[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

Expanding management strategies for cervical precancerous lesions in resource-limited settings: insights from a training center in a district hospital in Ghana.

BACKGROUND: Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population. METHODS: We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 - 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression. RESULTS: For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 - 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 - 31.8 each), CIN1 (7.7%; 95% CI, 2.5 - 17.0) and micro-invasion (4.6%; 95% CI, 1.0 - 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 - 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 - 0.99; p = 0.025). CONCLUSION: This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

Cold Knife Versus Carbon Dioxide for the Treatment of Preinvasive Cervical Lesion.

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.

Immunohistochemistry staining of Eag1 and p16/Ki-67 can help improve the management of patients with cervical intraepithelial Neoplasia after cold knife conversion.

BACKGROUND: Immunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN. METHODS: IHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1-2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers. RESULTS: The IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker. CONCLUSIONS: Eag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN.

Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study.

OBJECTIVES: This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model. METHOD: We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model. RESULTS: The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826. CONCLUSION: Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.

Analysis of the clinical characteristics and surgical methods of high-grade squamous intraepithelial lesions of the cervix in postmenopausal women: A retrospective case study.

The purpose of this study was to thoroughly evaluate the clinical features and surgical options for high-grade squamous intraepithelial lesions (HSIL) in postmenopausal women. A total of 308 patients diagnosed with HSIL through colposcopic cervical biopsy and endocervical curettage were included. Their clinical characteristics, surgical treatments, and postoperative pathology were analyzed. Key findings include: 1. Patients with positive preoperative thinprep cytologic test (TCT) results and postoperative pathology indicating HSIL or squamous cell carcinoma (≥HSIL) were significantly more frequent than those with negative preoperative TCT results (P < .05). 2. Univariate analysis indicated significant impacts of TCT, human papillomavirus (HPV) type, transformation zone (TZ) location, and surgical technique on postoperative pathology (P < .05). 3. Logistic regression analysis confirmed significant influences of TCT, HPV type, TZ location, and surgical method on postoperative pathology outcomes (P < .05), showing that each unit increase in TZ raised the probability of ≥HSIL in postoperative pathology by 49.7%. In surgical comparisons, cold knife conization (CKC) and extrafascial hysterectomy resulted in 8.379 and 4.427 times higher probabilities of ≥HSIL in postoperative pathology, respectively, compared to loop electrosurgical excision procedure (LEEP). 4. Surgical methods significantly influenced margin results (P < .05). After LEEP, 17.5% of cases had positive margins, compared to 9.4% after CKC, and 3.7% after extrafascial hysterectomy, indicating the highest rate of positive surgical margins occurred with LEEP. 1. Combined TCT and HPV screening is crucial for cervical cancer prevention, early detection, and management in postmenopausal women. Women with positive results for both TCT and HPV should undergo colposcopic cervical biopsy and endocervical curettage. 2. For patients with TZ3, CKC is the recommended surgical option. 3. CKC is the preferred treatment for postmenopausal women with HSIL, as it effectively diagnoses and treats the lesion, showing superior outcomes in managing postmenopausal HSIL.

Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study.

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience.

OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

The role of multiple high-risk human papillomavirus infection on the persistence recurrence of high-grade cervical lesions after standard treatment: A systematic review and a meta-analysis.

INTRODUCTION: The role of multiple high-risk human papillomavirus (HR-HPV) infections on the occurrence of persistence/recurrence of high-grade squamous intraepithelial lesion (HSIL) after conization/surgery for cervical intraepithelial neoplasia was evaluated. MATERIAL AND METHODS: A systematic search of Pubmed/Medine, Scopus, Cochrane databases from inception to June 30, 2023 was performed. Three reviewers independently screened the abstracts of the selected studies and extracted data from full-text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. PROSPERO registration number CRD42023433022. RESULTS: Out of 1606 records screened, 22 full text articles met the inclusion criteria. A total of 8321 subjects treated (loop electrosurgical excision, laser or surgery) because of HSIL were followed-up and included in the meta-analysis. The pooled prevalence of overall persistence and/or recurrence was 17.6 (95% CI: 12.3-23.5) in multiple and 14.3 (95% CI: 10.1-19.2) in single HR-HPV infections detected shortly before or at surgery. The pooled rate of multiple HR-HPV infections was 25% (95% CI: 20.4-30). The odds ratio of histologically confirmed HSIL persistence and/or recurrence was significantly higher (OR: 1.38, 95% CI:1.08-1.75, p = 0.01, heterogeneity = 39%) among multiple than single HR-HPV infections. Increased risk of HSIL persistence/recurrence was more marked among studies with multiple HR-HPVs prevalence ≥25% (12 studies, N = 3476) (OR: 1.47, 95% CI: 1.18-1.84, heterogeneity = 0%) and in those evaluating true histologically confirmed recurrence after at least 6 months of negative follow-up (9 studies, N = 5073) (OR: 1.67, 95% CI: 1.17-2.37, heterogeneity = 37%). Multiple HR-HPVs infection detected during follow-up visits had no effect on the risk of recurrence although the number of included studies was small (4 studies, N = 1248) (OR: 0.98, 95% CI: 0.68-1.39, heterogeneity = 0%). The risk of bias was rated as high in 10 and low-moderate in 12 studies, respectively. In subgroup analysis, the risk of bias of the included studies (low/moderate vs. high), had a small, although not significant effect on the odds ratios of persistence/recurrence of HSIL (OR: 1.57, 95% CI: 1.23-2 for low-moderate risk of bias and OR: 1.06, 95% CI: 0.65-1.75 for high risk of bias; p-value for subgroup differences = 0.17). CONCLUSIONS: Multiple HR-HPVs infections at the time of standard treatment of HSIL entail a small but significant increased risk of persistence/recurrence of HSIL and should be taken into account in the follow-up plan.

Comparative study of treatment efficacy in severe intraepithelial squamous cell lesions and preinvasive cervical cancer by conization and chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy.

BACKGROUND: Cervical cancer (CC) occupies a leading position in incidence among young women of reproductive age. In this connection, it is urgent to search for the most effective approaches to the diagnosis and treatment of this pathology. The purpose of the study was to evaluate the effectiveness of the PDT method using Cе6 with the control of the photobleaching using video and spectral fluorescence diagnostic methods, to develop the method of fluorescence-assisted systemic photodynamic therapy mediated with chlorin e6 for treatment CIN 3 and CIS. MATERIALS AND METHODS: A randomized comparative clinical study was conducted involving 94 women aged 18 to 49 years with histologically verified severe intraepithelial squamous cell lesions of the cervix or preinvasive cervical cancer. The patients were included in 2 groups: in the first group conization of the cervix was performed with curettage of the remaining part of the cervical canal; patients in the second group underwent the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy. RESULTS: The absolute majority of patients in the main group after the first course of chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy showed normalization of cytological parameters and colposcopic picture, while women from the comparison group showed signs of cervical lesions statistically significantly more often. These changes corresponded to the dynamics of the proliferation markers expression in the cells of intraepithelial squamous cell lesions. Also, patients of the second group who were planning a pregnancy had better reproductive outcomes after treatment compared to those of the first group. CONCLUSION: In general, higher clinical efficacy and safety of the use of the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy in the treatment of intraepithelial squamous cell lesions and preinvasive cervical cancer have been established compared to the use of standard treatment methods.

Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size.

BACKGROUND: Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. OBJECTIVE: We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. STUDY DESIGN: We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. RESULTS: A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. CONCLUSION: Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

Adenocarcinoma In Situ of the Uterine Cervix (AIS) Treated by Loop Electrosurgical Excision Procedure Strategy: An Observational Study.

OBJECTIVES: Evaluation of the results of treatment of adenocarcinoma in situ by loop electrosurgical excision procedure and the safety of a conservative strategy. METHODS: Identification of all cases of adenocarcinoma in situ treated by loop electrosurgical excision procedure at our institution and follow-up by a conservative strategy. Completeness of the identification of all cases was secured by data from the National Pathology Registry. The treatment strategy was based on cytologic follow-up performed by a general practitioner and, irrespective of margin status of the cone, only the results of the postoperative surveillance were indicative of further treatment. RESULTS: A total of 224 patients were identified. The overall recurrence rate with a mean follow-up time of 87.8 months was 7.6% (17/224). The recurrence rate in patients with involved margins was significantly higher than in patients with uninvolved margins, 15.7% vs 5.2%, respectively. Six recurrences were diagnosed at first examination 6 months postconization in patients with involved margins. They were treated with hysterectomy in 4 cases and reconization in 1 case. If involvement of margins alone had been an indication of further therapy (hysterectomy or reconization) immediately after conization, the conservative management strategy prevented 46 surgical procedures. Two cases of invasive cancer were diagnosed during follow-up, 150 months and 196 months after primary treatment, and after normal follow-up examinations. These 2 cases must be considered de novo cases and cannot be considered treatment failures. CONCLUSION: The conservative management strategy thus seems safe, and unnecessary surgical procedures were avoided.

Câncer de colo uterino na gestação / Cervical cancer in pregnancy

PONTOS-CHAVE • A incidência de câncer durante a gestação tem aumentado devido à tendência das mulheres em postergar a gravidez. O câncer de colo de útero é a terceira neoplasia mais comumente diagnosticada durante o período gestacional. • O rastreamento e o diagnóstico devem se dar como nas pacientes não gestantes; a citologia oncótica cervical é o exame obrigatório do pré-natal, e a colposcopia com biópsia pode ser realizada em qualquer período da gestação. • A gestação complicada pelo diagnóstico de um câncer deve sempre ser conduzida em centro de referência e por equipe multidisciplinar. • A interrupção da gestação em situações específicas, para tratamento-padrão, é respaldada por lei. • A quimioterapia neoadjuvante é uma alternativa segura de tratamento durante a gestação, para permitir alcançar a maturidade fetal. Apresenta altas taxas de resposta, sendo relatada progressão neoplásica durante a gestação em apenas 2,9% dos casos. O risco de malformações fetais decorrentes da quimioterapia é semelhante ao da população geral. Contudo, a quimioterapia está associada a restrição de crescimento intraútero, baixo peso ao nascer e mielotoxicidade neonatal. • Na ausência de progressão de doença, deve-se levar a gestação até o termo.

Satisfacción en pacientes sometidas a conización ambulatoria con anestesia local intracervical / Satisfaction in patients under conization ambulatory with local intracervical anesthesia

La técnica de la conización es un procedimiento muy empleado actualmente para el tratamiento de lesiones neoplasicas del cuello uterino; sin embargo, en la literatura sigue existiendo controversia acerca de cuál es el mejor método analgésico para su realización. OBJETIVO: conocer el grado de satisfacción y tolerancia al dolor de las pacientes sometidas a conizaciones ambulatorias utilizando anestesia intracervical. MATERIAL Y MÉTODOS: se llevó a cabo un estudio observacional de 55 conizaciones realizadas en nuestro centro; los criterios de inclusión fueron todas aquellas pacientes candidatas a una conización ambulatoria. Se hicieron un total de cuatro cuestionarios: dos a las pacientes y otros dos a los médicos que intervinieron en el procedimiento, uno el día de la conización y otro en la consulta de revisión. RESULTADOS: la mayoría de las pacientes definieron el dolor durante la intervención como tolerable o inferior, siendo la duración del dolor posquirúrgico muy escasa. El grado de satisfacción tanto de las pacientes como de los profesionales al realizar la técnica fue muy bueno. El sangrado posquirúrgico se limitó a la primera semana en la mayoría, lo que se correlaciona con una buena cicatrización objetivada en la revisión, sin que esto supusiera una disminución del tamaño del cono obtenido. CONCLUSIONES: la conización ambulatoria con la aplicación de anestesia local intracervical como método de analgesia es una técnica catalogada como de fácil aplicación por los profesionales y con muy buena colaboración y tolerancia por parte de las pacientes

The conization technique is a procedure currently used to treat neoplastic lesions of the cervix; however, in the literature there is still controversy about which is the best analgesic method for its realization. OBJECTIVE: To determine the degree of satisfaction and pain tolerance of patients undergoing ambulatory conization using intracervical anesthesia. MATERIAL AND METHODS: An observational study of 55 conizations made in our center was carried out; the inclusion criteria were all those patients who were candidates for ambulatory conization. A total of four questionnaires were made: Two to the patients and another two to the doctors who took part in the procedure, one on the day of the conization and the other one in the review consultation. RESULTS: The majority of the patients defined the pain during the intervention as tolerable or inferior, the duration of the postsurgical pain being very scarce. The degree of satisfaction of both the patients and the professionals when performing the technique was very good. Postsurgical bleeding was limited to the first week in the majority, which correlates with a good healing objectified in the review, without this implying a decrease in the size of the cone obtained. CONCLUSIONS: Ambulatory conization with the application of intracervical local anesthesia as an analgesic method is a technique cataloged as easy to apply by professionals and with very good collaboration and tolerance on the part of patients

Efficacy and safety of cryotherapy, cold cone or thermocoagulation compared to LEEP as a therapy for cervical intraepithelial neoplasia: Systematic review / Eficacia y seguridad de crioterapia, cono frio o termo-coagulación en comparación con LEEP como terapia para la neoplasia intraepitelial cervical: Revisión sistemática

ABSTRACT OBJECTIVES To determine the efficacy and safety of the use of cryotherapy, cold knife or thermocoagulation compared to Loop Electrosurgical Excision Procedure (LEEP) for the treatment of cervical intraepithelial neoplasia. METHODS Systematic review with meta-analysis of randomized controlled trials in women with cervical intraepithelial neoplasia undergoing treatment with cryotherapy, cold knife, or thermo-coagulation compared with LEEP, to estimate its efficacy and safety. The search was conducted on MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus, until September 2018. RESULTS The total of 72 studies were identified, of which only 8 studies met the inclusion criteria. The treatment of CIN with cold knife decreases the risk of residual disease compared with LEEP (RR, 0.54, 95%CI, 0.30-0.96, p = 0.04). The management of premalignant lesions with cryotherapy, compared with LEEP, increases the risk of disease recurrence by 86% (RR, 1.86, 95%CI, 1.16-2.97, p = 0.01), increases the risk of infections (RR, 1.17, 95%CI, 1.08-1.28, p < 0.001) and reduces the risk of minor bleeding by 51% (RR, 0.49, 95%CI) %, 0.40-0.59, p ≤ 0.001). CONCLUSIONS The treatment of premalignant lesions of cervical cancer with cold knife reduces the risk of residual disease. Nevertheless, cryotherapy reduces the risk of minor bleeding in the 24 hours after treatment and increases the risk of recurrence of disease and infections.

RESUMEN OBJETIVOS Evaluar la eficacia y seguridad del uso de crioterapia, cono frio o termo-coagulación en comparación con el procedimiento de escisión electroquirúrgica en asa (LEEP) para el manejo de neoplasias intraepiteliales cervicales. MÉTODOS Revisión sistemática de ensayos controlados aleatorizados en mujeres con neoplasia intraepitelial cervical en tratamiento con crioterapia, cono frio, o termo coagulación y LEEP, para estimar su eficacia y seguridad. La búsqueda se realizó en MEDLINE/PUBMED, Registro Cochrane Central de Ensayos Controlados (CENTRAL) y Scopus, hasta setiembre de 2018. RESULTADOS Se identificaron 72 estudios, ocho cumplieron los criterios de inclusión. Cono frio disminuyó el riesgo de enfermedad residual en comparación con LEEP (RR 0,54; IC del 95%, 0,30-0,96, p = 0,04). Crioterapia en comparación con LEEP incrementó el riesgo de recurrencia de enfermedad en un 86,0% (RR 1,86; IC del 95%, 1,16-2,97, p = 0,01) con un tiempo de seguimiento de seis a 24 meses, y de infecciones (RR, 1,17; IC del 95%, 1,08-1,28, p < 0,001); pero redujo el riesgo de sangrado menor en un 51,0% (RR 0,49; IC del 95%, 0,40-0,59, p ≤ 0,001). CONCLUSIONES Cono frio reduce el riesgo de enfermedad residual. Sin embargo, la crioterapia reduce el riesgo de sangrado menor en las 24 horas posteriores al tratamiento e incrementa el riesgo de recurrencia de enfermedad y de infecciones.

Resultados de la conización por radiocirugía en pacientesatendidas en consulta de patología de cuello uterino / Results of Conization by Radiosurgery in patients treated in a Cervical Pathology Clinic

Introducción: La radiocirugía tiene como objetivo proporcionar una herramienta de diagnóstico y tratamiento. Objetivos: Describir los resultados de la conización por radiocirugía en pacientes atendidas en la consulta de patología de cuello uterino de la institución. Métodos: Se realizó una investigación descriptiva de corte transversal en el Hospital General Docente Mártires del 9 de Abril de Sagua la Grande, Villa Clara, Cuba. La población de estudio estuvo conformada por la totalidad de 256 pacientes atendidas en la consulta de patología de cuello uterino que fueron sometidas a conización por radiocirugía, entre enero 2013 y diciembre 2015. Para la recogida de la información se empleó la revisión de documentos y se confeccionó un modelo de recogida de datos. Resultados: El diagnóstico preoperatorio que aportó mayor cantidad de casos fue el NIC III (displasia severa) (78 casos; 30,5 por ciento). Conclusiones: Las lesiones premalignas en el presente estudio comenzaron a aparecer con marcada incidencia a partir de los 20 años y hasta los 49, sobresaliendo el grupo de 30 - 39 años. El aumento en el número de parejas sexuales, así como el comienzo temprano de las relaciones sexuales incrementan el riesgo de padecer lesiones intraepiteliales en el cuello del útero. A partir de los cinco años de iniciada las relaciones sexuales comienzan a aparecer las lesiones intraepiteliales cervicales, el diagnóstico preoperatorio que aportó mayor cantidad de casos fue el NIC III (displasia severa). En los diagnósticos histológicos por sacabocado y cono existió correspondencia en todos los casos(AU)

Introduction: Radiosurgery aims to provide a diagnostic and treatment tool. Objectives: To describe the results of conization by radiosurgery in patients treated in the cervical pathology clinic of the institution. Methods: A descriptive cross-sectional investigation was carried out at Mártires del 9 de abril General Teaching Hospital, in Sagua la Grande, Villa Clara, Cuba. The study population consisted of 256 patients attended in the cervical pathology clinic who underwent conization by radiosurgery, from January 2013 to December 2015. For the collection of the information, the document review was used and a data collection form was made. Results: The preoperative diagnosis that contributed the greatest number of cases was IAS III (severe dysplasia) (78 cases; 30.5 percent). Conclusions: The premalignant lesions in the present study began to appear with a marked incidence from the age of 20 and up to 49, with the group of 30-39 years standing out. The increase in the number of sexual partners, as well as the early sexual intercourse increase the risk of suffering intraepithelial lesions in the cervix. After five years of beginning sexual intercourse, cervical intraepithelial lesions begin to appear, the preoperative diagnosis that contributed the greatest number of cases was IAS III (severe dysplasia). In histological diagnoses by punch and cone correspondence existed in all cases(AU)

Implicaciones obstétricas de los tratamientos escisionales de cérvix por lesiones premalignas / Excisional treatment for cervical dysplasia and obstetrics outcomes

Objetivo: Analizar los resultados obstétricos en mujeres con antecedente de tratamiento escisional de cérvix y si existen diferencias en los mismos según la técnica de conización empleada: LEEP (procedimiento de escisión cervical con asa de diatermia) o LLETZ (escisión de la zona de transformación [TZ] con asa de diatermia). Material y métodos: Estudio observacional retrospectivo en el que se han incluido las conizaciones realizadas entre 2007 y 2014 y las siguientes variables: edad materna, paridad, tabaquismo, parto, aborto, intervalo entre la conización y el parto, tipo de parto, rotura prematura de membranas pretérmino (RPMP), edad gestacional y peso del recién nacido. Grupo control: 100 pacientes que habían quedado gestantes en el mismo periodo de tiempo. Resultados: Cincuenta y tres (7,9%) pacientes quedaron gestantes tras la conización, de estas 4(7,5%) abortaron y 49(92,5%) tuvieron un parto. Se observó mayor tasa de prematuridad (18 vs. 8%, p=0,049) y de RPMP (22,4 vs. 3%, p=0,001) en el grupo de conización. En relación a la técnica empleada, hubo más casos de prematuridad en el grupo de LEEP frente al de LLETZ (25 vs. 10,5%), RR=1,7 (IC 95%:1,1-2,9), no encontrando diferencias en cuanto a la RPMP y el bajo peso. Por otro lado, también se observó mayor proporción de cesárea en el grupo de conización frente al control (38,8 vs. 20%) (57%-LEEP vs. 5,3%-LLETZ, p=0,013). Discusión: Es importante hacer un manejo conservador en mujeres con deseos genésicos y lesiones cervicales premalignas y seleccionar correctamente a las pacientes candidatas a conización. Cuando se utilizó LEEP los resultados obstétricos (en términos de prematuridad y RPMP) son peores frente a las gestantes en las que se realizó LLETZ

Objective: The aim of our study was to analyse the obstetric outcomes in women with a history of excisional treatment for cervical intraepithelial neoplasia and whether there were differences according to the methods of treatment used (loop electrosurgical excision procedure [LEEP] vs. large loop excision of the transformation zone [LLETZ]). Material and methods: A retrospective cohort study was conducted on patients who underwent conization between 2007 and 2014. Outcome measures included maternal age, parity, smoking, childbirth, abortion, interval between conization and delivery, mode of delivery, preterm prelabour rupture of the membranes (PPROM), gestational age and birth weight. A group of 100 patients who had been pregnant during the same period was used as a control group. Results: 53 (7.9%) patients became pregnant after conization, resulting in 4 (7.5%) miscarriages and 49 (92.5%) deliveries. Increased rate of preterm deliveries (18 vs. 8%, p=.048) and PPROM (22.4 vs. 3%, p=.001) was observed in the conization group. According to technique used, there were more cases of prematurity in the LEEP group against LLETZ (25 vs. 10.5%), RR=1.7 (95% CI: 1.1-2.9), no differences were found in PPROM and low weight. On the other hand, a higher proportion of caesareans was also observed in the conization group versus the control group (38.8 vs. 20%) (57%: LEEP vs. 5.3%: LLETZ, p=.013). Discussion: Conservative management and appropriate selection of candidates for conization are important in women with premalignant cervical lesions who wish to become pregnant. Worse results were observed in LEEP group (preterm delivery and PPROM) compared to women who underwent LLETZ

Estudio de piezas de conización tras cinco años de cribado de cáncer de cérvix con co-test / Study of conizations of the cervix after five years of cervical cancer screening with co-testing

Fundamentos: El cribado del cáncer de cérvix uterino (CCU) ha cambiado con la introducción del test del virus del Papiloma Humano de alto riesgo (VPH-AR) y es necesaria su evaluación. El objetivo de este estudio fue analizar la eficacia del cribado del CCU con las actividades orientadas a la detección y tratamiento precoz para modificar la historia natural del proceso y mejorar su pronóstico. Métodos: Se realizó un cribado con citología y VPH-AR (co-test) según el protocolo SEGO de 2010 entre los años 2011 y 2015 con seguimiento hasta 2017. El test de ADN VPH-AR fue Captura de Híbridos HC2 (Digene(R)) al inicio (16,1% de los casos) y Cobas 4800 (Roche(R)) después. La población diana fue el Área de salud de Barbastro. El tratamiento inicial fue la conización con asa (LLETZ). Se estudió la sensibilidad y el valor predictivo positivo de los test, así como la asociación entre variables demográficas y patológicas. Resultados: Se detectaron 238 displasias de alto grado (HSIL) o mayor con una media de edad de 37,9±10,3 años y el 60,0% fueron positivas a los genotipos 16 y/o 18. Se conizaron 220 pacientes (92,4%) y en 25 (11,4%) se precisó reconización o histerectomía. Se diagnosticó HSIL en 220 pacientes (92,4%) y carcinoma invasor en 18 (7,6%), 7 microinvasores (2,9%). En el 14,4% de los conos no se halló HSIL (conos blancos) y el 83,2% tuvo bordes libres. El 52,0% tenía afectación en un solo cuadrante y el tamaño tuvo de media 3,5±3,1mm. Sólo 14 pacientes (6,7%) continuaban enfermas (VPH-AR positivo) tras tratamiento. Se halló, en nuestros casos, asociación estadísticamente significativa entre bordes afectados y edad mayor de 45 años (p=0,005). Conclusiones: El co-test ha detectado lesiones preinvasoras, pequeñas, localizadas en un solo cuadrante y carcinomas microinvasores. La conización con asa fue eficaz logrando la curación del 93,3% de las pacientes

Background: Uterine Cervical Cancer (UCC) screening has changed with the introduction of the High Risk Human Papilloma Virus test (HRHPV) and its evaluation is necessary. The objective of this study is to analyze the effectiveness of UCC screening with activities aimed at early detection and treatment to modify the natural history of the process and improve its prognosis. Methods: Cytology and HR-HPV (co-testing) were performed according to the SEGO protocol of 2010 between 2011 and 2015 with follow-up until 2017. The HR-HPV DNA test was HC2 Hybrid Capture (Digene(R)) at the beginning (16.1% of the cases) and Cobas 4800 (Roche(R)) afterwards. Target population: Barbastro's health area. The initial treatment was conization with loop (LLETZ). Sensitivity and Positive Predictive Value of tests were studied, as well as the association between demographic and pathological variables. Results: 238 high-grade dysplasias (HSIL) or more (CIN2+) were detected with a mean age of 37.9±10.3 years and 60.0% were genotype 16 and/or 18 positive. 220 patients (92.4%) underwent conization completed thereafter with reconization or hysterectomy in 25 cases (11.4%). HSIL was diagnosed in 220 cases (92.4%) and invasive carcinoma in 18 (7.6%), 7 microinvasive (2.9%). 14.4% of cones had no HSIL (negative cone) and 83.2% got free margins. 52.0% had involvement in a single quadrant and the mean horizontal extension was 3.5±3.1mm. Only in 14 (6.7%) patients the disease (HR-HPV positive) persisted after treatment. A statistically significant association was found in our cases between affected borders and age over 45 years (p=0.005). Conclusions: The co-test has detected small preinvasive lesions, localized in a single quadrant and microinvasive cancers . Loop conization was effective, achieving the cure of 93.3% of the patients

Resultados de la conización por radiocirugía en pacientes atendidas en consulta de patología de cuello uterino / Results of conization by radiosurgery in cervical pathology patients

Introducción: la radiocirugía tiene como objetivo proporcionar una herramienta de diagnóstico y tratamiento. Objetivos: describir los resultados de la conización por radiocirugía en pacientes atendidas en la consulta de patología de cuello uterino. Método: se realizó una investigación descriptiva de corte transversal en el Hospital General Docente Mártires del 9 de abril, de Sagua la Grande, Villa Clara, Cuba. La población de estudio estuvo conformada por 256 pacientes atendidas en la consulta de patología de cuello uterino que fueron sometidas a conización por radiocirugía, desde enero de 2013 a diciembre de 2015. Para la recogida de la información se empleó la revisión de documentos mediante la confección de un modelo de recogida de datos. Resultados: el diagnóstico preoperatorio que aportó mayor cantidad de casos fue el NIC III (displasia severa) con 78 casos (30,5 por ciento). Conclusiones: en el presente estudio las lesiones premalignas comenzaron a aparecer con notada incidencia desde los 20 años y hasta los 49, con marcada ocurrencia en el grupo de 30 a 39 años. El aumento en el número de parejas, así como el comienzo temprano de las relaciones sexuales incrementan el riesgo de padecer lesiones intraepiteliales en el cuello del útero. A partir de los cinco años de iniciada las relaciones sexuales, comienzan a aparecer las lesiones intraepiteliales cervicales, el diagnóstico preoperatorio que aportó mayor cantidad de casos fue el NIC III (displasia severa). Existió correspondencia en todos los casos en los diagnósticos histológicos por sacabocado y cono(AU)

Introduction: radiosurgery aims to provide a diagnostic and treatment tool. Objectives: describe the results of radiosurgery conization in patients treated at the cervical pathology clinic. Method: adescriptive cross-sectional study was carried out at Mártires del 9 de Abril General Teaching Hospital, Sagua la Grande, Villa Clara, Cuba. The study population consisted of 256 patients treated at the cervical pathology clinic, who were submitted to radiosurgery conization, from January 2013 to December 2015. For the collection of the information, a review of documents was done by making a data collection model. Results: CIN III (severe dysplasia was) the preoperative diagnosis that contributed the most cases ( 78 cases (30.5 percent)). Conclusions: in the present study, premalignant lesions began to appear with a marked incidence from the age of 20 to 49, with a distinct occurrence in the group aged 30 to 39 years. The increase number of couples as well as the early beginning of sexual intercourse increase the risk of intraepithelial lesions in the cervix. After five years of sexual intercourse, cervical intraepithelial lesions began to appear, the preoperative diagnosis with the highest number of cases was CIN III (severe dysplasia). There was correspondence in all cases in the histological diagnoses by punch and cone(AU)