Search PubMed⌕ Search

Biomedical subjects

R J Salmon

Publications and source records attributed to R J Salmon.

At least 37 records · Page 2Linked to original sources
PubMed1999

TP53 status and gene amplification in human colorectal carcinomas.

Gene amplification is one of the characteristics of cancer cells. In vitro studies suggested that alterations of the TP53 gene might be responsible for gene amplification. We have examined the presence of TP53 mutations and looked for cytogenetic evidence of gene amplification in a series of 79 primary colorectal carcinomas. Other parameters such as the pattern of cytogenetic alterations, microsatellite instability, tumor site, and histological staging were also considered. A multiparametric study supported by statistical analyses suggests the existence of two major pathways of colorectal carcinogenesis. No relationships could be established between the presence of TP53 alterations and gene amplification.

Aged↗
PubMed1999

[Identification of sentinel lymph node in breast cancer: experience from the Institut Curie].

Sentinel lymph node (SN) biopsy is a recently developed, minimally invasive technique for staging the axilla in breast cancer. This new procedure of selective lymphadenectomy has been the subject of several studies, but there is not currently a consensus of opinion to define which is the best method of identification. At the Institut Curie since 1996, we have been using the Patent blue dye. The current series present the result of 122 patients with T1, T2, N0 or N1a breast cancer consecutively operated between december 1997 and august 1998. Sentinel nodes were identified in 107 out of 122 (87.7%) and accurately predicted axillary nodal status in 104 out of 107 (97.1%) cases. Three out of 35 node positive patients would have been missed with sentinel node biopsy alone, for a false negative rate of 8.5%. In all 3 cases, one lymph node presented with a micrometastases. In 15 cases out of 35 with metastatic axillary nodes, the only positive node was the SN (43%). The encouraging results of this study shows that it is possible to identify, in a large number of cases, the sentinel node by means of Patent blue dye only. This article detailed the technique used and reviews the literature concerning other methods of identification.

Adult↗
PubMed1998

[Demonstration of the sentinel lymph node in axillary dissection for breast cancer].

OBJECTIVES: The sentinel node is defined as the first-line axillary lymphatic drainage node in breast cancer. If the sentinel node can be identified, during axillary dissection for breast cancer, resection could be limited reducing subsequent morbidity. However, before modifying the standard dissection procedure, it is important to prove that the sentinel node is representative of the metastatic status of other axillary nodes. PATIENTS AND METHODS: Between March and December 1996, 86 patients (mean age 58 years, range 32-82) underwent amputation (n = 20), tumorectomy with dissection (n = 56) or tumorectomy followed by secondary dissection (n = 10) for breast cancer. Ten ml of diluted patent blue was injected either into the peripheral portion of the tumor or the tumorectomy cavity. Node dissection was performed 10 to 20 minutes after injection. The blue sentinel node was identified prior to standard dissection. RESULTS: A mean 12 nodes were removed (range 4-21). Seventy-nine sentinel nodes were identified (91%) and in 7 cases (8%) a sentinel node could not be identified. In 7 other cases the sentinel node was a false negative, i.e. non malignant despite metastases in other dissected nodes. In all the other cases, the status of the sentinel node predicted the status of the other nodes, i.e. a non-metastatic sentinel node associated with other metastatic nodes. Finally, in 7 cases, the sentinel node was the only invaded node among the nodes dissected. During the last 3 months of the study, the sentinel node was identified in 100% of the cases and was representative of the overall dissection. CONCLUSION: Identifying the sentinel node is an alternative to standard axillary node dissection procedures. The method requires a training period and identification can be improved with radioimmunologic guidance. Patient selection within the framework of a rigorous multidisciplinary protocol is indispensable. A nationwide study is currently being conducted to validate these preliminary results.

Adult↗
PubMed1998

Treatment of liver metastases from uveal melanoma by combined surgery-chemotherapy.

AIMS: To investigate sporadic results demonstrating prolonged survival after surgical resection and/or intraarterial chemotherapy (IACH) for liver metastases from uveal melanoma. METHODS: From December 1992 to March 1997 every patient with liver metastases from uveal melanoma was enrolled in a prospective study including: (1) aggressive surgical approach removing as much liver disease as possible; (2) implantation of an intraaterial catheter; (3) intraarterial chemotherapy for 6 months. 75 patients were enrolled: 38 men, 37 women, mean age 51 years (range: 18-72), mean time from initial diagnosis of uveal melanoma to liver metastases 37 months (ranged: 1-168). RESULTS: Disseminated disease in both lobes was present in all but one patient. Macroscopically curative surgery was possible in 27.5%. Significant tumour reduction was performed in 49.3% and a simple biopsy was possible in 23.2%. Eight patients did not receive chemotherapy and died soon after. IACH included Fotemustine and/or DTIC-Platinum for 4-9 cycles. Overall median survival was 9 months; very similar to non-operated historical controls. In the 61 patients receiving complete treatment surgery plus chemotherapy, median survival improved to 10 months. When curative resection was possible, survival increased to 22 months (P < 0.001). CONCLUSIONS: Aggressive surgical resection, when possible, appears to be the best method of improving survival of liver metastases from uveal melanoma. New drug combinations are also required to improve survival.

Adult↗
PubMed1998

Preservation versus section of intercostal-brachial nerve (IBN) in axillary dissection for breast cancer--a prospective randomized trial.

AIMS: Preservation of the intercostal-brachial nerve is advocated to reduce side effects of axillary dissection for breast cancer. We conducted a prospective randomized trail to compare functional results: sensory deficit and/or shoulder pain in preserved (group I) vs sacrificed (group II) intercostal-brachial nerve (IBN). METHODS: From July 1993 to April 1994, 128 patients presenting with an invasive operable breast cancer were operated on by mastectomy n = 28 or lumpectomy n = 100 and axillary dissection. The patients were eligible for randomization when the IBN was preserved at the end of the axillary dissection. Group I (nerve preservation) included 66 patients and group II (nerve section) 62 patients. RESULTS: The two groups were well balanced for TNM, type of surgery, number of nodes dissected and positive, post-operative adjuvant treatment. Examinations were conducted at 3, 6 and 12 months after surgery. Sensory deficit in the IBN area was reported by one patient in group I and four patients in group II, at 3 months (P = 0.36, NS). No patients, apart from one in group II, reported functional trouble at 18 months. Major shoulder motion, limitation and pain developed in four patients in group I and three in group II (NS). This was attributed to depression and treated adequately. Analysis of sensory deficit was impossible in these patients. CONCLUSIONS: Conservation of the IBN, while anatomically preferable, is not functionally necessary during axillary dissection for breast cancer.

Adult↗
PubMed1998

Conservative treatment of lower pole breast cancers by bilateral mammoplasty and radiotherapy.

AIMS: This series analyses the results of conservative surgery for large lower pole breast cancers by lumpectomy associated with a bilateral remodelling mammoplasty, in order to avoid residual deformities. METHODS: This retrospective study concerns 50 patients with a lower pole breast cancer treated between 1986 and 1996 by lumpectomy, mammoplasty and irradiation. The contralateral breast was immediately made symmetrical in all cases. The mean tumour size was 32.5 mm. RESULTS: The mean weight of the lumpectomy specimen was 270 g. Resection margins were tumour-free in 90% of cases. The main complication observed was delayed healing, thus postponing post-operative treatment in 6.5% of cases. The median follow-up was 48 months. The 5-year actuarial ipsilateral local recurrence rate was 7% and 5-year actuarial metastasis-free and overall survival rates were 81 and 97%, respectively. Cosmesis was satisfactory in 85% of patients. We observed better results when radiotherapy was performed after rather than prior to surgery (92 vs. 67%: NS). CONCLUSIONS: Performing a bilateral mammoplasty at the time of initial surgery for large breast cancers situated in the lower quadrants of the breast facilitates larger lumpectomies with good cosmetic results.

Adult↗
PubMed1998

[Surgical treatment of cancer of the anal canal].

The development of radiochemotherapy associations has raised the percentage of sphincters preserved in surgery for anal cancer. These protocols have also made the surgeon's task more difficult as abdomino-perineal amputations, progressively reserved for treatment failures, cause intraoperative and postoperative problems in this type of tissue. Programmed surgery would be the ideal solution and requires a multidisciplinary approach.

Anus Neoplasms↗
PubMed1998

[Evolution of the surgery of cancer of the breast].

Multiple technical and strategical improvements have modified surgical management of breast cancer. Screening mamographies are able to focus small tumors in which excision eventually after percutaneous biopsy can necessitate two surgical procedures. Reduction of axillary dissection in these small lesions can benefit from sentinel node biopsy technique. Immediate or delayed breast reconstruction reduces the mutilation of the mastectomies with their psycho-social disaster. Technically these reconstruction requires a multidisciplinary approach and psychological support. These surgical evolutions in parallel with other therapies for breast cancer developed with two major points: necessity of a good local control for cure, multidisciplinary approach which makes surgeons reals oncologists.

Breast Neoplasms↗
PubMed1997

Alternative genetic pathways in colorectal carcinogenesis.

The comparative typing of matched tumor and blood DNAs at dinucleotide repeat (microsatellite) loci has revealed in tumor DNA the presence of alleles that are not observed in normal DNA. The occurrence of these additional alleles is possibly due to replication errors (RERs). Although this observation has led to the recognition of a subtype of colorectal cancer with a high incidence of RERs (caused by a deficiency in DNA mismatch repair), a thorough analysis of the RER frequency in a consecutive series of colorectal cancers had not been reported. It is shown here that the extensive typing of 88 colorectal tumors reveals a bimodal distribution for the frequency of RER at microsatellite loci. Within the major mode (75 tumors, RER- subtype), the probability that a locus exhibited instability did not differ significantly among loci and tumors, being 0.02. The subsequent development of a statistical test for an operational discrimination between the RER- and RER+ subtypes indicated that the probability of misclassification did not exceed 0.001 in this series. The frequency of K-ras mutation was found to be equivalent in the two subtypes. However, in the RER+ tumors, the p53 gene mutation was less frequently detected, the adenomatous polyposis coli (APC) mutation was rare, and the biallelic inactivation of either of these genes was not observed. Furthermore, the concomitant occurrence of APC and tumor growth factor beta receptor type II gene alterations was found only once. These data suggest that the repertoires of genes that are frequently altered in RER+ and RER- tumors may be more different than previously thought.

Aged↗
PubMed1997

[Surgical treatment of cancers of the stomach].

Gastric cancer remains a serious health problem 5 years survival remains low and early diagnosis anecdotical in France. Gastrectomy is the only curative treatment and the extent of surgery depends upon the tumor location. The extent of the node dissection is under discussion, Japanese surgeons recommend extensive dissection and publish better results in term of survival than Europeans groups. Two randomized prospectives trials comparing limited and extensive dissection have not shown any difference but an increased morbidity in the group with extensive dissection. Adjuvant treatments radiation or chemotherapy should be given therapeutic trials because they have not been proved as efficient.

Combined Modality Therapy↗
PubMed1997

BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines.

Instability of microsatellites is a hallmark of the DNA replication error phenotype (RER+) due to the inactivation of mismatch repair genes. In humans, microsatellite instability has first been described in colorectal tumors developing in either hereditary nonpolyposis colorectal cancer or sporadic patients. Colorectal tumorigenesis in RER+ and RER- tumors is probably due to distinct mechanisms, and RER+ tumors have a better prognosis than RER- tumors. The study of the RER status of a tumor may thus be important in the future to determine biological prognosis factors and investigate therapeutical strategies. The RER status of 134 primary tumors and 26 cell lines derived from colorectal cancers was established by PCR amplification and analysis of a minimum of 32 microsatellite loci. This characterization allowed us to unambiguously classify 35 primary tumors and 7 cell lines as RER+. Typing of a single poly(A) tract, BAT-26, was sufficient to confirm the RER status of 159 of these 160 tumors and cell lines. Moreover, in DNA from unaffected individuals, normal tissues of a subset of the RER+ patients, and all RER- tumors or cell lines, BAT-26 was quasi-monomorphic, showing only minor size variations. BAT-26 alleles showing shortening from 4 to 15 bp were observed in all but 1 of the RER+ tumors and cell lines. The size difference between the range of normal large alleles and unstable small alleles was sufficient to be detected by electrophoresis on conventional polyacrylamide gels stained with ethidium bromide. We thus propose a simple, low-cost, and rapid method to screen for the RER status of colorectal cancer primary tumors and cell lines, even in the absence of matching normal DNA and, in most cases, without the need for radioactivity. This method could easily be set up in routine laboratories.

Alleles↗
PubMed1997

Colorectal carcinogenesis: from chromosomal evolution pathways to molecular pathogenesis.

Since the mid-1980s, research in the field of colorectal carcinogenesis has seen a series of breakthroughs such, as the process of loss of heterozygosity for large chromosomal segments and the consequent characterization of a series of suppressor genes considered to be the targets of the allelic deletions. More recently, a new perspective has been opened, with the discovery of germinal mutations of genes involved in mismatch repair in certain inherited forms of the disease. Through the retrospective analysis of our data on colorectal adenomas and cancers, we have tried to critically reassess a number of theoretical considerations relating to the instability of the genome viewed at the chromosome level and its consequence on tumor progression.

Adenoma↗
PubMed1997

BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group.

An account of familial aggregation in breast/ovarian cancer has become possible with the identification of BRCA1 germ-line mutations. We evaluated, for 249 individuals registered with the Institut Curie in Paris, the prior probability that an individual carried a mutation that predisposes to these diseases. We chose 160 women for BRCA1 analysis: 103 with a family history of breast cancer and 57 with a family history of breast-ovarian cancer. To detect small mutations, we generated and analyzed 35 overlapping genomic PCR products that cover the coding portion of the gene, by using denaturing gradient gel electrophoresis. Thirty-eight truncating mutations (32 frameshifts, 4 nonsense mutations, and 2 splice variants) were observed in 15% of women with a family history of breast cancer only and in 40% of those with a history of breast-ovarian cancer. Twelve of 25 distinct truncating mutations identified were novel and unique. Most BRCA1 mutations that had been reported more than five times in the Breast Cancer Information Core were present in our series. One mutation (5149del4) observed in two apparently unrelated families most likely originates from a common ancestor. The position of truncating mutations did not significantly affect the ratio of the risk of breast cancer to that of ovarian cancer. In addition, 15 DNA variants (14 missense mutations and 1 neutral mutation) were identified, 9 of which were novel. Indirect evidence suggests that seven of these mutations are deleterious.

Africa↗
PubMed1997

[Hepatic resection for breast cancer metastasis. The concept of adjuvant surgery].

Surgery for hepatic metastases from breast cancer remains anecdotal and controversial. This retrospective series of 21 patients analyses survival after hepatic resection. These patients presented with isolated metachronous metastases, controlled by systemic treatment; surgery was considered to be an adjuvant treatment. There was no surgical mortality. The TNM stage of the initial breast cancer, the time to onset of metastases and the number of hepatic metastases did not influence survival. The 5-year survival, after diagnosis of metastatic disease, was 60%; clearly better than the expected survival. Eleven patients are currently alive without recurrence. Six patients developed a recurrence in the remaining liver after a mean interval of 12 months, including 4 patients who died after a mean interval of 49 months. These results suggest that a subgroup of patients with hepatic metastases from breast cancer may benefit from surgical resection. This surgery must be proposed in patients with isolated disease progression controlled by systemic treatment. In our experience, adjuvant surgery of hepatic metastases from breast cancer is followed by an uneventful postoperative course, improves survival and, in 50% of cases, allows discontinuation of chemotherapy, improving the patient's quality of life.

Adult↗
PubMed1997

[Localization of a tumor suppressor gene distal to D22S270 in colorectal cancers].

Recurrent allelic losses on chromosome 22q have been reported in colorectal cancer, distal to the NF2 gene, suggesting that another tumor suppressor gene might be involved. We report here the typing of 256 sporadic colorectal tumors and 18 colonic cancer cell lines using a set of chromosome 22 polymorphisms, ranging from 20 to 45. A panel of somatic cell hybrids, that allows to distinguish 11 bins in the 22q13 region, was used to localize 19 of the 45 selected markers and the putative tumor suppressor gene BZRP. Allelic-loss was observed in 43% of tumors. The minimal region of deletion that could be determined, telomeric to locus D22S270, refines significantly the position of the gene. The localization of the BZRP gene in this region led to a systematic screening for somatic point mutation. Direct sequencing of its coding sequence in 36 tumors hemizygous for chromosome 22 allowed the identification of three polymorphisms but failed to detect somatic mutation.

Adenocarcinoma↗