A randomized trial comparing two methods of cold knife conization with laser conization

In a randomized study, 62 women were submitted to cold knife conization with application of Sturmdorf sutures, 60 to cold knife conization without sutures, and 61 to laser conization. Early hemorrhage occurred in 1.6, 13.3, and 6.6% of women, respectively (P less than .05), and late hemorrhage in 15.3, 3.6, and 11.7%, respectively. Considering early and late hemorrhage together, there was no significant difference among the three treatment groups. Dysmenorrhea tended to be more common after application of Sturmdorf sutures, as it was reported by 27.8, 13.2, and 14.3% of patients, respectively, but the difference was not statistically significant. Dysmenorrhea occurred in 13% of the cases with a cone height of 20 mm or less and in 26% of the cases with a cone height greater than 20 mm (P less than .05). Endocervical cells were present significantly more often after sampling with a cytobrush than with a cotton swab (P less than .0001), whereas the method of conization had no influence. In smears obtained with a cytobrush, endocervical cells were present in 88.0, 84.9, and 82.5% of the cases; in smears obtained with a cotton swab, endocervical cells were present in 46.6, 57.7, and 54.5%, respectively. We conclude that cold knife conization without Sturmdorf sutures is about equal to laser conization in overall complications, but the laser is preferable for outpatient treatment because of a lower frequency of early hemorrhage. Sturmdorf sutures should be avoided. Smears at follow-up should be taken with a cytobrush and a wooden spatula.     

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.     

Prognostic significance of DNA ploidy in stage I endometrial cancer

Objective.

To improve the outcome for patients with endometrial cancer, a more accurate prognostic assessment is needed. The current study was undertaken to determine the role of flow cytometric DNA ploidy as an independent prognostic factor in patients with stage I endometrial cancer and to verify if ploidy is able to identify high-risk cases among the apparent ‘low-risk’ patients, defined as stage (IA), grade (1 or 2), and histologic type (endometrioid).

Methods.

This was a retrospective study. DNA ploidy was evaluated from tumor samples in 217 patients with stage I endometrial cancer who underwent definitive surgery as the first treatment between 2003 and 2009. Ploidy and other classic parameters were analyzed in relation to the length of recurrence-free survival.

Results.

Among the 217 evaluated patients, 184 (84.8%) had diploid tumors and 33 (15.2%) had aneuploid tumors. There were 12 recurrences during the median follow-up intervals of 42.7 months. Stage, grade, histologic type, lymphovascular space invasion (LVSI), and ploidy were significantly correlated with recurrence-free interval by univariate Cox analysis. Based on multivariate Cox analysis, ploidy was an independent prognostic factor, with a hazard ratio of 4.5 (95% confidence interval [CI], 1.3-15.3; P = 0.017) adjusted for stage, grade, histologic type, and LVSI. In low-risk patients (n = 156), the recurrence rate was 2.1% for diploid tumors and 12.5% for aneuploid tumors (P = 0.038).

Conclusions.

DNA aneuploidy is an independent prognostic factor in patients with endometrial cancer and can identify high-risk patients among those considered ‘low-risk’ with stage I endometrial cancer.     

Evaluation of endometrial carcinoma on magnetic resonance imaging

Our aims were to assess diagnostic performance of T2-weighted (T2W) and dynamic gadolinium-enhanced T1-weighted (T1W) magnetic resonance imaging (MRI) in the preoperative assessment of myometrial and cervical invasion by endometrial carcinoma and to identify imaging features that predict nodal metastases. Two radiologists retrospectively reviewed MR images of 96 patients with endometrial carcinoma. Tumor size, depth of myometrial and cervical invasion, and nodal enlargement were recorded and then correlated with histology. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the identification of any myometrial invasion (superficial or deep) were 0.94, 0.50, 0.93, 0.55 on T2W and 0.92, 0.50, 0.92, 0.50 on dynamic T1W, and for deep myometrial invasion were 0.84, 0.78, 0.65, 0.91 on T2W and 0.72, 0.88, 0.72, 0.88 on dynamic T1W. The sensitivity, specificity, PPV and NPV for any cervical invasion (endocervical or stromal) were 0.65, 0.87, 0.57, 0.90 on T2W and 0.50, 0.90, 0.46, 0.92 on dynamic T1W, and for cervical stromal involvement were 0.69, 0.95, 0.69, 0.95 on T2W and 0.50, 0.96, 0.57, 0.95 on dynamic T1W. Leiomyoma or adenomyosis were seen in 73% of misdiagnosed cases. Sensitivity and specificity for the detection of nodal metastases was 66% and 73%, respectively. Fifty percent of patients with cervical invasion on MRI had nodal metastases. In conclusion, MRI has a high sensitivity for detecting myometrial invasion and a high NPV for deep invasion. MRI has a high specificity and NPV for detecting cervical invasion. Dynamic enhancement did not improve diagnostic performance. MRI may allow accurate categorization of cases into low- or high-risk groups ensuring suitable extent of surgery and adjuvant therapy.     

Anatomical and pathological study of retroperitoneal nodes in endometrial cancer

Benedetti-Panici P, Maneschi F, Cutillo G, D'Andrea G, Manci N, Rabitti C, Scambia G, Mancuso S. Anatomical and pathological study of retroperitoneal nodes in endometrial cancer. Int J Gynecol Cancer 1998; 8 : 322–327.
To assess the patterns of lymphatic spread in endometrial carcinoma, data from 91 endometrial cancer patients (surgical FIGO stage I: 59; II: 12; III–IV: 20) who underwent systematic pelvic and aortic lymphadenectomy were analyzed. The median number of nodes removed was 27 aortic (range 15–57) and 31 pelvic (range 20–68) nodes. Positive nodes were found in 16 patients (18%), seven having pelvic, one aortic, and eight both pelvic and aortic metastasis. The median number of positive nodes was three (range 1–29) aortic and two (range 1–18) pelvic nodes. Isolated pelvic node metastasis was observed in seven patients and aortic metastasis in one patient.
Pre-paracaval, pre-paraortic and intercavoaortic, with superficial obturator, external iliac and common iliac were the node groups most frequently involved. These nodes may be considered primarily invaded by the tumor. The higher prevalence of pelvic with respect to aortic metastasis, and the low risk of isolated aortic spread, suggest that endometrial cancer spreads preferentially to the pelvic area. Multivariate analysis showed that depth of myoinvasion and adnexal metastasis were independent factors predicting the risk of lymphatic spread. The risk of aortic spread was also predicted by the pelvic node status. These data may be useful for tailoring lymphadenectomy.     

Doxorubicin and/or cisplatin based chemotherapy for the treatment of endometrial carcinoma with retroperitoneal lymph node metastases

Selman AE, Fowler JM, Martinez-Monge R, Copeland LJ. Doxorubicin and/or cisplatin based chemotherapy for the treatment of endometrial carcinoma with retroperitoneal lymph node metastases. Int J Gynecol Cancer 1998; 8 : 423–429.
The objective of this review was to assess the effect of adjuvant doxorubicin and/or platinum-based chemotherapy on the survival and patterns of recurrence, of women with completely resected, poor-prognosis endometrial carcinoma with retroperitoneal lymph node metastases. A retrospective review of 31 cases of endometrial carcinoma with retroperitoneal lymph node metastases seen over a 10-year period at the James Cancer Hospital of The Ohio State University Medical Center is presented. Only patients with histologically documented retroperitoneal lymph node metastases and treated with postoperative doxorubicin and/or platinum-based chemotherapy were included.
With a median follow-up of 53 months (range 5–107), 17 patients (55%) have experienced continuous control of their tumor. Overall 5-year survival was 40% and 5-year disease free survival was 34%.
Post-operative chemotherapy with doxorubicin- and/or cisplatinum-containing regimens is well tolerated and provides results that appear to be as good as those achieved with surgery and radiotherapy in the treatment of endometrial carcinoma with nodal or other intra-abdominal metastases (Stages IIIC and IV). However, a randomized study is needed to establish a definitive comparison of these modalities.     

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.     

Resection of bulky positive lymph nodes in patients with cervical carcinoma

From January 1987 to April 1992, 34 patients had resection of bulky positive lymph nodes, detected either at the time of radical hysterectomy ( n = 23) or by computed tomographic (CT) scan of the pelvis and abdomen prior to radiation therapy for more advanced cervical cancer ( n = 11). Following nodal resection, 33 patients received pelvic external beam radiation, 28 received pelvic and para-aortic radiation, and 23 received four cycles of cisplatin chemotherapy. The median number of resected positive nodes was 4, with a range of 1–44. All macroscopic nodal metastases could be resected in each patient and morbidity was acceptably low. Positive nodes were confined to the pelvis in 17 patients, involved the common iliac group in nine patients, and involved the para-aortic area in eight patients. With a mean follow-up of 36 months, 23 patients (67.6%) were alive, of whom 20 were free of disease. For patients having a radical hysterectomy, actuarial 5-year survival was 80% for patients with disease involving pelvic and common iliac lymph nodes, and 48% for those with positive para-aortic nodes. Survival for patients with completely resected bulky pelvic and common iliac nodes was comparable to that for patients with micrometastases. This study suggests that every effort should be made to identify patients with cervical cancer who have bulky positive lymph node metastases, and to remove these nodes surgically prior to radiation therapy.     

Analysis of clinicopathologic factors predicting para-aortic lymph node metastasis in endometrial cancer

The purposes of this study were to compare the relationships between para-aortic lymph node metastasis and various clinicopathologic factors to evaluate whether para-aortic lymph node dissection is necessary when treating endometrial cancer. A retrospective study was performed on 841 patients with endometrial cancer, who underwent the initial surgery at the Keio University Hospital. Clinicopathologic factors related to para-aortic lymph node metastasis significant on a univariate analysis were analyzed in a multivariate fashion using a logistic model. According to the multivariate analysis, the clinicopathologic factor most strongly related to the existence of para-aortic lymph node metastasis was positive pelvic lymph node metastasis (P < 0.01). Among the 155 patients who underwent pelvic and para-aortic lymph node dissection, the difference of 5-year overall survival by the presence of retroperitoneal lymph node metastasis was examined by Kaplan-Meier method. The prognosis was poor even if para-aortic lymph node dissection was performed in cases of positive para-aortic lymph node metastasis. In conclusion, when deciding whether to perform para-aortic lymph node dissection in patients with endometrial cancer, it is necessary to consider the pelvic lymph nodal status. If there is no pelvic lymph node metastasis, it could not be necessary to perform para-aortic lymph node dissection.     

子宫内膜癌淋巴结切除适应证和争议

早期子宫内膜癌有淋巴转移风险,但是否对所有患者均需行区域淋巴结切除仍有争议。可根据术前、术中的评估决定是否行淋巴结切除及何种范围的淋巴结切除。高危病例应该实施系统性淋巴结切除。     

Randomized study comparing day 2 versus day 3 elective transfer of two good-quality embryos

Objective  The number of embryos transferred is very important to avoid multiple pregnancies without compromising pregnancy rates in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-embryo transfer (ET). We established criteria for the elective transfer of two embryos (age < 40, first treatment cycle, good-quality embryos > 3) to avoid high-order multiple pregnancies, and reported their usefulness. In the current study, we compared the clinical outcome of day 2 versus day 3 elective transfer of two good-quality embryos, in order to investigate the day of preferential transfer. Methods  A total of 228 cycles were treated with IVF/ICSIET from August 1999 to August 2002. From this total, 114 patients who were less than 40 years old and also had a first treatment cycle were enrolled in the present study (50.0%). The elective transfer of two good-quality embryos was carried out in 36 cycles (31.6%). Patients were randomized for transfer on either day 2 or day 3 after oocyte retrieval. Results  The pregnancy rate of women who received two goodquality embryos was 44.4% (16 out of 36). The multiple pregnancy rate was 12.5% (two out of 16) and all pregnancies outcomes were twins. There were no significant differences between day 2 and day 3 ET for the following criteria: the number of cycles (24, 12); age (32.8 ± 3.4 years, 32.5 ± 2.7 years); number of oocytes retrieved (10.0 ± 3.3, 9.0 ± 6.0); number of embryos developed (7.6 ± 3.5, 6.9 ± 3.7); and number of goodquality embryos cryopreserved (3.5 ±2.7, 3.6 ±2.1). Higher pregnancy and implantation rates were obtained in day 3 ET than day 2 ET (37.5 and 20.8% in day 2 ET vs 58.3 and 33.3% in day 3 ET); however, there were no significant differences. Conclusion  Day 3 ET appears to be preferable to achieve more viable embryos than day 2 ET.     

Noninvasive detection of inguinofemoral lymph node metastases in squamous cell cancer of the vulva by L-[1–11C]-tyrosine positron emission tomography

In the majority of patients with early stage squamous cell cancer (SCC) of the vulva, an inguinofemoral lymphadenectomy is performed (in retrospect) for diagnostic reasons: exclusion of inguinofemoral lymph node metastases. The morbidity of this procedure, however, is significant. The aim of the present study was to evaluate noninvasive detection of inguinofemoral lymph node metastases by positron emission tomography (PET) using L-[1–¹¹C]-tyrosine (TYR) as tracer.
In patients with SCC of the vulva, scheduled for resection of the primary tumor and uni- or bilateral inguinofemoral lymphadenectomy, results of preoperative palpation of the groins and TYR-PET imaging were compared with histopathology. PET imaging was performed using two different methods. In a first group ( n = 16), nonattenuation corrected 'whole body' scans were performed, and in a second group ( n = 9), attenuation corrected static emission scans.
Sensitivity, specificity, accuracy, and positive and negative predictive value for palpation were 62%, 89%, 82%, 67%, and 87% per groin. Sensitivity, specificity, accuracy, and positive and negative predictive value for TYR-PET were calculated for the two methodologies separately and overall. There were no significant differences. Overall values were 53%, 95%, 94%, 33%, and 98% per lymph node and 75%, 62%, 65%, 41% and 88% per groin.
Detection of inguinofemoral lymph node metastases by TYR-PET is not superior to palpation. Neither palpation nor TYR-PET is able to adequately predict or exclude presence of inguinofemoral lymph node metastases in patients with SCC of the vulva.     

Squamous cell carcinoma antigen: pretreatment levels as an indicator of advanced or metastatic disease

Pretreatment values of squamous cell carcinoma antigen (SCC) were obtained in 100 consecutive patients with squamous cell carcinoma of the cervix presenting to the Regional Gynaecological Oncology Centre in Gateshead, UK. Nine patients deemed to have locally advanced disease not suitable for primary surgery had elevated levels. Ninety-one patients were suitable for primary surgery. Sixty-seven had normal SCC levels, two of which had lymph node metastases. Twenty-four had elevated SCC levels, 14 of which had lymph node metastases. Two early recurrences have been detected in the raised SCC group where no lymph node metastases were present. Elevated levels of SCC in the pretreatment assessment indicate a high risk of lymph node metastases and of developing recurrent disease after primary surgery.     

Does the size of pelvic lymph nodes predict metastatic involvement in patients with endometrial cancer?

Whether the size of a retroperitoneal lymph node reflects its status is not clear. We measured the size of 125 positive and 160 negative pelvic lymph nodes in 32 consecutive patients with node-positive endometrial cancer. The measurements were compared with those of 143 pelvic lymph nodes of five randomly selected patients with endometrial cancer without node involvement. Overall, positive lymph nodes were larger than negative lymph nodes in both node-positive patients and node- negative controls ( P < 0.01). There was a positive correlation between the size of positive lymph nodes and the size of the metastasis therein ( P < 0.01). However, 68 of 125 (54%) positive lymph nodes measured less than 10 mm in maximum diameter, while 46 of 160 (29%) negative lymph nodes in node-positive patients measured more than 10 mm in maximum diameter. The metastasis was detected in more than 50% of step-serial sections in only 74% of positive lymph nodes. These data suggest that the size of a lymph node does not reliably reflect its status. Thus, these nodes may be missed if only enlarged nodes are removed. If only one section of a lymph node is performed, at least 26% of metastases will be missed.     

Flow cytometric DNA measurements in squamous cell carcinoma of the vulva: an important prognostic method

One hundred and thirty-one squamous cell carcinomas of the vulva were examined by FCM-DNA measurements. Samples were prepared from paraffin-embedded tissue. Of these, 66 were found to be diploid, 52 aneuploid and 13 could not be evaluated. The 5-year crude survival rate was 62% for the diploid and 23% for the aneuploid tumors ( P < 0.001). The aneuploid tumors without lymph node (LN) metastases showed a 5-year cancer-related survival rate of 44% as compared to 58% for the diploid tumors with LN metastases. In a multivariate Cox regression analysis the most important independent prognostic parameters were (1) LN involvement ( P < 0.0001), (2) tumor ploidy ( P = 0.0001) and (3) tumor size ( P = 0.0039). By using ploidy and lymph node involvement in this way as prognostic factors we are able to identify high- and low-risk groups of patients. We strongly believe that these results should lead to a different attitude towards therapy in vulva cancer patients.