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Does histological incomplete excision of cervical intraepithelial neoplasia following large loop excision of transformation zone increase recurrence rates? A six year cytological follow up.

OBJECTIVE: To determine the risk of recurrent cervical intraepithelial neoplasia (CIN) in women with complete or incomplete excision of cervical intraepithelial neoplasia treated by large loop excision of transformation zone (LLETZ). DESIGN: A retrospective study SETTING: One consultant-led colposcopy clinic at Leicester Royal Infirmary POPULATION: Three hundred and ninety-four women referred consecutively to the colposcopy clinic between 1991 and 1992. MAIN OUTCOME MEASURES: The histological recurrence rate of CIN, length of cytological follow up following treatment related to degree of completeness of excision at initial treatment. RESULTS: Three hundred and twenty-two women had complete cytological or histological follow up. The mean length of follow up was 73 months with a mean number of six smears. Women with incomplete excision of CIN had a significantly higher risk of recurrent CIN (relative risk 8.23) occurring in a significantly shorter time compared with women with complete excision. CONCLUSIONS: This study demonstrates that large loop excision of transformation zone is successful in over 95% of cases. Cytological surveillance is satisfactory for follow up of women who have complete excision of CIN. Women with incomplete excision of CIN at initial LLETZ remain at significant risk of developing further CIN and long term colposcopic and cytological follow up is necessary.

Adolescent↗

Completeness of excision and follow up cytology in patients treated with loop excision biopsy.

AIMS: To assess the relation between the grade and the status of follow up cytology, the completeness of loop excision biopsies with cervical intraepithelial neoplasia (CIN), and the findings at follow up cytology, as well as the differences between complete and incomplete exclusion, using the odds ratio. Treatment failure was assessed. METHODS: 1600 women with CIN (290 CIN1, 304 CIN2, 1006 CIN3) were followed for a minimum of six months and a maximum of 10 years. A database was created and comparisons performed. The mean age of the patients was 37 years. RESULTS: Excision was complete in over 84% of loops. Residual disease and recurrence of high grade dyskaryosis was more common in women with CIN 3 than CIN 2 or 1. No high grade dyskaryosis was seen in the fifth follow up smear in patients with CIN 1 and CIN 2. Residual, recurrent, and persistent disease was most common in patients with incompletely excised CIN at ectocervical and endocervical margins and deep margins of resection than in patients with completely excised CIN. The odds ratios were significantly higher in the women who had incomplete excision of CIN at ectocervical, endocervical, both ecto- and endocervical, and deep margins of resection compared with those with apparent complete excision of CIN lesions. One patient developed invasive squamous cell carcinoma 44 months after loop excision which showed CIN 3 invading endocervical crypts and extending to both ectocervical and endocervical margins of resection. CONCLUSIONS: At long term follow up, patients with CIN who have residual disease are at increased risk of persistent disease and should therefore be followed up regularly with cytology and colposcopy. The findings support national policy of returning women with treated CIN of any grade to normal recall after five years except for cases of CIN3 where excision was incomplete or equivocal. In these cases follow up with annual smear for 10 years is recommended.

Adolescent↗

Excision and marsupialization versus sinus excision for the treatment of limited chronic pilonidal disease: a prospective, randomized trial.

The treatment techniques for pilonidal disease are either associated with high recurrence rates or complex procedures. This prospective randomized study compared the outcome of excision and marsupialization technique with sinus excision technique. A total of 40 consecutive patients with limited, chronic pilonidal sinus disease were operated with either excision and marsupialization technique (Group 1, n=20) or sinus excision technique (Group 2, n=20). The demographics, perioperative data, complications and recurrences were recorded. Patient satisfaction was evaluated with a specific questionnaire 16-18 weeks after surgery. Demographic data, preoperative symptoms and the acute disease history were similar between the groups. Operation time, hospital stay and work-off periods were significantly shorter and the number of out-patient procedures was significantly more in Group 2. Although satisfaction scores were similar between the groups, the patients who had no complaint, were "completely satisfied" or would "absolutely recommend the operative technique to other patients" were significantly more in Group 2. In conclusion, the sinus excision technique requires a shorter operation time, hospital stay and work-off period than excision and marsupialization in the treatment of limited, chronic pilonidal disease. The sinus excision technique can be performed as an out-patient procedure in most cases, and seems to be associated with better patient satisfaction.

Adolescent↗

Nitric oxide inhibits DNA-adduct excision in nucleotide excision repair.

Sustained induction of nitric oxide (NO) in chronic inflammation may be mutagenic, through DNA damage induction and/or DNA repair inhibition. Although there is good evidence that NO can cause DNA damage, how NO is involved in DNA repair remains elusive. By using DNA synthesis inhibitors to accumulate DNA strand breaks in comet assay, we show that NO and peroxynitrite inhibit DNA-adduct excision in human fibroblasts damaged by UVC, 4-nitroquinoline 1-oxide, benzo[a]pyrene dihydrodiol epoxide, cisplatin, or mitomycin C, but not with methyl methane sulfonate. Treating cells with arsenite increased NO production and also inhibited the DNA-adduct excision induced by UVC, 4-nitroquinoline 1-oxide, benzo[a]pyrene dihydrodiol epoxide, cisplatin, and mitomycin C, but not by methyl methane sulfonate, H(2)O(2), sodium nitrosoprusside, or 3-morpholinosydnonimine. Arsenite inhibition of DNA-adduct excision was decreased by NO synthase inhibitors and NO scavengers. The nuclear extract prepared from fibroblasts pretreated with sodium nitrosoprusside, dipropylenetriamine NONOate, 3-morpholinosydnonimine, or arsenite also showed decreased activity in excising the DNA adducts induced by UVC and cisplatin but not by methyl methane sulfonate or H(2)O(2) plus Fe. These results are consistent with the notion that NO, peroxynitrite, and arsenite inhibit the DNA-adduct excision in nucleotide excision repair but not that in base excision repair.

4-Nitroquinoline-1-oxide↗

Acetylaminofluorene bound to different guanines of the sequence -GGCGCC- is excised with different efficiencies by the UvrABC excision nuclease in a pattern not correlated to the potency of mutation induction.

DNA fragments were constructed in which acetylaminofluorene adducts were introduced specifically at each one of the three different guanines of the 6-base-pair sequence -GGCGCC-. Incubation of the DNA with the UvrABC excision nuclease in vitro revealed major differences in the efficiency of adduct excision depending on the site of modification. Oligonucleotide excision of adducts bound to the second guanine was only 15% as efficient as excision of adducts at the first guanine, whereas the excision efficiency for adducts bound to the third guanine was intermediary. However, recognition of DNA damage appeared to occur with nearly 100% efficiency at all three adduct positions, as judged from DNase I footprint analysis of the DNA/protein binding complexes. Hence, it appears that the structural elements for DNA damage recognition by the UvrABC enzyme are different from the signals for excision. Furthermore, the repair pattern observed is not inversely correlated with the potential of these adducts to induce mutations since mutation analysis of single-adduct DNA has shown that only adducts at the third guanine are strongly premutagenic. We conclude that the effectiveness of excision repair depends on the context of the DNA sequence and that ineffectively repaired adduct sites are not necessarily mutational hot spots.

2-Acetylaminofluorene↗

Effect of margins of excision on recurrence after local excision of ductal carcinoma in situ of the breast.

AIMS: To determine important factors influencing recurrence after local excision of duct carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: The extent (size) in millimetres, classification (by cytonuclear grade (NHSBSP system), by extent of necrosis, and by the Van Nuys system), and excision margins of 115 cases of screen detected DCIS treated by local excision were measured. A prognostic index was calculated by the addition of the Van Nuys classification (low grade, 1; moderate grade, 2; high grade, 3), margin score (> or = 10 mm, 1; 1-9 mm, 2; < 1 mm, 3), and size score (< or = 15 mm, 1; 16-40 mm, 2; and > or = 41 mm, 3), giving a total score of 3-9. RESULTS: Classification using cytonuclear grade, extent of necrosis, or the Van Nuys system did not correlate significantly with recurrence. The excision margin (in millimetres) was associated with recurrence (p = 0.027) and if excision margin status was simplified using the scoring system (> or = 10 mm, 1; 1-9 mm, 2; < 1 mm, 3), the margin score was significantly associated with recurrence (p = 0.03). A prognostic index based on the Van Nuys score, margin status, and size was significantly associated with recurrence (p = 0.003). CONCLUSION: The results support the hypothesis that the margin of excision is the most important factor predicting the recurrence of DCIS after local excision.

Aged↗

Reconstitution of damage DNA excision reaction from SV40 minichromosomes with purified nucleotide excision repair proteins.

We previously constructed the cell-free nucleotide excision repair (NER) assay system with UV-irradiated SV40 minichromosomes to analyze the mechanism of NER reaction on chromatin DNA. Here we investigate the factor that acts especially on nucleosomal DNA during the damage excision reaction, and reconstitute the damage excision reaction on SV40 minichromosomes. NER-proficient HeLa whole cell extracts were fractionated, and the amounts of known NER factors involved in the column fractions were determined by immunoblot analyses. The column fractions were quantitatively and systematically replaced by highly purified NER factors. Finally, damage DNA excision reaction on SV40 minichromosomes was reconstituted with six highly purified NER factors, XPA, XPC-HR23B, XPF-ERCC1, XPG, RPA and TFIIH, as those essential for the reaction with naked DNA. Further analysis showed that the damages on chromosomal DNA were excised as the same efficiency as those on naked DNA for short incubation. At longer incubation time, however, the damage excision efficiency on nucleosomal DNA was decreased whereas naked DNA was still vigorously repaired. These observations suggest that although the six purified NER factors have a potential to eliminate the damage DNA from SV40 minichromosomes, the chromatin structure may still have some repressive effects on NER.

DNA Damage↗

[Excision of the duodenojejunal angle for tumor. From simple excision to locoregional excision].

Locoregional extensions are often observed in tumors of the duodenojejunal angle, either because of their anatomic situation or in cases diagnosed late. Endoscopic and radiographic explorations (basically abdominal CT scan) are indicated to search determine the degree of extensions to neighboring organs and vessels. Colic and mesocolic involvement are at the limit of preoperative explorations. Based on 4 observations of increasing complexity, we describe our operative strategy allowing tumor exeresis in a single block. Extension to the superior mesenteric artery is the main contraindication for exeresis.

Anastomosis, Surgical↗

Can intraductal breast carcinoma be excised completely by local excision? Clinical and pathologic predictors.

BACKGROUND: Microscopic evaluation of excised intraductal breast carcinoma (DCIS) specimens using a serial subgross technique reveals that in many patients the lesion is larger than expected, often making complete excision impossible with less than a true quadrantectomy. Data is presented on 181 patients with DCIS in whom the initial biopsy was performed using a more cosmetic wide local excision rather than a true quadrantectomy. METHODS: Clear margins were defined as no tumor within 1 mm of any inked or dyed margin. All of these patients subsequently underwent mastectomy or reexcision of the initial biopsy site. This allowed pathologic evaluation for residual disease. RESULTS: At mastectomy or reexcision, 76% of patients with initially involved margins had residual DCIS, as did 43% of patients with initially clear margins (P < 0.0001). Larger tumor size was a statistically significant predictor of initial margin involvement and residual DCIS (P < 0.05). Patients with comedo-DCIS had a greater tendency toward positive initial histologic margins and residual DCIS, but this trend was not statistically significant (P < 0.1). CONCLUSION: DCIS presents major problems to both surgeons and pathologists. It is difficult to excise completely using a wide local excision. Histologically negative margins do not guarantee that residual DCIS has not been left behind. Inadequate excision of the primary lesions may be the most important cause of local failure after conservative treatment for intraductal breast carcinoma.

Biopsy↗

Outcomes of re-excision after unplanned excisions of soft-tissue sarcomas.

BACKGROUND AND OBJECTIVES: Unplanned excisions of soft-tissue sarcomas of the extremities occur commonly. Our goal was to evaluate the presence of residual disease, the treatment outcomes as they relate to local and distant recurrence and 5-year survival, and the limb functional outcomes in patients with unplanned sarcoma excision who were treated with re-excision and adjuvant therapy. METHODS: Between 1993 and 1999, 42 patients presented to our institution after unplanned excision of soft-tissue sarcomas. Of those 42 patients, 38 without gross residual disease or metastatic lesions formed the basis of this review. All 38 patients underwent revision wide excision; most (31) also received adjuvant therapy (radiation and/or chemotherapy). Clinical data were obtained from analysis of patient records and radiographic studies. Univariate analysis was performed with logistical regression, and multivariate analysis was performed with Cox modeling. RESULTS: The overall 5-year survival rate was 91.3% and the disease-free 5-year survival rate was 82.2%. Univariate analysis showed that stage-III disease (American Joint Committee on Cancer classification of soft-tissue sarcomas), lesions below the fascia, a histologic high-grade, and the development of organ metastasis were statistically significant factors for mortality. Stage-III disease also was significant for mortality on multivariate analysis. Only stage-III disease was significant for the development of local recurrence. Eighty-four percent of the patients had good to excellent functional outcomes. CONCLUSIONS: Re-excision with adjuvant therapy proved to be a safe and effective method for treating the disease and preserving limb function.

Adolescent↗

A randomized study between excision and marsupialization and radiofrequency sinus excision in sacro-coccygeal pilonidal disease.

BACKGROUND: The surgical approach to pilonidal sinus disease is open to debate. This prospective, randomized study was aimed to compare the outcome of the excision and marsupialization and the sinus excision technique by radiofrequency. MATERIALS AND METHODS: Thirty patients of chronic pilonidal sinus disease were randomly assigned to radiofrequency sinus excision (n = 15) and excision and marsupialization (n = 15). The parameters measured included intraoperative and postoperative data, wound-related complications, and recurrence. Patient satisfaction score was assessed at 1-year follow-up. RESULTS: The operation time, postoperative pain, hospital stay, and off work periods were significantly less (p < 0.05) in the technique employing radiofrequency surgery. At 1-year follow-up, there was 1 case of recurrence in each group. The patients from radiofrequency group expressed better satisfaction than the patients operated by marsupialization. CONCLUSION: Radiofrequency sinus excision technique needs a shorter hospital stay with reduced postoperative pain and early resumption to work in comparison with the sinus excision and marsupialization technique.

Adolescent↗

Pilonidal sinus: how to choose between excision and open granulation versus excision and primary closure? Study of a series of 141 patients operated on from 1991 to 1995.

AIMS: The purpose of this study was to evaluate excision and open granulation versus excision and primary closure as treatments for pilonidal sinus. SUBJECTS AND METHODS: We evaluated a group of 141 patients operated on for a pilonidal sinus between 1991 and 1995. Ninety patients were treated by excision and open granulation, 34 patients by excision and primary closure and 17 patients by incision and drainage, as a unique treatment of an infected pilonidal sinus. RESULTS: The first group, receiving treatment of excision and open granulation, experienced the following outcomes: average length of hospital stay, four days; average healing time; 72 days; average number of post-operative ambulatory visits, 40; average off-work delay, 38 days; and average follow-up time, 43 months. There were five recurrences (6%) in this group during the follow-up period. For the second group treated by excision and primary closure, the corresponding outcome measurements were as follows: average length of hospital stay, four days; average healing time, 23 days; primary healing failure rate, 9%; average number of post-operative ambulatory visits, 6; average off-work delay, 21 days. The average follow-up time was 34 months, and two recurrences (6%) were observed during the follow-up period. In the third group, seventeen patients benefited from an incision and drainage as unique treatment. The mean follow-up was 37 months. Five recurrences (29%) were noticed, requiring a new operation in all the cases. DISCUSSION AND CONCLUSION: This series of 141 patients is too limited to permit final conclusions to be drawn concerning significant advantages of one form of treatment compared to the other. Nevertheless, primary closure offers the advantages of quicker healing time, fewer post-operative visits and shorter time off work. When a primary closure can be carried out, it should be routinely considered for socioeconomical and comfort reasons.

Adolescent↗

Thermal artefact after diathermy loop excision and laser excision cone biopsy.

Whether or not thermal artefact precludes accurate histopathologic assessment of excision biopsies of the uterine cervix is currently controversial. Some authors state that margins cannot be assessed at all while others feel that the pathologist can 'see through' the artefact in the majority of cases. Over a 7-month period, 164 patients had loop excision and 84 patients had laser cone biopsy. The zone of coagulation at the specimen periphery was measured and the adequacy of excision assessed. The average width for this zone of coagulation in diathermy loop was 0.32 mm and for laser cone biopsies was 0.31 mm. In 12% of the loop specimens the line of excision was compromised by dysplasia or its assessment was rendered uncertain by thermal artefact. This was far more common in fragmented specimens (20%) compared to those removed as a single specimen (6%). In this study, 40% of patients had fragmented loop specimens. Thus, in attempting to replace cone biopsy with loop excision, we are asking pathologists to reassemble a pathologic jigsaw, then look through the thermal artefact for a decision on margins. We believe that this fragmentation should preclude the use of loop excision for lesions which would previously have been managed by cone biopsy.

Journal Article↗

Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment.

OBJECTIVE: To quantify and analyse the influence of a histological report of incomplete excision of CIN after LLETZ on frequency of detection of residual CIN. DESIGN: Review of a computerised database of sequential women treated by LLETZ. Initial follow-up was three months post-treatment. SETTING: The Colposcopy Clinic, Regional Department of Gynaecological Oncology, Queen Elizabeth Hospital, Gateshead, Tyne and Wear, UK. SUBJECTS: 721 women with CIN diagnosed histologically on LLETZ specimens. RESULTS: In spite of a first time treatment success rate of 95% at 3 months, only 56% of the women were reported to have complete histological excision of CIN. A report suggesting incomplete excision was more likely with more severe CIN, extensive lesions and involvement of the endocervical canal. Furthermore, 21% with residual CIN had apparent complete excision of CIN at LLETZ. CONCLUSIONS: A histological report of incomplete excision of CIN at LLETZ does not equate with residual disease. The high treatment success rate of LLETZ means that a report of incomplete excision should stimulate close colposcopic and cytologic follow-up to identify the small number of women with residual CIN after therapy.

Carcinoma in Situ↗

Patterns of failure following local excision and local excision and postoperative radiation therapy for invasive rectal adenocarcinoma.

The clinical course of 40 patients undergoing conservative surgical excision and 26 patients undergoing local excision and postoperative radiation therapy of rectal carcinoma was reviewed. Surgical procedures were transanal excision (55 patients), Kraske procedure (ten patients), and fulguration (one patient). The five-year actuarial survival, disease-free survival, and local control of all 66 patients were 70%, 77%, and 63%, respectively. For patients undergoing local excision alone, the prognostic features of lesion size greater than 3 cm, poorly differentiated histology, invasion into muscularis propria or deeper, moderate to marked stromal fibrosis, vascular or lymph vessel invasion, fragmented resection, and positive resection margins were associated with a local failure rate of 20% or greater. Of the 26 patients receiving postoperative radiation therapy, four patients have developed local failure. For subgroups of patients with small rectal carcinomas confined to the mucosa, local excision may be a reasonable alternative to abdominoperineal resection. For tumors with deeper invasion but limited to the bowel wall, local excision plus pelvic irradiation can be offered to preserve anorectal function.

Adenocarcinoma↗

In vivo excision of a single targeted nucleotide from an mRNA by a trans excision-splicing ribozyme.

We have previously reported the development of a group I intron-derived ribozyme that can bind an exogenous RNA substrate and excise from that substrate an internal segment in vitro, which allows for sequence-specific modification of RNA molecules. In this report, the activity of this trans excision-splicing ribozyme in a cellular environment, specifically Escherichia coli, was investigated. The ribozyme was re-engineered to target for excision a single-base insertion in the transcript of a green fluorescent protein, and fluorescence was exploited as a reporter for trans excision-splicing. We show that the ribozyme is able to catalyze the trans excision-splicing reaction in vivo and can repair the mutant transcripts. On average, 12% correction is observed as measured by fluorescence and at least 0.6% correction as confirmed through sequence analysis. This represents the first report of a biomolecule (in this case a ribozyme) that can selectively excise a targeted nucleotide from within an mRNA transcript in vivo. This new class of biochemical tools makes possible a wide variety of new experimental strategies, perhaps including a new approach to molecular-based therapeutics.

Escherichia coli↗

Factors influencing the number needed to excise: excision rates of pigmented lesions by general practitioners.

OBJECTIVE: To identify doctor and patient characteristics associated with excision of benign versus malignant pigmented skin lesions. DESIGN, SETTING AND PARTICIPANTS: Retrospective audit of data on 4741 pigmented skin lesions excised from November 1998 to February 2000 by 468 general practitioners (39% response rate) from 223 practices in Perth, WA. (The data used were from the baseline period of a randomised controlled trial of a diagnostic aid for pigmented skin lesions.) MAIN OUTCOME MEASURE: The number needed to treat (NNT), defined as the number of pigmented lesions needed to be excised to identify one melanoma, in relation to demographic characteristics of GPs and patients. RESULTS: Relatively more benign lesions were excised per melanoma (NNT = 83) in the youngest patients (aged 10-19 years) compared with the oldest (aged > or = 70) (NNT = 11) (P [trend] < 0.001), in females (NNT = 37) compared with males (NNT = 23) (P = 0.02), and in the most socioeconomically disadvantaged (NNT = 60) compared with the least disadvantaged group (NNT = 20) (P [trend] < 0.001). The most recently graduated GPs excised more benign lesions for each melanoma (NNT = 59) than the least recently graduated (NNT = 22) (P [trend] = 0.01). CONCLUSIONS: GPs could raise their threshold for excising pigmented lesions in patients who are young, female, or from areas of low socioeconomic status, or if the GPs themselves are recent graduates.

Adolescent↗

Early surgical excision and grafting of burns including tangential excision.

Early excision and grafting of burns with the advent of infection control, has become a most important part of any successful therapy in burn management. By this technique, an open wound is primarily closed, and thus circumvents the possibility of infection. There is less discomfort, more rapid restoration of function, quicker discharge from hospital and earlier rehabilitation. Metabolic needs are lessened and with less scar, the cosmetic result is improved. Excision is made between the third and fifth day postburn if possible, but more delay may be necessary to determine which burns are superficial and able to spontaneously heal. No area greater than 10% of body surface area is excised and grafted at one operative session and for large burns staged excisions are necessary. A limitation of 1 1/2 hours on the operation is made so as to control shock and hypothermia and to assure a quick recovery with early re-establishment of nutrition. Ketamine is the common anaesthetic employed and viable fat is preferred as the surface on which to graft. Tangential excision is a complementary form of early excision grafting to a specific depth, and may be used alone or in conjunction with other techniques. It is of value in selected burns of the deep partial skin loss variety, especially scalds, which predominate in children. Several slices of necrotic skin are taken until a punctate bleeding surface is reached in the deep dermis and a thin to moderate thickness allograft is immediately applied. The conservation of the deep dermis limits the area to be grafted, with the likelihood of less scar formation and a resultant graft of improved texture.

Breast↗