Significance of the Ki-67 proliferation index in the assessment of the therapeutic response to cisplatin-based chemotherapy in patients with advanced cervical cancer.

OBJECTIVE: The purposes of this study were to examine the therapeutic response of advanced cervical cancer to Ki-67 proliferative index (Ki-67 PI) dependent cisplatin chemotherapy, and to determine Ki-67 PI referential value that is expected to provide a satisfactory therapeutic response of cervical cancer to cisplatin chemotherapy. PATIENTS AND METHODS: This prospective study enrolled 59 patients treated for cervical cancer at Clinic for Oncology, Clinical Center Nis, Serbia. According to the obtained Ki-67 PI values, patients were divided into three groups, and all the patients received the same cytostatic, cisplatin. Therapeutic response to chemotherapy was evaluated in relation to disease progression presence or absence and progression-free survival after a year follow-up since the first chemotherapy. RESULTS: Survival rate increases with an increase of Ki-67 PI by Kaplan-Meier survival analysis, meaning that survival rate is statistically significantly shorter in the group of patients with Ki-67 PI < 40% in comparison to patients from other two groups (p=0.010). Mann-Whitney test confirmed a statistically significant increase in survival rate among the groups of patients formed according to Ki-67 PI (p<0.05). Kaplan-Meier survival analysis confirmed that the mean survival rate in the group of patients with Ki-67 PI values over 60% is statistically significantly longer in comparison to patients with Ki-67 PI values below or equal 60% (p<0.001). CONCLUSIONS: Advanced cervical cancer with a high Ki-67 PI expression responds better to cisplatin-based chemotherapy, thus resulting in a longer survival rate. The values of Ki-67 PI were determined: high Ki-67 PI (≥ 60%), moderate Ki-67 PI (40-60%), and low Ki-67 PI (≤ 40%).

The application of magnetic resonance imaging in preoperative evaluation of patients with endometrial carcinoma.

PURPOSE: The aim of this paper was to assess the usefulness of the preoperative application of magnetic resonance (MRI) imaging in patients with confirmed endometrial carcinoma. METHODS: This prospective study included 50 patients with endometrial cancer. MRI was used for preoperative disease staging and in planning the operative treatment. The parameters monitored by MRI were compared with the findings of curettage pathological examination. Estimated were the depth of myometrial invasion, the involvement of the cervix by the tumor, the presence of adnexal metastases and regional lymph nodes. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the MRI in relation to the aforementioned clinicopathological parameters were assessed. RESULTS: The presence of myometrial invasion was estimated with 100% specificity, 86% sensitivity, 100% PPV and 40% NPV. The estimation of the depth of myometrial invasion (>or<50%) was defined with 89% sensitivity, 54% specificity, 83% PPV and 60% NPV. MRI provided valuable data about cervical invasion (100% PPV for the presence of cervical invasion and 55% PPV for the depth of cervical invasion), thereby helping to decide on the kind of surgical intervention, the choice of approach (open or laparoscopic surgery) and the choice of the surgeon. CONCLUSION: MRI is useful and reliable in preoperative evaluation. The information obtained by MRI provides space and time for planning the treatment modality.

Recurrence of cervical intraepithelial neoplasias with negative cone margins: risk factors.

PURPOSE: The percent of young patients treated for cervical intraepithelial neoplasias (CIN) has been increasing, thus it is very important to define patients in high risk for relapse. The aim of this study was to establish any possible association of persistent human papillomavirus (HPV) infection, age, smoking, parity, use of oral contraceptives, and Chlamydia infection, with relapse of CIN. METHODS: Between March 2006 and March 2009 a prospective clinical study was performed at the Clinic of Obstetrics and Gynecology in Nis, with the study group comprising the first 35 patients with disease relapse after conization and the control group consisting of 30 patients with more than one year after treatment without relapse. HPV typization was done at the Laboratory for Molecular Biology and Cytogenetics of the Clinical Centre Nis using polymerase chain reaction (PCR). RESULTS: A statistically significant higher percentage of recurrences with lower pathologic stage (CIN I) was found in younger women (below 29 years) (p<0.01). Women in the control group were more commonly non smokers (56.66 vs. 40%) but without statistical significance (p>0.05). The distribution of smoked cigarettes in the study and control subjects showed no statistically significant difference (p>0.05). Patients with recurrences were more commonly HPV-positive compared to controls (68.57 vs. 6.66%; p <0.05). In the study group, HPV-positive smokers recurred with more advanced grades (CIN III and microinvasive carcinoma/MIC; p<0.01). In non smokers, the severity of recurrence was not statistically correlated with HPV positivity. CONCLUSION: Persistent HPV infection, smoking associated with HPV infection and more advanced age were demonstrated to be of statistical significance for CIN recurrence. Parity, use of oral contraceptives, Chlamydia infection, and smoking as independent etiologic factors were not significantly associated with CIN relapse.

Risk factors and adjuvant chemotherapy in the treatment of endometrial cancer.

Endometrial carcinoma is the most common and potentially curable gynecologic malignant neoplasm. The staging of endometrial cancer, according to the International Federation of Gynecology and Obstetrics (FIGO), is surgical. Recent studies suggest a therapeutic benefit associated with extensive retroperitoneal lymph node evaluation to determine the disease extent and thereby more effectively direct potentially life-saving adjuvant therapy. Due to the increasing number of endometrial cancer patients who undergo surgical staging, some independent prognostic factors have been identified in early stages (stage I-II), including lymph-vascular space involvement, histologic grade 3, aggressive histologic subtypes (uterine papillary serous carcinoma, clear cell carcinoma), depth of myometrial invasion, cervical invasion and the age of patients. Adjuvant radiation therapy, known to offer survival benefit in advanced-stage disease, may also offer survival benefit in intermediate-risk surgical stage I, but this is followed by a significant risk of serious complications. Based on randomized clinical trials, this review identified that only a limited body of evidence is available which can help clinicians make decisions about adjuvant chemotherapy of patients with high-risk stage I and II, as well as stage IIIA endometrial cancer. Further investigations are required to define the subgroup of patients who benefit from postoperative adjuvant chemotherapy. In addition, the optimal regimen remains to be defined as all of them (doxorubicin/cisplatin--AP, cyclophosphamide/ doxorubicin/cisplatin--CAP, paclitaxel/carboplatin--TC, paclitaxel/doxorubicin/cisplatin--TAP) cause significant toxicity. Thereby, combination of carboplatin plus paclitaxel represents an efficacious, low-toxicity regimen for managing intermediate-risk surgical stage I, as well as advanced or recurrent endometrial cancer.

Operative treatment of cervical premalignant lesions and the presence of high-risk human papilloma virus as etiologic agent.

The conization as an excisional method is used as an operative treatment of high-risk premalignant cervical lesions. Early detection and removal may stop the developing process that leads to invasive carcinoma. The study presents a group of 100 women, operated with "cold knife" conization during the year 2002 at the 1st Operative Oncologic Department of the Gynecology and Obstetrician Clinic - Medical Faculty, Skopje. The operative material showed CIN 2 in 2 and CIN 3 in 31 women. In 7 of them, CIN 3 lesions were removed by punch biopsy or ECC, thus the cone showed only CIN 2. In two women out of the total of 67 with the preoperative diagnosis of CIS, CIN 3 lesions were postoperatively diagnosed. This is the result of the adequate punch biopsy during the diagnostic procedure. Three cones showed Ca microinvasivum and other 3 displayed Ca invasivum which then needed other surgical treatment. In 93 % of the women the conization had a therapeutic effect and in 7 % it was only of diagnostic value. HPV testing was made in 55 out of the operatively treated women. The most common type HPV 16 was identified in 27 % of the women. The second was HPV 31 in 25.5 %, then HPV 66 in 14.5 %, HPV 18 in 11%, HPV CP 8304 and HPV 38 in 5.5 %, HPV 58 as well as MM9 in 2 (3.6 %). The dichotomic presence of HPV 31+18 and HPV 6+16 was identified in two women. (Tab. 3, Ref: 10.)