as T1-T2].

INTRODUCTION: Our aim was to evaluate the results and the prognosis of squamous cell carcinoma of the mobile part of the tongue stage T1-T2 treated by surgery and radiotherapy at the Institute Jules Bordet from January 1950 to 31th December 1993. METHODS: According to the classification TNM (UICC 1978) 165 consecutive patients classified as follow: 73 T1No (stage I), 64 T2No (stage II), 7 T1N1 and 20 T2N1 (stage III) and 1 patient T2N2 (stage IV). All patients underwent surgery beforehand. 136 patients received additional brachytherapy. RESULTS: In this study were included 117 men and 48 women with an average age of 60 years. The rate of relapse on the primary tumoral site amounted to 16,4% and the residual relapse to 40%. The survival note without relapse was evaluated respectively at 3 years in 67% of the tumours T1 (against 28% for the T2), at 5 years for 59% for tumours T1 (against 26% for T2). From the clinical point of view the survival rate without relapse was of 5 years for 61% of stage I, 29% of stage II and 24% of stage III. A more extensive investigation shows the statistic influence, such as age (p<0.004), size of the tumour (p<0.007) and its shape (p<0.0007) on the total survive rate. The state of the nodes (p<0.02) and the safety margins (p<0.04) are statistically less associated. The survival rate with no relapse according to a study considering statistical factors, is significantly influenced by the size (p<0.0002) and age (p<0.0003). CONCLUSION: T1-T2 stages of the mobile tongue are characterized by a limited local spread but a more regional spread and diversified therapeutic approach with prognostic factors influencing the survival rate without forgetting the part played by the TNM classification.

Adult↗
PubMed1996

Contribution of cervical ultrasound and ultrasound fine-needle aspiration biopsy to the staging of thoracic oesophageal carcinoma.

This study was performed to evaluate the use of cervical ultrasonography and ultrasound-guided fine-needle aspiration for pretherapeutic staging of oesophageal cancer. 50 patients with a thoracic-oesophageal cancer (upper third = 8, middle = 36, lower = 6), previously untreated, underwent cervical ultrasonography to detect supraclavicular lymph node metastases (LN). An ultrasound fine-needle aspiration biopsy was attempted in 12 cases of suspected LN. 26 patients were operated on, of which 13 had surgical exploration of the neck. All patients were followed after treatment with special attention to the supraclavicular area. 14 patients (28%) were ultrasonography positive, 5 of 8 in the upper third, 9 of 42 in the two other thirds. Of the 12 patients where a fine-needle biopsy was attempted, 9 showed neoplastic cells (75%). 5 patients had cervical metastatic LN at surgery, and 5 other patients demonstrated supraclavicular LN metastases during the follow-up. There was one false positive and six false negatives from cervical ultrasonography and two false negatives of UGFAB (ultrasound-guided fine-needle aspiration biopsy). The sensitivity and the specificity of the cervical ultrasonography were 68 and 97%, respectively. The pretherapeutic staging was modified: 7 patients initially stage II-III were regraded to stage IV. Cervical ultrasonography is a reliable method of assessment of supraclavicular LN in thoracic oesophageal carcinoma.

Biopsy, Needle↗
PubMed1991

[Tumors of the submaxillary gland].

The tumors of the submaxillary gland are rare. The authors are reviewing 23 cases gathered from three Departments over ten years. The tumors of the submaxillary gland are malignant in as many as 50% of all cases! When the lesion is benign, pleiomorphic adenoma is the most frequent possibility. The authors emphasize the necessity of early and complete surgical treatment, requiring at least total submaxillectomy in case of benign tumor. Cervical mode dissection will be considered if the tumor is malignant.

Adenoma, Pleomorphic↗
PubMed1989

Human medullary thyroid carcinoma: cell cultures and xenotransplants in nude mice. Immunocytochemistry and calcitonin secretion.

Occult primary and recurrent medullary thyroid carcinomas (MTC) detected only by elevated calcitonin levels in the peripheral blood, generally after pentagastrin-test stimulation, are difficult to localize. Some new imaging procedures with radionuclide tracers or radiolabelled monoclonal antibodies against carcinoembryonic antigen seem to bring some potentially therapeutic benefits. We report our results with cell cultures and xenotransplants of human MTC with the intention of establishing reproducible models in vitro and in vivo. Cell cultures secrete calcitonin at up to 1200 pg/ml for periods ranging from 3 to 13 weeks. Immunocytochemistry detects cytoplasmic granules positive for calcitonin in polygonal epithelioid cells with dendritic processes. Xenotransplants in nude mice fare better in the subcutaneous axilla than in the subrenal capsule assay. In the former location the tumor-take is good and calcitonin is detected in the blood of the tumor-bearing animals, at levels ranging from 286 to more than 20,000 pg/ml. These models would be potentially usable as targets for radionuclide tracers and/or radiolabelled monoclonal antibodies.

Animals↗