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[Fluorescence diagnosis with 5-ALA thermogel of cervical intraepithelial neoplasia].

OBJECTIVE: To study the pharmacokinetics and selectivity of 5-aminolevulinic acid (5-ALA) from 5-ALA thermolabile gel formulation in cervical intraepithelial neoplasia (CIN). The novel thermogel Pluronic F127 is liquid at cold temperatures and turns into a gel-like consistency at body temperature, thereby improving adhesion of 5-ALA to the cervix uteri. METHODS: 27 female patients with CIN 1-3 were included in this study. Thirty minutes to 12 h before conisation, 10 mL of thermo-gel containing either 4, 10, or 20% of 5-ALA were topically applied to the cervix. Biopsies were taken from the lesions as well as normal surrounding epithelial tissue for histological examination, fluorescence microscopy and spectrometry. RESULTS: The thermogel Pluronic F127 was easy to handle and proved reliable as vehicle carrier. 5-ALA induced porphyrin fluorescence was maximal after application of 10% 5-ALA thermogel. We observed the higher porphyrin fluorescence intensity within the CIN lesions (1,116 +/- 241 AU), as compared to normal adjacent epithelium (704 +/- 166 AU). This difference was statistically significant (p < 0.05). Four to six hours after application, porphyrin fluorescence in dysplastic epithelium reached maximal intensity, and tumor selectivity was the highest in CIN 3 achieving a tumor-to-normal ratio of 3.5. Compared to other studies employing 5-ALA, the thermogel preparation of 5-ALA leads to twofold increase in the porphyrin selectivity. CONCLUSIONS: The thermogel Pluronic F127 seems to improve the local cervical drug application. Based on these results, we recommend the application of a 10% 5-ALA thermogel formulation 4-6 h prior to photodynamic therapy in CIN.

Adult↗

The case for cytologic follow-up after LEEP.

OBJECTIVE: To examine our loop electrocautery excisional procedure (LEEP) biopsy experience to assess the incidence of abnormal follow-up and relate this to margin status. STUDY DESIGN: Records of 162 LEEP procedures performed between January 1992 and April 1994 were reviewed to evaluate margin readability and status. All follow-up cytologic or histologic specimens were examined. RESULTS: After a mean 10.9-month follow-up, of 162 cases, 67 had a negative study (41.4%). Fifty-four (33.3%) had an abnormal result, with high grade squamous intraepithelial lesion (HSIL) in 16 cases (13.2%) of all LEEPs with follow-up, low grade squamous intraepithelial lesions in 27 (22.3%) and squamous atypia in 11 (9.1%). On microscopic review of these 54 cases, 37 had a readable margin (68.5%); of these readable margins, 12 (32.4%) were positive. Forty-one cases (25.3% of all LEEPs) had no follow-up study. CONCLUSION: The high incidence of HSIL after LEEP highlights the need for vigilant follow-up. Prediction of follow-up by margin status is dubious. Thermal artifact makes the margin uninterpretable in many cases, and two-thirds of cases with abnormal follow-up occurred where the LEEP margin was negative. Our finding of no follow-up for 25% of LEEPs performed is particularly disturbing in light of these results.

Artifacts↗

Carbon dioxide laser miniconization for treatment of human papillomavirus infection associated with cervical intraepithelial neoplasia.

BACKGROUND: The effect of the carbon dioxide laser miniconization for treatment of cervical intraepithelial neoplasia with concomitant human papillomavirus infection was evaluated. MATERIAL AND METHODS: One hundred and eighteen women with cytologically proven cervical intraepithelial neoplasia stage 1 and/or 2 were investigated with repeat vaginal smear, colposcopy and human papillomavirus DNA sampling. Seventy-five out of 118 women were subjected to laser miniconization or punch biopsy and cervical curettage. RESULTS: Out of 118 patients 37 proved to have positive human papillomavirus DNA with one or more oncogenic types (31.4%). Of these, 32 women were miniconized and five subjected to punch biopsy or cervical curettage. On the first follow-up after miniconization all 32 patients were HPV negative. With follow-up up to five years no recurrences of HPV or dysplasia were seen. CONCLUSION: A miniconization procedure with carbon dioxide laser for treatment of cervical intraepithelial neoplasia proved useful also for simultaneous therapy of concomitant human papillomavirus infection of the uterine cervix.

Carbon Dioxide↗

Endocervical cell retrieval following excisional treatment of CIN: a comparison study between large loop excision of the transformation zone and laser cone excision.

BACKGROUND: The purpose of our study was to compare laser cone excision with large loop excision of the transformation zone with particular respect to the retrieval of endocervical cells on follow-up cervical cytology. METHODS: Retrospective analysis of case records of 368 women who had large loop excision of the transformation zone and 188 women who had laser cone excision for suspected CIN changes at Middlemore Hospital, Auckland. RESULTS: The retrieval of endocervical cells on cervical cytology following large loop excision was 94.7% and 85.2% following laser cone excision. Laser cone excision was associated with a higher chance of normal follow-up cervical cytology. CONCLUSIONS: The retrieval of endocervical cells was satisfactory following both large loop excision and laser cone excision. Laser cone excision is recommended with large or more severe lesions.

Adenocarcinoma↗

Predictors of recurrent dysplasia after a cervical loop electrocautery excision procedure for CIN-3: a study of margin, endocervical gland, and quadrant involvement.

Loop electrocautery excision procedure (LEEP) increasingly is being used for the treatment of cervical intraepithelial neoplasia (CIN). Few published studies address the possible correlation between the histologic findings of the LEEP cone biopsy and the incidence of residual/recurrent dysplasia We identified 248 patients with CIN-3 treated by LEEP at the University of North Carolina from September 1991 through September 1996. Computerized files of these patients were then reviewed through August 1997 for pathology follow-up results. Two hundred patients had pathology follow-up and interpretable material. LEEP cone slides were reviewed to confirm CIN-3 and to assess involvement of margins, endocervical glands, and multiple quadrants. Cytologic and histologic follow-up data were categorized as negative or positive, with the latter including high-grade squamous intraepithelial lesions, low-grade squamous intraepithelial lesions, and atypical squamous cells of undetermined significance. Fifty-five patients (27.5%) had residual/recurrent dysplasia, including 36 high-grade squamous intraepithelial lesions (66%), 14 low-grade squamous intraepithelial lesions (25%), and 5 atypical squamous cells of undetermined significance (9%). Greater recurrence rates were noted for cases with high-grade dysplasia involving margins (39% positive vs. 15% negative; P = .0001), endocervical glands (33% positive vs. 14% negative; P = .0044), and multiple quadrants (33% multiple vs. 14% single; P = .0036). In cases with negative margins, greater recurrence rates were still observed with high-grade dysplasia involving endocervical glands (20% positive vs. 9% negative; P = .0808) and multiple quadrants (20% multiple vs. 8% single; P = .0495). Positive margins, positive glands, and multiple quadrant disease are all predictors of residual/recurrent dysplasia after LEEP. Surgical pathology reports for LEEP cone biopsy specimens should include information on the presence of high-grade dysplasia involving margins, endocervical glands, and multiple quadrants. Continued close follow-up is especially warranted for patients whose LEEP cone biopsy specimens contain any of these histologic predictors of residual/recurrent dysplasia.

Cervix Uteri↗

Management of adenocarcinoma in situ (ACIS) of the uteri cervix--a clinical dilemma.

OBJECTIVE: We retrospectively reviewed 24 cases of adenocarcinoma in-situ (ACIS) of the cervix, managed at KK Hospital, with the objective of determining our local approach to its treatment, the consequent clinical outcome and problems encountered. METHODS: Except for one case, all patients were treated between 1991-1996. Nineteen cone biopsies (17 laser and 2 cold knife) and eleven hysterectomies were performed. The mean follow-up duration was 20.5 months (range: 1-75 months). RESULTS: The mean age was 44.2 years (range: 32-68) with 80% of the cohort being more than 35 years old and the mean parity was 2.2. Six (25%) patients were symptomatic. Majority (21/23) had an abnormal initial Pap smear. Glandular lesions were found in 39% (9/23) of Pap smear, 28% (6/21) of colposcopy, 58% (8/14) of cervical biopsies and in 3 of 4 endocervical curettage. Of the 17 laser cone biopsy specimens, lesion involved the surgical margin in 6 patients (35%). ACIS was found in conjunction with CIN in 14 patients (58%). Five hysterectomies were performed for involved surgical margin and one for dubious surgical margin of the prior cone biopsy, of which 3 had residual ACIS. At the time of the study, there was no case of recurrent ACIS or overt adenocarcinoma developing following cone biopsy. CONCLUSION: Preconisation diagnosis of ACIS using Pap smear, colposcopy and cervical biopsy was found to be difficult in our series. Concurrent CIN occurred in a sizeable portion of patients. Laser cone biopsy was the preferred method employed. Total hysterectomy was frequently employed following cone biopsy for treating possible residual disease. We recommend greater vigilance for this condition especially in patients with CIN and the need for regular endocervical sampling in the follow-up of patients treated by cone biopsy.

Adenocarcinoma↗

[Contemporary model for treatment of erythroplakia].

In literature worldwide is still commonly used the term erosion to describe red areas within cervix around the external orifice. In such cases with negative cytology result, for cervical cancer prevention, the electrocoagulation or electro-conisation or other destructive operations are routinely used. Without colposcopy verification such management is inappropriate. The physician treats but does not know what he treats. It may be both common ectopy or regeneration zone so physiologic cervical states but it may be also CIN or even early cervical cancer, however cytologically negative. The first group of lesions is effectively diagnosed with colposcopy without additional diagnostic procedures and the CIN lesions are diagnosed in high percentage of accuracy. Not all of these lesions should be treated. In the group of colposcopically and cytologically unsuspected lesions just very extensive lesions with active mucous glands should be treated. Such lesions cause recurrent cervical inflammation. All other erythroplakia type lesions demand no treatment. The presence of ectopy around the external cervical orifice is just profitable for diagnosis of epithelial changes and cervical physiologic processes observation. All cases of abnormal colposcopy or cytology results, suspected of CIN should be treated as prevention of cervical cancer. In lower CIN grades electroresection (LEEP) is recommended, while in higher grades the cervical conisation is the appropriate mode of treatment.

Colposcopy↗

[LEEP in gynecologic practice].

The experience in performing LEEP electroconisation, the gaining popularity method of treatment in preneoplastic lesions of the uterine cervix was presented. The simplicity, safety and low number of complications of this out patient procedure was stressed. The attention was paid on diagnostic-therapeutic aspect of the procedure, the adequacy of histological specimen assessment, as well as on the excellent patient's toleration. The weak impact on anatomy and physiology of the uterine cervix was also pointed. The introduction of LEEP conisation to gynecological clinic bears in author's opinion simplification and cost effectiveness of diagnosis and treatment in selected cervical lesions.

Adult↗

[Electroconization with loop diathermy. A retrospective series of 307 cases].

The electroconization with diathermic loop is a good procedure in the cervical dysplasia because there is a respect of the cervical tissue with a low cost, low complications, easy and quickly technic and a precise histological analysis of the histologic specimen. The indications are represented by high grade lesions, cyto-histologic discordance and endocervical squamo-columnar junction with a low grade lesion. The authors proposed a retrospective study about 307 cases of the electroconization with diathermic loop realised between January 1993 and June 1998.

Adult↗

[Is there an increase of serum antisperm antibodies following surgery in the cervical transformation zone for cervical intraepithelial neoplasia (CIN)?].

OBJECTIVE: This prospective controlled study was performed to investigate whether operative procedures of the uterine cervix lead to a change in the titre of humoral antispermatozoal antibodies. MATERIAL AND METHODS: Humoral antispermatozoal antibodies were measured using an ELISA in 15 patients undergoing cervical scraping, 20 having conisation, 10 having a loop excision before and at least 3 months after surgery as well as in 10 fertile women as a control group. RESULTS: There were no significant differences in age between groups, in the distribution of initial and final levels of humoral antispermatozoal antibodies (IgG, IgA), and no significant change of the antibody titres (pre- and postoperative) within the individual groups. CONCLUSIONS: In patients of fertile age, the formation of humoral isoantibodies does not have to be taken into account in selecting the method of diagnosing and treating cervical intraepithelial neoplasia (CIN).

Adult↗

[Cervix dysplasias: study of Rb and p53 gene expression and correlation with mitotic activity].

OBJECTIVE: Certain HPV types have transforming properties. These oncogenic activities are related to the abilities of the viral proteins E6 and E7 to inhibit the products of two cellular tumor suppressor genes (p53 and Rb respectively). But the early steps of cervical carcinogenesis are not well known. The goal of our study was to evaluate cervical intraepithelial neoplasia (CIN) for the tumor suppressor genes p53 and pRb, the HPV status and the mitotic activity, in order to better understand the mechanism of carcinogenesis. MATERIAL AND METHODS: Twenty formalin-fixed paraffin-embedded cone biopsies were selected because they contained adjacent to normal epithelium different grades of CIN. Immunohistochemistry was performed for evaluation of PCNA, pRb and p53. Expression of these different biomarkers was assessed with the help of an image analysis system, in the different epithelial layers of the different normal and pathological cervical areas. The results were compared to normal controls. RESULTS: There is an increase of PCNA expression in normal epithelium adjacent to CIN, compared to normal controls. As tissues progress from adjacent normal epithelium to condylomatous lesion and to the different grades of CIN, PCNA expression increases (mainly in the superficial epithelial layers). For p53 and pRb, the expression is increased in the basal and parabasal layers of adjacent normal epithelium and condylomatous lesions. The observance of histologic signs of CIN is associated with a disappearance of p53 and pRB expression. CONCLUSIONS: These results indicate that the early steps of cervical carcinogenesis involve proliferative dysregulation in relation to the p53 and pRb modulatory mechanism. So expression of viral proteins of HPV is probably the earlier step of carcinogenesis in cervical carcinoma.

Conization↗

Large loop excision of the transformation zone for treating cervical intraepithelial neoplasia: a 12-year experience.

BACKGROUND: Although the existing evidence suggests that there is no obviously superior conservative method for treating cervical intraepithelial neoplasia (CIN), one of the most widely used is the large loop excision of the transformation zone (LLETZ). MATERIALS AND METHODS: A total of 897 women who were treated with LLETZ at our colposcopy clinic from 1989 to 2000 were retrospectively studied. RESULTS: Forty women did not have significant cervical pathology (4.5% over-treatment rate). Clear margins of excision were obtained in 748 (88.5%) of the 845 cases of CIN or microinvasive cancers. Treatment failure rates were 4.7% for clear margins and 26.8% for involved or uncertain. CONCLUSION: LLETZ is a fast and reliable method of treating CIN and microinvasive carcinoma. Generalized cauterization of the resulting crater should be avoided and satellite HPV lesions ablated. Involved margins have a higher treatmentfailure rate, therefore a larger excision is recommended as cervical craters regenerate. Treatment in pregnant women can be delayed until postpartum provided they have adequate surveillance during pregnancy.

Adult↗

Management of premalignant lesions of the cervix.

The screening, detection and treatment of precancer lesions of the cervix have resulted in a dramatic decline in the incidence of cervical cancer in many parts of the world. The effect is most pronounced in countries with organised screening. The proper management of premalignant lesions of the cervix is an important and integral part of any screening programme. The importance of proper colposcopic technique and the adherence to well-established colposcopic guidelines cannot be overemphasized to ensure appropriate treatment. The colposcope is indispensable in treatment planning as it guides the optimal amount of cervical tissue to be ablated or excised and the type of cone biopsy to be taken. Various methods of treatment involving ablative procedures and excisional procedures have been found to be highly efficacious and safe. The choice of treatment modality is very much dependent on individual preferences. However, in those with extensive high-grade lesions, an excisional method has the added advantage of detecting unsuspected microinvasive disease which can be missed if ablative methods are used. Although treatment for squamous intraepithelial neoplasia is well established, the treatment for adenocarcinoma-in-situ is more controversial. Newer methods of treatment are currently being developed to further improve on the good results achievable with present treatment modalities.

Catheter Ablation↗

[Cervical cytologic reports of ASCUS and LSIL. Cyto-histological correlation and implication for management].

BACKGROUND: The purpose of this retrospective study is to evaluate the appropriate management of ASCUS and LSIL pap smears by correlating the histological findings obtained by punch biopsy or excised specimens. METHODS: The study group included 584 women with abnormal pap smear: 358 with ASCUS and 226 with LSIL cytological abnormalities. All patients underwent colposcopy and, if necessary, directed-punch biopsy. In case of biopsy-proven dysplasia a destructive or excisional treatment was performed, as indicated. RESULTS: The prevalence of HPV-CIN histological lesions in ASCUS patients was 36.3% and in LSIL patients was 67.7%. High grade CIN was observed in 15.7 and 20.8% respectively. In one ASCUS patients an invasive lesion was diagnosed on punch biopsy and two LSIL patients showed stromal invasion on the final histopathologic report on excised specimens. CONCLUSIONS: Patients with ASCUS or LSIL pap smear exhibit a wide spectrum of histological findings ranging from no pathologic abnormality to frequent high grade CIN and invasive carcinoma in rare cases. Because of the histological assessment by directed-punch biopsy and its therapeutical indications, colposcopic examination is recommended for all women with a cytologic diagnosis of ASCUS and LSIL.

Adolescent↗

[Cancer and Pregnancy: the point of view of the obstetrician].

Onset of malignancy during pregnancy is distressing for the future parents and raises thorny problems for the oncologist and obstetric gynecologist. Many diagnostic and therapeutic approaches cannot be used. Some first-line reference treatments are known to cause fetal loss or severe birth defects, yet any delay in treatment may unacceptably worsen the maternal prognosis. In the absence of large randomized trials and cohort studies, it is difficult to know how best to manage these patients. An estimated one in ten thousand pregnancies are associated with malignancies, especially gynecologic tumors (cervix, breast, ovary), lymphomas, melanomas, brain tumors and leukemia. The obstetrician, in close collaboration with the oncologist, has a major role in choosing the most appropriate diagnostic and therapeutic strategy, and must keep the couple fully informed. Importantly, improvements in cancer cure rates and the development of conservative treatments mean that many of these young women can hope to start a new pregnancy after their treatment. The optimal interval between cure and conception must be carefully weighed up by a multidisciplinary team including oncologists and obstetric gynecologists. Chemotherapy, pelvic radiation therapy, and gynecologic surgery can impact not only on fertility but also on the course of a next pregnancy (increased risk of miscarriage and premature delivery, etc.). The obstetrician must take these risks into account.

Abortion, Induced↗