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[Discrepancy between histopathological diagnosis based on guided biopsy and cone biopsy of the cervix uteri: analysis of 346 cases of laser conization].

The conservative management of cervical intraepithelial neoplasia (CIN) essentially depended on the introduction and improvement of colposcopy. This technique, allowing to locate the lesion, to estimate its extension and to perform multiple punch biopsies, becomes discriminant in therapeutic choice. Whether colposcopy reveals endocervical involvement or abnormal transformation zone (ANTZ) may be only partially explored, excisional conization should be preferred to ablative therapy since the former advantageously can verify histopathologic diagnosis, confirm completely excision of lesion and rule out invasive carcinoma. The literature shows that cases of invasive lesions can be underestimated and therefore inadequately treated by ablative therapy, emphasizing colposcopy and punch biopsy limitations about suspect and diagnosis of microinvasion. We analyzed data concerning preliminary diagnostic investigations and results of 346 CO2 laser excisional conizations performed between 1984 and 1993. Histopathologic diagnosis on punch biopsy, performed in 111 cases of ANTZ1 and in 235 cases of ANTZ2, shows an agreement with cone biopsy in 30.8% of the cases of CIN1, of 40.9% in cases of CIN2 and of 66.3% in cases of CIN3. Whereas the lesion is overestimated in 30.6% of cases, in which it is likely that punch biopsy has removed the epicenter of the lesion or the lesion in toto, we had an underestimation in 15% of cases, particularly in 4 cases of CIN2, in 38 cases of CIN3 and in all microinvasive processes. The rate of invasive lesions previously ignored and detected only by histopathologic diagnosis on cone biopsy is 2.9%. In only one of these cases colposcopy, even if attributing to each of these the higher grading, shows the suspicion of invasion, whereas the detection of invasive processes is missed in every case by punch biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Laser conization guided by endocervical staining with methylene blue].

The authors report their experience of the use of a vital stain--methylene blue--as a surgical guide in laser cervical conization for CIN2-CIN3/CIS. During the period 1 October 1991-31 December 1992 a total of 40 laser cervical conizations were performed under local anesthesia using a CO2 laser connected to a microhandpiece and colposcope in patients with exo-endocervical lesions which were histologically positive for CIN2-CIN3/CIS. In 33/40 patients an aqueous solution of 1% methylene blue was introduced preoperatively in the endocervix using a cotton-wool bud with consequent impregnation of the pseudoglandular crypts: laser biopsy was performed along the guidelines of the stain itself. This enabled the direction of resection to be varied: in 3 patients due to an anomalous and eccentric direction of cervical canal; in 10 patients to remove glandular structures surrounding or underneath lesions; in 8 patients following pseudoglandular section to carry out deep vaporization (3 patients) or correct cutting edges (5 patients). The apex and edges of the cone were always intact. Fourteen patients completed a 12-month follow-up and a further 6 were followed up for 9 months; only 1/14 patients (with AIDS) showed recidivation after 1 year. In the authors' experience the use of a vital stain as a guide during laser cervical cone biopsy is an easily used method which ensures the greatest possible respect for healthy cervical structures, also in order to preserve fertility in young patients.

Adult↗

Cold-knife cervical conization.

Forty-six cervical conizations were performed over a ten-year period for diagnostic or therapeutic purposes. Twenty-nine women were under 45 years of age. The most common reason for conization was an abnormal Papanicolaou smear. The overall incidence of neoplasia was 80.4 per cent. The high complication rate of 28.4 per cent emphasizes the need for a less traumatic technique of excisional biopsy.

Adult↗

A comparison of laser and cold knife conization.

Currently, there are two methods of cervical conization, the laser and the cold knife. This retrospective review examined 217 laser cases and 205 cold knife cases to see which method was superior. The cold knife was shown to have a shorter operative time and a lower overall cost to the patient; however, it was associated with more intraoperative blood loss and more overnight admissions for observation. There were no differences in post operative bleeding complications requiring a visit to the emergency room or to the operating room. It is concluded that overall, there is no clearly superior method of conization for the treatment of cervical intra-epithelial neoplasia.

Adolescent↗

Prediction of residual neoplasia based on histopathology and margin status of conization specimens.

OBJECTIVE: To evaluate the status of cone margins and the severity of cervical neoplasia as predictors of residual lesions in the remaining cervices. METHODS: We performed a 7-year retrospective study and reviewed 172 patients who had undergone cervical conization followed by subsequent hysterectomy. Pathological findings of the cone margins and residual lesions in the postcone hysterectomy specimens were recorded for analysis. RESULTS: The prevalence rates of positive cone margins were 0, 18.6, 23.8, and 25%, respectively, in patients with low-grade squamous intraepithelial lesion (SIL) (n = 6), high-grade SIL (n = 129), stage IA1 cervical cancer (CC-IA1) (n = 21), and CC-IA2 (n = 16). The prevalence rates of positive residual lesions in postcone hysterectomy specimens were 0, 23.3, 23.8, and 43.8%, respectively, in those with low-grade SIL, high-grade SIL, CC-IA1, and CC-IA2. Residual lesions were significantly more frequently found in patients with positive cone margins (84.8%) than in those with negative margins (10.1%) (X2 = 76.81, P < 0.0001). All six patients with low-grade SIL had free cone margins. Positive predictive values of margin status for the presence of residual lesions were 83.3, 80, and 100%, respectively, in patients with high-grade SIL, CC-IA1, and CC-IA2. Only two (6.1%) of 33 patients with positive cone margins had more advanced residual lesions. Negative predictive values of margin status for the absence of residual lesions were 100, 90.5, 93.8, and 75%, respectively, in patients with low-grade SIL, high-grade SIL, CC-IA1, and CC-IA2. None of the 139 patients with negative margins had invasive residual lesion. CONCLUSIONS: (1) The prevalence of positive cone margin and residual lesion increased with higher severity of cervical neoplasia. (2) Patients with positive cone margins had significantly higher chances of having residual lesion than those with negative margins. (3) Free cone margin does not ensure the absence of residual lesion in the remaining cervix. However, the possibility of residual invasive cancer in the remaining cervix is remote. (4) Positive cone margin does not invariably indicate the presence and persistence of more severe residual lesion. Subsequent hysterectomy may be reserved for the patient with invasive cone pathology, the patient with concomitant morbid uterine condition, or the patient who is not reliable for continuous follow-up.

Conization↗

A comparison between loop electrosurgical excision procedure and cold knife conization for treatment of cervical dysplasia: residual disease in a subsequent hysterectomy specimen.

OBJECTIVE: The purpose of this study was to determine whether the loop electrosurgical excision procedure (LEEP) is as effective as cold knife conization (CKC) in the removal of cervical dysplasia. METHODS: One-hundred sixteen patients with cervical intraepithelial neoplasia were included: 73 cases treated with LEEP and 43 cases treated with CKC. All of these patients underwent subsequent hysterectomy within 6 months of treatment. A thorough histological evaluation of the cone specimens and post-cone hysterectomy specimens was performed. RESULTS: No residual disease in the post-cone hysterectomy specimens was identified in 63% of the LEEP group and 72.1% of the CKC group. There was no significant difference in the proportion of negative residual disease (P > 0.05). The mean diameters of the base as well as the depth of the cone specimens were smaller in the LEEP group than in the CKC group (P < 0.05). The operating time in the LEEP group was significantly shorter than that of the CKC group (P < 0.05). Although thermal artifacts of margin were found in 8.2% of LEEP specimens, there was no difficulty in histological interpretation. Furthermore, the postoperative complications were similar in both groups. CONCLUSION: The findings of this study demonstrate that the LEEP is a convenient, safe, and effective treatment for the management of cervical dysplasia. Cone specimens obtained during LEEP are adequate for thorough histological evaluation of cervical dysplasia.

Adult↗

Importance of surgical margins in conization for cervical intraepithelial neoplasia grade III.

We conducted a retrospective study on 201 conizations for CIN III done over the last 14 years. Of these, 53 (26.4%) had involvement of the margins, 114 (56.7%) had margins free of neoplasia, and 34 (16.9%) were not evaluated. Of the 53 cases with margin involvement, 28 (52.8%) had complementary surgery and 25 (47.2%) cytological follow-up. Residual CIN was identified in the surgical specimen in 15 cases (53.6%) and microinvasion was present in 2 cases (7.1%). Of the 114 patients with margins free of neoplasia in the cone, 12 had a hysterectomy during follow-up for CIN III diagnosed by cytology and biopsy. Seven of these 12 patients (58.3%) had CIN in the surgical specimen and none had microinvasive cancer.

Adult↗

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.

Adult↗

Diagnostic and therapeutic laser conization for cervical intraepithelial neoplasia.

OBJECTIVE: The clinical efficacy of conservative treatment using Nd-YAG laser technique for cervical intraepithelial neoplasia (CIN) was evaluated in a large series of CIN patients based on the long-term follow-up results. METHODS: We have treated 2107 women preoperatively diagnosed as having CIN by Nd-YAG contact laser conization with vaporization of the base. Their postoperative histologic findings and clinical outcomes were evaluated. RESULTS: The cone specimen was reported as showing that 1956 (92.8%) of 2107 cases had no CIN or CIN 1-3 and 151 (7.2%) cases had invasive diseases. 1956 cases without invasive diseases were followed up for 16 to 252 months. Incomplete excision occurred in 230 (12.3%) of 1874 patients with CIN lesion in the cone specimen, but failure rate (persistence or recurrence) was only 1.2%. 192 (83.5%) of 230 postoperative CIN patients with positive surgical margins showed no abnormal cytology or colposcopy during follow-up period. Preoperative underdiagnosis of biopsy results compared with cytologic or colposcopic findings elevated the risk for incomplete excision and failure rate. CONCLUSION: The combination of laser excision and vaporization of the base was useful to detect unexpected invasive disease and revealed excellent therapeutic effects for CIN. Preoperative cytologic or colposcopic findings should be taken into account for the conservative treatment of CIN.

Conization↗

Cytologic and biopsy findings leading to conization in adenocarcinoma in situ of the cervix.

OBJECTIVE: To investigate the utility of currently available screening tests in preoperatively detecting adenocarcinoma in situ of the cervix. METHODS: Patients with a cone biopsy diagnosis of adenocarcinoma in situ from 1987 to 2000 at our institution were identified. Results from Papanicolaou smears, cervical biopsies, and endocervical curettages preceding the diagnostic cone biopsy were collected from medical records and referring providers. Fisher exact test (two-tail) was used for statistical analysis. RESULTS: The preoperative screening results preceding a cone biopsy containing adenocarcinoma in situ were available in 118 patients. Among 94 Papanicolaou smears, 65 (69%) glandular lesions and 29 (31%) squamous or unspecified lesions were reported. Biopsy and/or endocervical curettage after the 29 squamous or unspecified lesions on Papanicolaou smear detected 15 additional glandular lesions, totaling 80 (85%) of 94 cases of glandular disease detected before conization. Among all 118 cases with some form of preoperative data available, glandular disease was predicted in 100 cases (85%). In cases of suspected glandular disease, 86% were treated with cold knife cone compared with 22% in cases of suspected squamous abnormalities (P <.001). CONCLUSION: The sensitivity of detecting a glandular abnormality before a cone biopsy containing adenocarcinoma in situ is 69% with the Papanicolaou smear and 85% with the addition of biopsy and endocervical curettage. This underscores the importance of using preoperative assessment to appropriately plan treatment for a suspected glandular lesion.

Adenocarcinoma↗

Residual and recurrent disease after laser conization for cervical intraepithelial neoplasia.

OBJECTIVE: To assess the risk of residual and recurrent disease after carbon dioxide laser conization treatment for high-grade lesions of the cervix uteri, and thus to refine intervals for follow-up. METHODS: The study population comprised all women treated for cervical intraepithelial neoplasia grade II-III over a 10-year period (1983-1992). All women who resided within the county for the entire follow-up period were followed for residual or recurrent disease, verified histologically until the closure date of January 31, 1996. The cumulative incidence of recurrent disease was assessed by survival analyses, and logistic regression was used to predict clinical features at initial treatment that were associated with the risk of residual or recurrent disease. RESULTS: Only 19 of 1081 women (1.8%) were lost to follow-up. Residual disease was diagnosed in 20 (1.9%) study participants. The cumulative incidence of recurrent disease was extremely low, increasing nearly linearly with an annual incidence of three per 1000 woman-years observed. Involved resection margins were associated significantly with both residual disease (crude odds ratio [OR] 18.1; 95% confidence interval [CI] 5.2, 64.0) and recurrent disease (adjusted OR 3.0; 95% CI 1.2, 7.5) when compared with disease-free resection margins as reference. CONCLUSION: We recommend a differential follow-up interval depending upon the histologic evaluation of cone margins. If there is no residual disease, women who have free resection margins should return at a 3-year interval for follow-up. Women who have disease extended to the cone margins are recommended Papanicolaou smears at annual intervals through the fourth postoperative year before returning at a 3-year interval as practiced in the general screening program.

Adolescent↗

Factors predicting human papillomavirus clearance in cervical intraepithelial neoplasia lesions treated by conization.

OBJECTIVE: The objective was to identify the factors, if any, that may predict long-term results of CIN treatment and HPV clearance/persistence after locally excisional therapy. METHODS: A series of 252 women with CIN lesions treated by conization were subjected to sequential HPV detection by repeated PCR during the prospective posttreatment follow-up. Factors predicting viral clearance during the follow-up (10.26 months) were elaborated using univariate and multivariate statistical techniques applied on epidemiological, clinical and biological data of the lesions. RESULTS: Sensitivity of the PAP test in detecting high-grade lesions was 93.9%, and specificity 27.3%. Odds ratio for having CIN 3/Stage IA1 squamous cervical cancer in the cone with HSIL PAP test was 5.69; 77.8 and 22.2% residual disease were found among PCR-positive and -negative cases, respectively. HPV DNA was negative in 74/252 (29.8%) samples at the first PCR. Multivariate logistic regression analysis showed that HPV 16 was an independent explanatory factor for high-grade CIN (P = 0.0001). HPV clearance increased to 63.5% at completion of the follow-up, corresponding to the monthly clearance rate of 5.27%. In Kaplan-Meier analysis, the highly significant (P = 0.0001) predictors of HPV clearance/persistence were age, lesion grade in the biopsy, lesion grade in the cone, volume of the cone, length of active sexual life, and involvement of endocervical margin (P = 0.0013). In chi-square tests, high-risk HPV type (P = 0.001) was such a predictor. In multivariate (Cox) model, the significant independent predictors of HPV clearance were involved endocervical margin (P = 0.001), lesion grade in the cone (P = 0.004), high-grade lesion in the colposcopic biopsy (P = 0.023), age (P = 0.029), and HSIL in PAP smear (P = 0.029). CONCLUSIONS: These data suggest that posttreatment follow-up should include both the PAP test and HPV detection techniques for early detection of any patients at increased risk for disease recurrence and progression, because of persistent oncogenic HPV types.

Adolescent↗

Long-term outcome of a randomized study comparing three techniques of conization: cold knife, laser, and LEEP.

OBJECTIVE: To evaluate the long-term recurrence rates and complication of different techniques of cervical ablation. METHODS: A randomized trial of three techniques of conization (cold knife, laser, and loop electrosurgical excisional procedure (LEEP)) for cervical intraepithelial neoplasia (CIN) in which 110 patients had been recruited. RESULTS: Eighty-six patients were followed-up for more than 3 years. Of these 28 had been treated with the cold knife, 29 with LEEP and 29 by laser. Five recurrences were observed, one in the cold knife group, two in the LEEP group and two in the laser group (P=NS). The only observed complication was cervical stenosis: zero cases in the laser group, one case in the LEEP group and four cases in the cold knife group (laser versus cold knife: P=0.03; LEEP versus cold knife: P=0.06). Fifty pregnancies were observed in 39 patients. First and second trimester outcomes of pregnancy were without complications. One patient treated with the LEEP presented with a premature rupture of membranes and premature labor at 36 weeks. A total of nine cesarean sections were performed with two cases for cervical dystocia. CONCLUSION: There is no major difference in obstetrical outcome between the three techniques.

Adult↗

Human papillomavirus (HPV) in high-grade cervical intraepithelial neoplasia (CIN) detected by morphology and polymerase chain reaction (PCR)-- a cytohistologic correlation of 277 cases treated by laser conization.

The aims of this study were to evaluate the cytohistologic correlation in women treated for high-grade lesions of the cervix uteri (HG CIN), to assess the distribution of HPV features and finally to test the validity of the morphological criteria of HPV infection. The smears and biopsy specimens from 277 women treated for HG CIN by laser conization were re-evaluated blindly. Tissue blocks (n = 188) and 52 archival smears were examined for HPV DNA using PCR. HPV changes were detected with equal frequency in the smears and biopsy specimens by light microscopy; 63% and 65%, respectively. The prevalence of HPV DNA in biopsies was 88% and in archival smears 85%; agreement was found in 89% of the cases. Using PCR as the gold standard, we found a sensitivity of 63% for cytology and 70% for histology; the specificity was 41% and 37%, respectively. The positive predictive value was > 80%, but the negative predictive value was < 20%. Our study confirms that HPV features are frequently associated with HG CIN and that morphology is a non-specific method of identifying HPV infection and should be followed by PCR, also allowing detection of oncogenic HPV types and latent infections.

Conization↗

Miniconization procedure with C-LETZ conization electrode for treatment of cervical intraepithelial neoplasia: a Swedish study.

BACKGROUND: Since 1989 large loop excision of the transformation zone (LLETZ) has become the treatment of choice for cervical intraepithelial neoplasia in many colposcopy clinics. This method has limitations however, in that the resection margins of the cone produced by LLETZ cannot give conclusive histological reassurance, because of thermal injury in 5 30% of the specimens. Furthermore, LLETZ are often taken in several sections, which makes the histopathological examination unnecessarily difficult. As a new and single treatment without these limitations, conization with the contoured loop excision of the transformation zone (C-LETZ) electrode was investigated in the present study. Material and methods. One hundred and seventy-four patients with CIN were treated with the C-LETZ electrode during 12 months at the Gynaecological Department, Karolinska University Hospital, Huddinge. The inclusion criteria were a histological diagnosis of CIN II-III, or persistent CIN I. RESULTS: Eighty-six per cent of the patients had a complete excision according to histological findings, and 12% had an incomplete excision. The frequency of incomplete excisions increased with the severity of the CIN but were found in all groups of patients: 1 (3%) in CIN I, 5 (12%) in CIN II, and 12 (17%) in CIN III. The resection margins and histological diagnoses were certain in 98% of the cases. A cure rate of 90% was observed. Conclusions. Miniconization with the C-LETZ electrode makes it possible to individualize the size of the minicones and produce the minicones as one-piece specimens for histopathological assessment. Our findings confirm that this method is a reproducible, safe, and economical way to treat CIN with a low rate of morbidity in a hospital outpatient setting.

Conization↗

Delayed hemorrhage after cervical conization unmasking severe factor XI deficiency.

BACKGROUND: Factor XI deficiency, a rare bleeding disorder found most commonly in patients of Ashkenazi Jewish background, may be present in patients with a history of abnormal bleeding after elective surgery. CASE: A patient of Ashkenazi Jewish descent presented 12 days after cervical conization for adenocarcinoma in situ with severe vaginal bleeding requiring multiple transfusions and uterine artery embolization. After a thorough workup, a severe factor XI deficiency was found. The patient ultimately required modified radical hysterectomy for treatment of early cervical cancer. With appropriate perioperative management, the patient underwent abdominal surgery without further bleeding complications. CONCLUSION: Factor XI deficiency can present with severe bleeding episodes after elective surgery. Adequate preoperative assessment and perioperative management are necessary to prevent bleeding complications in these patients.

Adenocarcinoma↗

p16(INK4A) expression is related to grade of cin and high-risk human papillomavirus but does not predict virus clearance after conization or disease outcome.

The role of p16(INK4A) as a marker of HR-HPV and in the diagnosis of CIN has been well established, but its predictive value in the clearance of the virus after CIN treatment and its use as a prognostic marker of cervical cancer has not been studied. A series of 302 archival samples, including 150 squamous cell carcinomas (SCCs) and 152 CIN lesions, were subjected to immunohistochemical staining for p16(INK4A) and HPV testing using PCR with three primer sets (MY09/11, GP5/GP6, SPF). Follow-up data were available of 88 SCC patients, and 67 of the CIN lesions had been followed-up with serial PCR after conization. HR-HPV types were closely associated with CIN (OR 19.12; 95%CI 2.31-157.81) and SCC (OR 27.25; 95%CI 3.28-226.09). There was a significant linear relationship between the lesion grade and intensity of p16(INK4A) staining (p = 0.0001). The expression of p16(INK4A) was also closely related to HR-HPV (p = 0.0001). p16(INK4A) staining was a 100% specific indicator of CIN, with 100% PPV, and showed 83.5% sensitivity and 80.1% PPV in detecting HR-HPV. However, p16(INK4A) staining did not predict clearance/persistence of HR-HPV after treatment of CIN. Similarly, despite a slightly more favorable survival in women with strong/intense p16(INK4A) staining in univariate analysis, p16(INK4A) expression was not an independent prognostic predictor in multivariate survival (Cox) analysis. After adjustment for p16(INK4A) staining, HR-HPV, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and age, only the last two were significant prognostic predictors (p = 0.0001 and p = 0.003, respectively). The present data confirm the role of p16(INK4A) as a highly specific marker of CIN and HR-HPV type, but expression of this protein does not seem to be of any prognostic value in cervical cancer or in predicting the clearance of HR-HPV after treatment of CIN. We speculate that different subgroups of cervical cancer are characterized by aberrant p16(INK4A)/cyclin D/Rb pathways that are due to different mechanisms that can be mutually exclusive.

Adolescent↗

Conization, frozen section examination, and planned hysterectomy in the treatment of high-grade cervical intraepithelial neoplasia.

PURPOSE: We tested the role of frozen section examination of the cone specimen in the evaluation of the resection margin status and to rule out invasion in patients with high-grade cervical intraepithelial neoplasia. METHODS: Twenty-five patients with cervical intraepithelial neoplasia underwent conization followed by frozen section examination and planned hysterectomy. The results of the definitive paraffin exam were compared with frozen section examination. RESULTS: In the evaluation of the margins by frozen section examination, 16 patients (64%) had positive cone margins and 9 (36%) had negative margins. The definitive paraffin examination of margin status was concordant in all the cases. Intraoperative diagnosis of invasion was made in 5 cases, and 1 of these was microinvasive. Among the remaining 20 cases, we detected 2 additional microinvasive carcinomas after paraffin study, so the diagnosis of the frozen section examination was concordant with the paraffin sections in 23/25 cases (92%). Two cases of microinvasive carcinoma were diagnosed as cervical intraepithelial neoplasia by frozen section examination and had less than 2 mm stromal invasion. CONCLUSIONS: In high-grade cervical intraepithelial neoplasia, frozen section examination can provide immediate and precise evaluation of the cone margin status in high-grade cervical intraepithelial neoplasia. It can identify frank invasion and permit adequate treatment in a one-stage procedure. In early microinvasive disease, frozen section examination fails to detect the area of invasion but reliably detects clear resection margins.

Adult↗