Therapy for cervical intraepithelial neoplasia and fertility

BACKGROUND: We reviewed the case records of patients of childbearing age treated with various types of surgical techniques for cervical intraepithelial neoplasia (CIN) to determine the impact of surgical treatment on their fertility. METHODS: Between 1983 and 1997 a total of 486 women with CIN received surgical treatment at out unit. Laser vaporization was used in 196 cases, cold-knife conization in 163 and REP in 127. The outcome of the various treatments was then compared. RESULTS: Independent of the surgical technique used, the percentage of pregnancies achieved after surgery was high: 93.33 and 96.66% of patients treated with laser vaporization and REP, respectively, and 87.69% of those who received cold-knife conization. The differences did not reach statistical significance nor were significant differences observed in the number of abortions or in the method of birth delivery (spontaneous, Cesarean section). However, a higher percentage of premature births was noted among women who received cold-knife conization (31.57%), which was statistically significant in the comparison among the three groups. CONCLUSIONS: The results from our study indicated which techniques for the treatment of CIN may be preferable. Compared with the other two techniques, cold-knife conization bears higher costs (hospitalization, general anesthesia) and has been superceded by laser vaporization and REP as evaluated in this series. When cold-knife conization must be used, cerclage of the cervix uteri should be performed in the event of future pregnancy. In contrast, laser vaporization and REP can be performed in an outpatient setting with local anesthesia. These techniques, because they are conservative, afford the advantages of complete lesion removal and maintenance of reproductive capability. Another important consideration is that REP is less costly and allows histological examination of the surgical specimen.     

Conization of the cervix with the CO2 laser as an office procedure

Conization of the cervix is usually done under general anesthesia in an operating room. The use of the CO2 laser has been shown to reduce the high morbidity associated with cervical conization, but, like cold-knife conization, laser excisional procedures are still usually done in an operating room under general anesthesia. Forty-one patients underwent conization of the cervix with the CO2 laser in an office setting. The procedure was well tolerated, and intraoperative bleeding was not a problem. Two cases of delayed postoperative bleeding were treated on an outpatient basis. The ability to perform cervical conization in an office setting offers significant advantages.     

Cervical intraepithelial neoplasia III: long-term outcome after cold-knife conization with clear margins

OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia or squamous cell carcinoma in situ (CIN III) after cold-knife conization with clear margins. METHODS: A total of 4417 women (mean age 36, range 18-72 years) with histologically confirmed CIN III had cold-knife conization with clear margins at our institution between 1970 and 1994. All patients were followed up with colposcopy, cytology, and pelvic examination for a mean of 18 years (range 5-30years). RESULTS: New high-grade squamous intraepithelial lesions (SILs) (CIN II and III) developed in 15 (0.35%) patients (mean age 35, range 25-65 years) after a median of 107 (range 40-201) months. A total of 4402 (99.65%) patients (mean age 36, range 18-72 years) were free of high-grade SILs after a mean follow-up of 18 (range 5-30) years. High-grade glandular intraepithelial lesions developed in two (0.05%) patients 14 and 17 years after conization. Twelve (0.3%) patients had metachronous vulvar intraepithelial neoplasia (VIN) grade III or vaginal intraepithelial neoplasia (VAIN) grade III, and one (0.02%) patient had invasive vaginal carcinoma 10 years after conization. CONCLUSION: Cold-knife conization with clear margins was an adequate method to definitively treat CIN III.     

Cold-knife and laser conization for cervical intraepithelial neoplasia

In a 5-year study, 425 women had conization performed for cervical intraepithelial neoplasia (CIN) I, II or III. Conization was performed only in cases of positive endocervical curettage or when colposcopy was inconclusive. In all other cases, local destruction was the operation of choice. In the early years of the study, conization was done by the cold-knife method (N = 201), whereas CO2 laser was used in the latter part of the study (N = 224). Success and complication rates were the same for the two methods. Abnormal cytology after conization was found in a total of 53 cases (12.5%), but a histologic confirmation of residual or recurrent CIN was made in only 27 women (6.4%). This corresponds to a success rate of 92% after cold-knife and 95% after laser conization. The CIN grading of the residual or recurrent CIN was similar to or less than the CIN diagnosis of the cone. Because our success rate was comparable to that of other series with much less strict referral criteria, our policy seems adequate.     

Cold-Knife Conization versus Loop Excision: Histopathologic and Clinical Results of a Randomized Trial

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

Cervical intraepithelial neoplasia III: long-term follow-up after cold-knife conization with involved margins

OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia (CIN) III or squamous carcinoma in situ after cold-knife conization with involved margins. METHODS: A total of 390 patients (median age 39 years, range 20-69) with positive margins after cold-knife conization for CIN III were followed expectantly for a mean of 19 (range 6-30) years. Follow-up consisted of colposcopy, cytology, histology, and pelvic examination. RESULTS: Overall, 306 (78%) patients remained free of CIN III, and 84 (22%) had persisting or recurrent CIN III (n = 78) or developed invasive carcinoma (n = 6). Fifty-three patients had persisting CIN III (diagnosed within 1 year of conization), 25 developed recurrent CIN III after a median of 3 (range 2-28) years, five developed microinvasive carcinomas (at 3, 6, 7, 12, and 23 years), and one developed a stage IB carcinoma at 8 years. Persisting or recurrent disease was more common in patients in whom both the endocervical and the ectocervical cone margins were involved than in those in whom only the ectocervical or the endocervical margin was positive (52% versus 17% and 21%, respectively, P <.001). CONCLUSION: Expectant management is reasonable for patients with CIN III and positive margins after cold-knife conization. However, these patients require careful follow-up, particularly during the first year.     

Resection margins in conization as prognostic marker for relapse in high-grade dysplasia of the uterine cervix in northern Norway: a retrospective long-term follow-up material

OBJECTIVE: The main intention of the current study was to evaluate free resection margins in cervical conization specimens as prognostic marker by investigating the statistical association between clear or unclear resection margins of cervical cones and the risk of recurrence. METHODS: In a retrospective material, 459 women with moderate (CIN II) and severe dysplasia (CIN III) were included. Fifty of the patients were diagnosed with CIN II (10.9%) and 409 with CIN III (89.1%). Cold knife conization was performed in 371 (81%) patients, the rest were treated with CO(2) laser (19%). All the patients had been treated with conization between 1980 and 1984, follow-up time being from 19 to 23 years. Mean age of the patients was 35.2 years (range 18-81 years) at operation. The histopathological material and the results of the follow-up biopsies and smears were accessible as archival material. RESULTS: A total of 379 (82.6%) patients had clear margins in the primary operation specimens, in 80 patients margins were unclear (17.4%). There were three recurrences in the CIN II group (6%) and 39 (9.5%) in the CIN III group. Further there were 42 (9.2%) relapses in the total group, 36 relapses in the cold-knife group and 6 in the laser group. When univariate analysis was performed to investigate the statistical relation between the resection margins and recurrences, there was no significant correlation (P = 0.7, P > 0.05). Nor did variables like CIN group, surgical procedure, age at disease, age at recurrence, and years till recurrence prove to be predictors of relapses. CONCLUSION: In our material, the relation between free margins and relapse was not statistically significant. According to the literature-free resection margin is not an optimal prognostic criterion for recurrence. The search for new prognostic markers for high-risk cases are important to give these patients adequate therapy and avoiding over-treatment of the low risk groups.     

冷刀锥切术切缘阴性的重度宫颈鳞状上皮内瘤变患者的预后影响因素分析

目的探讨冷刀锥切术切缘阴性的重度宫颈鳞状上皮内瘤变（HSIL）患者的预后影响因素。方法回顾分析1999年1月至2004年1月间,卫生部北京医院妇产科266例冷刀锥切手术切缘阴性的HSIL患者的临床资料,分析影响预后的因素,并随访治疗结局。其中宫颈上皮内瘤变（CIN）II20例,CIN11246例（包括原位癌82例）;腺体累及者40例,无腺体累及者226例;257例检测高危型人乳头状瘤病毒（HPV）患者中,高危型HPV阳性244例,阴性13例。结果中位数随访时间46个月,总复发率为8．6％（23／266）,无浸润癌发生。CINⅡ患者中1例（5．0％,1／20）复发,CINⅢ患者（不包括原位癌）中9例（5．5％,9／164）复发,而82例原位癌中13例（15．8％,13／82）复发,原位癌与CINⅡ及CINⅢ（不包括原位癌）患者复发率比较,差异均有统计学意义（P〈0．05）。腺体累及者中7例（17．5％,7／40）复发,无腺体累及者中16例（6．0％,16／226）复发,两者比较,差异有统计学意义（P〈0．05）。高危型HPV阳性者中21例（8．6％,21／244）复发,而13例高危型HPV阴性者中无一例复发,两者比较,差异有统计学意义（P〈0．05）。结论冷刀锥切术切缘阴性的HSIL复发率低;病理分级高和腺体受累是影响疗效及预后的因素。     

Loop conization for the treatment of microinvasive carcinoma of the cervix

The purpose of the study was to evaluate the specimen adequacy and diagnostic accuracy of loop conization in microinvasive carcinoma of the cervix. A retrospective study was conducted from 1997 to 2003 at the Colposcopic Clinic, Department of Gynecology and Obstetrics, Chang Gung Memorial Hospital, Taipei, Taiwan. Sixty-three consecutive patients with microinvasive carcinoma of the cervix receiving cold-knife conization (35 patients) or loop conization (28 patients) were included in the study. All patients underwent definitive hysterectomy. We reviewed the conization specimen together with the hysterectomied uterus to compare the two conization techniques with respect to the histopathologic interpretation and diagnostic accuracy. The mean depth of cone specimens was significantly less in the loop conization compared with cold-knife conization (1.65 versus 2.35 cm, P = 0.035). Regarding the application of conization, the loop conization was completed in a single slice in 27 patients (77.1%) and in multiple slices in 8 patients (22.9 %), in spite of encouragement to perform conization in a one-pass application when possible. However, the cold-knife specimens were invariably a single cone-shaped piece. As reviewed by microscopic examination, the rate of tissue transection was significantly higher in the loop group than in the cold-knife group (14.3% versus 0%, P = 0.04). Because of tissue transection and disorientation, pathologic evaluation of stromal status was inadequate in 11.4% (4/35) of the loop cones as opposed to none of the 28 cold-knife cones. After assessing the hysterectomy specimens, the clinical diagnoses in the loop group were downgraded in three patients compared with only one in the cold-knife group. Data from this investigation suggest that cervical cold-knife conization is superior to loop conization as a method to assess microinvasive cervical cancer.     

Conization by carbon dioxide laser or cold knife in the treatment of cervical intra-epithelial neoplasia

In a randomized trial concerning 123 women with CIN, 59 were treated with laser conization under colposcope without further hemostatic remedy and 64 with cold knife conization guided by Schiller's iodine dyeing supported by side sutures, vaginal packing and postoperative oral administration of tranexam acid. Follow-up with colposcopy and cytology was done 3 and 12 weeks post-conization and then every 6 months. The average follow-up period was 36 months (28-48). Peroperative bleeding was rather less pronounced in the laser group. Postoperatively, however, bleeding requiring treatment was significantly less common in the laser group (5%) than in the cold knife group (17%). The recurrence rate of CIN was 7% in the laser group and 10% in the knife group. Stenosis of the cervical canal developed in 7% of the patients in the laser group and in 3.5% in the knife group. After 12 weeks the squamocolumnar junction was visible in its full extent in 66% of the laser treated patients compared with 38% of the cold knife treated patients. It is concluded that laser conization is a safe procedure even without hemostatic procedures other than the coagulation abilities of the laser beam itself, as used in this work.     

A study of diagnostic failure of loop conization in microinvasive carcinoma of the cervix

OBJECTIVE: The aim of this study was to evaluate the specimen adequacy and the histological interpretation of loop conization for microinvasive cervical carcinoma. METHODS: We retrospectively reviewed the histopathological findings of the original cone specimens together with the final hysterectomy specimens in patients with microinvasive carcinoma of the cervix. From 1990 to 1995, 63 consecutive patients with microinvasive carcinoma of the cervix were included in the study, of which 35 patients underwent loop conization and 28 underwent cold-knife conization. All patients had a hysterectomy. RESULTS: The mean width, depth, and cone volume of the conization specimens were 2.44 cm, 2.15 cm, and 3.96 cm3, respectively, in the loop group versus 2.3 cm, 2.35 cm, and 4.38 cm3 in the cold-knife group. No significant differences were seen between the two groups. The application of loop conization was completed in a single slice in 27 patients (77.1%) and multiple slices by the loop in 8 (22.9%), in spite of the attempt to perform conization in a one-pass application when possible. In assessing these cone specimens microscopically, the rate of transection of tissue was significantly higher in the loop cone than in the cold-knife cone (17.1% versus 0%, P = 0.02). Because of transection of tissue and misorientation, pathologic determination of the depth and width of stromal invasion was undetermined in two loop cone specimens compared with none in the cold-knife cones. CONCLUSION: Our study suggests that cold-knife conization is a preferred method in assessing microinvasive carcinoma of the cervix if multiple applications of loop conization are inevitable.     

Rational use of cryosurgery and cold knife conization for treatment of cervical intraepithelial neoplasia.

In recent years a variety of conservative treatment modalities are being used to remove Cervical Intraepithelial Neoplasia (CIN). A series of 568 cases of patients affected by CIN, detected in our Department over a period of 10 years and treated following a balanced use of colposcopy guided cryosurgery and cold knife conization, has been reviewed. One-hundred-fifty-three patients, 111 with CIN 1 and 42 with CIN 2, were treated by the use of a nitrous oxide cryoprobe. The remaining 415 patients underwent cold knife conization, under general anesthesia and hospitalization. Routine follow-up for all cases included cytology, colposcopy and aimed biopsy when required. Cryotherapy had a success-rate of 90.1% (CIN 1-CIN 2 only) and "complete" conization 94.6% (included CIN 3 cases). Complications of conization, such as late haemorrhage and cervical stenosis, were more frequent with the "open technique" than the "suture technique". Nine pregnancies after cryotherapy and 34 after conization have been reported, no significant differences were noted in the pregnancy outcome following either treatment.     

Laser conization for cervical intraepithelial neoplasias,grade III. Personal experience of 77 cases

BACKGROUND: Evalutation of the efficacy of laser conization for cervical high-grade squamous intraepithelial lesions (Hg-SIL). METHODS: A retrospective evaluation. Case collection: A total of 77 women, 47 outpatients and 30 inpatients with endocervical CIN3 or CIN2, were treated by carbon dioxide (CO2) laser between 1993 and 1995. A preoperative diagnosis has been made by means of Pap-smear, colposcopy and marked biopsy. In 47 cases a laser conization was performed in Day Surgery, without vessel constrictors or local anesthetics. In 30 cases a narcosis (Diprivan ) was induced. The former were discharged 2-3 hours and the latter 24 hours after treatment. RESULTS: The histological examination confirmed preoperative diagnosis in 64 (86.5%) cases and negligible one grade discrepancy was reported in 7 cases (6 over- and 1 underestimated); missed invasion and no free margins were reported in the remaining 4 and 2 patients respectively, so these latter 6 patients were submitted to other surgical procedures. No serious complications occurred with the exception of mild vaginal postoperative bleeding. During the follow-up of 36-82 months, cervical alterations were described only in 12 out of 71 cases, flat condilomatosy in 8 cases, CIN2 in 2 patients and CIN3 in other 2 patients. At present, all the patients are free of disease. CONCLUSIONS: The conization with dioxide laser is a good therapy for cervical intraepithelial neoplasia, even if expensive; infact poor side-effects are observed as well as a very good reliability.     

Laser surgery for cervical intraepithelial neoplasia

The laser has provided a relatively easy and safe method for treating all types of CIN. The advantages of lasers include great conservatism due to tissue sparing, great precision because of microsurgical method, combination of excisions and vaporization possible, suitable for therapy of multifocal disease, uncluttered field, and good hemostasis. Although other modalities have also been used successfully in the therapy of this disease, it appears that none are so versatile as CO2 laser or possess its ability to accurately treat the multifocal disease that may involve large surface areas of the lower reproductive tract. It seems unlikely that any of the cervical ablation methods--chemical destruction, hot cautery, diathermy electrode, cryoprobe, laser, and diathermy loop--will completely disappear from use in the near future. Ablation is an attractive alternative to cold-knife excision in properly triaged patients, since it is almost always an outpatient procedure done without anesthesia or with only local anesthesia. Most importantly, a large number of patients have completely visible lesions of a severity less than that of in situ cancer; they really do not need excisional conization by any technique and benefit by quick ablation of the transformation zone. A conization, to be diagnostic and therapeutic, must remove the entire transformation zone to the proper depth. This procedure is almost always attended by a higher morbidity rate than is simple ablation. Laser excisional conization and the large loop excision of the transformation zone procedure are similar in a number of respects, because the operator must have certain capabilities and a through understanding of the disease to be treated to perform the operation correctly.     

Cervical conization: cold knife and laser excision in residency training.

During a 2-year period, 293 consecutive conizations performed by residents in obstetrics and gynecology were reviewed. One hundred sixty-one patients underwent laser excision and 132 women were treated by cold knife conization. Average operating times for laser excision and knife conization were 31 and 33 minutes, respectively. Combined minor and major complication rates for laser and knife cones were 19 and 30%, respectively. Major complications including cervical stenosis and heavy bleeding were seen in 20% of knife conizations and 6% of laser excisions. Average blood loss for knife conization was 65 mL, and average blood loss for laser conization was 34 mL. Among those examined in follow-up with cervical cytology and colposcopy, no patient in the laser excision group showed evidence of persistent dysplasia, compared with one patient (3%) in the knife conization group. The reported data suggest no difference in operating time, length of anesthesia, or success of treatment between laser excision and knife conization performed by residents in training. Fewer complications were seen in the laser excision group.     

CO2 laser vaporization in the treatment of cervical human papillomavirus infection in women with abnormal Papanicolaou smears.

In a randomized study, we have evaluated the treatment of cervical human papillomavirus (HPV) lesions by CO2 laser vaporization. Fifty patients with abnormal Papanicolaou smears and histological evidence of cervical HPV infection associated or not with cervical intraepithelial neoplasia (CIN) grade I were randomized to either a treatment or a control group. The cervical swabs were obtained every 3 months in both groups and examined for HPV type 16 DNA by the polymerase chain reaction. After a follow-up period of 12 months no significant differences were found between the laser treatment and the control groups in relation to the disappearance of the abnormal Papanicolaou smear. Two patients in the treatment group and 3 in the control group had a conization because of development of CIN I or aggravation of the concomitant CIN found at the initial visit. The percentage of women who demonstrated HPV in their cervical smears at 12 months' follow-up was identical in the two groups, supporting the hypothesis that HPV is a persistent infection during which the virus is widespread in the vaginal epithelium.     

Clinical significance of a negative loop electrosurgical excision procedure, conization and hysterectomy for cervical intraepithelial neoplasia

PURPOSE OF INVESTIGATION: The absence of cervical intraepithelial neoplasia (CIN) in a loop electrosurgical excision procedure (LEEP), cold-knife conization and hysterectomy for treatment of CIN is an occasional finding of uncertain clinical significance. The aim of this study was to estimate the frequency of a negative procedure and its relationship to disease recurrence. METHODS: A retrospective study was conducted on 263 specimens from women submitted to the LEEP (n = 142), conization (n = 101) or hysterectomy (n = 20) due to CIN. RESULTS: The frequency of negative conization, LEEP and hysterectomy were, respectively, 15.5%, 19.8% and 25%. Recurrence occurred from 16 to 44 (median = 42) months in women with negative surgical specimens (LEEP or cold knife conization), and after five to 31 (median = 20) months after histological findings of CIN in surgical specimens, respectively, 7.1% and 11.2%. CONCLUSION: The absence of CIN in those procedures of biopsy-confirmed CIN is a not an uncommon finding. Patients with positive or negative specimens should be carefully followed.     

子宫颈锥切术切缘阳性的相关因素分析

目的 分析宫颈锥切术后切缘阳性的相关因素.方法 回顾性分析2000年1月至2008年2月经阴道镜宫颈活检诊断为宫颈上皮内瘤变(CIN)并接受宫颈锥切术的患者1699例,对患者年龄、病变程度、病变范围、手术方式及是否绝经与宫颈锥切术切缘阳性率作单因素和多因素分析.结果 1699例宫颈锥切术患者中,切缘阳性者238例,阳性率为14.01%.切缘阳性者平均年龄(39±9)岁,切缘阴性者平均年龄(39±8)岁,两者比较,差异无统计学意义(P>0.05).行冷刀锥切术者788例,切缘阳性率8.63%(68/788);行环形电极切除术(LEEP)者911例,切缘阳性率18.66%(170/911),两者比较,差异有统计学意义(P<0.01).CIN Ⅰ者90例,CIN Ⅱ者339例,CIN Ⅲ者1113例[其中重度不典型增生972例,原位癌(CIS)141例],宫颈癌Ⅰ al期87例,Ⅰ a2期及以上70例,切缘阳性率分别为1.11%(1/90)、3.83%(13/339)、10.70%(104/972)、26.24%(37/141)、35.63%(31/87)和74.29%(52/70),CIN Ⅰ与CINⅡ者比较,差异无统计学意义(P>0.05);将CIN Ⅰ与CINⅡ者合并计算,并与CIN Ⅲ、宫颈癌Ⅰ a1期、Ⅰ a2期及以上者之间比较,差异均有统计学意义(P<0.05).未绝经者1569例,切缘阳性率为13.38%(210/1569);已绝经者130例,切缘阳性率为21.54%(28/130);两者比较,差异有统计学意义(P=0.010).多因素logistic回归分析发现,手术方式、病变程度、病变范围、宫颈外观、是否绝经是与切缘阳性高度相关的因素,相对危险度分别为5.147、3.048、1.271、1.905和1.860.结论宫颈病变程度严重、病变范围大、LEEP、绝经后是宫颈锥切术切缘阳性的高危因素,在制定宫颈锥切手术方式时应予以重视.     

Relation between vaginal and endocervical pH in patients undergoing cold-knife conization and hysterectomy

Objective This study aimed to investigate the influence of endocervical pH on vaginal pH, and also the changes in these pH values following hysterectomy and cold-knife conization. Vaginal pH is important for maintaining the equilibrium of the vaginal microflora. Patients and methods Two groups of women were studied: the first (n = 20, median age 45, range 33–50 years-old), before and after hysterectomy (without ovariectomy) for myomatosis; the second group (n = 18, median age 38.5, range 37–65 years-old), before and after cold-knife conization for cervical intraepithelial neoplasia (CIN) grade II or III. Four samples (before and 90 days after surgery) were collected from the women by means of swabs: (1) anterior vaginal fornix, (2) posterior vaginal fornix, (3) posterior wall of lower vagina, and (4) endocervix (except in cases after hysterectomy). The pH was measured using a digital pHmeter (Sentron). Results We observed that endocervical pH was less acidic than were all the vaginal locations measured, before both surgeries. After both surgeries, all vaginal pH measurements were higher, but without reaching statistical significance. Endocervical pH correlated with vaginal pH. Conclusions We concluded that recent hysterectomy does not alter vaginal pH and that vaginal and endocervical pH values are related.     

Laser conization: follow-up in patients with cervical intraepithelial neoplasia in the cone margin

Combination laser conization was performed in 469 patients for the treatment of cervical intraepithelial neoplasia (CIN). In 58 cases (12.4%), CIN was located in the margins of the cone. Fifty-one patients with involvement of the margins were evaluated by cytologic examination, using the Ayre spatula and the Cytobrush, and by cervical biopsy and endocervical curettage (ECC). In six cases, the histologic evaluation was positive, and in three of these cases, the cytology was positive too. Hysterectomy was performed in five cases, but in only one case was a significant lesion demonstrated in the uterus. These results justify expectant, conservative management of patients treated with combination laser conization. Follow-up based on colposcopy and cytology seems sufficient.