SEARCH · PubMed Health

Results for “excision”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

PubMed1998

Melanoma excision by general practitioners in north-east Thames region, England.

A retrospective study of pathology reports of melanomas excised by general practitioners (GPs) was undertaken in the course of a population-based study of melanoma, with a telephone survey of the current practice of those GPs who had excised melanomas. The objectives of this study were to identify all cases of cutaneous melanoma excised by GPs in the North-East Thames Region between 1989 and 1993, and to review the management of those patients. The main outcome measures of the study were: (i) the patterns of distribution of GP excisions within the region; (ii) the histological subtypes of melanomas excised, the accuracy of the pre-excision clinical diagnosis and the adequacy of treatment of the GP-treated tumours compared with the control group; and (iii) the reported current practice in the management of pigmented skin lesions by the GPs who had excised melanomas. Eight hundred and nineteen melanomas were excised in the region during the study period, of which 59 were excised by GPs. The Breslow thickness of tumours was similar in both GP-excised and non-GP-excised groups. Tumours were more likely to be amelanotic in the GP-excised group (P < 0.001). Incomplete excision was significantly more likely in the GP group (P < 0.001). The GPs made a confident clinical diagnosis of melanoma in only 17% of patients prior to surgery. The reported referral rate to specialists by this subset of GPs of patients with pigmented lesions was low, and at interview half of the GPs reported that they felt confident enough to manage patients with suspected skin cancers on their own. The majority of the GPs did not routinely obtain histological examination of skin lesions they believed to be benign. In conclusion, there are problems with the accuracy of clinical diagnosis and inadequacy of excision of melanomas removed in primary care. In the majority of cases, however, patients were subsequently appropriately treated by referral to specialist units. There was an under-usage of pathological examination of samples by the GPs interviewed.

Ambulatory Surgical Procedures↗

PubMed1998

Malignant melanoma re-excision specimens--how many blocks?

AIMS: Wide local excision is commonly undertaken as part of the further management of cutaneous melanoma. Although the original excision is usually complete, pathologists vary considerably in their macroscopic handling and sampling of the wide excision specimens. This study evaluates the sampling of reexcision specimens and the information gained from histological examination of tissue blocks in order to develop guidelines for the handling of these specimens. METHODS AND RESULTS: The study group comprises 219 cases of melanoma which underwent initial biopsy followed by wider excision. The macroscopic appearance, number of blocks taken and presence of residual melanoma in the wide excision specimen was assessed. Residual melanoma was detected in the wide excision specimen in only four cases out of the 167 in which the original melanoma had been described as completely excised and in these cases the detection of a residual lesion reflected either advanced local disease at the time of the original excision, or an incompletely excised extensive radial growth phase. The sampling of wide excision specimens varied (range of blocks 1-12, average 3.1) but statistical analysis showed no undersampling of the wide excision specimens in which no residual lesion was found. CONCLUSIONS: These results show that detection of a residual lesion in wide excision specimens of melanomas previously completely excised is unusual and offers no additional clinically useful information. Random block taking in the absence of a macroscopic abnormality is therefore unlikely to be clinically useful. Guidelines for the gross handling of these wide excision specimens are proposed which are likely to save resources in most histopathology departments by reducing block numbers.

Humans↗

PubMed1988

Insertion and excision of Caenorhabditis elegans transposable element Tc1.

The transposable element Tc1 is responsible for most spontaneous mutations that occur in Caenorhabditis elegans variety Bergerac. We investigated the genetic and molecular properties of Tc1 transposition and excision. We show that Tc1 insertion into the unc-54 myosin heavy-chain gene was strongly site specific. The DNA sequences of independent Tc1 insertion sites were similar to each other, and we present a consensus sequence for Tc1 insertion that describes these similarities. We show that Tc1 excision was usually imprecise. Tc1 excision was imprecise in both germ line and somatic cells. Imprecise excision generated novel unc-54 alleles that had amino acid substitutions, amino acid insertions, and, in certain cases, probably altered mRNA splicing. The DNA sequences remaining after Tc1 somatic excision were the same as those remaining after germ line excision, but the frequency of somatic excision was at least 1,000-fold higher than that of germ line excision. The genetic properties of Tc1 excision, combined with the DNA sequences of the resulting unc-54 alleles, demonstrated that excision was dependent on Tc1 transposition functions in both germ line and somatic cells. Somatic excision was not regulated in the same strain-specific manner as germ-line excision was. In a genetic background where Tc1 transposition and excision in the germ line was not detectable, Tc1 excision in the soma still occurred at high frequency.

Animals↗

PubMed1992

Mechanism of Ds1 excision from the genome of maize streak virus.

We have previously shown that the maize transposable element Ds1 introduced into maize plants by agroinfection can be excised from the genome of geminivirus maize streak virus (MSV). Excision depended strictly on the presence of an active Ac element in the plants. In this study, the excision products or "footprints" left in the MSV genome after Ds1 excision were extensively characterized and the effects of flanking sequences on Ds1 excision were analysed. Most types of footprints obtained were comparable to those described for Ds1 excision in the maize genome, and could be explained by the models proposed for excision of plant transposable elements. In two revertants, however, some terminal sequences of the Ds1 element were found to have been left behind at the excision site. The finding of this novel type of Ds1 footprint indicated that gene conversion events occurred during and/or after Ds1 excision from the MSV genome. A partial deletion of one copy of the 8 bp duplications flanking the Ds1 element had no effect on the frequency or on the types of footprints of Ds1 excision from the MSV genome. Thus, the duplicated 8 bp sequences flanking the transposable element are not involved in Ds1 excision. These results, as well as a statistical analysis of the modifications of the bases flanking the Ds1 element after excision, are discussed in terms of excision models.

Base Sequence↗

PubMed2001

A comparison of ink-directed and traditional whole-cavity re-excision for breast lumpectomy specimens with positive margins.

BACKGROUND: Excising a breast tumor with negative margins minimizes local recurrence. With a positive margin, the standard re-excision consists of excising the whole cavity and all surrounding breast tissue. By marking the sides of the lumpectomy specimen with six different colored inks, the surgeon can limit the re-excision to the involved margin. We compared the local recurrence rate after these two re-excision methods. METHODS: Records were reviewed of 527 women (546 breasts) treated with lumpectomy at two institutions. The log-rank test was used to compare the local recurrence-free survival. RESULTS: Of 546 tumors, 245 (45%) had negative margins on the initial lumpectomy and were not re-excised. Fifty-five percent had a positive or close margin; 181 underwent whole-cavity re-excision, and 120 had ink-directed re-excision. The mean follow-up time was 3.4 years. There was no significant difference in local recurrence for the patients whose initial margin was negative (3.7%) compared with the 243 patients with initially positive margins who underwent a re-excision (3.3%). Eleven of 181 (6%) patients undergoing a whole-cavity re-excision developed a local recurrence, compared with none of 120 (0%) patients with an ink-directed re-excision (P = not significant). Tissue mass excised was significantly smaller in the ink-directed group (23 vs. 83 g, P < .05). CONCLUSIONS: Ink-directed re-excision of lumpectomy specimens with positive margins minimizes the amount of breast tissue removed without increasing the incidence of local recurrence and is therefore preferable to the standard whole-cavity method.

Breast Neoplasms↗

PubMed1993

Incidence of gross and microscopic carcinoma in specimens from patients with breast cancer after re-excision lumpectomy.

OBJECTIVE: The aims of this study were to quantify the amount of the residual carcinoma in re-excision lumpectomy specimens and retrospectively analyze the relationship between clinical parameters and the characteristics of the primary excision to these quantities of the residual tumor. SUMMARY BACKGROUND DATA: Because complete gross surgical excision of the primary tumor is important in minimizing local recurrence in women undergoing breast conservation therapy, re-excision of the initial biopsy site is commonly practiced when the initial primary tumor excision shows inadequate or undeterminable margins. Several studies have reported a significant proportion of re-excision specimens to contain residual tumor (32% to 63%), but to the authors' knowledge, none have quantified the amount of residual tumor. METHODS: The authors reviewed 192 re-excisions retrospectively to quantify the amount of residual carcinoma and correlate the quantities with the characteristics of the primary tumor resection. RESULTS: No tumor was found in 105 (54.7%) specimens, 46 (23.9%) had minimal microscopic disease, 23 (12.0%) had extensive microscopic disease, and 18 (9.4%) had gross residual cancer. Characteristics significantly associated with the quantity of residual disease included clinical tumor stage (T stage), pathologic T stage, and the margin status of the primary excision. The majority (62.1%) of re-excision specimens containing residual carcinoma had an invasive component. CONCLUSIONS: It was concluded that re-excision lumpectomy yields an important number of patients with residual carcinoma and that characteristics of both the primary tumor and primary excision significantly predict the quantity of residual cancer in the specimen. In addition, these results support the policy of performing re-excision for patients with inadequate or undeterminable margins for the primary excision.

Adult↗

PubMed2001

Local excision of rectal cancer: what is the evidence?

PURPOSE: Although local excision of rectal cancers is a less morbid alternative to radical resection, its role as a curative procedure is unclear. The role of adjuvant therapy after local excision is also controversial. This review aims to examine current evidence on local excision of rectal cancers and how it fits into the management algorithm for rectal cancer. METHODS: A literature review was undertaken through the MEDLINE database and by cross-referencing previous publications, thus identifying 41 studies on curative local excision of rectal cancer published in English. Details of preoperative staging, surgical procedures, adjuvant therapy, follow-up, and outcome measures, including complications, survival data, recurrences, and salvage were examined. RESULTS: Preoperative staging of rectal cancers is variable. Digital rectal examination and computerized tomography are used in most studies. Endorectal ultrasound is used in some patients in 9 of 41 studies. Local excision preserves anorectal function, and seems to have limited morbidity (0-22 percent). Local excision alone is associated with local recurrences in 9.7 (range, 0-24) percent of T1, 25 (range, 0-67) percent of T2 and 38 (range, 0-100) percent of T3 cancers. The addition of adjuvant chemoradiotherapy after local excision yields local recurrence rates of 9.5 (range, 0-50) percent for T1, 13.6 (range, 0-24) percent for T2, and 13.8 (range, 0-50) percent for T3 cancers. Data on local excision after preoperative chemoradiotherapy for tumor down staging are limited. Factors other than T-stage that lead to higher local recurrence rates after local excision include poor histologic grade, the presence of lymphovascular invasion, and positive margins. Local recurrences after local excision can be surgically salvaged (84 of 114 patients in 15 studies), with a disease-free survival rates between 40 and 100 percent at a follow-up of 0.1 to 13.5 years. CONCLUSIONS: Local excision for rectal cancers is associated with a low morbidity and provides satisfactory local control and disease-free survival rates for T1 rectal cancers. There is, however, a need for a randomized, controlled trial for T2 cancers, comparing local excision with adjuvant chemoradiotherapy to radical resection.

Algorithms↗

PubMed1980

The role of dimer excision in liquid-holding recovery of UV-irradiated haploid yeast.

We have directly tested the theory that liquid-holding recovery is due to an increase in the efficiency of excision-repair during holding in non-growth conditions, by assaying the dimers present in UV-irradiated cells held in saline, in growth medium or first in saline then in growth medium. We observed no differences in the amount of excision in any conditions. By assaying the kinetics of excision and comparing that with the timing of DNA synthesis, we have tested the theory that holding in growth medium allows more repair by extending the time available for it. We found that the observations were more consistent with the onset of DNA synthesis being dependent on the amount of repair rather than the converse. We have analysed the role of repair in liquid-holding recovery in a series of split-dose experiments. As Parry and Parry found, yeast cells which have been irradiated and held in non-growth conditions were much more resistant to further UV-irradiation. The increase in resistance was proportional both to the degree of fractionation of the dose and to the size of the first dose. No effect was observed if this was below 30 J . m-2. We found that the cells were able to excise more of the dimers induced if the UV dose was fractionated. We have shown that part of this increase in efficiency of excision is due to the relief of "dimer interference". "Dimer interference" is the name given to the inhibition of excision of a dimer by the presence of a neighbouring dimer. Most of the increase in efficiency, however, was due to the induction of more efficient excision repair per se, that is the excision of a greater fraction of the dimers present than could be excised in uninduced cells. Among the incidental observations we have made which are new and likely to be of interest are (1) that stationary phase cells showed a lag in the onset of excision, but log phase cells did not; (2) that excision was nevertheless constitutive in that it occurred in the presence of concentrations of cycloheximide inhibitory to protein synthesis and (3) that caffeine affected but did not inhibit dimer excision.

Culture Media↗

PubMed2006

Basal cell carcinoma histological clearance margins: an analysis of 1539 conventionally excised tumours. Wider still and deeper?

An analysis of peripheral and deep margins of histological clearance around 1539 consecutive basal cell carcinomas excised by conventional surgery showed that 81 lesions (5.3%) were incompletely excised peripherally; 36 lesions (2.3%) were incompletely excised deeply; 13 lesions (0.8%) were incompletely excised peripherally and deeply. Nine hundred and ninety-six lesions (65%) were excised with a peripheral histological clearance margin<5mm (0.1-4.9mm), whereas 1303 lesions (85%) were excised with a deep histological clearance margin<5mm (0.1-4.9mm). Four hundred and eight lesions (27%) had a peripheral histological clearance margin of 5.0-9.9mm, whereas 170 lesions (11%) had a deep histological margin of 5.0-9.9mm. Peripheral histological clearance margins exceeded 10mm in 41 lesions (3%) and deep histological margins exceeded 10mm in 17 lesions (1%). Thus 30% of peripheral histological margins were 5mm or more but only 12% of deep histological margins were 5mm or more. Despite a relative sparing of deep tissue, incomplete excision in depth affected only 36 lesions compared with 81 incomplete peripheral excisions. Peripheral histological clearance was <5mm (0.1-4.9mm) for 55% of temple lesions, 50% of scalp lesions and 43% for limb lesions. In the cosmetically sensitive areas of peri-orbital region, nose, cheek, lip, neck and chin more than 70% of lesions were excised with a peripheral histological margin<5mm. This study of conventional surgical excision of basal cell carcinomas with an incomplete excision rate of 8% has shown that 65% of lesions were excised with <5mm histological clearance peripherally and 85% with <5mm deep clearance. These figures for 'normal tissue sacrifice' are not excessive when compared with those of 'tissue sparing' Mohs' micrographic surgery in which the operator may take a margin of several millimetres of normal tissue in the initial 'slice', or in the subsequent 'safety margin' beyond the eventual tumour free plane. However, peripheral margins did exceed 5mm in more than 30% of lesions of scalp, temple and forehead, and for these sites where even with loupe magnification the tumour edge could be difficult to define, either frozen section control or Mohs' technique, might with benefit be more often used in order to minimise normal tissue sacrifice.

Basal Cell Carcinoma↗

PubMed2002

Audit of intraoperative and early postoperative complications after introduction of mesorectal excision for rectal cancer.

OBJECTIVE: To compare complication rates after rectal resection using a conventional surgical technique (1983-1992) and mesorectal excision (1993-2000), and to find out whether the rate of complications changed with time after the introduction of mesorectal excision. DESIGN: Prospective, observational study. SETTING: University hospital, Norway. PATIENTS: All patients who had rectal resections for cancer in the period 1983-2000. INTERVENTIONS: In the conventional surgery period 217, and in the mesorectal excision period 176, patients had rectal resections. The mesorectal excision period was split in two, the early and the late mesorectal excision period, 88 rectal resections being performed in each period. Total mesorectal excision was done in 118 patients, and partial mesorectal excision in 58. MAIN OUTCOME MEASURES: Major surgical complications in both periods; intraoperative bleeding, transfusions during the hospital stay, and cardiovascular complications in the mesorectal excision period. RESULTS: 23/217 (11%) developed major surgical complications in the conventional surgery period, compared with 17/88 (19%) in the early mesorectal excision period (p = 0.04). This was caused by an increased incidence of anastomotic leaks after low anterior resection, being 11/122 (9%) in the conventional surgery period and 12/52 (23%) in the early mesorectal excision period (p = 0.01). The incidence of anastomotic leaks declined to 5/61 (8%) in the late mesorectal excision period (p = 0.03). Multiple regression analysis identified a low anastomosis, major bleeding, and age over 75 years as significant risk factors for the development of anastomotic leaks. Major intraoperative bleeding occurred in 36/84 (43%) of the patients in the early and 22/82 (27%) in the late mesorectal period (p = 0.04). Blood transfusions were given to 61/84 (74%) in the early mesorectal period and 41/82 (50%) in the late period (p < 0.01). CONCLUSIONS: The incidence of surgical complications increased significantly after the introduction of mesorectal excision, but declined with time.

Adult↗

PubMed1992

Imprecise excision of plasmid pE194 from the chromosomes of Bacillus subtilis pE194 insertion strains.

Plasmid pE194 has been shown to be rescued by integration after cultivation of infected Bacillus subtilis recE4 cells at a restrictive high temperature. The plasmid is also spontaneously excised from the chromosome at a low frequency by precise or imprecise excision (J. Hofemeister, M. Israeli-Reches, and D. Dubnau, Mol. Gen. Genet. 189:58-68, 1983). We have investigated nine excision plasmids, carrying insert DNA 1 to 6 kbp in length, either in a complete pE194 or in a partially deleted pE194 copy. Type 1 (additive) excision plasmids have the left- and right-junction DNAs preserved as 13-bp direct repeats (5'-GGGGAGAAAACAT-3') corresponding to the region between positions 864 and 876 in pE194. In type 2 (substitutive) excision plasmids, a conserved 13-bp sequence remains only at the right junction while the left junction has been deleted during the excision process. The type 3 excision plasmid carries at each junction the tetranucleotide 5'-TCCC-3', present in pE194 between positions 1995 and 1998. Although we isolated the excision plasmids from different integration mutants, the insert DNAs of eight independently isolated plasmids showed striking sequence homology, suggesting that they originated from one distinct region of the B. subtilis chromosome. Thus, we postulate that imprecise excision of pE194 occurs most frequently after its translocation from the original insertion site into a preferred excision site within the host chromosome. The imprecise excision from this site occurs at excision breakpoints outside the pE194-chromosome junctions in a chromosomal region which remains to be investigated further.

Bacillus subtilis↗

PubMed1991

Cortical somatosensory evoked potentials. II. Effects of excision of somatosensory or motor cortex in humans and monkeys.

1. To clarify the generators of human short-latency somatosensory evoked potentials (SEPs) thought to arise in sensorimotor cortex, we studied the effects on SEPs of surgical excision of somatosensory or motor cortex in humans and monkeys. 2. Normal median nerve SEPs (P20-N30, N20-P30, and P25-N35) were recorded from the cortical surface of a patient (G13) undergoing a cortical excision for relief of focal seizures. All SEPs were abolished both acutely and chronically after excision of the hand area of somatosensory cortex. Similarly, excision of the hand area of somatosensory cortex abolished corresponding SEPs (P10-N20, N10-P20, and P12-N25) in monkeys. Excision of the crown of monkey somatosensory cortex abolished P12-N25 while leaving P10-N20 and N10-P20 relatively unaffected. 3. After excision of the hand area of motor cortex, all SEPs were present when recorded from the cortical surface of a patient (W1) undergoing a cortical excision for relief of focal seizures. Similarly, all SEPs were present in monkeys after excision of the hand area of motor cortex. 4. Although all SEPs were present after excision of motor cortex in monkeys, variable changes were observed in SEPs after the excisions. However, these changes were not larger than the changes observed after excision of parietal cortex posterior to somatosensory cortex. We concluded that the changes were not specific to motor cortex excision. 5. These results support two major conclusions. 1) Median nerve SEPs recorded from sensorimotor cortex are produced by generators in two adjacent regions of somatosensory cortex: a tangentially oriented generator in area 3b, which produces P20-N30 (human) and P10-N20 (monkey) [recorded anterior to the central sulcus (CS)] and N20-P30 (human) and N10-P20 (monkey) posterior to the CS; and a radially oriented generator in area 1, which produces P25-N35 (human) and P12-N25 (monkey) recorded from the postcentral gyrus near the CS. 2) Motor cortex makes little or no contribution to these potentials.

Adolescent↗

PubMed2007

Intra-operative touch preparation cytology; does it have a role in re-excision lumpectomy?

OBJECTIVE: Breast carcinoma is the most frequently diagnosed malignancy in women of North America. The combination of breast conservation surgery and radiotherapy has become a standard of treatment for the majority of breast cancers. It is critical to obtain clear margins to minimize local recurrence. However, avoiding multiple re-excisions for margin clearance helps optimize cosmetic results in patients undergoing breast conservation surgery. Intra-operative touch preparation cytology (IOTPC) may decrease the need for multiple re-excisions and thereby improve cosmesis. The literature suggests that IOTPC can be useful in evaluation of margins. Klimberg et al. evaluated the touch preparation technique prospectively in 428 patients undergoing breast biopsy for undiagnosed breast masses. Margin evaluation was correct in 100% of the lesions and was used to re-excise the margins when touch prep results were positive. They reported a diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 100% for the touch prep technique. To the best of our knowledge, there has been no published data on the role of IOTPC for evaluation of margins in re-excision cases. This report describes our experience with IOTPC for margin assessment for re-excision partial mastectomy at Beth Israel Medical Center (BIMC). The purpose of this study is to determine whether IOTPC is reliable for evaluating margins in patients undergoing re-excision for involved or close margins. METHODS: A prospective study of 30 patients, who have undergone re-excision partial mastectomy for involved or close margins after breast conservation surgery with the use of IOTPC for margin assessment at BIMC was performed. The re-excision lumpectomy specimens were oriented by the surgeon intra-operatively and were submitted fresh to pathology for cytologic assessment. The touch prep method consisted of touching the corresponding margin onto the glass slide. The principle of this technique is that if cancer cells are present they will stick to the slide, while fat cells will not. A slide was prepared for each re-excision specimen. Air-dried samples were stained immediately using the Diff-Quik method and examined under the microscope by a cytopathologist. RESULTS: Thirty patients underwent re-excision lumpectomy for involved or close margins with touch preparation cytology for assessment of 68 margins. Twenty-six patients had invasive ductal carcinoma and/or ductal carcinoma in situ, three patients had invasive lobular carcinoma and the remaining one patient had a combination of invasive lobular and ductal carcinoma. There was a correlation between touch prep cytology and final pathology in 56/68 margins, which accounts for 82.4% of the cases. CONCLUSION: Intra-operative touch preparation cytology for assessment of margins in patients undergoing re-excision lumpectomy for involved or close margins has a sensitivity of 75%, specificity of 82.8%, positive predictive value of 21.4%, and negative predictive value of 98.2%. This high negative predictive value and a single false negative margin are quite significant. Therefore, based on our experience, IOTPC can be a useful tool for intra-operative assessment of margins for patients undergoing re-excision partial mastectomy.

Biopsy↗

PubMed1997

Characteristics of incompletely excised basal cell carcinomas of the skin.

OBJECTIVES: To determine the proportion of basal cell carcinomas (BCCs) treated by excision biopsy that extended to the margins of surgical excision (incompletely excised tumours) and to identify their characteristics. DESIGN: Case series of BCCs submitted to a single pathologist in the first six months of 1995. SETTING: Rural and metropolitan (Perth) Western Australia. PATIENTS: 268 patients with 353 histologically confirmed BCCs. OUTCOME MEASURES: Age and sex of patients; discipline of referring doctor; anatomical site of BCC; macroscopic features; histological growth pattern; and completeness of excision. RESULTS: Sixteen per cent of BCCs (58/353) extended to the margin of surgical excision. Most of these were situated on the head or neck (43/58; 74%) and were flat (47/58; 81%); a high proportion of incompletely excised BCCs (21/58; 36%) had an infiltrative growth pattern. Recurrent BCCs (28/353; 8%), categorised from the history or because of histologically identified surgical scarring, were even more likely to be flat (26/28; 93%) and to show a microscopic infiltrative growth pattern (18/28; 64%). Seven of the 28 (25%) recurrent BCCs were incompletely excised; all seven were on the head and five had an infiltrative growth pattern. CONCLUSION: Incompletely excised BCCs are those most likely to recur. Because most recurrent tumours are situated on the head and neck and have an infiltrative growth pattern, we recommend that: Pathologists report on the microscopic growth pattern of BCCs as well as on completeness of excision. Clinicians attempt to excise head and neck BCCs with wide margins initially, where possible. Tumours extending to the margin of excision which are infiltrative in pattern and located on the head and neck may be particularly likely to recur, and immediate re-excision should be considered in these patients.

Adult↗

PubMed1996

Excision of 2',2'-difluorodeoxycytidine (gemcitabine) monophosphate residues from DNA.

The activity of gemcitabine (dFdC), an effective agent against solid tumors, depends on the incorporation of its triphosphate into DNA. In vitro investigations demonstrated that, depending on the sequence of template DNA, polymerases may pause after incorporation of gemcitabine nucleotide at either the 3'-terminal or 3'-penultimate position. Proofreading enzymes such as 3'-->5' exonucleases, which are associated with DNA polymerases, can excise mismatched deoxynucleotides from DNA. To model this reaction, we evaluated excision of the gemcitabine nucleotide from oligodeoxynucleotide (19-mer) containing 3'-penultimate dFdC monophosphate (dFdCMP) or dCMP by the 3'-->5' exonuclease of the Klenow fragment. The rate of excision of the 3'-terminal deoxynucleotide was similar, with both primers resulting in formation of primers with terminal dCMP or dFdCMP. The primer containing dCMP was further excised, and by 40 min, more than 75% of total radioactivity was in excision products smaller than 18-mer. In contrast, most of the primers (90%) with terminal dFdCMP were unexcised. When primers terminated with either dFdCMP or dCMP were used as substrates, normal primer was hydrolyzed almost completely by 20 min; however, only 40% of primers containing dFdCMP had excision of dFdCMP molecule. Kinetic studies demonstrated that the enzyme had similar affinity for primers containing penultimate or terminal dFdCMP, but the apparent Vmax for excision was 4-5-fold greater for removal of a 3'-terminal deoxynucleotide than for cleavage of a dFdCMP molecule. Reaction conditions that permitted polymerization of one deoxynucleotide to primers containing either 3'-penultimate dCMP or dFdCMP were used to evaluate excision during DNA synthesis. The excised primers could not be extended because the reaction lacked the requisite deoxynucleotide triphosphate. After 5 min, more than one-half of the dCMP primers were extended, whereas only 15% had been excised. In comparison, 30% of the analogue-containing primers lost the terminal deoxynucleotide, with a proportional lower incidence of extension (30%). Lesser excision of dFdCMP-containing substrate was observed in reactions containing deoxynucleotide triphosphates required to make full-length products. Consistent with this result, in the absence of 3'-->5' exonuclease activity, both primers were extended similarly by the polymerization unit of the Klenow fragment. Taken together, these data demonstrate that dFdCMP residues are difficult to excise from DNA, and DNA polymerase can extend primers with 3'-dFdCMP. This results in the internal incorporation of dFdCMP into DNA, as observed in whole cells.

Antimetabolites, Antineoplastic↗

PubMed1997

Outcomes after cervical cold knife conization with complete and incomplete excision of abnormal epithelium: a review of 699 cases.

A retrospective analysis was undertaken of 699 cone biopsies performed at the Royal Women's Hospital in Melbourne from 1966 to 1992. In 572 cases (82%), abnormal epithelium was assessed as having been completely excised, and in 127 (18%) excision was incomplete. There were no significant differences in age, parity, cytology, histology, or indications for conization between patients in whom excision was incomplete and those in whom complete excision was achieved. Of the patients whose cone biopsy histology showed complete excision of abnormal epithelium, 96.7% were found to have been cured of disease on the basis of normal follow-up or normal histology of hysterectomy specimens. The overall cure rate after incomplete cone biopsy was found to be 77%, but was influenced by the site of incomplete excision. The cure rate for incomplete excision at the ectocervical margin was 86%; incomplete excision at the endocervix was 68% and only 40% if excision was incomplete at both edges. Cone biopsy undertaken for cervical intraepithelial neoplasia is likely to be curative when the lesion is completely excised, but recurrent disease may occur and adequate follow-up is an essential part of patient management after conization, regardless of histological findings in the conization specimen. Most cases of incompletely excised cervical intraepithelial neoplasia will also be cured, especially if the incomplete margin is ectocervical, and cytological and colposcopic follow-up may be an acceptable alternative to repeat cone biopsy or hysterectomy in the management of such cases.

Adolescent↗

PubMed1997

Abdominoperineal excision of the rectum--an endangered operation. Norman Nigro Lectureship.

PURPOSE: This study was undertaken to test the efficacy of an extreme policy of sphincter conservation by combining precise total mesorectal excision with low stapling techniques and endoluminal lavage to guard against implantation. METHODS: A total of 136 consecutive operations for cancer below 5 cm from the anal verge has been prospectively documented and followed for a mean of 7.7 (range, 1-18) years. A total of 105 of the operations were anterior resections (77 percent), and 31 were abdominoperineal excisions (23 percent). RESULTS: The oncologic results in the 105 patients who underwent anterior resections appear greatly superior to those of the patients who underwent abdominoperineal excisions, although the number of abdominoperineal excisions was small (31). Actuarial local recurrence at six years for anterior resection and total mesorectal excision was 1 percent for 85 curative procedures and 4 percent for all cases (n = 100), compared with 33 and 47 percent for abdominoperineal excisions (n = 15 and 31). Only four recurrences were observed below the level of the levators, three in the wound of an abdominoperineal excision and one in a stapled anastomosis after a palliative excision. No cases of nodal metastasis in the ischiorectal fossa were observed. CONCLUSION: In a unit specializing in sphincter conservation, precise total mesorectal excision from above appears oncologically superior to abdominoperineal excision. Three-fourths of patients with carcinoma of the lower one-third of the rectum can be offered sphincter-conserving surgery, although temporary defunctioning is probably prudent in such cases. The wound of an abdominoperineal excision may be a prerequisite for perineal recurrence, which may often be caused by implantation.

Abdomen↗

PubMed2000

Is local excision adequate therapy for early rectal cancer?

PURPOSE: Radical surgery of rectal cancer is associated with significant morbidity, and some patients with low-lying lesions must accept a permanent colostomy. Several studies have suggested satisfactory tumor control after local excision of early rectal cancer. The purpose of this study was to compare recurrence and survival rates after treating early rectal cancers with local excision and radical surgery. METHODS: One hundred eight patients with T1 and T2 rectal adenocarcinomas treated by transanal excision were compared with 153 patients with T1N0 and T2N0 rectal adenocarcinomas treated with radical surgery. Neither group received adjuvant chemoradiation. Mean follow-up time was 4.4 years after local excision and 4.8 years after radical surgery. RESULTS: The estimated five-year local recurrence rate was 28 percent (18 percent for T1 tumors and 47 percent for T2 tumors) after local excision and 4 percent (none for T1 tumors and 6 percent for T2 tumors) after radical surgery. Overall recurrence was also higher after local excision (21 percent for T1 tumors and 47 percent for T2 tumors) than after radical surgery (9 percent for T1 tumors and 16 percent for T2 tumors). Twenty-four of 27 patients with recurrence after local excision underwent salvage surgery. The estimated five-year overall survival rate was 69 percent after local excision (72 percent for T1 tumors and 65 percent after T2 tumors) and 82 percent after radical surgery (80 percent for T1 tumors and 81 percent for T2 tumors). Differences in survival rate between local excision and radical surgery were statistically significant in patients with T2 tumors. CONCLUSIONS: Local excision of early rectal cancer carries a high risk of local recurrence. Salvage surgery is possible in most patients with local recurrence, but may be effective only in patients with T1 tumors. When compared with radical surgery, local excision may compromise overall survival in patients with T2 rectal cancers.

Adenocarcinoma↗