Malcolm Coppleson

The efficacy of postoperative vaginal irradiation in preventing vaginal recurrence in endometrial cancer.

Between 1960 and 1985 hysterectomy was performed on 811 FIGO stage I and 116 stage II endometrial cancers which were divided into three groups: low-risk stage Ii (grade 1 and 2 lesions confined to the inner third of the myometrium; high-risk stage Iii (grade 3 and/or invading to the middle third of the myometrium or beyond); and FIGO stage II tumors (also high-risk). Hysterectomy was the only treatment in 492; in 145 the vaginal vault alone was radiated and in 290 the whole vagina, in each instance by an intracavity dose of 60Gy; in 34 of the latter high-risk tumors the pelvis received an additional 46Gy by external beam therapy. Forty isolated vaginal recurrences were detected; 10 in 308 low-risk and 22 in 184 high-risk tumors treated by surgery alone, and two and five in 40 low and 105 high-risk patients, respectively, who received adjuvant vault irradiation. No recurrences followed irradiation of the whole vaginal mucosa in 163 stage Ii low-risk and 40 stage II lesions and one, 9 years later, in 87 high-risk stage Iii tumors. Nearly 45% of patients with vaginal recurrence died from cancer within 1 year, 77% within 5 years and only 10% survived their recurrence 10 years. Total vaginal irradiation eliminated vaginal recurrences in low risk and reduced the incidence to 2.1% at 20 years after high-risk tumors.

Cervical carcinoma: A drug-responsive tumor—experience with combined cisplatin, vinblastine, and bleomycin therapy

Thirty-five patients with advanced cervical cancer were treated with a combination chemotherapy regimen comprising cisplatin, vinblastine, and bleomycin (PVB). Sixty-six percent of 33 evaluable patients showed objective tumor response and complete remissions were seen in six (18%) patients. The median duration of tumor response in patients with recurrent cervical cancer was 24 weeks (range 8 to 104 weeks). Multivariate analysis of pretreatment variables including prior radiotherapy did not identify patients with a higher response probability. Nausea and vomiting were usual side effects of chemotherapy and there was one definite treatment-related death. Cervical cancer is responsive to cisplatin based combination chemotherapy. The role of chemotherapy in conjunction with radiotherapy or surgery in the treatment of locally advanced cervical cancer remains to be defined.

A randomized trial comparing platinum-based chemotherapy followed by radiotherapy vs. radiotherapy alone in patients with locally advanced cervical cancer

Seventy-one patients with stage IIb-IVa cervical cancer were entered on a randomized trial comparing standard pelvic radiotherapy vs. 3 cycles of combination chemotherapy with cisplatin, vinblastine and bleomycin followed by pelvic radiotherapy. Four out of 34 patients randomized to PVB followed by radiotherapy received no PVB and a further 3 patients had only one or 2 cycles of chemotherapy prior to radiotherapy due to drug-related toxicity or progressive disease. After a median follow-up of 3.1 years, no significant difference in survival has emerged between the two randomized groups. However, a difference in the pattern of relapse is emerging with a relatively reduced frequency of systemic relapse in patients receiving chemotherapy prior to local radiotherapy compared to radiotherapy alone. Tumor response was seen following PVB treatment and prior to radiotherapy in 47% of patients. Overall the tumor response rate following completion of radiotherapy was 89% in those treated by radiotherapy and 94% after PVB+radiotherapy. Thirty-three percent of patients randomized to radiotherapy alone relapsed first at a distant (extra pelvic site), and only 18% of patients randomized to initial PVB followed by radiotherapy relapsed systemically initially. When results are presented according to treatment actually given, these trends in patterns of treatment failure are magnified. No treatment-related deaths were reported, and there was no excess of complications with pelvic radiotherapy in the group who had received prior PVB chemotherapy.

A randomized trial of adjuvant chemotherapy after radical hysterectomy in stage Ib-IIa cervical cancer patients with pelvic lymph node metastases

Seventy-one patients with Stage Ib-IIa cervical cancer treated by radical hysterectomy and found to have pelvic lymph node metastases were entered on a randomized trial comparing standard pelvic radiotherapy versus three cycles of combination chemotherapy with cisplatin, vinblastine, and bleomycin followed by pelvic radiotherapy. After a median follow-up of 2.5 years, 24 patients have relapsed. In 12 patients, the first evidence of relapse was in the pelvis, in 11 patients the first relapse was evident at a distant site, and in 1 patient the local recurrence and distant metastases were documented simultaneously. No difference in disease-free or overall survival has emerged between the two treatment groups. Relapse was more common in patients with non-squamous tumors (44%) and in those with metastases in several pelvic lymph nodes. We conclude that patients with pelvic lymph node metastases have a rather poor prognosis, but it remains to be determined how they should best be treated after radical surgery.

An electronic approach to the detection of pre-cancer and cancer of the uterine cervix: a preliminary evaluation of Polarprobe

We report on the testing of a prototype of an electronic device for the detection of cervix cancer and its precursors, known as the Polarprobe. The device monitors three aspects of the cervix tissue; two relate to optical properties and the other to dielectric characteristics. The response to tissue stimulation takes the form of an energy pattern which, in conjunction with spectroscopic discriminants, can be digitized to prepare an algorithm. The pattern algorithms are sufficiently characteristic to be afforded names which correspond to tissue states recognizable as normal or abnormal by the clinician. On a tissue observation basis the previously established recognition algorithms derived from 106 volunteers produced assessments which related strongly to colposcopy/histology diagnoses obtained on 77 additional volunteers. This concordance between colposcopy/histology and Polarprobe diagnoses on this primary analysis subgroup ranged from 85% on low-grade intraepithelial abnormalities, and 90% on high-grade cervical intraepithelial squamous neoplasia, to 99% on invasive cancer. An extrapolation of these results suggests false-positive/false-negative rates in the order of 10% are achievable with the current Polarprobe device.

A hypothesis: The role of a high-risk male in the etiology of cervical carcinoma: A correlation of epidemiology and molecular biology

Certain impressive epidemiological evidence appearing in the last few years leads to the conclusion that some males are more prone to have a spouse with squamous cancer of the cervix than others. Advances in knowledge in other fields, especially at the molecular biological level, enable speculation on reasons for this curious conclusion. These readily testable theories, together with an outline of the evidence on which they rest, form the substance of this hypothesis.

A COLOPOSCOPIC STUDY OF THE CERVIX DURING PREGNANCY AND THE PUERPERIUM

To establish the natural history of the process of metaplasia of columnar to squamous epithelium the cervixes of 105 pregnant women (64 primiparae 41 multiparae) were examined colposcopically at least once each trimester and 5 days and 6 weeks postpartum. Previous studies had indicated that pregnancy is the period of most active formation of new epithelium in Metaplasia. The colposcopic study showed that the greatest production of new squamous epithelium occurs during the 1st pregnancy during the second or third trimester. Eversion of the columnar epithelium occurs in most primiparae at this time; the few women who do not show this eversion have a higher incidence of caesarian deliveries. The eversion may retract into the canal postpartum. Less eversion of the canal occurs in later pregnancies; when it does it is covered with metaplastic squamous epithelium. Eversion results from retraction of a sphincter-like part of the cervical musculature. Metaplasia is an essentially physiological process; atypical changes begin insidiously during the metaplasia of the 1st pregnancy. Very little trauma to the cervical mucosa was seen after delivery.

Percutaneous urinary diversion in gynecologic oncology

During the 10-year period after 1979, percutaneous urinary diversion (PCUD) was performed on 35 patients whose mean age was 53.5 years (30-80 years). Twenty-one patients (60%) had Stage IIB-IV cervical cancer, 11 (31%) Stage IB-IIA cervical cancer, 2 (6%) Stage IB-II endometrial cancer, and 1 (3%) Stage IB vaginal cancer. All had radiological evidence of ureteric obstruction and 8 patients also had urinary tract fistulae. Serum creatinine levels were elevated in 24. Following diversion there was a significant fall in mean pretreatment creatinine levels from 482 mumol/liter (range, 70-1703 mumol/liter) to 131 mumol/liter (range, 60-290 mumol/liter; P less than 0.0001); those patients with normal creatinine levels prior to diversion also had a reduction in their levels. A significant fall in mean serum urea levels from 22.0 mmol/liter pre- to 11.9 mmol/liter post-PCUD (P less than 0.001) was also noted. Minor complications occurred and included hemorrhage, replacement/reinsertion, infection, and blockage. Median survival of the 35 patients after PCUD was 6 months (mean, 16.5 months). For the 11 with normal pretreatment renal function median survival was 16 months (mean, 41 months) compared to 2.5 months (mean, 5.1 months) for those with elevated pretreatment serum creatinine levels. Median survival with untreated malignancy was 7 months (mean, 19.6 months) and 6 months (mean, 12.3 months) in patients with previously treated cancer. PCUD is indicated in previously untreated patients with gynecologic cancer so that primary therapy can be instituted. The role of urinary diversion in patients with previously treated cancer must be individualized. Palliative diversion is appropriate in selected patients where additional therapy is expected to prolong life, where symptom control is needed, or to allow the patient to return home for a significant proportion of the remainder of life.

THE VALUE OF COLPOSCOPY IN THE DETECTION OF PRECLINICAL CARCINOMA OF THE CERVIX

DESPITE the continuing debate of surgeons and radiotherapists as to the best treatment of carcinoma of the cervix it is apparent that any significant improvement in the results of treatment lies not in any modification of existing treatment, but in the detection of earlier cases. The aim must be to detect this cancer before it is recognizable by the traditional methods of examination when it is in either a pre-invasive or early invasive stage (preclinical carcinoma of the cervix). The value of exfoliative cytology in this field is now universally accepted. However, there is a curious reluctance in many centres to employ the equally useful and complementary investigation of colposcopy. This method is in widespread use on the Continent of Europe but has made relatively little impression in the English-speaking countries. Recent valuable contributions on the subject include those of the inventor Hinselmann (1954), Mestwerdt (1953), Limburg (1952), Game (1953) and Navratil (1957). From the U S A . have come publications from Scheffey and his colleagues (1955) but as yet there have been no reports of its use in Great Britain although Stallworthy and Methuen (1958) are using the instrument in Oxford. The only report in British literature has been that of Youssefs (1957) experience in Egypt. It is necessary. to differentiate the techniques of colposcopy and colpomicroscopy. The colposcope with its stereoscopic magnification of 6 , 10 or 16 times shows mucous membrane changes on the cervix not visible to the naked eye, 5 P1. 11 whereas the colpomicroscope with magnifications of 80, 180 and 240 times, shows actual cell structure. A description of the technique of colpomicroscopy and favourable reports of its value are given by the inventors, Antoine and Grunberger (1 949, 1956) and Antoine (1 954), who use the method together with colposcopy and by Wolfe (1958). From my own personal experience, having studied both methods on the Continent and using both in this hospital, I believe the quicker method of colposcopy to be the more practical. Colpomicroscopy takes longer, is more uncomfortable for the patient, is more tedious due to the much smaller field of vision and the findings are more difficult to interpret. As neither method replaces cervical biopsy for the actual diagnosis, the value of colpomicroscopy would appear to be limited and the method will not be discussed further in this paper. The object of this paper is to discuss the first 3-years experience with colposcopy at King George V Memorial Hospital, Royal Prince Alfred Hospital, Sydney, and to assess the value of the method in the early diagnosis of carcinoma of the cervix.

Colposcopy in controversial problems associated with cervical carcinoma in situ.

On reading about cervical carcinoma in situ, one cannot fail to be impressed by the diametrically opposed views on certain basic points from leading clinics, usually where colposcopy is not practised. It is our contention that the latter technique will provide information of diagnostic, therapeutic and prognostic value that is unavailable by other methods. Colposcopic diagnosis depends mainly on the stereoscopic study of three phenomena otherwise unrecognisable: ( i ) changes in the capillary architecture of the epithelium, (ii) alterations in opacity of the (iii) alterations in epithelium.