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Preoperative predictors of positive margins after loop electrosurgical excisional procedure-Cone.

OBJECTIVE: A LEEP-Cone may not be necessary for all patients with traditional cone indications. This study defines populations where a single pass technique with the LEEP is appropriate. METHODS: We retrospectively reviewed patients undergoing LEEP-Cone procedures performed at the University of Oklahoma Health Science Center from February of 1994 to July of 2002. Patients include those for LEEP-Cone with traditional excisional indications and those who underwent LEEP-Cone at the operating physician's discretion. Statistical analysis was used to compare preoperative factors with the resultant pathologic results. RESULTS: A total of 248 women underwent LEEP-Cone. 50.0% (33/66) of the patients with positive margins on the first pass had dysplasia or worse (CIN I-III or CA) in the second pass (top hat), compared to 6.6% (12/182) of the patients with a negative first pass (P < 0.0001). Univariate analysis found CIN III on histology and parity to be predictive of dysplasia in the top hat and two-step discrepancy to predict absence of dysplasia. On multivariate analysis, two-step discrepancy and parity remained predictive. Age >35 was the greatest percentile predictor of dysplasia in the top hat, and 91.5% of women <21 had normal top hat pathology. CONCLUSION: The retrospective data reported regarding LEEP-Cones reveal increased parity to predict dysplasia in the top hat and two-step discrepancy as a poor predictor of dysplasia in the top hat. Women under 21 years of age should have a single pass LEEP technique. The "top hat" is more appropriate as parity and age increase.

Adult↗

Endocervical glandular involvement is associated with high-grade SIL.

OBJECTIVE: To examine whether endocervical glandular involvement (EGI) by squamous intraepithelial lesions (SIL) is associated with the grade of the squamous lesion and to assess the usefulness of such association for diagnostic purposes. METHODS: Histologic sections from two hundred successive cases of cervical SIL were reviewed retrospectively from the archives of the Department of Pathology of a tertiary care medical center. RESULTS: Nine of 93 (9.7%) low-grade lesions and 41 of 107 (38.3%) high-grade lesions showed glandular involvement (P = 0.001, Chi-squared test). The relative risk of having EGI in high-grade lesions as compared to low-grade lesions was 3.95. CONCLUSION: EGI is seen approximately four times more frequently in high-grade SIL than in low-grade SIL. Therefore, in cases that are difficult to grade, the presence of EGI is in favor of the lesion being a high-grade SIL.

Conization↗

Impact of therapy for cervical intraepithelial neoplasia on fertility.

Cervical intraepithelial neoplasia is endemic in young American women. Because the majority of these women have a strong desire to maintain fertility, the efficacy of treatment modalities for this condition must be weighed against potential negative effects on fertility. Except for cone biopsy, however, the peer-reviewed literature provides little information about the effects of such techniques on fertility. While there are no data demonstrating that the other commonly used therapies (loop electrical excision procedure, cryotherapy, laser vaporization, and diathermy cautery) have a negative impact on fertility, neither has it been definitively proved that they do not have an untoward impact on fertility. Thus further studies are needed, and patients should be educated regarding the limitations of available information when informed consent for treatment is obtained.

Cervix Uteri↗

Treatment of cervical carcinoma in situ in HIV positive women.

OBJECTIVES: To evaluate the safety and effectiveness of hysterectomy vs. cone biopsy in HIV seropositive patients with carcinoma in situ of the cervix (CIS). METHODS: We performed a retrospective case-control study of all HIV seropositive patients diagnosed with carcinoma in situ of the cervix from 1989 to 1995. A control group of HIV(-) women with CIS was also ascertained matched for date of diagnosis of CIS, race and age. RESULTS: There were 439 patients with CIS, of which 45 were HIV seropositive (10.3%). Nine were treated by hysterectomy, 30 by cone biopsy, and six remained untreated. Overall, 63% of HIV(+) patients did not receive any follow-up Pap smear (44% of hysterectomy patients, 50% of cone biopsy patients, and 83% of untreated patients; chi(2) P=0.41). According to Pap smear results, 67% (10/15) cone biopsy patients and 60% (3/5) hysterectomy patients had an abnormal Pap smear after treatment (P=0.9). Median time to recurrence was 12 months in hysterectomy patients vs. 14 months in cone biopsy patients. Deaths occurred in 22% of hysterectomy patients, 17% of cone biopsy patients, and 50% of untreated patients, none due to cervical cancer. Median time to death from presentation was 27.5 months for hysterectomy patients, 11 months for cone biopsy patients, and 7 months for untreated patients (P<0.05). There were no complications in the hysterectomy group, however, two patients were readmitted after cone biopsy for bleeding. When compared to HIV(-) women with CIS, HIV(+) patients were more likely to be treated by hysterectomy (chi(2) P=0.01). CONCLUSION: All patients diagnosed with CIS should be counseled regarding HIV prevention and testing because of a significant seropositive rate. Compliance with gynecologic follow-up is very poor in this patient population. Special efforts should be made to enhance compliance. Cone biopsy and hysterectomy appear to be equally safe and effective in the treatment of CIS. CIS in HIV patients is a poor prognostic indicator for death from any cause.

Adolescent↗

One-step management of cervical lesions.

OBJECTIVE: To test the value of diagnosing and treating cervical lesions at the first colposcopic visit using large loop excision of the transformation zone (LLETZ) based on abnormal colposcopic findings as compared with punch biopsies followed by subsequent therapy accordingly. PATIENTS AND METHODS: Among 1255 patients with a clinically suspicious cervix, 119 patients with abnormal and satisfactory colposcopy were divided into two groups. In group A (53 patients) multiple cervical punch biopsies were taken. In group B (66 patients), LLETZ under local paracervical anesthesia was done. RESULTS: Cervical intraepithelial neoplasia was diagnosed in 25 and 29 cases, condyloma acuminatum in seven and six cases, granulomatous cervicitis including tuberculous and bilharzial cervicitis was diagnosed in two and four cases in groups A and B, respectively. Endocervical adenocarcinoma was diagnosed in two cases in group B whereas microinvasive squamous cell carcinoma was diagnosed in one case in each group. Histopathologic assessment of the specimens obtained in group B revealed minimal coagulation artifact, adequate biopsies and free margins in all but three cases (4.5%) who needed further treatment by hysterectomy. In group B, only one case was complicated by a second hemorrhage and the overtreatment rate was 30.3%. On follow-up visits 20 patients (38%) and 59 patients (89%) were satisfied with the procedure in both groups, respectively. Further treatment was required in 29 cases in group A (55%) after initial assessment of punch biopsies and in three cases in group B (4.5%). Persistent abnormal colposcopic findings at follow-up visits 3 months after diathermy coagulation were seen in five patients (9.4%) in group A. CONCLUSIONS: LLETZ at the first colposcopic visit is a practical and fast method of treating most cervical lesions with limited complications and has the advantage of eliminating a second session of treatment. These advantages, particularly in developing countries, may outweigh the high overtreatment rate of this procedure. Many cervical lesions can be properly treated using large loop excision of the transformation zone at the first colposcopic visit. This may help save time and resources, especially in developing countries.

Adult↗

Risk factors for early cytologic abnormalities after loop electrosurgical excision procedure.

OBJECTIVE: To evaluate risk factors for early cytologic abnormalities and recurrent cervical dysplasia after loop electrosurgical excision procedure (LEEP). METHODS: A retrospective analysis was performed of all pathology records for LEEPs performed at our institution from January 1996 through July 1998. Follow-up cytology from 2 through 12 months after LEEP was reviewed. Patients with abnormal cytology were referred for further colposcopic evaluation. Statistical analysis using chi2 test for trend, proportional hazards model test, Fisher exact tests, and life table analysis were performed to identify risk factors for early cytologic abnormalities after LEEP and to determine relative risk of recurrent dysplasia. RESULTS: A total of 298 women underwent LEEP during the study period, and 29% of these had cytologic abnormalities after LEEP. Grade of dysplasia, ectocervical marginal status, endocervical marginal status, and glandular involvement with dysplasia were not found to be independent risk factors for early cytologic abnormalities. However, when risk factors were analyzed cumulatively, the abnormal cytology rate increased from 24% with no risk factors to 67% with three risk factors present (P =.037). Of patients with abnormal cytology after LEEP, 40% developed subsequent dysplasia, and the mean time to diagnosis was approximately 6 months. The relative risk of subsequent dysplasia ranged from a 20% increase to twice the risk if post-LEEP cytology was low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion, respectively. CONCLUSION: Based on these results, consideration should be given for early colposcopic examination of patients who have evidence of marginal involvement or endocervical glandular involvement with dysplasia. These patients are at increased risk for abnormal cytology and recurrent dysplasia. This initial visit should occur at 6 months, as the mean time to recurrence of dysplasia was 6.5 months.

Carcinoma, Squamous Cell↗

A stiff bristled, spiral-shaped ectocervical brush: a device for transepithelial tissue biopsy.

OBJECTIVE: To compare a new spiral-shaped tissue-sampling brush with a standard cervical punch biopsy. METHODS: Before large loop excision of the transformation zone, women with cervical intraepithelial neoplasia underwent a transepithelial brush biopsy of a portion of a colposcopically identified lesion, followed by a punch biopsy of the remaining portion. Brush biopsy samples were processed using liquid-based cytology and cell block techniques. Diagnoses were made using a consensus of three pathologists. Brush biopsy samples without basal cells were considered inadequate. The histological diagnosis was compared with the brush biopsy and punch biopsy samples. Patient-reported pain and physician-reported bleeding for punch and brush biopsies were compared. RESULTS: Fifty-two women were enrolled in the study; 47 successfully completed the study protocol. Eight brush biopsy specimens were inadequate. Thirty-nine women showed abnormal pathology (human papillomavirus/cervical intraepithelial neoplasia I or worse) on large loop excision of the transformation zone, and 32 women had high-grade (or worse) lesions. The punch biopsy correlated with high-grade disease in 53.1% of these women. The brush biopsy result correlated with high-grade disease in 79.3% of these women using a cell block technique and 76.7% using liquid cytology. There was significantly less pain (P <.001) and significantly less bleeding (P <.001) with the brush biopsy. CONCLUSION: When an adequate sample is collected, spiral brush biopsy is as good as a standard punch biopsy for detecting cervical pathology, with substantially less pain and bleeding. User training and guidelines for sampling are needed to assure that an adequate sample is collected.

Adolescent↗

Immunohistochemical expression of laminin-5 in cervical intraepithelial neoplasia.

OBJECTIVES: Laminin-5 is an attachment protein for epithelial cells. Several studies of a variety of cancers have reported increased expression of laminin-5 in carcinoma in situ and invasive cancer. This study was designed to investigate the correlation between the grade of cervical intraepithelial neoplasia and the immunohistochemical expression of laminin-5 in the cytoplasm and in the basement membrane underlining dysplastic squamous cells. METHODS: We used immunohistochemical methods to stain paraffin-embedded sections of cervical cone biopsies with a monoclonal antibody specifically targeting the 2-chain of human laminin-5 protein. The study sample included 175 slides: 7 normal cervical epithelium, 36 lesions of mild dysplasia, 50 lesions of moderate dysplasia, 81 lesions of severe dysplasia, and 1 invasive squamous cell carcinoma. RESULTS: We found a statistically significant correlation between the grade of cervical intraepithelial neoplasia and laminin-5 immunoreactivity in the cytoplasm (P < 0.01) and in the basement membrane (P = 0.03) by use of the Wilcoxon rank-sum test. CONCLUSIONS: According to previously published reports we confirmed with a higher number of cases a correlation of laminin-5 expression in the cytoplasm and/or basement membrane and grade of dysplastic lesion in the cervical epithelium. This study warrants further investigations with special interest to follow-up to investigate whether laminin-5 is a marker to predict the risk of progression of cervical intraepithelial neoplasia lesions.

Adolescent↗

Office procedures. Electrosurgical loop excision of the cervix.

This article discusses the technique of cervical electrosurgical loop excision, which allows for treatment of premalignant conditions of the cervix. The primary goal of cervical loop excision is to provide a method of managing preneoplastic cervical conditions in a safe, effective manner while minimizing the chance of missing invasive cancer. Topics discussed include equipment and supplies, procedural pearls, complications, and so forth.

Conization↗

Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis.

BACKGROUND: Conservative methods to treat cervical intraepithelial neoplasia and microinvasive cervical cancer are commonly used in young women because of the advent of effective screening programmes. In a meta-analysis, we investigated the effect of these procedures on subsequent fertility and pregnancy outcomes. METHODS: We searched for studies in MEDLINE and EMBASE and classified them by the conservative method used and the outcome measure studied regarding both fertility and pregnancy. Pooled relative risks and 95% CIs were calculated with a random-effects model and interstudy heterogeneity was assessed with Cochrane's Q test. FINDINGS: We identified 27 studies. Cold knife conisation was significantly associated with preterm delivery (<37 weeks; relative risk 2.59, 95% CI 1.80-3.72, 100/704 [14%] vs 1494/27 674 [5%]), low birthweight (<2500 g; 2.53, 1.19-5.36, 32/261 [12%] vs 905/13 229 [7%]), and caesarean section (3.17, 1.07-9.40, 31/350 [9%] vs 22/670 [3%]). Large loop excision of the transformation zone (LLETZ) was also significantly associated with preterm delivery (1.70, 1.24-2.35, 156/1402 [11%] vs 120/1739 [7%]), low birthweight (1.82, 1.09-3.06, 77/996 [8%] vs 49/1192 [4%]), and premature rupture of the membranes (2.69, 1.62-4.46, 48/905 [5%] vs 22/1038 [2%]). Similar but marginally non-significant adverse effects were recorded for laser conisation (preterm delivery 1.71, 0.93-3.14). We did not detect significantly increased risks for obstetric outcomes after laser ablation. Although severe outcomes such as admission to a neonatal intensive care unit or perinatal mortality showed adverse trends, these changes were not significant. INTERPRETATION: All the excisional procedures to treat cervical intraepithelial neoplasia present similar pregnancy-related morbidity without apparent neonatal morbidity. Caution in the treatment of young women with mild cervical abnormalities should be recommended. Clinicians now have the evidence base to counsel women appropriately.

Adult↗

Risk factors for cervical stenosis after laser cone biopsy.

OBJECTIVE: To evaluate the incidence of cervical stenosis after laser cone biopsy and to identify risks factors for this adverse outcome. METHODS: Prospective study evaluating all patients (n = 375) treated by laser cone biopsy for suspected cervical intraepithelial neoplasia between 1 January 1990 and 31 December 1996. Patients were contacted by mail for a clinical evaluation, 37 +/- 26 months after surgery. Two hundred and thirty-eight patients (63%) reply to this clinical follow-up examination including colposcopy, cervical smear and evaluation of cervical stenosis. Cervical stenosis was defined as cervical os narrowing preventing the insertion of a cotton swab. RESULTS: Forty patients (16.8%) had cervical stenosis at follow-up. The risk of postoperative cervical stenosis increases when patients were older (mean age of women with stenosis 42 years versus 35 years; P < 0.0001), when the depth of surgical excision increases (mean surgical specimen height 18.2 mm in women with stenosis versus 15.9 mm; P < 0.01), when preoperative junction was endocervical (2.5; 95% confidence interval (CI) 1.4-4.7), when vaginal packing was necessary (2.4; 95% CI 1.4-4.2), and when continuous laser mode was used (2.1; 95% CI 1.2-3.7). Stenosis incidence was lower when human papilloma virus (HPV) was present on cervical biopsy (0.47; 95% CI 0.3-0.8), when women were smokers (0.48; 95% CI 0.3-0.9), and when a Surgicel compress was placed in the excision site (0,4; 95% CI 0.2-0.8). Patient age was the only significant independent predictor of stenosis identified by a multivariate analysis using logistic regression. CONCLUSIONS: Patient with advanced age should be counselled regarding the risks for cervical stenosis after laser cone biopsy. Other surgical options may be considered when patient age exceeds 40 years.

Adult↗

Evaluation of cervical dysplasia treatment by large loop excision of the transformation zone (LLETZ). Does completeness of excision determine outcome?

OBJECTIVES: To evaluate the therapeutic and diagnostic potential of large loop excision of the transformation zone (LLETZ) in the management of cervical dysplasia (CD) when colposcopy is satisfactory; to determine if there is a relationship between completeness of excision and outcome. STUDY DESIGN: Ninety loop diathermies performed in the management of CD were studied prospectively. RESULTS: Eighty (88.89%) were indicated due to a high grade CD, 7 (7.78%) due to a low grade CD and 3 LLETZ (3.35%) due to a cytology-biopsy discordance. The margins were free of disease on 69 occasions (76.67%); on 15 (16.67%) the margins were affected by the disease and on 6 (6.67%) they were not evaluable. Using the Kaplan-Meier approach to survival analysis, the cumulative probability of continuing free of disease at the end of our study (36 months) was 0.89. In the margins free of disease group, patients stayed free of disease for an average of 32.98 months, and the cumulative probability of continuing free of disease at 36 months was 0.97. In the affected-margins group, patients stayed free of disease for an average of 20.91 months and the cumulative probability of continuing free of disease at 36 months dropped to 0.70. In the unevaluable-margins group, patients stayed free of disease for an average of 19.50 months and the cumulative probability of continuing free of disease at 36 months dropped still further to 0.67. Applying the Mantel-Cox Log-Rank Test we obtained differences among these three groups that are statistically significant (P<0.005). CONCLUSIONS: LLETZ could be considered the treatment of choice for CD when colposcopy is satisfactory, as it is effective, simple, fast, inexpensive, unaggressive, and of low morbidity. It also permits adequate pathology reporting. When a pathology report states that the margins of the specimen are not free of disease or are not evaluable, special caution in follow-up may be warranted.

Adult↗

Recent problems with paracervical vasopressin: a possible synergistic reaction with nicotine.

Vasopressin is now commonly used to control bleeding during surgery of the cervix. In larger intravenous doses, vasopressin can cause coronary artery vasoconstriction and increase systemic vascular resistance. Nicotine has a similar effect on the coronary circulation. The effects of combining both these drugs has not been studied. We describe a 22-year-old woman who developed severe hypotension and bradycardia after receiving a small dose of paracervical vasopressin. She was using a transdermal nicotine patch at the time of her surgery. We suspect her cardiac problems, and recently reported cardiac events in other women receiving small doses of paracervical vasopressin, could be caused by a synergism of the vasoconstrictive properties of nicotine and vasopressin. Caution is urged when vasopressin is to be administered to patients who smoke or use nicotine transdermal patches.

Administration, Cutaneous↗

Noninvasive cervical cancer complicating pregnancy.

The management of abnormal cytology during pregnancy has changed dramatically during the last 3 decades. The goal has been and remains timely diagnosis of and treatment planning for invasive carcinoma of the cervix. Because therapy for preinvasive disease can safely be postponed until the postpartum period, the ability to distinguish CIN from invasive cancer without cone biopsy has been a major step forward in the management of cervical disease in pregnancy. The data presented herein demonstrate the safety and accuracy of the more conservative approach of colposcopy and biopsy. The use of cone biopsy during pregnancy, associated with substantial morbidity, has been significantly reduced by the diligent application of colposcopy. As is true in the nonpregnant state, cone biopsy is necessary when colposcopic examination is nonsatisfactory. Cone biopsies cannot be considered therapeutic during pregnancy owing to the high incidence of positive margins and residual disease on postpartum evaluation. For this reason, the importance of postpartum reevaluation cannot be overemphasized.

Cervix Uteri↗