Prediction of disease persistence after conization for microinvasive cervical carcinoma and cervical intraepithelial neoplasia grade 3

We attempted to determine the significant variables and to predict the probability of disease persistence after conization for microinvasive cervical carcinoma and cervical intraepithelial neoplasia grade 3 (CIN3). We analyzed 133 patients from 2001 to 2002 who had a subsequent hysterectomy after conization. The histological findings of the cone specimens, together with the clinical parameters, were correlated with the presence of residual dysplasia in the hysterectomy specimen. The probability of having residual dysplasia was calculated based on the function of the significant variables obtained by logistic regression analysis. Of the 133 patients, 42 (31.6%) had residual disease in their hysterectomy specimens. Using multivariate analysis only for the postmenopausal state, positive endocervical curettage, positive margin, and microinvasive carcinoma were predictive of residual dysplasia. The probabilities of having residual dysplasia were about 0.99, 0.84, 0.4, 0.07, and 0.01 in patients with a presence of all four, any three, any two, any one, and no risk factors, respectively. The best cutoff probability determined by the receiver operating characteristic curve was 0.32, yielding a sensitivity of 81% and a specificity of 88%. Based on these results, patients with the presence of any two or more of the risk factors mentioned above should be considered as a high-risk group for having disease persistence after conization for the treatment of CIN3 and microinvasive carcinoma.     

Prognostic factors in microinvasive cervical squamous cell cancer: long-term results

We examined tumor-related pathologic factors and cone-related characteristics to identify parameters related to recurrence in microinvasive squamous cell carcinoma of the cervix treated with conization. This is a retrospective study on 67 consecutive cases of microinvasive carcinoma of the cervix [depth of invasion (DI) < 3 mm] treated with conization. The mean follow-up was 121 months (range 72-276 months). Four (6%) invasive recurrences were observed. Presence of lymphvascular space involvement (LVSI) was significantly related with recurrences (P < 0.05). The mean distance between tumor margin and apex of the cone (apical clearance) was 10.6 mm (range 5-22 mm), and the mean distance between lateral border of the cone and tumor margin (lateral clearance) was 6.5 mm (range 1.7-15 mm). We adopted cut-off values of 10 and 8 mm for apical and lateral clearances, respectively. We found a statistically significant difference between apical clearance and recurrence rate (P < 0.02). The LVSI was, other than DI, an important prognostic factor. Apical clearance was significantly correlated with recurrence. The cone-related characteristics, other than tumor-related pathologic factors, could help the decision concerning the definitive therapy for microinvasive carcinoma of the cervix.     

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.     

Factors associated with positive margins in patients with cervical intraepithelial neoplasia grade 3 and postconization management

Objective

To evaluate the risk factors for positive margins in cervical intraepithelial neoplasia (CIN) grade 3 and the outcomes of postconization management.

Methods

A retrospective review of the records of 1113 women who underwent conization for CIN 3 between 2000 and 2008.

Results

Positive margins occurred in the following: 104 (10.7%) women with severe dysplasia versus 37 (26.2%) with carcinoma in situ; 32 (4.8%) treated with cold knife conization versus 109 (24.1%) treated with the loop electrosurgical excision procedure (LEEP); and 124 (11.6%) premenopausal versus 17 (35.4%) postmenopausal women. None of the women with severe dysplasia had invasive disease in the repeat excision specimen, whereas 3 (8.6%) women with carcinoma in situ had residual microinvasive carcinoma.

Conclusion

LEEP, carcinoma in situ, menopausal status, and larger area of lesion are risk factors for positive margins. For women with CIN 3 and positive margins, follow-up at an interval of 6 months or repeat excision are treatment options. However, when repeat excision is technically impossible, whether simple hysterectomy or radical surgery is a rational treatment option requires further investigation.     

Predictors of residual carcinoma or carcinoma-in-situ at hysterectomy following cervical conization with positive margins

Objectives

Identify predictors of residual carcinoma or carcinoma-in-situ (CIS) at hysterectomy following cervical conizations with CIS and positive margins or endocervical curettage (ECC) or microinvasive cervical cancer.

Methods

Patients with cervical conization with CIS and positive margins, ECC or microinvasive carcinoma who underwent hysterectomy within 6 months of conization were identified. Conization and hysterectomy specimens were re-reviewed to assess volume of disease, ECC and margin status and residual carcinoma. Standard statistical tests were used.

Results

83 patients were included. 34 (41%) had residual carcinoma in the hysterectomy specimen: 23 CIS, 9 microinvasive and 2 invasive disease. In patients with squamous histology predictors of residual disease included a positive ECC (p = 0.04), combined endocervical margin and ECC (69% if both positive, 38% either positive, 11% if both negative, p = 0.01) and volume of disease ≥ 50% (p = 0.01). In patients with glandular histology no factor predicted residual disease. Type of conization, > 2 involved quadrants, and the presence of microinvasion in the conization specimen did not predict residual disease. No patient with squamous histology had > Stage IA1 disease at hysterectomy, whereas 2 (2.4%) with adenocarcinoma had > Stage IA1 disease at hysterectomy.

Conclusions

Residual carcinoma or CIS is present in nearly half of hysterectomies after conization with CIS and positive ECC, margins or microinvasion. Patients with squamous histology may not require repeat conization prior to definitive therapy. No factors predict residual disease with adenocarcinoma. In women with AIS with negative margins and ECC and no microinvasion, it appears reasonable to proceed with simple hysterectomy.     

Loop conization for the treatment of microinvasive carcinoma of the cervix

The purpose of the study was to evaluate the specimen adequacy and diagnostic accuracy of loop conization in microinvasive carcinoma of the cervix. A retrospective study was conducted from 1997 to 2003 at the Colposcopic Clinic, Department of Gynecology and Obstetrics, Chang Gung Memorial Hospital, Taipei, Taiwan. Sixty-three consecutive patients with microinvasive carcinoma of the cervix receiving cold-knife conization (35 patients) or loop conization (28 patients) were included in the study. All patients underwent definitive hysterectomy. We reviewed the conization specimen together with the hysterectomied uterus to compare the two conization techniques with respect to the histopathologic interpretation and diagnostic accuracy. The mean depth of cone specimens was significantly less in the loop conization compared with cold-knife conization (1.65 versus 2.35 cm, P = 0.035). Regarding the application of conization, the loop conization was completed in a single slice in 27 patients (77.1%) and in multiple slices in 8 patients (22.9 %), in spite of encouragement to perform conization in a one-pass application when possible. However, the cold-knife specimens were invariably a single cone-shaped piece. As reviewed by microscopic examination, the rate of tissue transection was significantly higher in the loop group than in the cold-knife group (14.3% versus 0%, P = 0.04). Because of tissue transection and disorientation, pathologic evaluation of stromal status was inadequate in 11.4% (4/35) of the loop cones as opposed to none of the 28 cold-knife cones. After assessing the hysterectomy specimens, the clinical diagnoses in the loop group were downgraded in three patients compared with only one in the cold-knife group. Data from this investigation suggest that cervical cold-knife conization is superior to loop conization as a method to assess microinvasive cervical cancer.     

Is conization once following by simple hysterectomy sufficient for all clinical stage IA1 cervical squamous cell carcinoma?

ObjectiveThe goal of this study is to assess the feasibility of simple extrafascial hysterectomy for patients with clinical stage IA1 cervical squamous cell carcinoma (SCC) after once conization regardless of any pathologic risk factor.Materials and MethodsAll cases with T1a1, SCC lesion in their cervical cone specimen were retrospectively collected after chart and pathology review for the period between January 2002 and December 2009. All cases underwent subsequent hysterectomies within a month of diagnosis. Pathologic risk factors of conization, surgical scale of hysterectomy, residual lesion of the uterus, necessity of adjuvant radiation therapy, complications, and survival were analyzed in this study.ResultsEighty-one cases were identified from the registry. Most were managed by simple hysterectomy (SH; 60/81, 74%), and the remaining 21 cases underwent modified radical hysterectomy (MRH). All cases without any risk factors in their cone specimens demonstrated residual lesion ≤T1a1 in both SH and MRH groups, whereas those with existing risk factor were confirmed positive for residual lesions ≤T1a1 [SH, 95.8% (46/48) vs. MRH, 75% (15/20)]. Only two cases in the SH group received adjuvant radiation for residual lesions >T1a1. On the contrary, 15 cases in the MRH group can receive smaller scale surgery than MRH. All cases were recurrence-free without any permanent treatment-related complication by the end of the study.ConclusionExtrafascial simple hysterectomy may be recommended for clinical T1a1 cervical SCC regardless of the pathologic risk factor.     

The predictive value of LEEP specimen margin status for residual/recurrent cervical intraepithelial neoplasia

Robinson WR, Lund ED, Adams J. The predictive value of LEEP specimen margin status for residual/recurrent cervical intraepithelial neoplasia. Int J Gynecol Cancer 1998; 8 : 109–112.
The objective of this study was to determine the impact of margin status of LEEP specimens on the rate of recurrent/residual cervical intraepithelial neoplasia (CIN). Also, we determined the effect of other clinical or pathologic factors on recurrent/residual disease. In this prospective cohort study, 227 women underwent LEEP excision of the cervix using standard techniques. Data concerning clinical factors and pathologic and cytologic results were collected. Patients had follow-up at three month intervals with Pap smears and indicated colposcopy/biopsy. 145/227 were confirmed as having CIN in the LEEP specimen. 66/145 (45%) had involved (positive) margins, and 79/145 (55%) had noninvolved (negative) margins. 27/57 (47%) with positive margins had recurrent disease compared with 22/65 (34%) with negative margins. ( P = 0.18) HIV infection was found in 8/227 (3.6%). 8/8 HIV-infected patients had involved margins and recurrent/residual disease. Endocervical curettage (ECC) was positive in 39 cases and negative in 106. 13/34 (38%) cases with a positive ECC had recurrent disease vs. 32/88 (36%) with a negative ECC. ( P = 0.85) Also, 8/58 (14%) patients whose specimens did not show CIN were found to have CIN at follow-up. In conclusion, the risk of residual/recurrent CIN at follow-up after undergoing LEEP is not statistically different in margin positive vs. margin negative patients (47% vs. 34%) ( P = 0.18) or ECC positive vs. ECC negative patients. (38% vs. 36%) ( P = 0.85) If HIV infected patients are excluded, the rate of recurrent disease in the two groups is very similar. (39% vs. 34%) ( P = 0.73) Follow-up is important for patients with negative LEEP specimens as 14% were later diagnosed with CIN.     

The oncological and obstetric outcomes of cervical squamous cell carcinoma at stage IA1 managed with the loop electrosurgical excision procedure

ObjectiveTo evaluate the efficacy and superiority of loop electrosurgical excision procedure (LEEP) in managing stage IA1 cervical microinvasive squamous cell carcinoma (MISCC) without lymph-vascular space invasion (LVSI).Materials and methodsThe oncological and reproductive outcomes of a series of patients affected by stage IA1 MISCC without LVSI, initially treated by LEEP between February 2006 and December 2017, were retrospectively reviewed.ResultsUltimately, 109 patients were included. The mean age at diagnosis was 35.4 years old, and 36 patients were nulliparous. Multifocal lesions were identified in 15 patients (13.8%). The mean cone depth was 17.4 mm. Resection margins were positive/unevaluable and negative in 26 (23.9%) and 83 (76.1%) cases, respectively. Among cases undergoing salvage treatments, the residual disease rate for patients with positive/unevaluable margins was significantly higher than those with negative margins (P = 0.003). During the follow-up period of 43.0 ± 28.9 months, no relapse was identified. Fifteen of 20 patients (75.0%) conceived successfully, with a full-term live birth rate of 93.3%.ConclusionsFor stage IA1 MISCC without LVSI unexpectedly found in a loop excision, initial LEEP with clear margin is efficient and adequate. For cases with multifocal MISCC, or for those young patients who wish to become pregnant in the future, LEEP is the optimal choice.     

Patterns of recurrence following hysterectomy and radiation for cervical carcinoma: relationship to residual disease and brachytherapy techniques

Conventional postoperative irradiation following hysterectomy for cervical carcinoma has consisted of external pelvic with or without intra-cavitary vaginal irradiation. In the presence of macroscopically positive margins after initial hysterectomy or in the subsequent context of a central recurrence, such techniques may not be optimum as manifested by the significant rate of local recurrence following conventional irradiation in these settings. The purpose of the retrospective review was to: (a) evaluate pelvic recurrence patterns following initial hysterectomy and radiation in relationship to margin status and brachytherapy techniques in 24 group 1 patients; and (b) evaluate pelvic recurrence patterns in 10 group 2 patients with recurrent disease in relationship to the bulk of residuum after salvage external beam and the brachytherapy techniques used to address this disease. The use of interstitial implantation in select patients with macroscopically positive margins after hysterectomy or persistent central pelvic disease after salvage external beam irradiation is proposed.     

宫颈锥切术在诊断宫颈上皮内瘤样病变和早期宫颈癌中的价值

目的探讨宫颈锥切术能否被阴道镜多点活检所代替以及宫颈锥切术在诊断宫颈上皮内瘤样病变（CIN）和早期宫颈癌中的价值。方法回顾分析近5年来,在江苏大学附属宜兴医院妇产科因宫颈病变同时行阴道镜多点活检和宫颈锥切术（包括冷刀和电圈环切术即LEEP术）的患者120例,采用自身对照法,对比研究宫颈锥切术和阴道镜多点活检的病检结果的差异。结果宫颈锥切术与阴道镜下多点活检病理符合者59例（49．17％）;不符合者61例（50．83％）,宫颈锥切术后病理诊断加重者35例（占29．17％）,浸润癌漏诊率达10．00％。宫颈锥切术的主要并发症为出血。结论宫颈锥切术在诊断CIN和早期宫颈癌具有重要价值,不能被阴道镜多点活检所取代。要重视切缘是否阳性和加强术后的随访。     

Conservative management of stage IA1 squamous cell carcinoma of the cervix with positive resection margins after conization

Objective

To evaluate the efficacy of cold knife conization with electrocauterization and the feasibility of conservative management in patients with stage IA1 carcinoma of the cervix according to margin status after conization.

Methods

Medical and histopathological records of 108 patients with stage IA1 cervical carcinoma were reviewed retrospectively. Patients underwent cold knife conization with electrocauterization or conization followed by hysterectomy. Disease recurrence was defined as a histologic diagnosis of cervical intraepithelial neoplasia (CIN) 2 or higher grade lesion.

Results

Forty patients underwent conization followed by hysterectomy; of 27 women with positive margins, 14 (35%) had a residual lesion. Sixty-eight patients underwent conization without further surgical intervention. Forty patients had a negative resection margin without recurrence, while 28 had a positive resection margin: positive exocervical (n = 11), positive endocervical (n = 17). Among these, there were 7 cases of recurrence: positive exocervical (n = 1); positive endocervical (n = 6).

Conclusion

Cold knife conization with electrocauterization appears to be a safe treatment option for patients with stage IA1 cervical carcinoma if careful follow-up is guaranteed for patients with CIN 3 exocervical resection margins. However, patients with CIN 3 endocervical resection margins should be managed surgically with repeat conization or hysterectomy.     

宫颈鳞癌和宫颈上皮内瘤变组织中人乳头瘤病毒16型及18型的表达

目的从分子水平探讨宫颈鳞状细胞癌(CSCC)及宫颈上皮内瘤样病变(CIN)组织中人乳头瘤病毒(HPV)16型和18型的表达及临床意义。方法2001年1月至2005年1月在中国医科大学附属第一医院采用原位杂交技术分别检测CSCC60例、CIN60例和20例正常宫颈组织中HPV16型和18型DNA的表达。结果在上述各组织中HPV16型表达阳性率分别为73.3%(44/60)、35.0%(21/60)和10.0%(2/20),均明显高于正常对照组(P<0.01和P<0.05);而HPV18型在各组间表达的阳性率比较差异均无显著性意义(P>0.05)。HPV16型表达与CIN的发展有关,在CINⅠ～Ⅱ和CINⅢ的表达分别为23.7%和54.6%,且差异有显著性意义(P<0.05),而HPV18型表达情况与CIN的发展无关(P>0.05)。HPV16和18型的表达与CSCC分化程度及有无淋巴结转移无关。结论宫颈组织中HPV16型的过度表达与CSCC及CIN的发展密切相关,为阐明宫颈癌病因和发病机制以及预测CIN进一步发展的可能性提供了理论依据。     

宫颈上皮内瘤变锥切术后残留或复发相关因素Meta分析

目的 探讨宫颈上皮内瘤变锥切术后残留或复发相关因素。 方法　以宫颈上皮内瘤变、锥切、残留、复发因素的中英文为检索词,检索2006年1月至2013年6月Pubmed、中国知网、万方数据库收录的文献,研究设计类型为病例对照研究或队列研究,提取信息,应用RevMan 5.0软件进行Meta分析。结果　检索到符合纳入标准的文章15篇,随访总例数2721例。Meta分析结果显示：锥切术后残留或复发危险因素为：年龄超过50岁（OR =3.67,95%CI 2.44 ～5.52）、切缘阳性（OR=4.43,95%CI 3.42 ～5.75）、腺体累及（OR=4.54,95%CI 2.22 ～9.30）、术前人乳头瘤病毒高负荷（OR=6.51,95%CI 4.32 ～9.81）、术后高危人乳头瘤病毒持续阳性（OR=33.39,95%CI 16.86 ～66.14）、人类免疫缺陷病毒（HIV）感染（OR=5.60,95%CI 3.10 ～10.11）、绝经（OR=2.32,95%CI 1.35 ～3.99）;而吸烟（OR＝1.37,95%CI 0.75 ～2.51）是锥切术后残留或复发的相关因素尚无统计学意义。结论　年龄≥50岁、切缘阳性、腺体累及、术前高危人乳头瘤病毒高负荷、术后高危人乳头瘤病毒持续阳性、HIV感染和绝经是锥切术后病灶残留或复发的危险因素,而吸烟不是锥切术后病灶残留或复发的危险因素。     

Positive margins after conization and risk of persistent lesion

OBJECTIVE: The aim of this study was to investigate a method to reduce the frequency of uterine reoperation with no persistent lesion and to identify factors predictive of persistent or recurrent lesions. MATERIALS AND METHODS: Of 505 conizations performed by the same surgeon, 71 had positive margins (average patient age = 35.7 +/- 7.7 years). The patients underwent either immediate reoperation or monitoring with a Pap smear and colposcopy. RESULTS: Histologic assessment of the cervical cone after conization showed positive margins in 14.1% of cases [endocervical and exocervical margins affected in 50 of 505 (9.9%) and 21 of 505 (4.2%) cases, respectively]. Of 59 of these patients (83.1%) who underwent follow-up monitoring over an average of 35.2 months (range: 2.6-180. 8), 12 patients (average age: 40.8 +/- 6.4 years) underwent immediate hysterectomy and 47 (average age 34.0 +/- 7.4 years) benefited from monitoring first [secondary discovery of 19 persistent lesions within 6 months and 9 recurrences within 18 months on average (range: 8.8-48 months)]. Of the 9 patients with recurrent lesions, 7 underwent reintervention and 2 monitoring. Of the 19 patients with persistent lesions, 18 underwent reintervention and 1 monitoring. Normal histology was observed in 29.4% of patients undergoing secondary reoperation for an abnormal smear compared with 66.7% of patients undergoing immediate reoperation (P = 0.04). Severity of lesion and age of patients could not be used to predict the incidence of a persistent or recurring lesion. Seventy-nine percent of conizations had positive endocervical margins in patients with a recurring or persistent lesion compared with 48% in patients with normal follow-up (P = 0.03). CONCLUSION: Cytology and colposcopy follow-up in cases of positive conization margins may help to establish justification for the choice of reoperation, thereby limiting morbidity following repeated surgery.     

Laser conization for microinvasive carcinoma of the cervix. Short-term results

Thirty-one patients with microinvasive carcinoma of the uterine cervix (less than 3.0 mm invasion, no lymph vascular involvement), were treated with combination laser conization. The mean follow-up period was 36 months. No cases of invasive disease have been diagnosed during follow-up. Examination during follow-up revealed atypical columnar epithelium in one case, but the hysterectomy specimen was normal. Based on these short-term results, combination laser conization for microinvasive carcinoma of the cervix seemed a sufficient therapy. A precise and careful histopathologic evaluation, and the patient acceptance of a strict follow-up schedule are mandatory to a decision to employ conservative management of microinvasive cervical carcinoma. Only long-term follow-up in patients treated by conservative therapy will be able to finally justify this approach.     

宫颈癌术后尿潴留的临床分析

目的　探讨宫颈癌术后尿潴留发生的相关因素及防治方法。方法　 1990年 1月～ 2 0 0 2年 6月我院共收治宫颈癌患者 12 6例 ,其中 4 4例行广泛或次广泛全子宫切除术 ,回顾性分析本组病例的尿潴留发生率、术前放化疗情况、手术范围、术后泌尿系统感染情况及其诱发因素。结果　尿潴留的发生率为 2 9 6 %。手术范围大组尿潴留的发生率高。手术范围大组、术后尿潴留组、行膀胱体操组泌尿系统感染率较高。术前放化疗对术后尿潴留及泌尿系统感染的发生没有显著影响。结论　手术范围广易造成神经损伤 ,尿潴留发生率增加。但神经损伤并非术后尿潴留的唯一原因。膀胱体操虽然对术后尿潴留有一定改善 ,但应注意加强对泌尿系统感染的防治。术前半量放疗并不增加泌尿系统发病率。选择合适的手术范围及恰当的辅助治疗方案 ,加强术后并发症的防治是保证患者尽快恢复 ,如期进行后续治疗的关键     

Feasibility and outcome of laser CO2 conization performed within the 18th week of gestation

The purpose of this study is to evaluate the feasibility, safety, and potential therapeutic benefit of laser CO(2) conization of the cervix for in situ and minimally invasive carcinoma diagnosed during pregnancy. Twenty-six pregnant patients with biopsy-proven carcinoma in situ/cervical intraepithelial neoplasia III but colposcopically suspicious for invasion underwent laser CO(2) conization during the 18th week of gestation in an outpatient setting under local anesthesia. No major intraoperative or postoperative complications occurred, and cervical cerclage was not required in any case. Two cases (7.7%) of occult FIGO stage IA1 minimally invasive cervical cancers with free surgical margins were diagnosed. Both patients delivered vaginally at term and were free of disease at postpartum follow-up. Median length of gestation was 39.1 weeks with a median birth weight of 3450 g. All 1-min Apgar scores were 8 or greater. Twenty patients (76.9%) delivered vaginally, while six patients underwent cesarean section for indications not related to the prior conization. After a mean postpartum follow-up of 18 months (range 3-42), 92.3% of patients continued to have both cytologic and colposcopic evaluations negative for persistent or recurrent disease. Two cases of persistent intraepithelial disease were successfully managed by reconization. In summary, our data suggest that laser CO(2) conization performed within the 18th week of gestation is safe for both the patient and the fetus, provides reliable histologic diagnosis, and can be curative. Further studies are required to confirm the favorable risk-benefit ratio of laser CO(2) conization in the management of non-reassuring cervical lesions observed in the first half of pregnancy.