Laser and cryo surgery for cervical intraepithelial neoplasia. A randomized trial with longterm follow-up. Cryotherapy and carbon dioxide laser management of cervical intraepithelial neoplasia: a controlled comparison. Laser or cryotherapy for cervical intraepithelial neoplasia: a randomized study to compare efficacy and side effects. One-Session Management of Cervical Intraepithelial Neoplasia: A Solution for Developing Countries. A Prospective, Randomized Trial of LEEP versus Laser Excisional Conization A randomised clinical trial of loop electrosurgical excision procedure (LEEP) versus cryotherapy in the treatment of cervical intraepithelial neoplasia. Outpatient excisional management of cervical intraepithelial neoplasia. A prospective, randomized comparison between loop diathermy excision and laser excisional conization. Laser vaporization versus laser excision conization in the treatment of cervical intraepithelial neoplasia. Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial. Conization by carbon dioxide laser or cold knife in the treatment of cervical intra-epithelial neoplasia.
In a randomized study, 204 patients with exocervical intra-epithelial neoplasia were allocated to either laser evaporation (103) or cryocoagulation (101). The patients were treated on an outpatient basis without anesthesia. In the case of initial treatment failure the same method was to be used for retreatment. One hundred and eighty-seven patients were followed-up for an average of 50 months (12-80). Eighty-six of 94 laser-evaporated patients (91%) and 89 of 93 cryocoagulated patients (96%) were cured after one treatment. Five of 8 laser failures and 3 of 4 cryo failures were cured by retreatment. The cure rate after one or two laser evaporations was 97% (91 of 94 patients), and after one or two cryo coagulations, 99% (92 of 93 patients). Eighty per cent of residual or recurrent neoplasia occurred within 15 months and 96% within 2 years of treatment. No invasive neoplasia occurred during the follow-up period and no tendency was seen towards higher grades of intra-epithelial neoplasia in the failures compared with the initial diagnoses. It is concluded that laser evaporation and cryocoagulation are equally effective for the treatment of exocervical intra-epithelial neoplasia. Two hundred patients with cervical intraepithelial neoplasia were treated alternately by cryotherapy and carbon dioxide laser therapy on an outpatient basis after appropriate triage with colposcopy, cervical biopsy, and endocervical curettage. Results of treatment were not significantly different from one another, with failure occurring in 7% of patients treated with cryotherapy and 11% of those treated with carbon dioxide laser therapy. The cryotherapeutically treated patients had less pain but more discharge than those treated by the carbon dioxide laser. The laser patients' cervices healed more rapidly than did the cervices treated with cryotherapy. There appears to be no advantage in replacing cryotherapy with carbon dioxide laser therapy. A randomized study was performed to compare efficacy and side effects of laser and cryotherapy: 51 patients were treated with laser vaporization and 50 patients with cryotherapy. Success rates for laser and cryotherapy were not significantly different. Success rates were significantly related to lesion size. Grade of CIN, positive endocervical curettage, parity, and age at treatment were not found to be related. Vaginal discharge, both in duration and amount, was significantly less in patients treated with laser vaporization, compared with cryotherapy, but pain and bleeding occurred more often in patients treated with laser vaporization. A brief review of possible sources of bias in comparative studies on laser and cryotherapy is given, indicating the preference for a randomized study. It is concluded that widespread introduction of laser facilities in smaller centers is not justified, because the success rates are not better than those of cryotherapy, and because the advantages of less discharge are outweighed by the high cost. Six hundred thirty-nine patients with CIN on referral Pap were evaluated cytocolposcopically at the first visit and decided whether to be treated the same day or not. One hundred ninety-two patients (30%) were considered negative. Follow-up evidenced later appearance of CIN in five of them. One hundred fifty-three (24%) were candidates for delayed treatment due to conditions contraindicating same-day treatment. Two hundred ninety-four patients (46%) were randomly allocated in LEEP (149) or excisional laser (145) arms, and treated the same day under local anesthesia. Both arms were comparable. There were three microinvasive carcinomas diagnosed in the surgical specimen. LEEP was faster and produced less bleeding than laser, although required a mean of four slices to remove the lesion. Arterial hypertension after anesthetic infiltration was detected in 26% of cases. Two intraoperative and two delayed bleeders required surgery. The size of lesion and surgical defect were larger than those reported in the literature. Margins were involved in 8 patients (2.7%). Only 4.7% (7/149) of patients randomized to LEEP and 3.4% (5/145) with excisional laser had persistent or recurrent CIN on follow-up. Factors predisposing to failure included depth of surgical defect, grade of lesion, and operator's expertise. With this approach, 69% of patients referred for cytology of CIN were adequately managed in the first visit, which contrasts to classical management that reaches the state of treatment in 30% of patients. LEEP appears to be faster, less costly, and requires less expertise. Its use in conjunction with adequate screening is recommended for developing countries. The objective of the treatment of cervical intraepithelial neoplasia (CIN) is the prevention of invasive carcinoma of the cervix, which still remains the most common cancer in Zimbabwean women, as in most other low-resource countries where screening facilities are grossly inadequate. We conducted a randomised prospective study to compare CIN treatment outcome after cryotherapy and loop electrosurgical excision procedure (LEEP) in 400 women with histologically confirmed high grade squamous intra-epithelial lesions (HGSIL). Treatment outcome measures were immediate complications, persistent disease and recurrent disease evaluated at follow-up visits. Eighty-two per cent of the women (159 cryotherapy, 168 LEEP) completed their 6-month and 12-month follow-up visits. LEEP had a significantly higher overall cure rate of 96.4% (absence of persistent or recurrent disease) compared to 88.3% cryotherapy (P=0.026). Although cryotherapy was not superior to LEEP, its cure rate (88.3%) is acceptable and therefore provides a viable treatment option for low resource countries such as Zimbabwe where the majority of women at risk for cervical cancer reside in rural areas. The purpose of our study was to compare loop diathermy excision and laser excisional conization with respect to treatment time, reliability, effectiveness, and safety.
                Three hundred women with cervical intraepithelial neoplasia attending our colposcopy clinic were randomized to treatment with either loop diathermy excision (group 1, n = 150) or carbon dioxide laser excisional conization (group 2, n = 150), both performed with local anesthesia on an outpatient basis. Student's t or Mann-Whitney test were used to compare continuous data; the chi 2 test was used for categoric data.
                The mean age, parity, histologic features, depth of excision, and occurrence of residual or recurrent disease were similar; however, the mean time required to complete treatment and hemostasis (2.5 +/- 3.6 vs 24.2 +/- 11.8 min), patient discomfort, blood loss (2.77 +/- 3.76 vs 27.15 +/- 17.51 ml; p < 0.001), and considerable thermal artifact affecting histologic interpretation of excision margins (5 cases vs 25 cases; p < 0.01) were significantly less in group 1 than in group 2.
                In our experience outpatient loop diathermy excision is an equally effective, quicker, safer, and more reliable excisional technique than laser excisional conization. One hundred patients with histologically confirmed cervical intraepithelial neoplasia suitable for ablative therapy were randomly allocated to treatment by either laser vaporization or laser excision conization under local anesthesia in the outpatient colposcopy clinic. The two methods were compared with respect to the immediate surgical complications, ease of performance, and long-term complications. They were comparable in most respects, and both were well accepted by the patients. Laser excision had the added advantage of providing further material for histologic examination to confirm the absence of invasion and the completeness of excision of the lesion. Retinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%.
                This randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN.
                Analyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test.
                RA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible.
                A short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects.
                A derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible. 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.
The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity.