Pathology of colposcopic findings in 2635 diethylstilbestrol-exposed young women

An analysis of 6055 colposcopically directed biopsy specimens from 2635 diethylstilbestrol (DES)-exposed women and 445 biopsy specimens from 277 nonexposed women was undertaken to correlate microscopic findings with colposcopic patterns. All examinations were performed using a standardized protocol which required that each participant have colposcopy, cytologic smears, and biopsy of abnormal colposcopic lesions. The findings of colposcopic "columnar epithelium, gland openings, and Nabothian cysts" correlated most often with glandular epithelium in the biopsy specimen. "White epithelium," which includes three related colposcopic patterns, mosaicism, punctation, and white epithelium, was associated most frequently (82-93% of cases) with squamous metaplasia, but occasionally with dysplasia and carcinoma in situ (CIS)(0-6%). The presence of dysplasia or CIS in any individual biopsy specimen occurred most frequently with the observation of higher graded lesions by colposcopy or a prior diagnosis of dysplasia.     

Colposcopy in dysplasia, carcinoma in situ and microinvasive cancer of the cervix--systematic diagnosis

Recently colposcopy has come to be increasing used in the diagnosis of the early cervical cancer. We studied colposcopic findings (epithelial, vascular and glandular findings) of dysplasia, carcinoma in situ and microinvasive cancer of the uterine cervix. The results were as follows. We could classify the cases without white epithelium into microinvasive cancer and carcinoma in situ according to elevation or hollowness and roughness and the cases with I grade white epithelium (thin white epithelium) into severe dysplasia and mild or moderate dysplasia according to the existence of elevation, roughness, II type vessels and elevation of gland opening. Among the cases with II grade white epithelium (thick white epithelium) those without roughness, II type vessels and increased gland opening were mild or moderate dysplasia and most case with III or IV type vessels were microinvasive cancer. We concluded that more than half of the cases without III or IV type vessels spread to transverse pollution of white epithelium and lack or indefiniteness of gland opening, severe dysplasia with 0 finding, carcinoma in situ with 1 or 2 finding and microinvasive cancer with 3 findings. With these criteria, we were able to obtain high (93.4% with mean) correct diagnostic ratios.     

Advances in the management of advanced and recurrent uterine papillary serous carcinoma

Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer that accounts for 5–10% of all cases. Over 50% of the patients with UPSC present with advanced stage disease ⁽¹⁾ . Among patients with noninvasive uterine disease, 40% have advanced stage UPSC ⁽¹⁾ ; therefore, complete surgical staging is crucial to determine prognosis and treatment ⁽²⁾ . Optimal tumor debulking (<1cm) is associated with a better prognosis and improved overall survival ⁽³⁾ . After initial surgical staging, patients with high stage UPSC have an improved overall survival if treated with chemotherapy (platinum-based or paclitaxel-based therapy) ⁽¹⁾ . Even with chemotherapy, the disease free interval is approximately 1 year ^(4–6) . The role of radiation in these patients is unclear. Up to 30% of recurrences occur outside of the abdomen and pelvis (unpublished data). While the response rate to chemotherapy in the recurrent setting is up to 80%, the duration of response is approximately 7 months ^(4–6) . Because the disease free interval in the adjuvant setting and the duration of response in patients with recurrent disease is limited, better strategies are needed to treat patients with this disease. We have recently evaluated Her-2/neu overexpression and amplification in a series of patients with UPSC. Her-2/neu overexpression was independently associated with a poor prognosis, however the rate of specific gene amplification was only 3% ⁽⁷⁾ . We have found that imatinib-targeted kinases are overexpressed in UPSC ⁽⁸⁾ . We currently are evaluating imatinib (Gleevec, Novartis) and paclitaxel for the treatment of UPSC in patients with advanced or recurrent disease.     

Epidermal growth factor receptor status in four carcinoma of the cervix cell lines

We have evaluated aspects of the EGF receptor content of four human cell lines derived from patients with previously untreated carcinoma of the cervix. Scatchard analysis revealed that three of the lines possessed approximately 2×10⁵ low-affinity and 2×10⁴ high-affinity receptors, whereas the fourth line had approximately 9×10⁴ low-affinity receptors and 9×10³ high-affinity receptors. Immunocytochemical staining using the monoclonal antibody EGFR1 showed wide intra- and inter-line variation in staining intensity. Flow cytometric analysis of EGFR1 demonstrated a fivefold difference in staining intensity between lines. Thirteen cloned derivatives of one of the lines exhibited a 200% variation in EGFR1 staining intensity. There were no differences in radiosensitivity in four of the cloned lines with different EGF receptor levels. Southern blotting analysis did not reveal any rearrangement or amplication of the EGF receptor gene. These three different methods for determining receptor content produced variations in the ranking of receptor number across the four cell lines. These studies with cervix carcinoma cell lines demonstrate the presence of varied levels of EGF receptors according to the methodology used. This may reflect differences in biological characteristics of the cell lines evaluated.     

The serum pregnancy-specific β1-glycoprotein to betahuman chorionic gonadotrophin ratio as an index of prognosis in patients with choriocarcinoma

Summary. The ratio of serum pregnancy-specific β₁-glycoprotein (SP1) to the β-subunit of human chorionic gonadotrophin (β-hCG) before and after chemotherapy was measured in 12 patients with metastatic choriocarcinoma. The ratios before chemotherapy ranged between 0^.03 and 0^.75, with a mean value of 0^.34 (SD 0^.21). The ratio increased to over 1^.0 (1^.05–53^.3) after one or two courses of chemotherapy in seven of the 12 patients. These women achieved complete remission. In the other five patients who died of the disease due to drug resistance of the tumour, the ratio after chemotherapy was low (0^.04–0^.74) and tended to decline. These data suggest that the serum SPl/β-hCG ratio can be used to predict the prognosis of patients with choriocarcinoma.     

White Gland Openings of the Uterine Cervix — A Colposcopic, Cytological and Pathological Study

Summary: The significance of the gland openings with a white ring, in the colposcopic transformation zone, is reviewed and its importance discussed.
This picture was present in 9.8% of colposcopic examinations on 914 patients selected on cytological and/or clinical basis. In these 90 patients cytology suggested mild dysplasia in 22.4% and severe dysplasia, carcinoma in situ or invasive carcinoma in 14.4%. Histological study in 73 of the 90 patients showed mild dysplasia in 20.5%, severe dysplasia in 13.7%, carcinoma in situ in 9.6% and invasive carcinoma in 1.3%.
We were impressed by the fact that these carcinomas showed very striking, easily identifiable glandular openings. We believe that the colposcopic study of the white gland openings is important, since they can be the only site where lesions are detected.     

Paclitaxel in combination with cisplatin is less effective for peripheral blood progenitor cell mobilization

Abstract. Kurata H, Takakuwa K, Tsuneki I, Aoki Y, Tanaka K. Paclitaxel in combination with cisplatin is less effective for peripheral blood progenitor cell mobilization.
The purpose of this study was to determine the efficacy of paclitaxel in combination with cisplatin and granulocyte-colony stimulating factor (G-CSF) for mobilization of peripheral blood progenitor cells (PBPC). Twenty-seven patients with gynecological cancer received paclitaxel and cisplatin (TP, n = 9) or other platinum-based chemotherapy ( n = 18) (etoposide and cisplatin [ n = 5]; cyclophosphamide, adriamycin, and cisplatin [ n = 8]; or pepleomycin, etoposide, and cysplatin [ n = 5]). Each combination was followed by G-CSF. The mean number of colony-forming unit granulocyte macrophage (CFU-GM)/kg and CD34⁺ cells/kg collected per cycle was 1.2 × 10⁵ and 0.8 × 10⁶ after the TP regimen, compared with 2.6 × 10⁵ ( P < 0.05) and 2.0 × 10⁶ for patients who received other platinum-based chemotherapy. The CFU-GM target yield (≥1.0 × 10⁵/kg) was achieved in 56% and 83% patients in the TP and comparison group, respectively. With the TP regimen, a younger age (≤50 years of age) and fewer prior chemotherapy cycles (≤2) were associated with the CFU-GM targeted yield (<0.05). In conclusion, TP mobilized PBPC less effectively than other platinum-based chemotherapy. Therefore, the TP regimen may need to be changed to another appropriate regimen when PBPC mobilization is planned for high-dose chemotherapy in gynecological cancer patients.     

Vaginal intraepithelial neoplasia: Biologic aspects and treatment with topical 5-fluorouracil and the carbon dioxide laser

A review of 41 evaluable patients was made in order to study vaginal intraepithelial neoplasia (VAIN) and to investigate new methods of treatment. Colposcopic examination of the vagina revealed white epithelium alone in 20 patients and white epithelium associated with vascular punctation in 15. No lesion had a vascular mosaic pattern. Most patients had multifocal disease located in the vaginal apex. Iodine staining was positive in six patients with negative colposcopic examinations. Twenty-four patients had severe dysplasia or carcinoma in situ, and 17 had minimal or moderate dyplasia. Associated genital disease occurred in 17 patients with antecedent cervical or vulvar squamous neoplasia, and six additional patients had coexistent lesions. The chronology of vaginal disease that appeared after treatment of cervical neoplasia suggests a persistent but decreasing likelihood of the development of VAIN with the passage of time. In patients followed without therapy, six had spontaneous remission of disease. Treatment was successful in 12 of 15 patients with topical 5-fluorouracil and in nine of 10 patients with the carbon dioxide laser. The advantage of these methods of treatment for patients with VAIN relative to surgical procedures and radiation therapy are considered.     

Infection by human papillomavirus types 6, 11, 16, 18, 31, 33 and 35 of the cervix in Japanese women

Exfoliated cervical cells from 321 Japanese women were examined for human papillomavirus (HPV) DNA types 6, 11, 16, 18, 31, 33 and 35 using polymerase chain reaction (PCR) and dot-blot hybridization methods. HPV DNA was present in 9.3% of patients with normal cervixes, 72.7% of patients with cervical intraepithelial neoplasia (CIN) and 77.8% of patients with invasive carcinoma. Younger patients (29 years) with normal cervixes had a 18.5% incidence of HPV DNA, whilst similar older patients (50 years) had a 1.9% incidence, a significant difference (χ²= 6.478, P < 0.01). In the CIN I and II groups, an incidence of 11.1% of types 16 and 18 was found, while in the CIN III or invasive carcinoma group the incidence was 58.1%, again a significant difference (χ² = 12.075, P < 0.01). Furthermore, persistence or progression of CIN showed a significant correlation with infections by types 16 and 33 (χ²= 4.904, P < 0.01). However, no significantly different incidence of HPV infection was found between the CIN and the invasive carcinoma groups. It is suggested that (a) younger patients with normal cervixes have a higher incidence of HPV infection than do older patients; (b) HPV types 16, 18 and 33 are important etiologic agents of CIN III and invasive carcinoma, as well as in the persistence and progression of CIN; (c) progression of CIN to invasive carcinoma may depend on factors other than HPV infection in the cervix.     

Colposcopic accuracy in the diagnosis of microinvasive and occult invasive carcinoma of the cervix

One hundred eighty patients with microinvasive and occult invasive squamous cell carcinoma of the cervix who were examined by colposcopy during a ten-year period are reviewed. Forty-two percent of patients with microinvasive carcinoma and 28% of patients with occult invasive carcinoma had an unsatisfactory colposcopic examination. Colposcopy led to the correct management in 90% of patients with occult invasive cancer and in 84% of patients with microinvasive carcinoma. Colposcopy appeared to be less sensitive in detecting microinvasive lesions than in detecting occult carcinoma. Two-thirds of the errors made were colposcopist-related, either failure of interpretation or protocol violation. A small but definite group of patients will have lesions whose colposcopic appearance is not sufficiently distinct or characteristic to permit a diagnosis of early invasion.     

Immunocompetent for immunotherapy? A study of the immunocompetence of cervical cancer patients

Sixty-five patients with cervical carcinoma and 17 control subjects were studied to determine immunocompetence as a prerequisite for immunotherapy using live virus vectors. T-cell immunity, measured by surface phenotype and proliferative assays, was reduced with increasing volume of invasive disease, and independent of treatment effects. Both the CD4⁺ and CD8⁺ subsets were affected so that the CD4:8 ratio remained within normal limits. In contrast B-cell number, immunoglobulins and complement were normal as were in vivo responses to a polysaccharide vaccine. Thus, determination of immunocompetence prior to use of live vector immunotherapy requires assessment of each individual subject, especially in those with advanced disease.     

2468例阴道镜检查与病理学诊断结果分析

用阴道镜活检２４６８例妇科门诊患者，在异常阴道镜图像中，白色上皮、腺口白环、白斑、点状血管、异形血管、镶嵌、明显癌及非典型增生的检出率分别为５．６％、１０．４％、１６．０％、１６．０％、１７．４％、２０．３％和７９．２％。腺口白环的癌及非典型增生的检出率为１０．４％。阴道细胞涂片中的Ⅲ、Ⅳ和Ⅴ级涂片中癌的检出率分别为２１．７％、６５．５％和９２％。涂片的级别与异常阴道镜图像有明显的关系。     

Comparison of CO2 laser surgery and loop electrosurgical excision/fulguration procedure (LEEP) for the treatment of vulvar intraepithelial neoplasia (VIN)

The aim of this open clinical trial was to evaluate the therapeutic effectiveness of CO₂ laser vs. loop electrosurgical excision/fulguration procedure (LEEP) in 28 patients with vulvar intraepithelial neoplasia (VIN) (mean linear extent = 6 cm²). To avoid selection bias, in each patient half of the lesional area was treated with CO₂ laser excision/vaporization and the other half was electro-excised/fulgurated. All but three patients (89%) were followed for a minimum of 9 months, maximum 26 months, mean 12 months after last therapy. Complete response was obtained in 12 of 25 patients (48%) after a single laser/LEEP most of whom had 6 cm² or less lesional area. Repeated treatments(mean 3) yielded 19 of 25 (76%) disease-free patients at 9 months or longer. There was no significant (χ²) difference between the CO₂ laser- or LEEP-treated areas with respect to recurrence of disease, healing time (mean 18 days), postoperative discomfort (61%) and complications (11%)). The overall operating time when controlled for lesional size was twice as fast with the CO₂ laser (mean 8 min) than LEEP (mean 20 min). Laser and LEEP were more suitable for ablational and excisional procedures, respectively. LEEP may be an alternative to CO₂ laser for treating VIN, particularly those with a linear extent less than 6 cm².     

Colpo-cyto-histological correlations in intraepithelial lesions of the uterine cervix]

The aim of this study was to assess the clinical efficiency of colposcopic findings as diagnostic tests for intraepithelial lesion using the analysis of colpo-cyto-histological correlations. The results of 3340 colposcopic tests performed in the Colposcopy Unit of the Second Clinic of Obstetrics and Gynecology between March 1990 and May 1991 were analysed, taking into account 326 (9.7%) cases of Abnormal Transformation Zone (ANTZ). The colpo-histological correlation in ANTZ 1 cases (52 cases of white epithelium, 92 standard mosaic, 42 standard dotted and 61 mixed cases) was 65.2% (52.3%) for HPV; 12.9% for CIN). The colpo-histological correlation in ANTZ 2 cases (30 cases of thickened white epithelium, 5 irregular mosaic, 4 irregular dotted, 2 atypical vessels, 4 thickened gland outlets and 6 mixed cases) was 70.5% (43.3% for HPV; 27.2% for CIN an and Ca). In this retrospective study colposcopy showed a diagnostic accuracy of 64.6% in the cases examined and played a decisive role in the diagnosis of intraepithelial lesions of the uterine cervix.     

Standard dose cisplatin with rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer

We have investigated the feasibility of a program of autologous peripheral blood stem cell (PBSC) harvesting and transplantation in patients with ovarian cancer. From four patients, PBSC was collected during hematopoietic recovery following aplasia induced by standard dose cisplatin 70 mg m⁻² with etoposide 500 mg m⁻² or adriamycin 40 mg m⁻² and cyclophosphamide 500 mg m⁻² plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) at a dose of 75 µg day⁻¹ given intracutaneously. In apheresed patients, we harvested an average of 2.31 × 10⁵ kg⁻¹ colony-forming unit granulocyte/macrophage (range 0–5.22) per cycle. Low hematologic toxicity was observed during the hematopoietic reconstitution of the four patients subjected to PBSC support with G-CSF (5 µg kg⁻¹ day⁻¹ given by continuous infusion) after high-dose chemotherapy (carboplatin 900 mg m⁻² and etoposide 900 mg m⁻²). The patients were not evaluable for a response because we performed consolidated high-dose chemotherapy. However, no evidence of recurrence has been observed 11.8 months (range 2–19) after high-dose chemotherapy. We can conclude that standard dose cisplatin in combination with etoposide or adriamycin and cyclophosphamide plus rhG-CSF allows sufficient harvesting of PBSC for autotransplantation in patients with ovarian cancer.     

Incidence of urinary incontinence and constipation during pregnancy and postpartum: survey of current findings at the Rotunda Lying-in Hospital

Objective To assess the impact of pregnancy upon continence and constipation.
Design A questionnaire survey.
Setting Maternity wards in the Rotunda Lying In Hospital, Dublin, Republic of Ireland.
Population 7771 women who were delivered of liveborn infants.
Methods Questionnaires were delivered and collected by physiotherapy staff as part of routine postnatal care.
Results Analysis of data using χ² tests showed significant differences between three parity groups [primigravidae, multigravidae (2–4) and multigravidae (5+)] for symptoms of both urinary incontinence (  χ²= 119.54  , df = 2, P = 0.000) and constipation (  χ²= 12.53  , df = 3, P = 0.002); the incidence of both constipation and urinary incontinence increased with parity.
Conclusion The results of this survey have emphasised the relation between parity and postpartum incontinence which stresses the importance of early diagnosis and intervention.     

Platelet angiotensin II binding sites in normotensive and hypertensive women

Summary. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10⁹ cells) when compared with the non-pregnant women (9.0 fmol/10⁹ cells   P <0.001  ). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10⁹ cells) when compared with the 25 normotensive pregnant women (   P <0.001  ). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10⁹ cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10⁹ cells) although the difference was not statistically significant (   P <0.04  ). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy.     

Histologic and immunohistochemical analysis of tissue response to adenovirus-mediated herpes simplex thymidine kinase gene therapy of ovarian cancer

Abstract. Hasenburg A, Fischer DC, Tong X-W, Rojas-Martinez A, Nyberg-Hoffman C, Orlowska-Volk M, Kohlberger P, Kaufman RH, Ramzy I, Aguilar-Cordova E, Kieback DG. Histologic and immunohistochemical analysis of tissue response to adenovirus-mediated herpes simplex thymidine kinase gene therapy of ovarian cancer.
Herpes simplex virus (HSV) thymidine kinase (tk) gene incorporated into adenovirus was delivered intraperitoneally (ip) followed by an antiherpetic prodrug and topotecan in patients with recurrent epithelial ovarian cancer. Tissue response was evaluated. Ten patients underwent secondary debulking with subsequent delivery of ADV-HSV-tk therapy. Two patients each were treated at dose level 1 (2 × 10¹⁰ vector particles = VP), 2 (2 × 10¹¹ VP), and 3 (2 × 10¹² VP); four patients were treated at dose level 4 (2 × 10¹³ VP). Five patients underwent second-look surgery about one month after gene therapy (GT). Treatment response, presence of vector DNA, protein expression of steroid hormone receptors, p53, c-erbB2 and Ki67 protein were analyzed.   At second-look, two out of five patients were tumor-free and none of their peritoneal biopsies showed vector DNA. After GT, the vital tumor mass was smaller, desmoplastic reaction had increased, and tumors were less differentiated with an increase of Ki67 expression. There was no change in expression of hormone receptors, p53, or c-erbB2. ADV-HSV-tk GT appears to eliminate cells with higher differentiation first and might induce fibrosis. Dedifferentiation might render residual cells more sensitive to chemotherapy secondary to their subsequent higher mitotic activity.     

Dexamethasone-induced leucocytosis in pregnancy

The effect of intramuscular dexamethasone administration in late pregnancy on the maternal peripheral white cell count was examined in 20 women. The mean total white cell count increased from a baseline of 11–3 × 10⁹/L (SD 2–3) to 16–2 × 10⁹/L (SD 4–6) on day 1, normalising thereafter. This 43% increase represented composite changes in the neutrophil and lymphocyte counts which, on average, increased by 62% and decreased by 22%, respectively. It is concluded that prenatal dexamethasone induces a significant neutrophilia on the first day following administration. This information may be helpful when monitoring for infection.     

The role of 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG PET) in diagnosis of ovarian cancer

We evaluated the clinical significance of ¹⁸F-FDG PET to detect malignant ovarian neoplasms and tumor spread. 40 patients (median age: 57.5 years) underwent laparotomy because of clinical suspicion of malignant ovarian tumors or recurrent disease. The results of the preoperatively performed PET were correlated with the postoperative histologic diagnosis and the intraoperatively assessed tumor spread. In 10 of 40 patients benign tumors were found, among which a tubo-ovarian abscess was the only one diagnosed as false positive. 4/30 malignant neoplasms did not originate from the coelomic epithelium, but all were correctly recognized as malignant tumors by PET, as was recurrent ovarian cancer in 12 patients. Out of 14 primary ovarian carcinomas, 2 borderline tumors and 1 well-differentiated adenocarcinoma FIGO stage I were not correctly identified. Considering the tumor type, sensitivity, and specificity were 90%, calculating for the positive and negative predictive value 96% and 75%, respectively, and 90% for the diagnostic accuracy. Those statistical parameters were slightly lower for PET detection of lymph node metastasis and peritoneal carcinomatosis. Although its diagnostic accuracy may vary depending on the clinical application, ¹⁸F-FDG PET is basically a suitable method for detecting ovarian malignancies, particularly in patients with relapsed ovarian carcinoma.