[New challenges to the treatment of cervical intraepithelial neoplasia].

Due to the progress of intracavitary afterloading technology and dosage of brachytherapy, a similar dose distribution as that of cervical conization can be achieved and can be applied to the treatment of cervical intraepithelial neoplasia (CIN), it is called "afterloading conization" . Being adjusted the radioactive source movement and weight, low exposure doses to the ovary, endometrium and vagina can be assured. So a high quality of life after treatment could be maintained and overcomes the shortcomings of cervical conization and hysterectomy, such as anesthesia, bleeding, over or insufficient treatment, early ovarian ageing and operative complications.

Low-dose-rate definitive brachytherapy for high-grade vaginal intraepithelial neoplasia.

BACKGROUND: Treatment of high-grade vaginal intraepithelial neoplasia (VAIN) is controversial and could include surgical excision, topical medication, brachytherapy, or other treatments. We report the results of low-dose-rate (LDR) vaginal brachytherapy for grade 3 VAIN (VAIN-3) over a 25-year period at Gustave Roussy Institute. PATIENTS AND METHODS: We retrospectively reviewed the files of all patients treated at Gustave Roussy Institute for VAIN-3 since 1985. The treatment consisted of LDR brachytherapy using a personalized vaginal mold and delivered 60 Gy to 5 mm below the vaginal mucosa. All patients had at least an annual gynecological examination, including a vaginal smear. RESULTS: Twenty-eight patients were eligible. The median follow-up was 41 months. Seven patients had a follow-up <2 years, and the median follow-up for the remaining 21 patients was 79 months. The median age at brachytherapy was 63 years (range, 38-80 years). Twenty-six patients had a history of VAIN recurring after cervical intraepithelial neoplasia and 24 had a previous hysterectomy. The median brachytherapy duration was 4.5 days. Median doses to the International Commission of Radiation Units and Measurements rectum and bladder points were 68 Gy and 45 Gy, respectively. The median prescription volume (60 Gy) was 74 cm(3). Only one "in field" recurrence occurred, corresponding to a 5- and 10-year local control rate of 93% (95% confidence interval, 70%-99%). The treatment was well tolerated, with no grade 3 or 4 late toxicity and only one grade 2 digestive toxicity. No second cancers were reported. CONCLUSION: LDR brachytherapy is an effective and safe treatment for vaginal intraepithelial neoplasia.

Ovarian Function Preservation in Patients With Cervical Cancer Undergoing Hysterectomy and Ovarian Transposition Before Pelvic Radiotherapy.

To examine the factors associated with ovarian failure (OF) and assess the effectiveness of ovarian transposition (OT) before pelvic irradiation for preserving ovarian function in patients with cervical cancer (CC) undergoing hysterectomy. During 2003 to 2017, patients who underwent hysterectomy with preservation of one or both ovaries were retrospectively enrolled. Patients were divided into 4 groups, depending on whether radiotherapy (RT) and OT were performed: group 1, RT(+) and OT(+); group 2, RT(+) and OT(-); group 3, RT(-) and OT(+); group 4, RT(-) and OT(-). OF was defined as serum follicle-stimulating hormone levels of ≥30 mIU/mL. Sixty-six patients (59 [89.4%] invasive CC and 7 [10.6%] cervical intraepithelial neoplasia) were included. The 2-year OF-free survival rate was 61.4% (95% confidence interval [CI] 37.8-86.0), 0%, 91.7% (95% CI 76.0-100), and 75.8% (95% CI 58.2-93.4) for groups 1, 2, 3, and 4, respectively. In groups 1 and 2 receiving RT, OT, and combination of external beam radiotherapy and vaginal brachytherapy were associated with OF on multivariate analysis (MVA) (P-value = .002 and .046, respectively). In groups 3 and 4 without RT, older age (40 years old) and OT did not affect OF; however, the number of remaining ovaries was independently associated with OF in MVA (P = .035). OT could effectively preserve ovarian function in patients treated with adjuvant RT, while OT procedure itself did not affect ovarian failure. OT should be considered in the management of premenopausal cervical cancer patients.

Villoglandular papillary adenocarcinoma of cervix associated with cervical intraepithelial neoplasia: a case report and review of literature.

Well differentiated villoglandular adenocarcinoma of uterine cervix is a rare tumour which usually occurs in young women. It is considered to be an indolent tumour with favorable prognosis and most of them were treated by conservative procedures. We report a 35 year old lady who came with complaints of 3 months amenorrhoea and an episode of spontaneous bleeding. Urine pregnancy test was negative. Physical examination revealed a cervical polyp. Histopathological findings were consistent with villoglandular papillary adenocarcinoma associated with high grade cervical intraepithelial neoplasia (CIN-3). Left parametrial and left ureteral involvement, proved by biopsy, causing left hydroureteronephrosis was detected. The patient was thus found to be in an advanced stage, stage- III b (FIGO). The patient is currently undergoing radiotherapy. A review of literature showed that only occasional cases showing disease spread have been reported, suggesting caution in the management and regular follow up of the patient.

Endocervical gastric-type adenocarcinoma, an unrelated HPV tumour: difficulties in screening and diagnosis.

Gastric-type adenocarcinoma of the cervix (GAS) is an uncommon and aggressive tumour unrelated to human papillomavirus (HPV) infection with distinctive histological and immunohistochemical characteristics. GAS may be associated with lobular endocervical glandular hyperplasia (LEGH), another unusual lesion. We report a case of a 59-year-old woman with screening cytology 'AGC-Neo' and cervical conisation exhibiting cervical intraepithelial neoplasia grade 1, extensive LEGH and canal sampling with abundant mucinous cells. Based on the possible association between LEGH and GAS, a total hysterectomy was performed. The histological diagnosis revealed a morphological gradient of lesions: LEGH, minimal deviation adenocarcinoma and GAS with lymphatic invasion. Immunohistochemistry revealed strong MUC6 expression and no p16 staining. After pelvic radiotherapy, the patient continues follow-up evaluation. The diagnostic difficulties of GAS and its relationship with LEGH are discussed. This rare tumour is important because it is poorly symptomatic and potentially aggressive. In addition, the methods for cancer control related to HPV do not affect this tumour.

Oxidative status in patients submitted to conization and radiation treatments for uterine cervix neoplasia.

BACKGROUND: Cervical cancer is a major cause of morbidity among women. We investigated the treatment effect on oxidative status from patients submitted to radiotherapy or conization surgery to high-grade SIL (squamous intraepithelial lesion) treatment, and oxidative profile from patients newly diagnosed for uterine cervix cancer, without treatment. METHODS: We determined the catalase activity in blood, reduced glutathione (GSH) in plasma, TBARS and protein carbonyl content from serum samples of the patients. RESULTS: The catalase activity, GSH levels, TBARS and protein carbonyl content had no statistical differences related to the controls, neither when the 2 treatments were compared, possibly because the antioxidant defense may be acting in the first period of the neoplasic transformation, and maybe indicating a possible arrest of the tumor cells caused by the efficiency of the treatments. In the non-treated patients, TBARS and protein carbonyl contents, GSH levels and catalase activity were shown to be increased comparing with the treated patients and compared with the controls indicating an tumor effect on oxidative profile, and the antioxidant activity been increased in the beginning of the tumor development. CONCLUSIONS: We suggest that the treatments were efficient in arrest of the tumor.

High-dose-rate intracavitary brachytherapy in the management of cervical and vaginal intraepithelial neoplasia.

PURPOSE: To assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3). METHODS AND MATERIALS: This was a retrospective analysis in 20 patients with CIN-3 (n = 14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa Cancer Center. Two patients with CIN-3 with microinvasive foci and 11 other patients with CIN-3 were treated with HDR-ICR for cervical lesions. Six patients with CIN-3 after hysterectomy received HDR-ICR for recurrent or residual VAIN-3 lesions. One patient received radiation therapy for both CIN-3 and VAIN-3 lesions. All these patients but one were postmenopausal. RESULTS: Seventeen patients were treated with HDR-ICR alone, and three with combined external radiation therapy. The dose was calculated at Point A located 2 cm superior to the external os and 2 cm lateral to the axis of the intrauterine tube for intact uterus. For lesions of the vaginal stump, the dose was calculated at a point 1 cm superior to the vaginal apex or 1 cm beyond vaginal mucosa. In the 14 patients treated for CIN-3 lesions, the mean total dose of HDR-ICR was 26.1 Gy (range 20-30). Six patients received HDR-ICR for VAIN-3 lesions with mean dose of 23.3 Gy (range 15-30). At follow-up (mean 90.5 months; range 13-153), 14 patients were alive and 6 had died owing to nonmalignant intercurrent disease. No patient developed recurrent disease. Rectal bleeding occurred in three patients, but this symptom subsided spontaneously. Moderate and severe vaginal reactions were noted in two patients, in whom the treatment had included the entire vagina. CONCLUSIONS: HDR-ICR can be employed as the primary management strategy for postmenopausal women with CIN-3. In intraepithelial neoplasia involving the vaginal wall after hysterectomy, HDR-ICR should be considered as an alternative to total vaginectomy.

Bilateral radical radiotherapy in a patient with uterus didelphys.

We report a case of congenital abnormality of uterus didelyphys in a patient who developed invasive carcinoma of the cervix. She received radical radiotherapy by a combination of external beam pelvic radiotherapy and high dose rate brachytherapy by insertion of afterloading catheters into both uterine canals. A newly defined prescription point was used midway between the two catheters and 2 cm above the mean cervical os position. The classical point A was regarded as inappropriate in this patient with a rare condition. Acute toxicity was minor and the patient is tumour free with no significant normal tissue late effects after follow-up of nearly 3 years.

Treating intraepithelial lesions of the uterine cervix by laser CO2. Evaluation of the past, appraisal for the future.

BACKGROUND AND OBJECTIVE: Carbon dioxide laser (CO2) has been widely used in the past for the treatment of squamous intraepithelial lesions (SIL) of the uterine cervix. We present our 10-year experience of using this modality while evaluating its current and future use. MATERIALS AND METHODS: From 1988 to 1998, 3,078 women were treated for an intraepithelial lesion of the uterine cervix (SIL) by laser CO2 either by vaporization or conization. The procedure was performed on an outpatient basis and was well tolerated by the great majority of patients. The mean age of the women treated by vaporization was 27.5 years whereas of those managed by conization, 34.8 years. RESULTS: From the 3,078 women, 750 (24.4%) underwent laser vaporization and the remaining 2,328 (75.6%), conization of the cervix. Complications were minimal and consisted of intraoperative and postoperative bleeding (0.56%), pelvic infections (0.04%) and cervical stenosis (1.1%). Mean follow-up time was 83 months (range 24-142). Relapsing disease (either persistent or recurrent) was detected in 5.6% of the vaporization and 3.9% of the conization group. CONCLUSIONS: The management of SIL of the uterine cervix by laser CO2 offers excellent success rates with minor complications. The preservation of the anatomical integrity of the cervical tissue offers a better follow-up of these patients and the potential for repeat treatment. Although other treatment modalities are available, we believe that laser CO2 represents an excellent surgical tool for the management of intraepithelial lesions of the uterine cervix.

Epidemiological evaluation of the efficiency of treatment of pre-invasive cervical cancer in Warsaw, 1969-1988.

An analysis of 2,281 cases of pre-invasive cervical cancer registered in Warsaw Cancer Registry during the years 1969-1988, showed that the rate of cervical cancers detected at the pre-invasive stage declined from 46.8% in 1970, to 26.8% in 1988. New cases of this cancer were diagnosed mainly in the age group up to 49 years of age (86.1%). Conservative treatment was applied relatively rarely (in 43.0% of cases) while the uterus with adnexes were removed fairly frequently (26.0%). The results of treatment were good (100.0% of 5-year survivals.). The 5-year survivals seem not to differ in relation to any particular treatment method used.

[Treatment of intraepithelial cervical neoplasia with REP Radiosurgical Excision Procedure)]. / Intervento di REP (Radiosurgical Excision Procedure) nel trattamento della neoplasia cervicale intraepiteliale.

Radiosurgical cervical excision has been performed in 59 patients affected by CIN of various stages. This non-traumatic method uses 3.8 MHz radio waves to cut and/or coagulate without postoperative pain and tissue destruction. The radiosurgical excision has been performed in local anesthesia by a loop electrode or microneedle according to the seat of the lesion. The therapy was "effective" in 98% of cases (58/59) whereas the "incomplete excision" of CIN was observed in 6.7% (4/59). Complications (postoperative and late bleeding) occurred in 3.2% of the patients (2/59). Therefore, the Radiosurgical Excision Procedure (REP) can be considered an easy technique in ambulatory surgery; this method is effective in the treatment of CIN with either therapeutic and economic advantages and guarantee the functional and anatomic integrity of the cervix.

Invasive and in situ carcinoma of the cervix in young Nigerians: a clinico-pathologic study of 27 cases.

A study of young Nigerians aged 30 years and below with invasive and in-situ cervical carcinoma confirms the notion that cervical cancer occurs in all age group. All patients except one were married while all were parous. Forty four percent of the patients presented with stages III and IV disease and hence, were unsuitable for surgery. The youngest patient was aged 17 years, indicating the need tare cancer screening among adolescents and a vigorous family planning programme that emphasizes barrier contraception.

[Condylomata acuminata. The correlation between affecting sexual partners and the risk of developing preneoplasia of the cervix uteri. The therapeutic potentials of the Nd-Yag laser]. / Condylomata acuminata. Korelatsiia mezhdu zasiagiane na seksualnite partn'ori i riska ot razvitie na preneoplazii na matochnata shiika. Terapevtichni vuzmozhnosti na Nd YAG laser.

The present study summarized results from 206 patients (120 females and 80 males) with diagnosis condylomata acuminata. The diagnostic and surveillance methods used in the present work were: clinical, colposcopic, histologies and microbiological examination. 114 from all patients--46.5% females, and 62.2% males were sexual partners. In 25 women (43.8%) from that group HPV-lesions were found. In 8 patients with cervical lesions CIN I-III was diagnosed. Our results confirmed the previously announced literary data about an enhanced risk for CIN development in women with HPV infection, whose sexual partners had clinical data of Condylomata acuminata. Our therapeutic protocol with Nd-YAG laser treatment in a determined scheme and number of applications according to the stage of the disease and pathological diagnosis was very successful, as compared to data from the literature.

Factors contributing to high ThinPrep® Pap test unsatisfactory rates in an academic medical center laboratory.

Specimen adequacy is a key component in the cytologic evaluation of cervical Pap tests. At our institution, yearly unsatisfactory rates continue to be high, placing our laboratory in the 95th percentile for CAP benchmark data for unsatisfactory Pap test rates. Using the 2001 Bethesda System criteria, unsatisfactory Pap test rates were calculated over a ten year period (January 2002 to December 2011) and contributing factors were analyzed. Of the 124,457 ThinPrep Pap tests performed, 4,163 (3.3%) were unsatisfactory for evaluation, the majority (90%) due to too few squamous epithelial cells. Peri/postmenopausal women and those who had received radiation/chemotherapy had the highest unsatisfactory rates; 55% and 25%, respectively. Higher unsatisfactory Pap test rates are related to the patient population served. Defined, reproducible adequacy criteria need to be defined for Pap tests from patients in certain clinical conditions.

High-dose-rate intracavitary radiotherapy in the management of cervical intraepithelial neoplasia 3 and carcinoma in situ presenting with poor histologic factors after undergoing excisional procedures.

PURPOSE: To assess the effectiveness of high-dose-rate intracavitary radiotherapy (HDR-ICR) in patients with cervical intraepithelial neoplasia 3 (CIN 3) and carcinoma in situ (CIS) presenting with poor histologic factors for predicting residual disease after undergoing diagnostic excisional procedures. METHODS AND MATERIALS: This study was a retrospective analysis of 166 patients with CIN 3 (n=15) and CIS (n=151) between October 1986 and December 2005. They were diagnosed by conization (n=158) and punch biopsy (n=8). Pathologic analysis showed 135 cases of endocervical gland involvement (81.4%), 74 cases of positive resection margins (44.5%), and 52 cases of malignant cells on endocervical curettage (31.3%). All patients were treated with HDR-ICR using Co6° or Ir¹9² at a cancer center. The dose was prescribed at point A located 2 cm superior to the external os and 2 cm lateral to the axis of the tandem for intact uterus. RESULTS: Median age was 61 years (range, 29-77). The median total dose of HDR-ICR was 30 Gy/6 fractions (range, 30-52). At follow-up (median, 152 months), 2 patients developed recurrent diseases: 1 CIN 2 and 1 invasive carcinoma. One hundred and forty patients survived and 26 patients died, owing to nonmalignant intercurrent disease. Rectal bleeding occurred in one patient; however, this symptom subsided with conservative management. CONCLUSIONS: Our data showed HDR-ICR is an effective modality for CIN 3 and CIS patients presenting with poor histologic factors after excisional procedures. HDR-ICR should be considered as a definitive treatment in CIN 3 and CIS patients with possible residual disease after undergoing excisional procedures.