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PubMed1994

Selection factors for local excision or abdominoperineal resection of early stage rectal cancer.

BACKGROUND: This study reviews the experience of patients with early stage rectal cancer managed by local excision or abdominoperineal resection to clarify the relative indications and results of these two approaches. METHODS: From 1962 to 1991, 125 patients with T1 and T2 rectal cancer underwent local excision (56 patients) or abdominoperineal resection (69 patients). Outcome was analyzed by stage, treatment, and pathologic features of tumor grade and vessel involvement. RESULTS: The 5-year actuarial recurrence-free survival and local control was 87% and 96%, respectively, for 28 patients undergoing local excision with favorable histologic features (well or moderately well differentiated histologic findings without venous/lymph vessel involvement). These results were 57% and 68% for 28 patients with unfavorable histologic features (poorly differentiated histology and/or venous/lymph vessel involvement). For patients undergoing abdominoperineal resection, the 5-year actuarial recurrence-free survival and local control of 49 patients with favorable histologic features was 91% and 91%, respectively. These results were 79% and 89%, respectively, for patients with poorly differentiated histology or venous/lymph vessel involvement. CONCLUSIONS: For patients with T1 and T2 tumors having favorable histologic features, a satisfactory survival and local control was achieved for patients undergoing local excision or abdominoperineal resection. In contrast, patients with T1 and T2 tumors having poorly differentiated histologic features and/or venous/lymph vessel involvement undergoing local excision or abdominoperineal resection appeared to have decreased rates of survival and of local control. For these patients, radical resection combined with pelvic irradiation and 5-fluorouracil-based chemotherapy should be investigated.

Abdomen↗

PubMed2006

Multicenter evaluation of the breast lesion excision system, a percutaneous, vacuum-assisted, intact-specimen breast biopsy device.

BACKGROUND: Percutaneous, vacuum-assisted, large-gauge core needle biopsy (VACNB) provides an alternative to open surgical biopsy as an initial diagnostic tool for breast lesions, yet rates of underestimating malignant diagnoses remain sufficiently high to warrant surgical biopsy in some cases. The current study was performed to determine if the Breast Lesion Excision System (BLES) provides a feasible alternative to VACNB. METHODS: A retrospective review was conducted of 742 consecutive mammographic lesions with microcalcifications classified as Breast Imaging Reporting and Data System (BIRADS) IV or V that had stereotactic percutaneous biopsy using BLES. Initial diagnoses obtained from the histopathologic examination of tissues retrieved at biopsy were compared with the histopathologic examination of tissues received from surgical excision or lumpectomy. Underestimation rates for atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were recorded if open surgical biopsy revealed DCIS or invasive cancer, and invasive cancer, respectively. RESULTS: Of the 742 breast lesions, 34 displayed ADH upon biopsy with the BLES device. Two patients did not receive open surgical biopsy. Of the 32 patients who had open surgical excision, 3 (9.4%) had DCIS or invasive cancer. There were 119 diagnoses of DCIS upon biopsy with the BLES device. Four patients did not receive open surgical biopsy. Of the 115 patients who had open surgical excision, 6 (5.2%) had invasive cancer. CONCLUSIONS: Breast biopsy can be performed accurately using the BLES device. Compared with VACNB, it does not alter the need for surgical excision in women diagnosed with ADH or DCIS at core biopsy.

Biopsy, Needle↗

PubMed1986

Immunological consequences of tumor excision: from active immunity to immunological memory.

Excision of the immunogenic Meth-A fibrosarcoma during generation by the host of concomitant antitumor immunity resulted in the appearance in sequence of two qualitatively distinct states of post-excision immunity. Immunity expressed on the day of excision was dependent on Ly-1-2+, cyclophosphamide-sensitive T cells, whereas immunity expressed 2 weeks later was dependent on cyclophosphamide-resistant T cells which can be functionally eliminated by either anti-Ly-1 or anti-Ly-2 monoclonal antibody and complement. The data suggest that antitumor immunity expressed shortly after tumor excision represents active concomitant immunity that is acquired by the host before excision is performed. In contrast, immunity expressed 2 weeks later is based on immunological memory.

Animals↗

PubMed2001

Relationship between excision volume, margin status, and tumor size with the development of local recurrence in patients with ductal carcinoma-in-situ treated with breast-conserving therapy.

BACKGROUND AND OBJECTIVES: We reviewed our institution's experience treating patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy (BCT) to help define the interrelationship between excision volume, margin status, and tumor size with local recurrence. METHODS: From January 1980 to December 1993, 146 patients received BCT for DCIS. All patients underwent excisional biopsy and 95 cases (64%) underwent re-excision. Each patient received whole breast radiation to a median dose of 45 Gy. An additional 139 cases (94%) received a supplemental boost to the tumor bed (median total dose 60.4 Gy). The median follow-up is 7.2 years. RESULTS: Seventeen patients developed an ipsilateral breast failure for a 5- and 10-year actuarial rate of 10.2 and 12.4%, respectively. On multivariate analysis, patient age, margin status, the number of slides containing DCIS, the number of DCIS/cancerization of lobules (COL) foci near (< 5 mm) the margin, and a smaller volume of excision (< 60 cm(3)) were all independently associated with outcome. Although the local recurrence rate generally decreased as margin distance increased, these differences did not achieve statistical significance unless the volume of excision was taken into consideration. CONCLUSIONS: These findings suggest that the success of BCT is directly related to the degree of surgical removal of DCIS and that margin status alone may be suboptimal in defining excision adequacy.

Adult↗

PubMed2007

Effects of delayed excision of oviducts/ovaries on mouse oocytes and embryos.

To achieve the best and reproducible results of experiments, effects of delayed excision of oviducts/ovaries on mouse ovarian/ovulated oocytes and embryos have been studied. Oviducts/ovaries were excised at different times after death of mice and effects of the postmortem interval on ovarian/ovulated oocytes and embryos were analyzed. When oviduct excision was delayed 10 min, many ovulated oocytes lysed or underwent in vitro spontaneous activation, and this postmortem effect aggravated with the extension of postmortem interval and oocyte aging. Oocytes from different mouse strains responded differently to delayed oviduct removal. Delayed oviduct excision did not cause lysis of zygotes or embryos but compromised their developmental potential. When ovaries were excised at 30 min after death, percentages of atretic follicles increased while blastocyst cell number declined significantly after oocyte maturation in vitro. Preservation of oviducts in vitro, in intact or opened abdomen at different temperatures and histological analysis of oviducts from different treatments suggested that toxic substance(s) were secreted from the dying oviducts which induced oocyte lysis and spontaneous activation and both this effect itself and the sensitivity of oocytes to this effect was temperature dependent. It is concluded that a short delay of oviduct/ovary removal had marked detrimental effects on oocytes and embryos. This must be taken into account in experiments using oocytes or embryos from slaughtered animals. The data may also be important for estimation of the time of death in forensic medicine and for rescue of oocytes from deceased valuable or endangered mammals.

Animals↗

PubMed1994

Cervical intraepithelial neoplasia in women infected with the human immunodeficiency virus: outcome after loop electrosurgical excision.

Our clinical experience with loop electrosurgical excision as therapy for cervical intraepithelial neoplasia (CIN) in women infected with human immunodeficiency virus is described. Information for this analysis was obtained from a retrospective chart review of all women with biopsy-confirmed CIN treated by loop electrosurgical excision who attended our colposcopy clinic during January 1991 to September 1992. Outcomes in women known to be HIV-seropositive were compared to those in women of unknown HIV serostatus. Patients included in the analysis were followed for at least 6 months or until the documentation of recurrent/persistent CIN, and all had at least one post-treatment colposcopic examination, including endocervical curettage and cervical biopsy of any acetowhite lesions. Recurrent/persistent CIN following loop excision was documented in 56% (19 of 34) HIV-infected women compared with 13% (10 of 80) women of unknown serostatus (OR 8.9, P < 0.001). HIV-infected women had a significantly higher rate of recurrent/persistent CIN than women of unknown serostatus, regardless of grade of CIN. In HIV-infected women, recurrent/persistent CIN following loop excision developed in 20% (1 of 5) with CD4+ T-lymphocyte counts > 500 cells/microliters compared to 61% (11 of 18) with CD4+ counts < or = 500 cells/microliters (P = 0.13). Loop electrosurgical excision has a high failure rate in HIV-infected women, and this failure rate may increase as the level of immunosuppression increases.

Adult↗

PubMed1994

Cold-knife conization versus loop excision: histopathologic and clinical results of a randomized trial.

Ninety patients with cervical intraepithelial neoplasia (CIN) were randomly assigned to loop excision (n = 38) or cold-knife conization (n = 52). All specimens were well evaluable at histology. The average width of the lesions at histology was 10.2 and 9.7 mm, respectively (ns). The average weight of the specimens was 2.6 and 5.6 g (P < 0.01) and the average depth was 9.2 and 15.8 mm (P < 0.01), respectively. The distance between the cervical resection margin and CIN was 14 mm after loop excision and 24 mm after cold-knife conization (P < 0.06). The margins of the specimen were not clear of disease in 8 patients after loop excision and in 12 patients after conization (ns). Two patients after loop excision and in three patients after cold-knife conization had postoperative bleeding. The results suggest that, compared with cold-knife conization, loop excision removes less healthy tissue without reducing the chances for cure.

Adult↗

PubMed1993

Characterization of the left 4 kb of conjugative transposon Tn916: determinants involved in excision.

The rate-limiting step in movement of the conjugative transposon Tn916, originally identified in Enterococcus faecalis, is believed to be an excision event that generates a non-replicative circular intermediate. When present on a plasmid vector in Escherichia coli, Tn916 generally excises at a high frequency. It was reported previously that insertion of Tn5 in a region near the left end of Tn916 eliminated the ability to excise; and the mutation could be complemented in trans. In this communication the nucleotide sequence of 4 kb of Tn916 DNA connecting the recently sequenced tet(M) determinant (Su et al., 1992; Burdett, 1990) with the left end of the transposon. Ten open reading frames (ORFs) were deduced, two of which (ORF3 and ORF4) were encoded in-frame within a third (ORF2). Mutants with Tn5 insertions in the ORF1 or ORF2 (ORF3 and ORF4) were defective in excision, but could be complemented in vivo by a co-resident plasmid containing the ORF1 or ORF2 determinant, respectively. The data support the view that both ORF1 and ORF2 are essential for excision. ORF1 and ORF2 are essentially identical to determinants designated xis-Tn and int-Tn, respectively, in the closely related Tn1545. A Tn5 insertion in ORF5 eliminated conjugative transfer between E. faecalis strains. Functions for the remaining ORFs (ORF6 through ORF10) remain unknown; however, nucleotide sequences within ORF6 and ORF9 had significant homology with sequence downstream of other tet(M) determinants.

Amino Acid Sequence↗

PubMed1986

Molecular approaches to the study of nucleotide excision repair in eukaryotes.

Very little is known about the molecular mechanism of nucleotide excision repair in eukaryotes. Studies on human cells have been stimulated by the availability of excision repair-defective cell lines from patients suffering from the autosomal recessive disease xeroderma pigmentosum (XP). Such studies have contributed significantly to an understanding of the genetic complexity of excision repair in human cells. However, to date, no human excision repair genes or gene products known to complement the repair defect in XP cells have been isolated. The yeast Saccharomyces cerevisiae is an interesting model for exploring the molecular mechanism of nucleotide excision repair in eukaryotic cells. As is true in human cells, multiple yeast genes are involved and at least five genes are required for the specific incision of UV-irradiated DNA in vivo. These five genes have been isolated by molecular cloning and the nucleotide sequences of four of them have been determined. Each of these cloned genes is being used for overexpression of protein.

Base Sequence↗

PubMed1975

Excision-repair of gamma-ray-damaged thymine in bacterial and and mammalian systems.

The selective excision of products of the 5,6-dihydroxy-dihydrothymine type (t') from gamma-irradiated or OSO4-oxidized DNA or synthetic poly[d(A-T)] was observed with crude extracts of Escherichia coli and isolated nuclei from human carcinoma HeLa S-3 and Chinese hamster ovary cells. The results with E. coli extracts allow the following conclusion: (1) The uvrA-gene product is not required for t' excision. (2) Radiation-induced strand breakage is not required for product excision. (3) Experiments with extracts of E. coli polAexl showed that the 5' in equilibrium 3' exonuclease associated with polymerase I is responsible for the removal of t'. (4) Experiments with extracts of E. coli endo I lig 4 and the ligase inhibitor nicotinamide mononucleotide showed that polynucleotide ligase accomplishes the last strand resealing step in the excision-repair of t'. Isolated nuclei from HeLa and Chinese hamster ovary cells possess the necessary enzymes for the selective excision of t' from gamma-irradiated or osmium tetroxide oxidized DNA. Approximately 25 to 35% of the products were removed from DNA within 60 min. Unspecific DNA degradation was very low. Radiation-induced strand breakage is not required for product removal.

Cell Line↗

PubMed1975

Dependence upon growth medium and the polA, polC, recA, recB, recC, and exrA genes of separate branches of the uvr Gene-dependent excision-repair process in Escherichia coli K12 cells.

The repair of single-strand breaks which arise in DNA during the uvr gene-dependent excision-repair process was examined in certain radiation-sensitive strains of Escherichia coli K12. The results suggest that the excision-repair process may be divided into two branches, one which is dependent on the presence of growth medium and also the rec+ exr+ genotype, and a second which can occur in buffer (growth medium independent) and is largely dependent on DNA polymerase I. DNA polymerase III appears to be involved in the growth-medium-dependent branch of excision repair, and also in the residual growth-medium-independent repair which occurs in polA1 cells. Chloramphenicol, dinitrophenol, and impurities present in some brands of agar all appear to inhibit the growth-medium-dependent branch of excision-repair. The similarities of the two branches of excision-repair to two known pathways for the repair of X-ray-induced DNA chain breaks are discussed.

Chloramphenicol↗

PubMed1975

Excision-repair of 4-nitroquinolin-1-oxide damage responsible for killing, mutation, and cancer.

Excision-repair of DNA base damage produced by 4-nitroquinoline-1-oxide (4NQO) was compared in Escherichia coli, human cells, and mouse cells. Paper chromotography of acid hydrolysates of DNA extracted from cells treated with 3H-labeled 4NQO revealed four peaks; two kinds of 4NQO-guanine adduct, one kind of 4NQO-adenine adduct, and free 4-aminoquinoline-1-oxide (4AQO). About 80% of the initially formed 4NQO-purine adducts were excised from DNA in E. coli uvrA+ cells during 60 min postincubation, but not at all in uvrA- (excisionless for uv damage) cells. Normal human cells excised about 60% of 4NQO-purine adducts during 24 hr postincubation, but xeroderma pigmentosum (excisionless) cells did not. A mouse cell line susceptible to repair of 4NQO-induced pretransformational damage also showed excision-repair ability for the 4NQO adducts. From these and other results, we conclude that the 4NQO-purine adducts and unstable 4NQO-guanine products (which release 4AQO) are, like pyrimidine dimers, repairable by excision-repair universal among E. coli, mouse, and human being, and that unexcised ones are probably the major cause of killing, mutation, and cancer.

4-Nitroquinoline-1-oxide↗

PubMed1998

Local excision of rectal cancer through windowed specula: long-term results.

Transanal local excision of rectal cancer has been advocated as a curative option in patients with early rectal cancer and for patients unsuitable for radical surgery. We report our long-term experience with an easy-to-use and inexpensive technique based on windowed specula. From 1982 to 1994, 137 patients with rectal cancer were treated by local excision with curative intention. An R0 resection was possible in 74% of all patients and in 80% of the patients with a tumor surface of less than 9 cm2. Ninety patients with a follow-up of more than 3 years (T1: n = 50, T2: n = 30, T3: n = 14) were evaluated for survival. Seventy-four of these 90 patients are currently alive. The cause of death is known for all 16 deceased patients. In 4, death was tumor-related; 3 of these patients had a component of local failure. In 6 of 8 patients with local recurrence, a radical reresection was possible. The rate of recurrence increased with T category and with tumor grade. There has been one recurrence in a patient with a T1G1 cancer. The instrumentation enables adequate local excision of rectal cancers of less than 9 cm2 surface area. In this group of patients including a considerable number with T2 and T3 cancers, only 3 died of tumor-related causes with a component of local failure, which compares well with mortality rates above 4% for abdominoperineal excision. Comparison with international data on radical surgery shows that the overall survival is not reduced by local transanal excision for early rectal cancer.

Adult↗

PubMed1990

Excision of a Ds-like maize transposable element (Ac delta) in a transient assay in Petunia is enhanced by a truncated coding region of the transposable element Ac.

The excision of a Ds-like transposable element (Ac delta) is mediated in trans by the transposable element Ac or its derivatives in Petunia protoplasts cotransfected with two plasmid DNAs. Excision restores the activity of the beta-glucuronidase (GUS) gene that is otherwise shut off by the presence of Ac delta in its leader sequence. A transient expression assay (histochemical test) is used to detect the beta-glucuronidase activity at the protoplast to detect the beta-glucuronidase activity at the protoplast level. The number of blue-stained protoplasts is a measure of the excision frequency. With Ac delta alone a near-zero background of GUS activity is detected, which is weakly enhanced by the presence, in trans, of either the wild-type Ac or the coding region (ORFa) transcribed from the 2' promoter of Agrobacterium tumefaciens TR-DNA. A strong enhancement is observed when a truncated Ac coding region, also under the control of the 2' promoter, is supplied in trans. The truncated version has ATG10 at codon 103 in frame with ORFa and is preceded by 7 out-of-frame ATGs. The assay is quick and well suited for detection of excision frequencies above the value obtained with the wild-type Ac. The presence of empty donor sites following excision can be demonstrated by PCR amplification and direct sequencing of the appropriate DNA fragment.

Base Sequence↗

PubMed1992

Directed excision of a transgene from the plant genome.

The effectiveness of loxP-Cre directed excision of a transgene was examined using phenotypic and molecular analyses. Two methods of combining the elements of this system, re-transformation and cross pollination, were found to produce different degrees of excision in the resulting plants. Two linked traits, beta-glucuronidase (GUS) and a gene encoding sulfonylurea-resistant acetolactate synthase (ALSr), were integrated into the genome of tobacco and Arabidopsis. The ALSr gene, bounded by loxP sites, was used as the selectable marker for transformation. The directed loss of the ALSr gene through Cre-mediated excision was demonstrated by the loss of resistance to sulfonylurea herbicides and by Southern blot analysis. The beta-glucuronidase gene remained active. The excision efficiency varied in F1 progeny of different lox and Cre parents and was correlated with the Cre parent. Many of the lox x Cre F1 progeny were chimeric and some F2 progeny retained resistance to sulfonylureas. Re-transformation of lox/ALS/lox/GUS tobacco plants with cre led to much higher efficiency of excision. Lines of tobacco transformants carrying the GUS gene but producing only sulfonylurea-sensitive progeny were obtained using both approaches for introducing cre. Similarly, Arabidopsis lines with GUS activity but no sulfonylurea resistance were generated using cross pollinations.

Acetolactate Synthase↗

PubMed1993

Factors affecting the excision frequency of the maize transposable element Ds in Arabidopsis thaliana.

A two-element transposon system based on the maize elements Ac and Ds is currently being used for insertional mutagenesis in Arabidopsis. With the aim of making this system as efficient as possible we have continued to analyse several parameters which affect Ds activity in Arabidopsis. The influence of genomic position on Ds excision has been analysed in five lines carrying Ds integrated in different genomic locations. Differences in both somatic and germinal excision were observed between the different lines. The relationship between somatic and germinal excision, the timing of excision events and environmental influences on transposition frequency have been investigated. The effect of varying dosage of the different elements was also analysed. A strong positive dosage effect was observed for the transposase source, but not for the Ds element. Analysis of germinal excision events showed that the majority of them occurred very late in the development of the plant, resulting in the majority of Ds transpositions being independent events.

Arabidopsis↗

PubMedDate not supplied

Recommended width of excision for primary malignant melanoma.

Wide local excision for melanoma with margins of 3 to 5 cm have been advocated in the literature for nearly 140 years. These reports have grouped all stages of melanoma rather than addressing primary early stage disease. Breslow first advocated limited excision margins for these tumors. We have been excising all thicknesses of melanoma with a limited margin (1.00-1.50 cm, mostly 1.00 cm) since 1975. We advocate a 1 cm excision margin irrespective of tumor thickness. Clark has shown that melanoma invades in a vertical fashion, and thus one would expect to be more generous in depth than in width on a pathologic basis. Two studies have shown that there is no difference in the increase in locoregional recurrence and no change in death rate from the disease with more conservative treatment margins. Excision of this lesion is not an office procedure. It should be performed meticulously in an operating room, preferably under light general anesthesia.

Adolescent↗

PubMedDate not supplied

The effect of rec-2 on repeat-induced point-mutation (RIP) and recombination events that excise DNA sequence duplications at the his-3 locus in Neurospora crassa.

In Neurospora crassa, duplicated DNA suffers both extensive repeat-induced point-mutation (RIP) and also excision by recombination events during the dikaryotic phase of the life cycle that precedes karyogamy and meiosis (reviewed by Selker 1990). This paper describes experiments designed to test the effect of rec-2, a gene known to modulate the local level of meiotic recombination at his-3, on RIP and the excision of tandem duplications. Duplications carrying his-3 sequences and a marker, hygr, that confers hygromycin resistance were constructed by targeted transformation. RIP and excisive recombination were assessed from the progeny of crosses heterozygous for a duplication and having different combinations of rec-2 alleles. In the presence of rec-2+, excision of hygr was reduced to about half of that in crosses homozygous for rec-2. In contrast, rec-2+ had little influence on the frequency of duplications that escaped RIP. Thus, in addition to reducing recombination between his-3 alleles during meiosis, rec-2+ also influences recombination events that lead to the excision of duplications carrying his-3. However, RIP may be independent.

Crosses, Genetic↗