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Microinvasive carcinoma of the cervix.

The clinical and pathologic features of 51 cases of microinvasive carcinoma of the cervix treated by radical hysterectomy and pelvic lymphadenectomy are presented. Microinvasion was defined as stromal penetration by carcinoma not exceeding a depth of 5 mm from the surface at the point of origin. Patients with confluent patterns and lymphatic invasion were not excluded. Lymphatic invasion was demonstrated in 24% of the patients, but none of the resected lymph nodes from the entire series contained metastatic tumor. Residual invasive disease was present in 9 of 47 patients who underwent conization including 1 in which the residual tumor invaded to 8 mm, although the depth of invasion in the cone biopsy was only 2.5 mm. Factors related to the presence of residual invasive disease included the pattern and extent of invasion and involvement of the cone margin. There were no surgery-related deaths or fistulae in this series; the actuarial survival rate at 5 years was 100%. Simple hysterectomy seems justified if the cone margin is free of tumor since none of these patients has residual disease. In contrast, radical hysterectomy may be indicated if the cone margins are involved in view of high frequency of residual tumor (39%) and the possibility of invasion in the cervix exceeding 5 mm.

Adult↗

[Management of female genital HPV infections by the LEEP method (Loop Electrosurgical Excisional Procedure)].

METHOD: Two different groups of women have been selected: group A (120 patients), affected by genital warts and ectropion, treated only with destructive therapy by means of LEEP (Loop Electrosurgical Excisional Procedure) with spheric electrod, while group B (20 patients), of which two affected by CIN I and resistant to other treatments for a period longer than 12 months, and 18 patients with a histologic diagnosis of CIN II, CINIII/HPV, treated with conization by LEEP method. After therapy, a follow-up has been carried out, with colposcopic, cytologic, histologic control, scheduled 1-3-6-12 months after therapy. RESULTS: The results proved positive, since recovery in the two groups (A and B), after treatment, has been 100% with no complications, verified by follow-up after 12 months. CONCLUSIONS: The introduction of LEEP, represents a simple alternative, fast, painless practical, at a minimum cost to the patient and the community, devoid of complications, without general anaesthesia in the treatment of CIN as well as of genital warts, substituting in this last case the loop with a sphere electrode. Moreover, it does not affect the function, as well as the anatomy of the organ, a primary factor is young patients desiring children. This technique permits to obtain at the end of the operation one or more tissue fragments to be used for histological examinations, with free margins from necrotic border, assuring the integrity of the tissue, and thus leading a correct diagnosis.

Adult↗

Cidofovir, a new approach for the treatment of cervix intraepithelial neoplasia grade III (CIN III).

Cervix intraepithelial neoplasia grade III (CIN III) is an intraepithelial proliferative process with different levels of severity depending on both the extension of the proliferation in the epithelium and the presence of cellular atypia. Human papillomavirus (HPV) has been clearly associated with such lesions. The results of a preliminary study are described on the local application of cidofovir, an acyclic nucleoside phosphonate derivative with broad-spectrum anti-DNA virus activity for the treatment of CIN III. Cidofovir 1% in gel was applied three times, every other day, on the cervix of each of 15 women with biopsy proven CIN III. Within 1 month after the start of treatment, the cervix was removed surgically. Histology and human papillomavirus polymerase chain reaction (HPV-PCR) were carried out. In 7 of the 15 patients the histology showed a complete response, whereas 5 patients had a partial response characterized by the persistence of CIN II-III lesions, 1 patient had a dysplasia of lower grade (CIN I), and 2 patients did not show differences in the histology. Complete response was confirmed by PCR in 4 of the 7 patients, with complete response histologically. Cidofovir was not toxic to the normal epithelium. Cidofovir 1% gel was able to inhibit partially or completely cervical dysplasia lesions after only three applications (every other day). This effect was specific and tissue other than the dysplastic epithelium was not affected by the treatment.

Adult↗

Management of pre-invasive disease of the cervix.

The management of pre-invasive disease of the cervix is based on local control and prevention of progression to invasive malignancy. Screening continues to be an effective tool for detecting cervical neoplasia in a pre-invasive state due to the long natural history of progression from low-grade dysplasia to invasion. When abnormal cells are detected with a Papanicolaou (Pap) smear, a thorough evaluation should consist of colposcopy, directed biopsy, and cone biopsy, where appropriate. In the absence of invasion, local control may be achieved by excisional or ablative techniques including traditional cold-knife cone, laser cone, loop electrosurgical excision, cryotherapy, laser or electrocoagulation diathermy. The benefit of excisional therapy is the ability for histologic specimen assessment. Ablative therapies are associated with lower complication rates (<2%). Success rates for these modalities are comparable, exceeding 90%. Eradication of human papilloma virus (HPV) from the genitourinary tract [associated with over 90% of condylomas, cervical intraepithelial neoplasia (CIN) and invasive malignancies] is not possible with currently available techniques.

Colposcopy↗

Second trimester therapeutic abortion using mifepristone and oral misoprostol in a woman with two previous caesarean sections and a cone biopsy.

Most regimes for medical termination use an antiprogesterone and a vaginal prostaglandin. Concern remains about its safety in women with previous caesarean births. We present a case of successful therapeutic mid-trimester termination in a woman with two previous caesarean births and cervical surgery using an antiprogesterone and an oral prostaglandin.

Abortifacient Agents↗

Surgery for cervical intraepithelial neoplasia.

OBJECTIVES: Cervical intra-epithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the severity of the disease. The objective of this review was to assess the effects of alternative surgical treatments for cervical intra-epithelial neoplasia. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to July 1997. SELECTION CRITERIA: Randomised and quasi-randomised trials of alternative surgical treatments in women with cervical intra-epithelial neoplasia. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two reviewers abstracted data independently. MAIN RESULTS: Twenty-three trials were included. Seven surgical techniques were tested in various comparisons. No significant difference in eradication of disease was shown, other than between laser ablation and loop excision. This was based on one trial where the quality of randomisation was doubtful. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology. Morbidity was lower than with laser conisation, although all five trials did not provide data for every outcome. There were not enough data to assess the effect on morbidity compared with laser ablation. REVIEWER'S CONCLUSIONS: The evidence suggests that there is no obviously superior surgical technique for treating cervical intra-epithelial neoplasia.

Conization↗

False-positive squamous cell carcinoma in cervical smears: cytologic-histologic correlation in 19 cases.

Cytologic features of squamous intraepithelial lesions (SIL) can mimic those of invasive squamous-cell carcinoma. We compare and correlate the cytological findings of 19 false-positive squamous-cell carcinomas with follow-up cone biopsies or hysterectomy specimens to define which type of dysplasia is more prone to diagnostic errors on cervical Papanicolaou (Pap) smears. Out of 128 patients diagnosed with invasive squamous-cell carcinoma from 1994-2000, 19 (14.8%) with follow-up cone biopsies or hysterectomy specimens were false-positive cases, showing only cervical intraepithelial neoplasia (CIN). We reviewed tissue sections from these 19 cases of CIN for cytologic features of squamous-cell carcinoma, such as markedly pleomorphic and/or dysplastic squamous cells, necrosis, and nucleoli. Twelve of 19 patients (63%) were menopausal. The mean age was 50.5 yr. On review of cervical smears, 18 cases qualified for the cytologic diagnosis of squamous-cell carcinoma, keratinizing type, and one case qualified for squamous-cell carcinoma, nonkeratinizing type. Pleomorphic and/or keratinizing dysplasia was found in 15 out of 19 patients (79%), necrosis within superficial endocervical glands in 9 out of 19 patients (47%), and conspicuous nucleoli in 12 out of 19 patients (63%). One or more of these changes were seen in all but 2 patients (89%). Endocervical gland involvement was present and extensive in 18 of the 19 cases (94%). The mean age was older than expected for SIL (50.5 vs. a reported 40), and matched the mean age found in patients with invasive squamous-cell carcinoma. Pleomorphic and/or keratinizing dysplasia involving endocervical glands may exhibit the cytologic features of squamous-cell carcinoma on cervical Pap smears.

Carcinoma, Squamous Cell↗

Microinvasive carcinoma of the uterine cervix: histological findings on cone specimens related to residual neoplasia on hysterectomy.

The treatment of cervical microinvasive carcinoma is controversial. Hysterectomy is performed in almost all cases, associated or not with more radical procedures. Currently, there is a tendency to adopt conservative management to treat patients with early invasion, as long as it can be assured that the whole lesion has been removed. The aim of this study was to establish which histological information should be obtained from the cones that would give the best possible assurance of absence of residual neoplasia in the patient. This was done by comparing cone and hysterectomy specimens from each patient. One hundred sixty-three cases, treated from 1967 to 1994, underwent simple or radical hysterectomy following cone biopsy. We evaluated the following histological features in the cones: (i) invasion depth, (ii) lateral extension of the lesion, (iii) unifocal or extensive lesion, (iv) vascular invasion, (v) morphological signs of HPV infection, and (vi) free or involved cone surgical margins. Residual neoplasia in the hysterectomy was more frequent when the margins of the cone were involved by atypical epithelium, and in cases with signs of HPV infection. However, according to statistical analysis, these two variables were not mutually independent, and the only important parameter to predict residual neoplasia in the hysterectomy specimens was involved surgical margins in the cone.

Adult↗

Adenocarcinoma in situ of the cervix: management and outcome.

OBJECTIVE: The aim of this study was to review the management and outcome of patients with adenocarcinoma in situ of the cervix and to evaluate the significance of endocervical cone margin status in these patients. METHODS: A retrospective review of records between January 1988 and December 1996 identified 40 patients with adenocarcinoma in situ on cone biopsy for whom complete information was available. The median follow-up was 38 months. RESULTS: The mean age was 37 years, and the mean parity was 1.3. Fifty-three percent of the patients had prior abnormal cervical cytology. The initial Pap smear that led to the patient's referral was abnormal in 39 (98%). Initial cervical biopsies showed adenocarcinoma in situ and/or glandular dysplasia in 28 (70%), squamous dysplasia in 2 (5%), chronic inflammation in 2 (5%), and no pathologic changes in 2 (5%) patients. Initially no biopsies were performed in 3 (7.5%) patients and the results of 3 (7.5%) biopsies were unknown. Subsequently, all patients had cone biopsies. The endocervical margins were positive for glandular abnormalities in 24% of cold knife cones (CKC), 75% of LEEPs, and 57% of laser cones. The ectocervical margins were positive for squamous and/or glandular abnormalities in 8% of CKCs, 13% of LEEPs, and 57% of laser cones. ECCs above the cone were obtained in 28 patients, and only 1 (3%) was positive. The definitive treatment was hysterectomy in 27, repeat cone in 5, and no additional therapy in 8 patients. The pathology showed residual disease in 44% of treated patients. From 16 cone biopsies with negative margins who had subsequent treatment, there was residual disease in 5 (31%) specimens (1 adenocarcinoma in situ, 1 mild glandular dysplasia, 3 glandular atypia). From 16 cones with positive margins who had subsequent treatment, there was residual disease in 9 (56%) specimens. The patients with negative ECCs above the cone regardless of margin status had residual disease in 58% of treated specimens. CONCLUSION: Women with adenocarcinoma in situ of the uterine cervix had residual disease in 31% of cases with negative margins in cone biopsies and/or with negative ECCs and in 56% of cases with positive endocervical margins. LEEP cones had higher rate of positive endocervical margins (75%) compared to CKC (24%) and laser cone (57%). If maintaining reproductive capacity is desired, we would recommend CKC; however, this does not guarantee absence of the disease.

Adenocarcinoma↗

Unusual recurrence of cervical adenosquamous carcinoma after conservative surgery.

The use of less radical procedures for the treatment of early cervical cancers is gaining interest among physicians and young patients. Some authors have described surgical procedures aimed at reducing the surgical aggressiveness but the safety of such procedures remains debated. After a polypectomy, a young patient had a diagnosis of stage Ia(2) cervical adenosquamous carcinoma in 1995. As she wished to preserve her fertility, she underwent a cone biopsy and pelvic lymphadenectomy, without evidence of tumor spread. In 1998, at the 13th week of gestation, she had a diagnosis of a pelvic mass. The mass was a recurrence of carcinoma involving the myometrium, just underneath the peritoneum. She underwent a radical hysterectomy with bilateral oophorectomy. An ovarian metastasis was also detected at pathological exam. She received chemotherapy postoperatively and remains alive without evidence of disease. The recurrence of cervical cancer is traditionally regarded as an issue concerning the cervix, the parametria, or the lymph nodes. When the uterus is preserved we must also consider the possibility of a recurrence involving the corpus. With wider acceptance of limited therapeutic approaches we must be prepared for the detection of previously unknown patterns of recurrence and the follow-up modalities must be consequently adapted.

Adult↗

Conservative management of adenocarcinoma in situ of the cervix.

OBJECTIVE: The purpose of this study was to determine the method of treatment and outcome of women with cervical adenocarcinoma in situ (AIS). METHODS: Following institutional review board approval, all women diagnosed with cervical AIS from 1987 to 1999 were identified. Data were retrospectively collected by record review and correspondence with medical providers. RESULTS: Of 132 women treated with cone biopsy for AIS, 95 (72%) were managed conservatively after cold knife cone or loop electrical excisional procedure alone; 37 (28%) eventually underwent hysterectomy. The median age of diagnosis was 29 years (range, 17-47) in the conservative management group and 40 years (range, 25-72) in the hysterectomy group (P < 0.0001). Seventy-four percent were nulliparous in the conservative group compared with 27% in the hysterectomy group (P < 0.0001). Of the 95 conservatively managed patients, 92 obtained negative margins; three were followed despite positive or unevaluable margins. During a median follow-up of 30 months, 9 women required evaluation for follow-up abnormalities after cone biopsy with negative margins. None had pathologic evidence of recurrent AIS. Twenty-three infants were delivered. Hysterectomy was generally performed for undesired fertility or persistently positive cone margins. One woman required hysterectomy for recurrent AIS. Thirteen (62%) of twenty-one hysterectomy specimens had residual AIS following cone biopsy with positive or unevaluable margins; 1 (6%) of 16 had residual AIS following cone biopsy with negative margins (P < 0.0001). No patient developed invasive adenocarcinoma. CONCLUSIONS: Younger women with cervical AIS may be effectively treated with cone biopsy alone if negative margins can be achieved.

Adenocarcinoma↗

Negative MRI findings with invasive cervical biopsy may indicate stage IA cervical carcinoma.

OBJECTIVE: We attempted to prospectively determine the role of magnetic resonance imaging (MRI) in very early cervical cancer. STUDY DESIGN: T2-weighted and T1-dynamic enhanced images from patients with invasive or noninvasive lesions of the cervix were reviewed by two radiologists who had no clinical information on these patients. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. RESULTS: Seventy-nine cases were entered into the study and 75 were evaluable. Accuracy of T2 MR images for invasive and noninvasive disease by Radiologist 1 and Radiologist 2 was 0.8533 and 0.7733, respectively. Accuracy was greater (0.9867 and 0.9467, respectively) for the detection of noninvasive plus microinvasive lesions </=5 mm vs invasive lesions >5 mm. Dynamic technique provided only limited additional value in the detection of microinvasive cervical carcinoma. CONCLUSION: Simple T2 MRI is useful in differentiating noninvasive or microinvasive cervical lesions from invasive cervical carcinoma of the cervix >5 mm.

Adult↗

Laparoscopic assessment of the sentinel lymph node in early stage cervical cancer.

OBJECTIVE: The aim of this study was to describe a minimally invasive technique enabling us to identify the sentinel lymph node in patients affected by early stage cervical cancer and to report the preliminary data. METHOD: Patent Blue Violet was injected around the tumor. Laparoscopy was undertaken and the blue-dyed lymph nodes (BDLN) were sought. The evidenced BDLN were removed, and then the systematic dissection was carried out. Material. Thirty-five patients were submitted to surgery. A systematic dissection was performed on 69 pelvic sidewalls (no dissection was performed on the second side of the patient for whom we decided to renounce surgery after assessment of the first side). RESULTS: One or more BDLN was evidenced in 59 of 69 dissections. The rate of failure depends on the quantity of injected blue dye. Failure to identify a BDLN depended on the quantity of injected blue dye: 3 of 6 (50%) for 1.5 ml or less, 3 of 18 (17%) for 2 ml, and only 4 of 45 (10%) after injection of 4 ml (P = 0.05). Among the 63 BDLN (in 4 cases 2 BDLN were identified), 53 were located in contact with the external iliac vein, lateral to the inferior vesical artery, and ventral to the origin of the uterine artery, 7 were located close to the origin of one of the collaterals of the internal iliac artery, and 3 were adjacent to the left common iliac vein. One or more positive pelvic lymph nodes was found in 11 pelvic wall dissections done on 8 patients. The BDLN was the positive node or one of them in all cases. CONCLUSION: If the sensitivity of the assessment of the BDLN is confirmed to be 100%, this laparoscopic approach could transform the management of early cervical cancer.

Adenocarcinoma↗

LLETZ.

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Colposcopy↗

Delivery outcomes following loop electrosurgical excision procedure for microinvasive (FIGO stage IA1) cervical cancer.

OBJECTIVE: The goal of this study was to report the delivery outcomes in women who had loop electrosurgical excision procedure (LEEP) for microinvasive cervical cancer (stage IA1 without lymphovascular invasion) and became pregnant and progressed beyond 24 weeks. METHODS: A case-control study was performed. Twenty-eight women who were managed exclusively with LEEP for microinvasive cervical carcinoma had at least one pregnancy beyond 24 weeks and were the cases. Each case was matched with one woman who delivered at the same department without prior treatment of her cervix (controls) and their delivery outcomes were compared with those of the cases. Known risk factors for preterm delivery were used as matching factors. RESULTS: There was no statistically significant difference (P > 0.05) between cases and controls in the duration of pregnancy (37.6-38.4 weeks respectively), birth weight (3212-3315 g), cesarean section rate (17.8-32.1%), neonatal unit admission rate (21.4-10.7%), and precipitate labor rate (13-10.5%). The duration of labor was significantly shorter in cases (5.5-7.1 h, P = 0.032). After LEEP the relative risk for preterm delivery is 3.67 (95% confidence interval, 0.97-20.27), for low birth weight infant 0.67 (0.06-5.8), for precipitate labor 1 (0.05-3.88), and for delivery by cesarean section 0.5 (0.17-4.46). CONCLUSIONS: Women treated for microinvasive cancer with LEEP did not have significantly more delivery complications compared with controls apart from shorter duration of labor. There was a possible non-statistically significant trend toward shorter duration of pregnancy in cases. While caution should be advised when selecting and treating women with microinvasive carcinoma by LEEP, the apparent safety of the management and the satisfactory delivery outcome seem to justify this approach in many cases.

Case-Control Studies↗

Laser "miniconisation' and the outcome of subsequent pregnancy.

We routinely use the carbon dioxide laser miniconisation procedure for cervical interepithelial neoplasia I-III. A retrospective case control study was conducted in 1,485 miniconised women during 250 subsequent pregnancies (including three twin pregnancies). The analysis showed that the miniconised subjects had no significant pregnancy complications and the same preterm birth ratio (8.0%) as controls matched for age and parity.

Adolescent↗