8 Electrocoagulation diathermy

8 Electrocoagulation diathermy WILLIAM

CHANEN

HISTORICAL BACKGROUND

Electrosurgical techniques have had a long association with gynaecological treatment. They can be categorized as methods involving electrocautery or electrocoagulation diathermy. Electrocautery achieves destruction of tissue by the passive transfer of heat, either in the form of a simple red hot wire or fulguration from an arcing spark. The hot wire method was used for many years to destroy 'chronic cervicitis' or 'cervical erosion' presenting particularly as persistent or excessive mucous vaginal discharge. There was a widely held view at the time that 'chronic cervicitis' was a possible precursor for carcinoma of the cervix, and that assiduous eradication would be effective prophylaxis against the development of malignancy (Hunner, 1906; Huggins, 1929; Pemberton and Smith, 1929; Peyton and Rosen, 1963). With the advent of colposcopy, it was realized that 'cervicitis' or 'erosion' was really nothing more than exposed columnar epithelium on the ectocervix, in varying stages of transformation zone. An explanation to account for the claims of these early authors that elimination of 'chronic erosion' prevented the onset of cancer may simply be that areas of dysplasia or precancerous change were unknowingly and inadvertently eradicated during the cauterization process. Furthermore, the transfer of the squamocolumnar junction from the vaginal environment, away from adverse oncogenic factors, would discourage subsequent development of an abnormal metaplastic process manifesting as dysplasia. Younge et al (1949) appear to have been among the first to observe that electrocauterization might be an effective treatment for selected patients with cervical intraepithelial neoplasia (CIN). They did not specifically champion its use, but noted that in a small series of patients with carcinoma in situ, electrocautery appeared to be effective in association with what they called 'step sectioning' of the lesion. In their series of 43 patients, the failure rate was 15 % when surface involvement only was present, but, significantly, if gland involvement was present, the failure rate was 63%. Although since that time there have been publications specifically describing the use of electrocautery for CIN lesions (Ortiz et al, 1973; Dergan et al, 1986), the main pitfall of hot cautery appears to be that Bailli~re's Clinical Obstetrics and Gynaecology-157 Vol. 9, No. 1, March 1995 Copyright © 1995, by Bailli~re Tindall ISBN 0-7020-1930-5 All rights of reproduction in any form reserved

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destruction may be too superficial to ensure consistent eradication and, consequently, will not adequately cope with deep gland involvement, a feature more likely to be associated with major dysplasia and anatomically extensive lesions. Electrocoagulation diathermy With the development of the triode vacuum tube, electrosurgical units were introduced in the 1920s. These generators converted a standard electrical supply into high frequency alternating current, able on the one hand to exert, with an appropriate electrode, a cutting effect on human tissue, whilst on the other, generating specific wave forms capable not only .-ff fulguration but also deep coagulation or desiccation, with subsequent tissue destruction. Since the early 1970s, more sophisticated transistorized units have been •

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Figure 1. Electrosurgical generator suitable for outpatient use (Courtesy of Valleylab, Boulder, Colorado).

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developed along with modern solid state electrosurgical generators, producing small, compact and easily transportable units, many with additional inbuilt safety features protecting the patient from accidental burn. There are currently many models on the market suitable for outpatient use (Figure 1).

Electrocoagulation diathermy for treatment of CIN Late in 1966, a Dysplasia Unit was established at the Royal Women's Hospital, Melbourne, Australia, dedicated specifically to the evaluation and treatment of abnormal cytology smears and precancerous lesions of the cervix. All patients with abnormal smears, either routinely reported or specifically referred to the hospital, were to be managed by the Unit. At that time, routine colposcopic evaluation was introduced for all patients with a significantly abnormal Papanicolaou smear. Cervical dysplasia and carcinoma in situ were considered to be part of the same biological spectrum. Consequently, it was argued at that time that carcinoma in situ did not require treatment that was any more radical than that of dysplasia, nor did dysplasia need any lesser treatment than carcinoma in situ. Because of the significant surgical morbidity and jeopardy to future childbearing, it was felt that cone biopsy, which was then the accepted method, was far too drastic an investigatory procedure for routine evaluation of abnormal smears. The use of the colposcope was advocated (Chanen and Hollyock, 1971, 1974; Hollyock and Chanen, 1972), not only for achieving a definitive diagnosis but also as a means of selecting those patients suitable for ablative therapy, rather than accepting the significant morbidity associated with routine excision (Jones et al, 1979). Electrocoagulation diathermy was chosen as the specific mode of physical destruction. Providing invasive disease could be confidently excluded, it was argued that it should be the anatomical limits of the lesions and not its purported histological severity which should determine whether electrocoagulation ablation was to be utilized.

RATIONALE OF ABLATIVE THERAPY

The validity of superficial ablative therapy, whatever its nature, is based upon the following fundamental concepts: 1. 2. 3.

4.

Dysplasia and carcinoma in situ are one and the same disease process-all severities being capable of progression to invasive disease. CIN originates within the anatomical confines of the transformation zone (TZ). With appropriate colposcopic expertise, true invasive disease can be excluded, backed up with cytology and directed biopsy, providing the whole of the atypical TZ is in view or is able to be brought into view for colposcopic assessment. Once true invasive disease is excluded, it is the size and anatomical boundaries which should determine the mode of treatment and not the purported histological severity.

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The belief that any one discipline holds a monopoly as to the final diagnosis is totally erroneous. It has often been said that 'biopsy is the final arbiter' and yet pitfalls and disparity in pathological assessment have been clearly demonstrated on numerous occasions, both between pathologists and even with the same pathologist viewing the same slides on different occasions (Govan et al, 1966; Ismail et al, 1989). 'Final' diagnosis always should be a marriage of all three disciplines. In choosing the ideal modality of ablative therapy, a fundamental requirement is that the method should be able to destroy, with minimal morbidity to physiological and reproductive function, the whole of the abnormal TZ together with adjacent columnar epithelium, including any extension into gland crypts. The underlying reasons as to why ablation may fail should be fully understood. Failure of treatment may be due to:

1.

2.

3.

Residual lesion. This is usually defined as a confirmed lesion diagnosed within the first 12 months of follow-up. It can be attributed simply to inadequate destruction of the primary focus due, for example, to inadequate or poor technique, particularly when there are physical limitations with the ablative method chosen. Simple hot wire cautery, superficial fulguration and cryosurgery appear to have physical limitations with regard to the depth of penetration and therefore destruction of underlying tissue, particularly the deep gland crypts, may not occur. Fixed probe shapes make it difficult to secure uniform destruction of an extensive area. Failure to provide adequate anaesthesia may create such discomfort for the patient that the ablative process cannot be completed. Recurrent lesion. This is usually defined as a confirmed lesion diagnosed at least 12 months after an apparent cure of the original lesion. It usually implies a subsequent episode of fresh abnormal metaplasia which manifests as a dysplastic lesion. Development of invasive disease. 'Subsequent' development of invasive disease may be due to failure to have diagnosed clinical cancer in the first instance, particularly where the lesion is apparently 'concealed' in the endocervical canal. A clinical clue to this is an irregular, nodular feel which is often associated with 'ballooning' of the cervix. It may also be due to inadequate destruction of what may have been a minute, missed, minimal stromal lesion, hence the importance of using an ablative method that will destroy just beyond the limits of the actual lesion. Such neoplastic development will tend to manifest sooner rather than later following initial treatment. Longer term development of invasive cancer is more likely to be due to progression of a neglected or missed focus of residual or recurrent CIN.

Electrocoagulation diathermy fulfills the requirements of an ideal ablative method, and possesses distinct advantages over other ablative methods because of its ability to consistently destroy the gland crypts. Because of the flexibility of the electrodes utilized, it is able to cope with the destruction of extensive areas of cervical change and even with lesions exhibiting signifi-

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cant extension into the endocervical canal (providing the whole of the abnormal TZ can be brought into view for colposcopic assessment). Although the original technique described was performed under general anaesthesia, with minor modifications utilizing intracervical local anaesthetic infiltration, it can be accomplished as a truly pain-free, outpatient procedure on a 'walk-in, walk-out' basis (Chanen, 1989).

CRITERIA FOR SELECTION FOR ELECTROCOAGULATION DIATHERMY

All patients in whom the abnormal TZ is 'in range', irrespective of the purported severity, are suitable for electrocoagulation diathermy providing frank invasion can be confidently excluded. By the term 'in range', it is meant that the limits of the abnormal TZ can be seen colposcopically or can be brought into view for assessment by means of either manipulation of the cervical lips or a suitable endocervical speculum (Figure 2) (Chanen, 1979). Histological confirmation of CIN should be obtained before proceeding with operative ablation.

Figure 2. Modified endocervical speculum.

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CONTRAINDICATIONS There are definitive specific indications for excisional cone biopsy. This protocol should not be transgressed, but in essence, the frequency of cone biopsy will be related to the experience, expertise and confidence of the colposcopist. Electrodiathermy is contraindicated and cone biopsy required when: 1.

2. 3.

4.

The abnormal TZ extends into the endocervical canal out of range, and cannot be evaluated with a colposcope. When an associated microinvasive focus (or loci) is present, it is frequently situated in the endocervical canal (Rome et al, 1985). The suspected abnormal TZ is located entirely within the endocervical canal---only the tail end may be visible. There is colposcopic and/or histological suspicion of microinvasive disease. The only way in which microinvasive disease can be accurately diagnosed, and its specific dimensions and metastatic potential assessed, is by detailed pathological examination of the whole specimen with clear access to the margins (Howell et al, 1991; Montz et al, 1993). A significant high grade glandular lesion or possible adenocarcinoma is suspected.

EQUIPMENT REQUIRED Suitable electrosurgical apparatus is required. A number of compact transistorized units are currently available. All operating room suites will already possess some type of electrosurgical unit suitable for such use. A Grave's bivalve speculum with a suitably fitted smoke extractor is required. Needle and ball electrodes are utilized to achieve the desired

Figure 3. Disposable needle and ball electrodes and abrasive cleaning pad, together with long diathermy handle (Courtesy of Valleylab, Boulder, Colorado).

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destruction. Because of the versatility of these electrodes, they are able to accommodate any pattern of anatomical distribution of the precancerous lesion, irrespective of the surface and contour of the cervix itself. The electrodes may be either reusable or disposable. A long chuck handle, preferably with foot control, is particularly useful for outpatient procedures, as greater control of the electrode can be exercised, working well away from the vulva (Figure 3). An abrasive pad is useful for cleaning the electrodes as required, in order to maintain clear contact. A standard dental syringe with disposable cartridges of local anaesthetic is ideal for intracervical local anaesthetic infiltration, using a fine 27 G needle of 47 mm length (Figure 4).

Figure 4. Dental syringe with disposable fine gauge needle and disposable cartouche of local anaesthetic.

TECHNIQUE

Outpatient procedure Recolposcopy of the patient prior to embarking on the procedure is desirable. It provides a second opportunity to recheck the findings and confirm the extent of the lesion and exclude a frank invasive process. Any previous infection confounding colposcopic appearances should have been eliminated. Further biopsies can be taken at the time of treatment as a further fail-safe measure, but only if considered necessary. After inserting the Grave's speculum and inspecting the cervix colposcopically, the cervix is then painted with Lugol's iodine solution which will serve both as an antiseptic and help delineate the area to be diathermied. Local anaesthetic infiltration is achieved by injecting into the cervix at the junction with iodine-negative tissue in the 6, 3, 12 and 9 o'clock positions, in

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this sequence, to achieve overlapping anaesthesia and to avoid bleeding puncture holes obscuring the view. The sensation of needle insertion can be blunted by asking the patient to cough deeply, so that the cervix impacts onto the needle injecting at the same time, and angling the needle towards the endocervical canal. Two ampoules (4.4ml) usually suffice, injecting in equal amounts at each quadrant. Nurocaine (lignocaine [lidocaine USP] with Sympathin 1:50 000 [adrenaline 1:200 000; nor-adrenaline 1:64 000]), Xylocaine (lignocaine) 2% with adrenaline (epinephrine USP) 1 : 80 000 or Citanest with Octapressin (prilocaine 3% with felypressin) have been the most frequently used local anaesthetic combinations. No significant sideeffects have been experienced with these preparations. With the ball electrode inserted into the long chuck handle and the coagulation setting on approximately 40 W, the abnormal TZ and adjacent columnar epithelium is systematically subjected to fulguration and deep coagulation. The cervical mucus should be mopped periodically with dry gauze and the ball held in close contact with the cervical surface, so that deep coagulation will be more effective. Relying on spark alone will achieve only superficial destruction. The current may be applied continuously or periodically for 2-3 seconds at a time. Rapid movement of the ball with continuous current will tend to produce too much spark, whereas slower movement and direct contact onto the tissue will achieve the desired deeper coagulation. In order to destroy the deep gland crypts, which may extend at least 5 mm into the stroma (Anderson and Hartley, 1980), the needle electrode is then inserted to a depth of at least 7 mm into the long axis of the cervix. Multiple punctures are made over the whole TZ and adjacent columnar epithelium and into all nabothian cysts. The number of insertions is purely empirical and will be related to the area and extent of the lesion. Insertion and withdrawal of the needle is facilitated by keeping the current on at the time. Each insertion of the needle should last for at least 2 seconds, placed at intervals of approximately 2-3 mm, the purpose being the destruction of the deeper gland crypts. It will also encourage an inversion effect on the cervix, which will tend to confine the columnar epithelium to just within the endocervical canal. Too rapid activity with the needle electrode can build up excessive heat and make the procedure uncomfortable, despite effective local infiltration. The end-pointof diathermy is when the area is desiccated and no further mucus exudes, indicating the probable destruction of the deeper gland crypts of the cervix. Destruction of abnormal tissue should be total and complete, extending into the lower endocervical canal (Figure 5). There is more risk of underuse rather than overuse of diathermy. Use of general anaesthesia Although the technique of electrocoagulation diathermy was originally described for use under general anaesthesia (Hollyock and Chanen, 1976), nowadays general anaesthesia should be reserved for those in whom dilatation and curettage or another gynaecological procedure is already

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Figure 5. Colpophotograph of cervix immediately after electrocoagulation diathermy.

indicated (e. g. tubal sterilization, diagnostic laparoscopy, etc.) or where the patient may be unduly apprehensive. When performed under general anaesthesia, dilatation and curettage was at one stage part of the protocol. The results of this experience has allowed us to confirm the concept that CIN originates within the anatomical confines of the TZ, as 'skip' lesions beyond these confines have not been demonstrated. It was suggested at one stage that dilatation prior to electrocoagulation diathermy may have been an important factor in preventing cervical stenosis, but since adopting the omt~rtient procedure the incidence of stenosis has-trot significantly increased (Chanen, 1989). Role of endocervical curettage

Advocacy of endocervical curettage as part of a routine preoperative assessment appears to be an idiosyncrasy of the North American continent. Where the limits of an abnormal TZ are visible or can be exposed for colposcopic evaluation, we have never been protagonists of routine outpatient or

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preoperative endocervical curettage. This belief is supported by past experience with routine curettage performed at the time of diathermy under general anaesthesia. Unless frank invasive endocervical cancer is present, endocervical curettage provides a poor quality specimen with minimal, fragmented tissue, a deficient stroma and poor orientation. As an outpatient procedure, it is often painful and uncomfortable to perform. It may lead to false positive reports, scraping across the squamocolumnar junction. As a result unnecessary cone biopsies may be performed. Furthermore, because of the trauma to the epithelial surface, it may well interfere with the subsequent cone biopsy assessment. There is frequently a clinical clue that endocervical cancer is present, when 'ballooning' and nodularity of the cervix will be felt. POSTOPERATIVE MANAGEMENT Written instructions should be supplied to the patient indicating that nuisance discharge and spotting may occur. Instructions should include avoiding intercourse and the use of internal tampons for at least 3 weeks. The routine use of a postoperative course of antibiotic is debatable, but it is certainly indicated if there has been any past history of pelvic infection or if there is evidence of associated infection at the time of treatment. Sultrin (Triple Sulpha) cream (which contains sulphacetamide, sulphabenzamide and sulphathiazole) is usually prescribed for intravaginal use nightly for approximately 10 days to reduce the risk of infection. RESULTS OF TREATMENT Data from just under 3000 patients with histologically confirmed CIN treated with electrocoagulation diathermy has been collated and published (Chanen, 1990). The number that have currently been treated well exceeds this figure. Follow-up has extended to well over 20 years. Almost 90% of all patients with histologically confirmed CIN under the age of 40 years were able to be treated in this fashion. Almost two thirds of the patients so treated were histologically classified as CIN 3, with approximately 1000 patients fulfilling the strict histological criteria of absolute or frank carcinoma in situ (Figure 6). In this series, significant extension into the canal was present in one third of the patients, and in at least 50% of the CIN 3 patients electrodiathermy was performed where three to four quadrants were involved. All these factors are acknowledged as being unfavourable with other methods of ablative therapy. With one single, first-time treatment with electrodiathermy, 98% of these

Figure 6. (a) Colpophotographshowingextensivearea of abnormalTZ on anterior lip ('in range') consistent with an underlyinghistologicaldiagnosisof major dysplasia. (Directed biopsyreportedas carcinomain situ.) (b) Colpophotographofsamecervixtaken2 monthsafter electrocoagulationdiathermy,withcompleteeradicationof the lesion.

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patients were cured of their precancerous lesion, postoperative monitoring being performed with both smears and colposcopy. This high cure rate of 98% with first-time treatment was equally applicable to lesions classified histologically as fulfilling the criteria of carcinoma in situ. Table 1 summarizes treatment failures according to the purported severity of CIN.

Table 1. Electrocoagulation diathermy for CIN: failure rate with one single treatment. Histology of original lesion CIN 1 (mild dysplasia) CIN 2 (moderate dysplasia) CIN 3 Severe dysplasia Carcinoma in situ Total

Number treated

Number with residual disease

460 610

12 (2.6%) 13 (2.1%)

927 993

15 (1.6%) 23 (2.3%)

2990

63 (2.1%)

In the most recent years, the overall cone biopsy rate has been effectively reduced to approximately 5%, whilst the hysterectomy rate was as low as 3.5 %, once those procedures performed for diagnosed invasive cancer were excluded.

COMPLICATIONS OF TREATMENT There are no significant intraoperative problems encountered with this technique. Nuisance discharge or intermenstrual spotting is not uncommon, and the patient needs to be warned of this possibility to allay any anxiety. Table 2 summarizes the incidence and nature of significant complications encountered in the published series (Chanen, 1990). Long-term follow-up has not revealed any noteworthy adverse effects on cervical function, fertility, pregnancy or subsequent labour (Johnstone, 1974; Hollyock et al, 1983).

Table 2. Complications in 2990 patients treated by electrocoagulation diathermy. Number of patients

%

Secondary haemorrhage Pelvic infection Cervical stenosis

37 13 12

1.2 0.4 0.4

Total

62

2.0

Complications

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FOLLOW-UP The regimen of follow-up is a first postoperative visit at 8 weeks, 6-monthly visits for the next 2 years, and then at each anniversary of the original treatment. Monitoring for residual or recurrent disease consists of examination using colposcopy, cytology (endo- and ectocervical sampling) and, only where indicated, target biopsy. Cytobrushes provide an excellent means for endocervical sampling. Follow-up experience has indicated that the first 2 to 3 years are the most critical (Chanen and Rome, 1983). If there is no suggestion of residual or recurrent disease at this stage, further followup may not need to be quite so rigid. Residual disease

Failure to eradicate CIN by diathermy is not related to the histological severity of the original lesion. Of 63 patients diagnosed with residual disease, cytological abnormalities were not present in all cases, five being reported as having 'no cytological abnormality'. Abnormal TZ was visible in only 59, but cytology was positive in the four patients in whom the TZ was located entirely in the canal (Chanen, 1990). This would suggest that a combination of cytology and colposcopy is required to effectively detect all occurrences of residual disease. Most of the failures of treatment were suspected even at the first postoperative visit, either because of an atypical colposcopic appearance or atypicalities of the smear (Chanen and Rome, 1983). Recurrent disease

As with residual CIN, there is no relationship between the severity of the original CIN and the likelihood of recurrence. Of the 20 patients in whom recurrent disease was detected, the lesion was still intraepithelial and did not necessarily correspond with the original histological pattern (Chanen and Rome, 1983). The interval between treatment and recurrence ranged from 12 months to over 10 years. However, most of the recurrences (55%) were detected between the first and third year of follow-up. In each instance, the recurrent lesion could be seen on the ectocervix with the colposcope, but cytology was positive for abnormality in only t6 of the 20 patients (80%), demonstrating once again the fallibilRyofretying on cytology smears alone (Chanen, 1990). The fact that all recurrences were visible on the ectocervix suggested that the columnar epithelium, exposed once again to oncogenic factors in the vagina, had generated abnormal squamous metaplasia which manifested as dysplasia. Persistent exposed columnar epithelium is due either to failure to completely eradicate the columnar epithelium in the first instance, or to re-exposure as a result of a subsequent pregnancy. For this reason, I do not subscribe to the belief that the new squamocolumnar junction must be readily and anatomically visible after treatment. Ideally the junction should be situated just inside the canal, away from exposure to oncogenic factors in

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the vagina, but able to be exposed by manipulation or the use of an endocervical speculum. It should be stressed that in the series of patients so treated, there has been no recorded instance of subsequent development of invasive carcinoma of the cervix. This has been reinforced by a nationwide questionnaire through oncology, colposcopy and gynaecological society newsletters requesting information on any patient who may have subsequently come under the care of others. The significant factor is that, for practical purposes, the hazard of subsequent development of invasive cancer of the cervix has been virtually eliminated in a group known to be at a significantly high risk (McIndoe et al, 1984). Of the 83 patients with either residual or recurrent disease, the lesion was small enough to be cured by biopsy alone in approximately one third. A second diathermy successfully eradicated the lesion in an additional third, whilst hysterectomy or cone biopsy was utilized in the remainder (Chanen and Rome, 1983; Chanen, 1990). Because of the greater risk of a 'skip' lesion after previous ablative treatment, repeat ablative therapy should only be used if there are very clear margins around the abnormal focus.

SUMMARY

With experience extending over an interval of 25 years, one single application of electrocoagulation diathermy has been substantiated as a most consistent and effective method of eradicating precancerous lesions of the cervix. Although there is a protocol for selection that must be adhered to, the vast majority of patients with CIN lesions are suitable for this method of ablative therapy. Ablation by electrocoagulation diathermy appears to have distinct advantages over other methods because of the following: 1. 2. 3. 4. 5. 6. 7. 8.

Very high cure rates (98%) with first-time treatment can be achieved, even for major dysplasia and/or carcinoma in situ. Extensive and deep lesions can be effectively eradicated irrespective of the purported histological severity. Electrodiathermy is capable of eradicating lesions extending into the endocervical canal, providing anatomical limits can be evaluated colposcopically. The technique is simple and rapid. The versatility of the electrodes facilitates eradication of the lesion irrespective of the shape and contour of the cervix. No expensive capital outlay nor costly maintenance of equipment is required. There are no physical hazards for medical personnel. It is cost-effective--the technique is readily adaptable as a true outpatient procedure on a 'walk in, walk out' basis. It has a very low incidence of surgical morbidity and does not jeopardize physiological and reproductive function.

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F o r p r a c t i c a l p u r p o s e s , t h e s u b s e q u e n t risk o f d e v e l o p m e n t o f i n v a s i v e cancer of the cervix can be effectively eliminated.

REFERENCES

Anderson MC & Hartley RB (1980) Cervical crypt involvement by intraepithelial neoplasia. Obstetrics and Gynecology 55: 546-550. Chanen W (1979) An endocervical speculum. Australian and New Zealand Journal of Obstetrics and Gynaecology 19: 40-41. Chanen W (1989) The efficacy of electrocoagulation diathermy performed under local anaesthesia for the eradication of precancerous lesions of the cervix. Australian and New Zealand Journal of Obstetrics and Gynaecology 29: 189--192. Chanen W (1990) Recent advances in cervical pathology and colposcopy. In Carenza L, Atlante G & Pozzi V (eds) Vol. 3. The Proceedings of the 7th World Congress of Cervical Pathology and Colposcopy, Rome 1990, pp 417--420. Parthenon Publishing Group. Chanen W & Hollyoek VE (197t) Colposcopy and electrocoagulation diathermy for cervical dysplasia and carcinoma in situ. Obstetrics and Gynecology 37: 623-628. Chanen W & Hollyock VE (1974) Colposeopy and the conservative management of cervical dysplasia and carcinoma in situ. Obstetrics'and Gynecology 43: 527-534. Chanen W & Rome RM (1983) Electrocoagulation diathermy for cervical dysplasia and carcinoma in-situ: A fifteen year survey. Obstetrics and Gynecology 61(6): 673-679. Dergan E, Carmichael JA, Ohlke D & Karchmar J (1986) Treatment of cervical intraepithelial neoplasia with electrocautery: A report of 776 cases. American Journal of Obstetrics and Gynecology 154: 255--259. Govan ADT, Haines RM, Langley TA et al (1966) Changes in the epithelium of the cervix uteri. A study by the panel of pathologists engaged in the survey of carcinoma in situ carried out by the Royal College of Obstetricians and Gynaecologists. Journal of Obstetrics and Gynaecotogy of the British Commonwealth 73: 883. Hollyock VE & Chanen W (1972) The use of the colposcope in selection of patients for cervical cone biopsy. American Journal of Obstetrics and Gynecology 114: 185-189. Hollyock VE & Chanen W (1976) Electrocoagulation diathermy for the treatment of cervical dysplasia and carcinoma in situ. Obstetrics and Gynecology 47: 196-199. Hollyock VE, Chanen W & Wein R (1983) Cervical function following treatment of intraepithelial neoplasia by electrocoagulation therapy. Obstetrics and Gynecology 61: 79-81. Howell R, Hammond R & Pryse-Davies J (1991) The histologic reliability of laser cone biopsy of the cervix. Obstetrics and Gynecology 77(6): 905-911. Huggins RR (t929) Problems associated with the cervix. American Journal of Obstetrics and Gynecology 17: 589-596, Hunner GL (1906) The treatment of leucorrhea with the actual cautery. Journal of the American Medical Association 46: 191-192. Ismail SM, Colclough AB & Dinner JS (1989) Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia. British Medical Journal 298: 707-710. Johnstone NR (1974) Pregnancy following conservative management of dysplasia and carcinoma in-situ of the uterine cervix. Australian and New Zealand Journal of Obstetrics and Gynaecology 14: 9-11. Jones JW, Sweatman P & Hibbard BM (1979) The outcome of pregnancy after cone biopsy of the cervix. A case control study. British Journal of Obstetrics and Gynaecology 86: 913-916. McIndoe WA, McLean MR, Jones RW & Mullins PR (1984) The invasive potential of carcinoma in situ. Obstetrics and Gynecology 64: 451-458. Montz F J, Holschneider CH & Thompson LD (1993) Large-loop excision of the transformation zone: effect on the pathologic interpretation of resection margins. Obstetrics and Gynecology 81(6): 974-982. Ortiz R, Newton M & Tsai A (1973) Electrocautery treatment of cervical intraepithelial neoplasia. Obstetrics and Gynecology 41: 113-116.

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