Cryotherapy and carbon dioxide laser management of cervical intraepithelial neoplasia: a controlled comparison. Randomized study comparing two techniques of conization: cold knife versus loop excision. A randomised clinical trial of loop electrosurgical excision procedure (LEEP) versus cryotherapy in the treatment of cervical intraepithelial neoplasia. Utility of bipolar electrocautery scissors for cervical conization. The large loop excision of the transformation zone cut or blend thermal artefact study: a randomized controlled trial. Cold knife conization and loop excision for cervical intraepithelial neoplasia. Cold-knife conization versus conization by the loop electrosurgical excision procedure: a randomized, prospective study. Thermal tissue damage following laser and large loop conization of the cervix. Conization by carbon dioxide laser or cold knife in the treatment of cervical intra-epithelial neoplasia. Laser vaporization versus laser excision conization in the treatment of cervical intraepithelial neoplasia. Cryosurgery for dysplasia of the uterine ectocervix. A randomized study of the efficacy of the single- and double-freeze techniques. Laser or cryotherapy for cervical intraepithelial neoplasia: a randomized study to compare efficacy and side effects. Long-term outcome of a randomized study comparing three techniques of conization: cold knife, laser, and LEEP. Outpatient excisional management of cervical intraepithelial neoplasia. A prospective, randomized comparison between loop diathermy excision and laser excisional conization. A randomized trial comparing two methods of cold knife conization with laser conization. Loop diathermy or laser excisional conization for cervical intraepithelial neoplasia. Laser and cryo surgery for cervical intraepithelial neoplasia. A randomized trial with longterm follow-up. Which is more painful? A randomized trial comparing loop with laser excision of the cervical transformation zone. One-Session Management of Cervical Intraepithelial Neoplasia: A Solution for Developing Countries. A Prospective, Randomized Trial of LEEP versus Laser Excisional Conization Needle versus loop diathermy excision of the transformation zone for the treatment of cervical intraepithelial neoplasia: a randomised controlled trial. A study of cryosurgery and the CO2 laser in treatment of carcinoma in situ (CIN III) of the uterine cervix.
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. To compare the histomorphologic and colposcopic results of cold knife conization and loop excision.
                Sixty-six women were randomly allocated to have the cone specimen removed by cold knife excision (n = 38) or loop excision (n = 28). Subjects eligible for inclusion were those who presented histologically verified grade 3 cervical intraepithelial neoplasia (CIN) or grade 2 CIN with squamocolumnar junction not seen.
                The mean height of the cone specimens was greater in the cold knife group [18.9 mm (SD = 5. 5) and 12.8 mm (SD = 4.3), respectively; P = 0.0001], as was the frequency of clear margins (100 and 80%, respectively; P = 0.001). In the loop excision group, thermal injuries were present in half of the cone sections. The median (range) thickness of thermal injury was 0.98 mm (0-1.5 mm) in the ectocervix and 0.95 mm (0-1.75 mm) in the endocervix. Histologic evaluation of the endocervical margins was not possible in 2 cases (7%). At follow-up colposcopy, evaluation of the entire squamocolumnar junction was possible in 15 (39%) and 20 (71%) women, respectively (P < 0.01). Four patients in the cold knife group and 6 in the loop group had histologically confirmed persistent dysplasia (P > 0.05), yielding success rates of 90 and 79%, respectively (P > 0.05).
                Loop excision provides a sample that is adequate for histologic evaluation in most cases, results in the same success rate as cold knife conization, and allows optimal colposcopic surveillance in significantly more cases than cold knife excision.
                Copyright 1999 Academic Press. 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. To evaluate the usefulness of bipolar electrocautery scissors for cervical conization.
                Forty patients with severe dysplasia/in situ carcinoma of the uterine cervix underwent cervical conization: 20 randomly selected patients were operated on with the unipolar energy scalpel and the other 20 were operated on with bipolar electrocautery scissors. In both groups operating time, number of ligations, blood loss, duration of recovery, perioperative complications and adequacy of the margins of the lesion were assessed. Data were compared by analysis of variance.
                In the bipolar group the average operating time and duration of recovery were significantly reduced (halved), no ligations were needed and the amount of blood loss was significantly reduced. Regarding perioperative complications, in the bipolar group there were no hemorrhages nor need of a second operation or transfusion. Infections did not occur in either group. We found no difference between the two groups regarding adequacy of the margins of the lesion for a good pathologic examination.
                Bipolar electrocautery scissors were safe and useful in cervical conization by reducing the operating time and blood loss without increasing postoperative morbidity. The objective of this randomized controlled trial was to determine whether the pure cut setting results in less thermal artefact than the traditional blend setting when performing a large loop excision of the transformation zone (LLETZ). Forty-nine consenting women were randomized to undergo an LLETZ procedure using either the pure cut or the blend setting. Two histopathologists, who were blind to the randomization, examined the specimens and then graded and measured the degree of thermal artefact. No significant difference was noted at the epithelial margin. At the deep stromal margins, in the blend group, the mean thickness of thermal artefact was 0.382 mm (95% CI, 0.350-0.414) and in the cut group 0.325 mm (95% CI, 0.297-0.353). This was statistically significant. No significant difference was detected in terms of grading of thermal artefact, the presence of dysplasia at the specimen margins, or in positive follow-up smears. Although there was less thermal artefact at the deep stromal margin, cautery at this margin does not generally interfere with pathological assessment of the specimen and the pure cut setting does not produce a clinically significant decrease in the degree of thermal artefact. Our aim was to investigate whether loop excision is an acceptable alternative to traditional cold knife conization of the cervix.
                240 with cervical intraepithelial neoplasia (CIN) were randomly assigned to loop excision (n = 120) or cold knife conization (n = 120). Success and complication rates of both methods were analysed.
                100% of cold knife conization and 98% of loop excision surgical specimens were positive for dysplasia. The rate of complete resection was 91% in the cold knife and 82% in the loop excision group, but histologic confirmation of residual CIN was obtained in only 2 (1.7%) women after cold knife conization and in 5 (4.2%) after loop excision. Loop excision cones were significantly shallower than those obtained by a cold knife. Secondary surgical procedures due to early hemorrhage were performed in 9 (7.5%) patients treated with cold knife conization and in 8 (6.7%) treated with loop excision. Elevated temperature postoperatively was observed in 16.4% of patients after cold knife conization and in 13.9% after loop excision. There were no other postoperative complications.
                The results suggest that cold knife conization and loop excision are comparable and equally effective diagnostic and therapeutic procedures for CIN. Our purpose was to compare the diagnostic ability and treatment efficacy of conization by the loop electrosurgical excision procedure with cold-knife conization.
                One hundred eighty women who required conization for diagnosis and treatment of cervical dysplasia or microinvasive cervical carcinoma were prospectively enrolled in a randomized clinical trial to receive either cold-knife conization or conization by the loop electrosurgical excision procedure. Conization complications, rate of lesion clearance, and therapeutic outcome were assessed for the 2 study groups.
                There were no statistically significant differences in the complication rate (P = 1.00), the rate of lesion clearance (P =.18), or the rate of disease recurrence (P =.13) between the 2 study groups. The mean follow-up was 11.2 months in the cold-knife conization group and 10.4 months in the loop-excision conization group.
                Cold-knife conization and loop-excision conization yield similar diagnostic and therapeutic results. To compare thermal injury zones produced with laser and diathermy loop conization.
                Excisional cervical specimens (cones and cervices) were obtained from 40 consecutive women who underwent abdominal hysterectomy. The subjects were assigned to have either laser or diathermy loop conization (20 in each group). The duration of each procedure was recorded. Histopathologic measurements of thermal injury zones were performed in all specimens.
                The techniques produced cone specimens of similar depth. The mean depth of thermal injury produced with laser conization in cone specimens (mean +/- standard deviation 0.49 +/- 0.16 mm) and cervical craters (0.58 +/- 0.24 mm) was significantly greater (P < .001) than the corresponding depth in cone specimens (0.22 +/- 0.09 mm) and cervical craters (0.27 +/- 0.11 mm) obtained by diathermy loop excision. The mean time of the two procedures was also significantly different (P < .001); laser conization 11 +/- 4.5 minutes and loop conization 2 +/- 1.2 minutes.
                For routine conization, loop diathermy causes less thermal damage to the specimen and is a faster procedure than laser. 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. 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. This prospective, randomized study of 142 women with mild or moderate dysplasia of the uterine ectocervix shows that the double-freeze technique is significantly more effective than the single-freeze technique, the recurrence rates being, respectively, 6.2% and 16.3%. The highest recurrence rate was found in the group treated with a single freeze and having the most extensive portio involvement. All patients were examined colposcopically before cryosurgery in order to exclude patients with lesions extending into the cervical canal and in order to evaluate the size of the lesion. Recurrent lesions were usually diagnosed within the first year (75%) and in only one patient more than 2 years after treatment. None of the patients developed invasive cancer. The mean follow-up period was 27 months (24-42 months). We consider cryosurgery to be an acceptable treatment for selected patients. Our criteria for entry were mild or moderate dysplasia of the uterine ectocervix, and colposcopic visualization of the entire transformation zone to ensure that the lesion does not extend into the cervical canal. Our experience from the present study is that the following criteria should be added: the portio involvement must not be too extensive and the patient must agree to follow-up examination. When these conditions are fulfilled, future treatment in our department will consist of a double freeze extending 3 mm beyond the lesion, with a thaw interval of 4 min. 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. To evaluate the long-term recurrence rates and complication of different techniques of cervical ablation.
                A randomized trial of three techniques of conization (cold knife, laser, and loop electrosurgical excisional procedure (LEEP)) for cervical intraepithelial neoplasia (CIN) in which 110 patients had been recruited.
                Eighty-six patients were followed-up for more than 3 years. Of these 28 had been treated with the cold knife, 29 with LEEP and 29 by laser. Five recurrences were observed, one in the cold knife group, two in the LEEP group and two in the laser group (P=NS). The only observed complication was cervical stenosis: zero cases in the laser group, one case in the LEEP group and four cases in the cold knife group (laser versus cold knife: P=0.03; LEEP versus cold knife: P=0.06). Fifty pregnancies were observed in 39 patients. First and second trimester outcomes of pregnancy were without complications. One patient treated with the LEEP presented with a premature rupture of membranes and premature labor at 36 weeks. A total of nine cesarean sections were performed with two cases for cervical dystocia.
                There is no major difference in obstetrical outcome between the three techniques. 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. In a randomized study, 62 women were submitted to cold knife conization with application of Sturmdorf sutures, 60 to cold knife conization without sutures, and 61 to laser conization. Early hemorrhage occurred in 1.6, 13.3, and 6.6% of women, respectively (P less than .05), and late hemorrhage in 15.3, 3.6, and 11.7%, respectively. Considering early and late hemorrhage together, there was no significant difference among the three treatment groups. Dysmenorrhea tended to be more common after application of Sturmdorf sutures, as it was reported by 27.8, 13.2, and 14.3% of patients, respectively, but the difference was not statistically significant. Dysmenorrhea occurred in 13% of the cases with a cone height of 20 mm or less and in 26% of the cases with a cone height greater than 20 mm (P less than .05). Endocervical cells were present significantly more often after sampling with a cytobrush than with a cotton swab (P less than .0001), whereas the method of conization had no influence. In smears obtained with a cytobrush, endocervical cells were present in 88.0, 84.9, and 82.5% of the cases; in smears obtained with a cotton swab, endocervical cells were present in 46.6, 57.7, and 54.5%, respectively. We conclude that cold knife conization without Sturmdorf sutures is about equal to laser conization in overall complications, but the laser is preferable for outpatient treatment because of a lower frequency of early hemorrhage. Sturmdorf sutures should be avoided. Smears at follow-up should be taken with a cytobrush and a wooden spatula. Cervical intraepithelial neoplasia (CIN) can be managed by ablative or excisional procedures. We have compared the excision time, effectiveness, and safety of loop diathermy (loop) against laser conization.
                In a prospective study in two hospital departments 222 women were randomized to loop or laser conization. Data were collected by questionnaires after operation and at two follow-up examinations.
                At department A (122 women), two physicians performed 27% of the loop and 35% of the laser excisions; at department B (100 women), the corresponding figures were 69% and 59%. Loop was quicker than laser conization in both departments (median 3-4 min versus 10-20 min), while laser conization was more time consuming in department A (median A/B = 20/10 min). Peroperative bleeding dominated during the laser procedure in both departments and complicated the loop procedure more frequently in department A. Postoperative bleeding occurred with equal frequency in the four groups (41.8%, 52.7%, 59.2%, 64.7%). At both departments, bleeding for more than two weeks was reported twice as often after laser conization (A:13.8%, B:24.2%), when compared to loop excision (A:7.1%, B:13.7%). Residual CIN was found in all of three re-conizations and in one of eight hysterectomy specimens.
                Loop was quicker than laser excision, per- and postoperative bleeding diminished, and the success rates were comparable. Physicians mastered Loop excision after a few attempts. However, the results improved, when performed by a restricted number of physicians. Histological incomplete excision indicates close colposcopic and cytologic follow-up to identify residual CIN. 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. We compared the pain of excisional cervical surgery by the laser or loop diathermy (LLETZ) in a randomised controlled clinical trial. Eighty women with CIN III were recruited from a laser colposcopy clinic specifically adapted to run randomized trials. They were scheduled for excision of their cervical transformation zone and both groups were matched for age, parity, and size of lesion. We measured linear analogue pain scores, subjective pain scores, and operative time. The laser and loop diathermy inflicts similar discomfort and there is no detectable difference between the median pain scores of women in either group (P = 0.99). However, in the hands of an experienced surgeon it takes 4 min extra to excise the cervical transformation zone with a laser compared to loop diathermy. The average time from sitting in the chair to the end of the procedure was 13.02 min (SD 3.65) for the group allocated diathermy surgery compared to 17.30 min (SD 5.33) for a laser excision log transformed t(log transformed data) = 3.7 (P < 0.001). 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. To determine whether lower rates or incomplete resection of cervical intraepithelial neoplasia (CIN) may be achieved by needle excision of the transformation zone (NETZ) than with loop excision (LLETZ).
                A prospective randomised controlled trial.
                A gynaecological oncology centre and a teaching hospital in West London.
                Four hundred and four women due to receive treatment for suspected CIN.
                Women were randomised to receive either LLETZ or NETZ.
                The study was designed to demostrate a difference in the proportion of women with clear histological margins of 82% for LLETZ compared to 94% for NETZ with 90% power at a 5% significance level, allowing for absence of CIN in the treatment specimen in 15%.
                Four randomised women were excluded from the analysis, as they were ineligible for the study. Three hundred and forty-seven (87%) had CIN in the treatment specimen and could be included in the analysis of excision margins. More women in the NETZ arm had clear histological margins (84.8%vs 75%, (P= 0.03). The median volume of specimens in the NETZ arm was 739 mm(3) larger (P= 0.33) and they were less likely to be removed in multiple pieces (2.5%vs 29.5%, RR 0.09, 95% CI 0.04 to 0.20). Needle excision took longer to perform (median treatment time 210 vs 90 seconds, P<0.0001) and surgeons more often reported the procedure as 'difficult' (9.5%vs 3.0%, RR = 3.17%, 95% CI 1.33 to 7.58). No difference in peri-operative or post-operative complication rates could be demonstrated between the two groups.
                NETZ is more likely to produce a specimen in one piece and with clear margins compared to LLETZ. The results of laser and cryosurgical treatment in 106 patients with histologically proven carcinoma in situ of the uterine cervix (CIN III) are presented. Seventy-one patients were treated with the laser and in 63 of these further follow-up with colposcopy and cytology failed to show any abnormality. This represents an initial success rate of 89%. In 8 patients (11%) initial treatment was considered to have failed because of persistent dyskaryotic smears and histological evidence of cervical intraepithelial neoplasia (CIN II-III). Six of these patients were treated successfully with a further laser application and two patients had conization. The overall success rate for the laser was 97%. Thirty-five patients were treated with cryosurgery and subsequent follow-up was negative in 29 of these patients (83%). The 6 treatment failures (17%) were subsequently successfully treated with local destructive therapy (4 with cryosurgery, 1 with laser, and 1 with needle diathermy). The overall success rate for cryofreezing was 94.2%. In cases of CIN III the laser is more likely to achieve eradication of the lesion with a single application than cryofreezing.
The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity.