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Conservative excision of wire-bracketed breast carcinomas: a community hospital's experience.

We report our experience with excision of hooked-wire bracketed breast carcinomas in a community hospital setting. The mammographic and pathology reports from 36 nonpalpable or minimally palpable breast cancers were retrieved from a single surgical oncologist's office records and a number of factors that might influence a successful initial surgical excision were examined. The median lesion size was 1 cm. The radiographic abnormalities were microcalcifications only in 14 cases (39%), combined mass/density and microcalcifications in 9 cases (25%), and mass/density without microcalcifications in 13 cases (36%). The median number of bracketing wires placed was two. A prior fine-needle aspiration (FNA) or core biopsy was performed in 29 of the 36 cases (81%). Of these, 27 were positive for malignancy. The tumor was considered to be inadequately excised if it was present within 5 mm of any surgical margin; this outcome occurred in 21 of the 36 cases (58%). Fifteen cases (42%) had tumor involving either the margin or extending to within 1 mm of the margin. Inadequately excised lesions were more commonly seen with increasing tumor size, a radiographic appearance of microcalcifications without an associated mass, and a pathologic diagnosis of ductal carcinoma in situ (DCIS). An intraoperative consult led to taking additional marginal tissue in 23 cases and was successful in achieving final clear histologic margins in 8 of these (35%). Our experience suggests that there are at least two ways to optimize the adequacy of conservative excision of nonpalpable or difficult-to-palpate breast cancers using standard modalities presently available in most community hospitals. These are (a) having the pathologist and radiologist available for intraoperative consultation and (b) obtaining a tissue diagnosis of malignancy preoperatively. The use of bracketing wires to better delineate the margins of tissue to be excised may also be helpful, but this needs to be further evaluated in a randomized study.

Adult↗

Histologic grading at breast core needle biopsy: comparison with results from the excised breast specimen.

The purpose of this study was to evaluate the correlation between histologic tumor grade obtained at breast core needle biopsy (CNB) with that obtained from the excised breast specimen. A total of 899 records from all patients with breast cancer from January 1999 to January 2003 were reviewed. Of these, 341 lesions had CNB for diagnosis and had pathology results prospectively graded for both the core and excised specimens. Patient age, lesion type and size, imaging method for biopsy, number of cores, core pathology, surgery performed, final diagnosis, nuclear grade, and combined grade were recorded. In 286 lesions (83.9%), nuclear grade was reported for both core and excised specimens. Of these, 219 (76.6%) were in agreement. Of the 67 that differed, 66 (98.5%) differed by one grade; 46 (68.7%) were upgraded. The groups did not differ in average tumor size, tumor pathology, or number of cores. In 288 lesions (84.5%), combined grade was reported for both core and excised specimens. Of these, 214 (74.3%) were in agreement. Of the 74 that differed, 71 (95.9%) differed by one grade and 50 (67.6%) were upgraded. Again, there were no significant differences in tumor size, type, or number of cores. Overall, nuclear grade and combined grade obtained at CNB each showed agreement with the corresponding excised specimen grading approximately 75% of the time. Grading obtained by CNB, if changed by pathologic evaluation of the excised tumor, is most commonly upgraded. Differences, when they occurred, could not be attributed to tumor size, type, or the number of cores obtained.

Adult↗

Excision of skin tumours without wound closure.

Sixty-two patients with 67 large or poorly defined skin tumours predominantly on the head and neck (58 basal cell carcinomas) were treated by excision of the lesion and allowing the defect created to heal by second intention. Histological control of the adequacy of excision was monitored using routine vertical sections of formalin-fixed tissue. Further re-excisions were performed in 17 patients in whom tumour extended up to or within 1 high power field (approximately 0.44 mm) of the excision margin. The formalin-fixed specimens ranged from 6-60 (mean 21) mm in diameter and 2-12 (mean 5) mm in depth. After one excision the time to complete re-epithelialization was directly proportional to the surface area (r = 0.73) and ranged from 13 to 60 days (mean 33 days). Measurements of the movements of fixed reference points tattooed at the wound edges in six patients showed that movement of surrounding tissue into the defect accounted for 39-62% (mean 45%) of the reduction in surface area of the defect during healing. Post-operative complications were rare and the cosmetic results were considered good or excellent in 48 patients, fair in nine and poor, i.e. requiring corrective surgery, in three patients. Poor results were due to distortions of free margins, e.g. lower eyelid and nasal margin. The major benefit of this technique is the ease with which further excisions can be performed when histologically indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinical, dermoscopy and histological correlation study of melanotic pigmentations in excision scars of melanocytic tumours.

BACKGROUND: Melanotic pigmentations in scars consecutive to the excision of melanocytic tumours can be secondary to a reactive phenomenon related to the scar tissue or to a recurrence of the melanocytic lesion excised in the first case. Recurrent naevi may sometimes adopt unusual features that make them difficult to differentiate from a melanoma. OBJECTIVES: To describe the clinical, dermoscopic and histological features of melanotic pigmentations in scars consecutive to the excision of melanocytic tumours, and to correlate the histological diagnosis with the dermoscopic features. METHODS: This was a prospective cohort study using macrophotography, dermoscopy and histopathological study. Ninety-five melanotic pigmentations (77 patients) in scars secondary to the excision of melanocytic tumours were prospectively collected in the Department of Dermatology at the Instituto Valenciano de Oncología in Valencia, Spain. Histopathological study was performed in 57 scars. RESULTS: Thirteen dermoscopic structures were identified. Four criteria allowed a differentiation between reactive and specific melanocytic pigmentations. Presence of globules and presence of heterogeneous pigmentation were features associated with specific melanocytic pigmentations (P < 0.0001). Presence of a regular network and presence of streaks were more frequently found in reactive pigmentations (P = 0.023 and 0.026, respectively). CONCLUSIONS: Dermoscopic examination of melanotic pigmentations in excision scars of melanocytic tumours provides useful information about the origin of that pigmentation. Based on such information, recurrent naevi can be differentiated from reactive pigmentations in most cases. Excision and histopathological diagnosis continue to be imperative in some cases of recurrent naevi with atypical clinical features.

Cicatrix↗

A novel illegitimate recombination event: precise excision and reintegration with the Mu gem mutant prophage.

The bacteriophage Mu is known to insert its DNA more or less randomly within the Escherichia coli chromosome, as do transposable elements, but unlike the latter, precise excision of the prophage, thereby restoring the original sequence, is not observed with wild-type Mu, although it has been reported with certain defective mutants. We show here that the mutant prophage Mu gem2ts can excise precisely from at least three separate loci -- malT, lac and thyA (selected as Mal+, Lac+ and Thy+, respectively). This excision occurs under permissive conditions for phage development, is observed in fully immune (c+) lysogens, and is independent of RecA and of Mu transposase. Mu gemts2 excision is invariably accompanied by reintegration of a Mu gem2ts prophage elsewhere in the chromosome. In the case of Mal+ revertants, this prophage is systematically located at 94 min on the E. coli chromosome. Mu gem2ts excision therefore sheds some light on the long-standing paradox of the lack of precise Mu excision.

Bacterial Proteins↗

Molecular genetics of the chloramphenicol-resistance transposon Tn4451 from Clostridium perfringens: the TnpX site-specific recombinase excises a circular transposon molecule.

The chloramphenicol-resistance transposon Tn4451 undergoes precise conjugative deletion from its parent plasmid plP401 in Clostridium perfringens and precise spontaneous excision from multicopy plasmids in Escherichia coli. The complete nucleotide sequence of the 6338 bp transposon was determined and it was found to encode six genes. Genetic analysis demonstrated that the largest Tn4451-encoded gene, tnpX, was required for the spontaneous excision of the transposon in both E. coli and C. perfringens, since a Tn4451 derivative that lacked a functional tnpX gene was completely stable in both organisms. Because the ability of this derivative to excise was restored by providing the tnpX gene on a compatible plasmid, it was concluded that this gene encoded a trans-acting site-specific recombinase. Allelic exchange was used to introduce the tnpX delta 1 allele onto plP401 and it was shown that TnpX was also required for the conjugative excision of Tn4451 in C. perfringens. It was also shown by hybridization and polymerase chain reaction (PCR) studies that TnpX-mediated transposon excision resulted in the formation of a circular form of the transposon. The TnpX recombinase was unique because it potentially contained the motifs of two independent site-specific recombinase families, namely the resolvase/invertase and integrase families. Sequence analysis indicated that the resolvase/invertase domain of TnpX was likely to be involved in the excision process by catalysing the formation of a 2 bp staggered nick on either side of the GA dinucleotide located at the ends of the transposon and at the junction of the circular form. The other Tn4451-encoded genes include tnpZ, which appears to encode a second potential site-specific recombinase. This protein has similarity to plasmid-encoded Mob/Pre proteins, which are involved in plasmid mobilization and multimer formation. Located upstream of the tnpZ gene was a region with similarity to the site of interaction of these mobilization proteins.

Amino Acid Sequence↗

Excision and transfer of the Mesorhizobium loti R7A symbiosis island requires an integrase IntS, a novel recombination directionality factor RdfS, and a putative relaxase RlxS.

The Mesorhizobium loti strain R7A symbiosis island is an Integrative Conjugative Element (ICE), herein termed ICEMlSymR7A, which integrates into a phetRNA gene. Integration reconstructs the phetRNA gene at one junction with the core chromosome, and a direct repeat of the 3-prime 17 bp of the gene is formed at the other junction. We show that the ICEMlSymR7AintS gene, which encodes an integrase of the phage P4 family, is required for integration and excision of the island. Excision also depended on a novel recombination directionality factor encoded by msi109 (rdfS). Constitutive expression of rdfS resulted in curing of ICEMlSymR7A. The rdfS gene is part of an operon with genes required for conjugative transfer, allowing co-ordinate regulation of ICEMlSymR7A excision and transfer. The excised form of ICEMlSymR7A was detectable during exponential growth but occurred at higher frequency during stationary phase. ICEMlSymR7A encodes homologues of the traR and traI genes of Agrobacterium tumefaciens that regulate Ti plasmid transfer via quorum sensing. The presence of a plasmid with cloned island traR traI2 genes resulted in excision of ICEMlSymR7A in all cells regardless of culture density, indicating that excision may be similarly regulated. Maintenance of ICEMlSymR7A in these cells depended on msi106 (rlxS) that encodes a putative relaxase. Transfer of the island to non-symbiotic mesorhizobia required intS, rlxS and rdfS. The rdfS and rlxS genes are conserved across a diverse range of alpha-, beta- and gamma-proteobacteria and identify a large family of genomic islands with a common transfer mechanism.

Amino Acid Sequence↗

Mohs micrographic surgery for elliptical excision of skin tumors: a surgical and histologic study.

BACKGROUND: Elliptical excision is a standard form of treatment for cutaneous neoplasms, but routine pathologic sectioning results in incomplete histologic control of surgical margins. OBJECTIVE: The objective was to describe a technique of complete histologic margin control for tumors removed by excision as an ellipse. METHODS: A retrospective study of 100 consecutive nonmelanoma skin cancers of the head and neck removed using elliptical excisions with complete histologic margin control was performed. The technique is described and depicted in detail. RESULTS: Seventy-one tumors were removed in one excision, and 29 required additional excisions for complete histologic tumor clearance. Linear repairs were used for 93 tumors. CONCLUSION: Elliptical excision, combined with our technique of complete histologic margin control, provides a simple, efficient, and effective method for surgical removal and repair of nonmelanoma skin cancers and provides an alternative variation of performing Mohs micrographic surgery for selected tumors.

Female↗

Surgical excision of soft tissue fibrosarcomas in cats.

OBJECTIVE: The purpose of this study was to determine the tumor-free interval and survival times of cats who had one (group 1) or more (group 2) surgeries, or surgery and radiation therapy (RTH) (group 3) for treatment of soft tissue fibrosarcomas (FSA). STUDY DESIGN: Retrospective study. ANIMALS OR SAMPLE POPULATION: 45 client-owned cats. METHODS: Medical records of cats with soft tissue FSA were examined. Vaccination and feline leukemia virus (FeLV) status, age, sex, breed, tumor location, number of surgeries, completeness of excision, and histopathological grade were evaluated to correlate with tumor-free interval and survival periods. RESULTS: Overall median tumor-free interval and survival times were 10 and 11.5 (range, 1 to 40) months. Median tumor-free interval and survival times were more than 16 months each in group 1, more than 5 and 13 months in group 2, and 4.5 and 9 months in group 3. Age, sex, breed, vaccination or FeLV status, tumor location, or histopathological grade did not affect median tumor-free interval or survival times (P > .05). Cats with complete excisions had significantly longer median tumor-free interval (> 16 versus 4 months) and survival time (> 16 versus 9 months) than those with incomplete excisions (P = .008). Radiation therapy did not seem to extend tumor-free interval and survival times (P = .013). However, most group 3 cats had incomplete surgical excisions, resulting in recurrent or progressive disease. CONCLUSIONS: Complete surgical excision of FSA in cats is possible and can be curative. CLINICAL RELEVANCE: Aggressive surgical excision with wide margins appears to contribute to extended tumor-free interval and survival times in cats with soft tissue FSA. Controlled prospective studies are needed to determine the efficacy of RTH in treatment.

Animals↗

Nucleotide excision repair.

Nucleotide excision repair is the major DNA repair mechanism in all species tested. This repair system is the sole mechanism for removing bulky adducts from DNA, but it repairs essentially all DNA lesions, and thus, in addition to its main function, it plays a back-up role for other repair systems. In both pro- and eukaryotes nucleotide excision is accomplished by a multisubunit ATP-dependent nuclease. The excision nuclease of prokaryotes incises the eighth phosphodiester bond 5' and the fourth or fifth phosphodiester bond 3' to the modified nucleotide and thus excises a 12-13-mer. The excision nuclease of eukaryotes incises the 22nd, 23rd, or 24th phosphodiester bond 5' and the fifth phosphodiester bond 3' to the lesion and thus removes the adduct in a 27-29-mer. A transcription repair coupling factor encoded by the mfd gene in Escherichia coli and the ERCC6 gene in humans directs the excision nuclease to RNA polymerase stalled at a lesion in the transcribed strand and thus ensures preferential repair of this strand compared to the nontranscribed strand.

Animals↗

A subset of Staphylococcus aureus strains harboring staphylococcal cassette chromosome mec (SCCmec) type IV is deficient in CcrAB-mediated SCCmec excision.

The gene encoding resistance to beta-lactam antibiotics in the staphylococci is found on the chromosome in a genomic island designated staphylococcal cassette chromosome mec, or SCCmec. In addition to the resistance gene mecA, SCCmec also contains site-specific recombinase genes that are capable of catalyzing the chromosomal excision and reintegration of SCCmec. SCCmec is found in five major isotypes partially defined by the recombinase genes present, either ccrAB or ccrC. Of these, SCCmec type IV is presumed to be mobile in the environment, and this mobility may be partially responsible for the rise in community-associated methicillin-resistant staphylococcal infections. In this study, we investigate the presumptive first step in type IV SCCmec mobility: chromosomal excision of the element. CcrAB from a panel of six Staphylococcus aureus and four Staphylococcus epidermidis strains were able to catalyze chromosomal excision of SCCmec types I and II, indicating that these proteins maintain recombinase activity despite varying by up to 3.7% at the amino acid level. Excision of type IV SCCmec was not universally seen, as a subset of S. aureus strains with type IV SCCmec did not excise their element. These strains are all highly related and represent a lineage of successful community-associated pathogens. In addition, the inability to excise SCCmec in these strains is associated with the insertion of a presumptive mobile element containing the gene for staphylococcal enterotoxin H (seh) immediately downstream of SCCmec on the chromosome. Acquisition of this mobile element, containing a known virulence gene, appears to have stabilized the chromosomal integration of the methicillin resistance gene in these strains.

Anti-Bacterial Agents↗

Mismatch excision and possible polarity effects result in preferred deoxyribonucleic acid strand of integration in pneumococcal transformation.

Heteroduplex deoxyribonucleic acid molecules having a drug resistance marker on one strand and its wild-type allele on the other have been used as donors in pneumococcal transformation. Opposite strands are not equally effective in producing transformants, and this strand bias is not the same, either in direction or magnitude, for various different genetic markers. Selective excision of mismatched base pairs is probably responsible for the large differences in strand efficiency seen with discriminating (hex+) strains, for when the recipient is nondiscriminating (hex-), and therefore presumably lacking an excision enzyme system, strand bias is drastically reduced or altered. The evidence also indicates that excision occurs after integration, as it is provoked by specific donor-recipient mismatch and not by the same mismatch when introduced within donor heteroduplex molecules. Excision can extend to include a neighboring linked marker which would otherwise not be excised, thus altering its intrinsic strand bias as well as its efficiency in transformation. There is a small bias in relative strand efficiency for some markers, not caused by mismatch excision, which perhaps is due to polarity in the integration process itself.

Aminopterin↗

Pyrimidine dimer excision in Escherichia coli strains deficient in exonucleases V and VII and in the 5' leads to 3' exonuclease of DNA polymerase I.

An isogenic series of Escherichia coli strains deficient in various combinations of three 5' leads to 3' exonucleases (exonuclease V, exonuclease VII, and the 5' leads to 3' exonuclease of DNA polymerase I) was constructed and examined for the ability to excise pyrimidine dimers after UV irradiation. Although the recB and recC mutations (deficient in exonuclease V) proved to be incompatible with the polA(Ex) mutation (deficient in the 5' leads to 3' exonuclease of DNA polymerase I), it was possible to reduce the level of the recB,C exonuclease by the use of temperature-sensitive recB270 recC271 mutants. It was found that, by employing strains deficient in exonuclease V, postirradiation DNA degradation could be reduced and dimer excision measurements could be facilitated. Mutants deficient in exonuclease V were found to excise dimers at a rate comparable to that of the wild type. Mutants deficient in exonuclease V and the 5' leads to 3' exonuclease of DNA polymerase I are slightly slower than the wild type at removing dimers accumulated after doses in excess of 40 J/m2. However, although strains with reduced levels of exonuclease VII excised dimers at the same rate as the wild type, the addition of an exonuclease VII deficiency to a strain with reduced levels of exonuclease V and the 5' leads to 3' exonuclease of DNA polymerase I caused a marked decrease in the rate and extent of dimer excision. These observations support previous indications that the 5' leads to 3' exonuclease of DNA polymerase I is important in dimer removal and also suggest a role for exonuclease VII in the excision repair process.

DNA Polymerase I↗

Excisive recombination of the SLP1 element in Streptomyces lividans is mediated by Int and enhanced by Xis.

The functions mediating site-specific recombination of the SLP1 element have been mapped to a 2.2-kb region that includes the site of integration (attP), a gene (int) that specifies a function both necessary and sufficient for integration of SLP1, and an open reading frame, orf61, suspected of encoding a protein, Xis, that shows limited similarity to the excisionases of other site-specific recombination systems. Here we describe experiments that investigate the respective roles of orf61 and int in the excision of SLP1. We constructed derivatives of the high-copy-number Streptomyces plasmid pIJ101 that express orf61, int, or both orf61 and int from transcriptional fusions to the Tn5 aph gene and tested the ability of these constructs to promote excision of an adventitious attP-containing plasmid that had been integrated site-specifically into the attB site of the Streptomyces lividans chromosome. Expression of the int gene product alone from an exogenous promoter was sufficient for excision of the integrated plasmid. This result indicates that the SLP1 int-encoded protein can carry out excisive, as well as integrative, recombination. The orf61 gene product, when expressed from an exogenous promoter, inhibited int-mediated integration at the chromosomal attB site. Moreover, under conditions in which excision and transfer normally occur, precise excision of SLP1 was enhanced by the orf61-encoded protein. On the basis of these findings, we here designate the orf61 gene as xis.

Ampicillin Resistance↗

Lambda excision revisited: testing a model for synapsis of prophage ends.

Excision of lambda prophage was reexamined to test a model for prophage end synapsis. The model proposes that, during in situ prophage replication, following induction, the diverging replication forks are held together. Consequently, prophage DNA is spooled through the replication machinery, drawing the prophage ends together and facilitating synapsis. The model predicts that excision will be slowed if in situ lambda replication is inhibited, and the predicted low rate of excision of a nonreplicating prophage was observed after thermoinduction. However, excision was rapid if additional Int protein was supplied or if the temperature was reduced after induction, showing that (i) Int is partially thermosensitive for excision at 42 degrees C and (ii) in situ replication is not required for rapid excision, a finding that is inconsistent with the model.

Bacteriophage lambda↗

Production of two proteins encoded by the Bacteroides mobilizable transposon NBU1 correlates with time-dependent accumulation of the excised NBu1 circular form.

NBU1 is a mobilizable transposon that excises from the Bacteroides chromosome to form a double-stranded circular transfer intermediate. Excision is triggered by exposure of the bacteria to tetracycline. Accordingly, we expected that the expression of NBU1 genes would be induced by tetracycline. To test this hypothesis, antibodies that recognized two NBU1-encoded proteins, PrmN1 and MobN1, were used to monitor production of these proteins. PrmN1 is essential for excision, and MobN1 is essential for transfer of the excised circular form. At first, expression of the genes encoding these two proteins appeared to be regulated by tetracycline, because the proteins were detectable on Western blots only after the cells were exposed to tetracycline. However, when the prmN1 gene and/or the mobN1 gene was cloned on a multicopy plasmid, production of the protein was constitutive. Initially, we assumed that the constitutive expression was due to loss of a repressor protein that was encoded by one of the other genes on NBU1. Deletions or insertions in the other genes (orf2 and orf3) on NBU1 and various integrated NBU1 derivatives abolished production of PrmN1 and MobN1. This is the opposite of what should have happened if one or both of these genes encoded a repressor. A second possibility was that when NBU1 excised, it replicated transiently, increasing the gene dosage of prmN1 and mobN1 and thereby producing enough PrmN1 and MobN1 for these proteins to become detectable. In fact, after the cells entered late exponential phase the copy number of NBU1 increased to 2 to 3 copies per cell. Production of PrmN1 and MobN1 showed a similar pattern. Any mutation in NBU1 that decreased or prevented excision also prevented elevated production of these two proteins. Our results show that the apparent tetracycline dependence of the production of PrmN1 and MobN1 is due to a growth phase- or time-dependent increase in the number of copies of the NBU1 circular form.

Bacterial Proteins↗

A multicomponent system is required for tetracycline-induced excision of Tn4555.

Bacteroides spp. are the predominant organisms in the intestinal tract, and they also are important opportunistic pathogens. Antibiotic therapy of Bacteroides infections often is complicated by the prevalence of drug-resistant organisms which acquire resistance genes from a variety of mobile genetic elements including conjugative transposons (CTns) and mobilizable transposons (MTns). Tn4555 is an MTn that encodes beta-lactam resistance, and it is efficiently mobilized by the Bacteroides CTns via a tetracycline (TET)-inducible mechanism. In this study a model system with CTn341 and a Tn4555 minielement was used to examine Tn4555 excision from the chromosome. Using PCR and mobilization assays it was established that excision was stimulated by TET in the presence of CTn341. In order to determine which Tn4555 genes were required for excision, int, tnpA, tnpC, xis, and mobA mutants were examined. The results indicated that int plus two additional genes, tnpC and xis, were required for optimal excision. In addition, there was no requirement for the mobA gene, as had been shown for another MTn, NBU1. The Xis protein sequence is related to a family of plasmid excisionases, but the TnpC gene product did not match anything in the sequence databases. Evidence also was obtained that suggested that Xis is involved in the control of TET-induced excision and in control of mobilization by CTn341. Overall, these results indicate that excision of MTns is a complex process that requires multiple gene products.

Bacterial Proteins↗

A recombinant plasmid from which an infectious adeno-associated virus genome can be excised in vitro and its use to study viral replication.

A recombinant plasmid carrying an infectious adeno-associated viral genome was constructed that differs in several key respects from previously described recombinants. First, the vector is pEMBL8(+), which allows isolation of viral plus and minus strands. Second, the inserted viral sequences contain two XbaI cleavage sites that flank the viral coding domain. These inserts do not affect replication of the virus, and they allow nonviral sequences to be easily inserted between the cis-acting terminal repeats of adeno-associated virus. Third, the viral genome is flanked by PvuII cleavage sites that allow the entire, infectious viral chromosome to be excised from plasmid sequences in vitro. Viral DNA was replicated more efficiently within adenovirus-infected 293 cells if it was excised from the vector with PvuII before transfection. Presumably, the increased efficiency reflects bypass of the excision step which must normally precede replication when a recombinant plasmid enters the nucleus. The ability to bypass the excision step was exploited to search for a viral function required specifically for excision of the viral genome from the integrated state. None of the mutants tested identified a gene product required for excision that was not also essential for replication. The ability to produce pure populations of viral plus and minus strands was used to demonstrate that both strands are infectious.

Cell Line↗