Prognostic value of systemic inflammatory response markers in cervical cancer.

We investigated the association between preoperative ratios of inflammatory markers and the prognosis in patients with invasive cervical cancer (CC). In this single-centre study, we retrospectively enrolled 163 CC patients who underwent radical hysterectomy between February 2008 and October 2018. Among the evaluated ratios, a high neutrophil-to-lymphocyte ratio (N/L) was significantly associated with deep stromal invasion and tumour size larger than 2 cm, whereas a high M/L was significantly related to advanced-stage CC (IB3-IIIC2), lymphatic metastasis (total) and pelvic lymph node metastasis (p= .002, p= .046 and p= .046, respectively). The neutrophil count plus monocyte-to-lymphocyte ratio (NM/L) and platelet-to-lymphocyte ratio (P/L) were significantly higher in patients with deep stromal invasion, advanced stage and tumour size larger than 2 cm (p=.01, p=.044 and p=.007; p=.004, p=.005 and p=.003, respectively). In the multivariate analysis, high NM/L (>168) was associated with a statistically significant hazard ratio of 3.04 (95% CI: (1.38-6.72); p=.006) for recurrence and 9.05 (95% CI: (2.10-38.99); p=.003) for death. Both stage and NM/L are independent prognostic factors that are significantly associated with recurrence and overall survival in CC.Impact StatementWhat is already known on this subject? Previous studies suggested that there is a relationship between inflammation and the formation, development and progression of cancer. However, the relationship between cervical cancer (CC) and inflammatory blood parameters is incompletely understood.What do the results of this study add? This study investigated the relationship between systemic blood inflammatory ratios and clinicopathological patient characteristics and disease outcomes in CC.What are the implications of these findings for clinical practice and/or further research? According to this study, systemic blood inflammatory ratios may help predict the prognosis and survival of patients with CC.

Risk factors for evisceration in gynecological oncology surgeries

Background/aim: To investigate the risk factors for evisceration in a gynecological oncology population. The secondary aim was to evaluate the impact of evisceration on survival. Materials and methods: Inclusion criteria consisted of having had an elective surgery performed through a xiphoidopubic incision in our institution and having a gynecological malignancy based on pathology. A total of 198 patients were evaluated, 54 with evisceration and 144 without evisceration. Due to the widely varied prognosis of female genital cancers, the survival was analyzed on a homogenized group, including only 62 patients with primary advanced stage epithelial ovarian-tubal-peritoneal cancer. Results: The preoperative factors associated with evisceration in the univariate analysis were old age, high body mass index (BMI), hypertension, smoking, comorbidities, high American Society of Anesthesiologist (ASA) score (3 and 4), and low preoperative albumin level. The associated intraoperative factors were bleeding volume, receiving more than two units of erythrocyte suspension or fresh frozen plasma, and having had a major operation. The associated postoperative factors were the albumin transfusion and the antibiotic use in the early postoperative period. In the multivariate analysis, smoking, low levels of preoperative albumin, high BMIs, and high ASA scores (3 and 4) were independent prognostic factors for evisceration. Evisceration was not associated with recurrence and survival in the patients with primary advanced stage epithelial ovarian-tubal-peritoneal cancer. Conclusion: Smoking, preoperative hypoalbuminemia, obesity, and high ASA scores (3and 4) were the prognostic factors for evisceration. Short-term modifiable factors such as smoking cessation and improved nutritional status should be considered in elective gynecological oncology surgeries. Evisceration had no impact on survival and recurrence in the patients with primary advanced stage epithelial ovarian-tubal-peritoneal cancer.

Can we predict surgical margin positivity while performing cervical excisional procedures?

We designed this study to evaluate any factors associated with positive surgical margin in conisation specimens and to determine the optimal cone size. The medical records of patients who had undergone a loop electrosurgical excision procedure (LEEP), cold-knife conisation (CKC) and needle excision of the transformation zone (NETZ) procedure were reviewed retrospectively. Two hundred and sixty eight women fulfilled the inclusion criteria. Univariate analyses showed that 'postmenopause', 'HSIL on smear', 'previous colposcopic examination revealing HSIL in endocervical curettage (ECC) material and in two or more ectocervical quadrants' and 'managing with LEEP' were significant predictors of surgical margin positivity. Nulliparous patients showed significantly lower rate of surgical margin positivity. 'Postmenopause', 'previous colposcopic examination revealing HSIL in ECC material and in two or more ectocervical quadrants' and 'HSIL on smear' were identified as independent predictors of surgical margin positivity according to multivariate analyses.IMPACT STATEMENTWhat is already known on this subject? Previous studies demonstrated 'menopause', 'Age ≥50', 'managing with LEEP', 'disease involving >2/3 of cervix at visual inspection', 'training level of the surgeon', 'cytology squamous cell carcinoma' and 'mean cone height' as factors associated with positive surgical margin in conisation specimens.What do the results of this study add? In our study, univariate analyses showed that 'postmenopause', 'HSIL on smear', 'previous colposcopic examination revealing HSIL in endocervical curettage material and in two or more ectocervical quadrants' and 'managing with LEEP' were associated with surgical margin positivity. On the other hand, nulliparous women showed significantly lower rate of surgical margin positivity compared with parous women. Multivariate analyses showed that 'postmenopause', 'previous colposcopic examination revealing HSIL in endocervical curettage material and in two or more ectocervical quadrants' and 'HSIL on smear' were independent predictors of surgical margin positivity in conisation specimens.What are the implications of these findings for clinical practice and/or further research? We can predict high-risk patients with regard to surgical margin positivity. Prediction of high-risk patients and management with a tailored approach may help minimise surgical margin positivity rates.

Does tumor size have prognostic value in patients undergoing lymphadenectomy in endometrioid-type endometrial cancer confined to the uterine corpus?

Background/aim: We aimed to define the effect of tumor size on recurrence and survival rates in patients with stage I­II endometrioid-type endometrial cancer. Materials and methods: A total of 550 patients who had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic-paraaortic lymphadenectomy were included. Patients with extrauterine spread, sarcomatous components, or synchronized tumor and those who did not undergo lymphadenectomy or did not have data on tumor size were excluded. Results: The median tumor size was 35 mm (range: 3­335 mm). According to the 2009 International Federation of Obstetrics and Gynecology (FIGO) criteria, 245 cases were defined as stage IA, 271 as stage IB, and 34 as stage II. The 5-year disease-free survival (DFS) rate was 92% and the 5-year disease-specific survival (DSS) rate was 99%. The effects of prognostic factors on DFS were evaluated. Older age, stage II disease, deep myometrial invasion, and receiving adjuvant radiotherapy were associated with decreased DFS. There was no statistically significant association between tumor size and DFS. The 5-year DFS for patients with a tumor diameter of <35 mm, which was the median tumor size of the entire group, was 94%, while it was 89% for patients having a tumor diameter of >35 mm (P = 0.128). Conclusion: Tumor size was not a risk factor predicting recurrence in patients with stage I or II endometrioid-type endometrial cancer who had lymphadenectomy.

Carcinosarcoma of the ovary compared to ovarian high-grade serous carcinoma: impact of optimal cytoreduction and standard adjuvant treatment.

OBJECTIVE: The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner. METHODS: A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case-control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models. RESULTS: Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0-59, standard error (SE) 15.35] versus 27 months (95% CI 22.6-31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02-5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32-11, p < 0.001] were found to be independent risk factors for decreased OS. CONCLUSION: DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.

Impact of lymph node ratio on survival in stage IIIC endometrioid endometrial cancer: a Turkish Gynecologic Oncology Group study.

OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in women with stage IIIC endometrioid endometrial cancer (EC). METHODS: A multicenter, retrospective department database review was performed to identify patients with stage IIIC pure endometrioid EC at 6 gynecologic oncology centers in Turkey. A total of 207 women were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 2 groups: LNR1 (≤0.15), and LNR2 (>0.15). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: One hundred and one (48.8%) were classified as stage IIIC1 and 106 (51.2%) as stage IIIC2. The median age at diagnosis was 58 (range, 30-82) and the median duration of follow-up was 40 months (range, 1-228 months). There were 167 (80.7%) women with LNR ≤0.15, and 40 (19.3%) women with LNR >0.15. The 5-year progression-free survival (PFS) rates for LNR ≤0.15 and LNR >0.15 were 76.1%, and 58.5%, respectively (p=0.045). An increased LNR was associated with a decrease in 5-year overall survival (OS) from 87.0% for LNR ≤0.15 to 62.3% for LNR >0.15 (p=0.005). LNR >0.15 was found to be an independent prognostic factor for both PFS (hazard ratio [HR]=2.05; 95% confidence interval [CI]=1.07-3.93; p=0.03) and OS (HR=3.35; 95% CI=1.57-7.19; p=0.002). CONCLUSION: LNR seems to be an independent prognostic factor for decreased PFS and OS in stage IIIC pure endometrioid EC.

Comparison of stage III mucinous and serous ovarian cancer: a case-control study.

BACKGROUND: The purpose of this case-control study was to compare the prognoses of women with stage III mucinous ovarian carcinoma (MOC) who received maximal or optimal cytoreduction followed by paclitaxel plus carboplatin chemotherapy to those of women with stage III serous epithelial ovarian cancer (EOC) treated in the similar manner. METHODS: We performed a multicenter, retrospective review to identify patients with stage III MOC at seven gynecologic oncology departments in Turkey. Eighty-one women with MOC were included. Each case was matched to two women with stage III serous EOC in terms of age, tumor grade, substage of disease, and extent of residual disease. Survival estimates were measured using Kaplan-Meier plots. Variables predictive of outcome were analyzed using Cox regression models. RESULTS: With a median follow-up of 54 months, the median progression-free survival (PFS) for women with stage III MOC was 18.0 months (95% CI; 13.8-22.1, SE: 2.13) compared to 29.0 months (95% CI; 24.04-33.95, SE: 2.52) in the serous group (p = 0.19). The 5-year overall survival rate of the MOC group was significantly lower than that of the serous EOC group (44.9% vs. 66.3%, respectively; p < 0.001). For the entire cohort, presence of multiple peritoneal implants (Hazard ratio [HR] 2.39; 95% confidence interval [CI], 1.38-4.14, p = 0.002) and mucinous histology (HR 2.28; 95% CI, 1.53-3.40, p < 0.001) were identified as independent predictors of decreased OS. CONCLUSION: Patients with MOC seem to be 2.3 times more likely to die of their tumors when compared to women with serous EOC.

Vanishing endometrial carcinoma in hysterectomy specimens: probable implications for fertility sparing management

Background/aim: The vanishing cancer phenomenon was first reported in radical prostatectomy specimens in the absence of neo-adjuvant treatment. Reported cases are mostly well-differentiated and low-volume tumors. A similar entity was described for hysterectomy specimens of patients with biopsy proven endometrial cancer (EC). In this study, we discuss the probable reasons for vanishing EC and long-term follow-up results of EC patients without residual tumors in hysterectomy specimens. Materials and methods: This study was carried at two institutions in Ankara, Turkey, in a retrospective design. The computerized databases of both institutions were searched for endometrioid type EC patients whose final pathological specimens failed to show any residual tumor. Results: We evaluated 38 endometrial biopsy confirmed EC patients with no residual tumor detected in the hysterectomy specimens among a total of 224 women (17%) with the disease confined to the endometrium. During the follow-up period, no recurrences were noted among the patients. Conclusion: It can be suggested that premenopausal women with FIGO grade 1 endometrioid type EC with MRI proven "absent myometrial invasion" would have a significant probability of having no residual tumor after endometrial biopsy without any further medical treatment.

Extraperitoneal lymph node dissection in locally advanced cervical cancer; the prognostic factors associated with survival.

OBJECTIVE: Surgical staging was recently recommended for the decision of treatment in locally advanced cervical cancer. We aimed to investigate clinical outcomes as well as factors associated with overall survival (OS) in patients with locally advanced cervical cancer who had undergone extraperitoneal lymph node dissection and were managed according to their lymph node status. MATERIAL AND METHODS: The medical records of 233 women with stage IIb-IVa cervical cancer who were clinically staged and underwent extraperitoneal lymph node dissection were retrospectively reviewed. Paraaortic lymph node status determined the appropriate radiotherapeutic treatment field. Surgery-related complications and clinical outcomes were evaluated. RESULTS: The median age of the patients was 52 years (range, 26-88 years) and the median follow-up time was 28.4 months (range, 3-141 months). Thirty-one patients had laparoscopic extraperitoneal lymph node dissection and 202 patients underwent laparotomy. The number of paraaortic lymph nodes extracted was similar for both techniques. Sixty-two (27%) of the 233 patients had paraaortic lymph node metastases. The 3-year and 5-year OS rates were 55.1% and 46.5%, respectively. The stage of disease, number of metastatic paraaortic lymph nodes, tumor type, and paraaortic lymph node status were associated with OS. In multivariate Cox regression analyses, tumor type, stage, and presence of paraaortic lymph node metastases were the independent prognostic factors of OS. CONCLUSION: Paraaortic lymph node metastasis is the most important prognostic factor affecting survival. Surgery would give hints about the prognosis and treatment planning of the patient.

Prognostic factors and treatment outcomes in surgically-staged non-invasive uterine clear cell carcinoma: a Turkish Gynecologic Oncology Group study.

OBJECTIVE: To assess the prognosis of surgically-staged non-invasive uterine clear cell carcinoma (UCCC), and to determine the role of adjuvant therapy. METHODS: A multicenter, retrospective department database review was performed to identify patients with UCCC who underwent surgical treatment between 1997 and 2016 at 8 Gynecologic Oncology Centers. Demographic, clinicopathological, and survival data were collected. RESULTS: A total of 232 women with UCCC were identified. Of these, 53 (22.8%) had surgically-staged non-invasive UCCC. Twelve patients (22.6%) were upstaged at surgical assessment, including a 5.6% rate of lymphatic dissemination (3/53). Of those, 1 had stage IIIA, 1 had stage IIIC1, 1 had stage IIIC2, and 9 had stage IVB disease. Of the 9 women with stage IVB disease, 5 had isolated omental involvement indicating omentum as the most common metastatic site. UCCC limited only to the endometrium with no extra-uterine disease was confirmed in 41 women (73.3%) after surgical staging. Of those, 13 women (32%) were observed without adjuvant treatment whereas 28 patients (68%) underwent adjuvant therapy. The 5-year disease-free survival rates for patients with and without adjuvant treatment were 100.0% vs. 74.1%, respectively (p=0.060). CONCLUSION: Extra-uterine disease may occur in the absence of myometrial invasion (MMI), therefore comprehensive surgical staging including omentectomy should be the standard of care for women with UCCC regardless of the depth of MMI. Larger cohorts are needed in order to clarify the necessity of adjuvant treatment for women with UCCC truly confined to the endometrium.

Lack of relation of survivin gene expression with survival and surgical prognostic factors in endometrial carcinoma patients.

BACKGROUND: The relation of survivin gene expression to survival and surgical prognostic factors in the patients with endometrial carcinoma is unclear. MATERIALS AND METHODS: In this study, 62 cases who were operated due to endometrial carcinoma were investigated between 2003 and 2011 in the the gynecological oncology clinic of Female Disease Training and Investigation Hospital of Etlik Zubeyde, Hanim, Turkey. Clinical and surgical prognostic factors were investigated by screening the records of these cases. With the standard streptavidin-biotin immune peroxidase method, cytoplasmic and nuclear expression of survivin was investigated in sections with specific antibodies (1:100, diagnostic Bio Systems, USA) primer. The aim was to elucidate any relation between survivin expression and defined prognostic factors and survival. RESULTS: There was no statistically significant relationship between cytoplasmic and nuclear indexes identified for survivin and age, body mass index, the levels of preoperative hemoglobin, platelet and Ca 125, stage, grade, lymph node meastasis, the number of metastatical lymph nodes (total, paraaortic and pelvic), myometrial invasion, serosal invasion, adnexal involvement, the presence of acid in the first diagnosis, the involvement of omentum, the adjuvant treatment application of the cases, the presence of recurrence and rate of mortality (p>0.05). Statistical significance was noted for the presence of advanced stage lymph node metastasis (pelvic, paraaortic, pelvic and paraaortic), serosal involvement, positive cytology, lymph vascular space invasion, intra abdominal metastasis, and omentum involvement. When investigated the relation between cytoplasmic and nuclear survivin indexes and total survival, the result was not statistically significant (p>0.05). CONCLUSIONS: In our study, there was no statistically significant relationship between the rates of cytoplasmic and nuclear survivin expression with identified prognostic factors and total or non-disease survival.

Does lymph node involvement affect the patterns of recurrence in stage IB cervical cancer?

BACKGROUND/AIM: To investigate the variations in the recurrence patterns of stage IB cervical cancer according to lymph node involvement. MATERIALS AND METHODS: We reviewed the medical records of 170 patients who had undergone type III radical hysterectomy and systematic lymphadenectomy from 1993 to 2007. RESULTS: Among the patients in the study group, 115 did not have lymph node metastases, whereas 55 did. A total of 27 patients developed recurrences. Twelve were in the lymph node-negative group, and 15 were in the lymph node-positive group. The recurrence rate was higher in lymph node-positive group (27.3% versus 10.4%, P = 0.011). The recurrence pattern was not affected by lymph node involvement. However, distant recurrence was more common in the lymph node-positive group (53.3% versus 25%, P = 0.137). Additionally, distant failure was observed only in the patients in the lymph node-negative group who received adjuvant radiotherapy. In this group, 3 patients who did not receive adjuvant radiotherapy developed recurrences only in the pelvic region. CONCLUSION: The presence of lymph node involvement in stage IB cervical cancer does not affect the site of recurrence. However, distant recurrence was more frequent in the lymph node-positive group.

Addition of epirubicin to conventional chemotherapy in patients with advanced ovarian cancer: sequential therapy -a retrospective evaluation. .

AIM: To evaluate the effectiveness of the addition of epirubicin to conventional chemotherapy as a first-line therapy for stage III-IV epithelial ovarian cancer. MATERIALS AND METHODS: A total of 132 patients who had undergone primary cytoreductive surgery between January 1998 and March 2003 were enrolled in the study. Twenty-four cases were excluded. Out of the remaining 108 subjects, 35 received epirubicin/paclitaxel/ carboplatin (Group EPC) and 73 were treated with paclitaxel/platinum (cisplatin.or carboplatin) (Group PC). RESULTS: The median follow-up period was 66.5 months. The clinical complete response was 94% in the EPC group and 97% in the PC group. The recurrence rate in the first 6 months after treatment was significantly higher in the PC than the EPC group (47% vs. 23%, P = 0.018). Triplet chemotherapy was not found to improve 2- and 5-year disease-free survival (DFS) statistically. No significant difference in overall survival was observed between the 2 groups (80% vs. 83% at 2 years and 56% vs. 57% at 5 years for the PC and the EPC group, respectively). The main toxicity in both groups was hematological, and it was particularly severe in the EPC group. CONCLUSION: The addition of epirubicin to the standard treatment protocol yielded an improvement in the DFS rate that was not statistically significant and caused a tolerable increase in toxicity.

The effect of cell type on surgico-pathologic risk factors in endometrial cancer.

OBJECTIVE: In this study the effect of histologic subtype as a surgicopathologic risk factor in endometrial cancer is evaluated. MATERIAL AND METHODS: We evaluated 182 patients who underwent systematic lymphadenectomy up to the level of the renal vessels and at least 15 lymph nodes were dissected from the pelvic area and 10 lymph nodes from the para-aortic area. investigation of whether endometrioid and aggressive cell types (serous papillary cell and clear cell) affect the distribution of surgicopathologic risk factors among endometrial cancer cases was carried out. RESULTS: Patients in the aggressive cell type group were older and the tumor size was significantly smaller. There was no difference between the two groups for the total number of dissected lymph nodes except for the external iliac area. Although the difference is not statistically significant, the total number of lymph nodes dissected in the aggressive group was less (54.3 vs 62.9, p=0.067) than that of the endometrioid cell type group. While the incidence of pelvic lymph node metastasis in the aggressive group was 59.1% the incidence was 15.6% in the endometrioid cell type group (p>0.001). The possibility of lymph node metastasis for aggressive cell type endometrial carcinoma in the para-aortic area was twice the endometrioid cell type group. It was found that the presence and type (stromal/glandular) of cervical invasion, depth of myometrial invasion and presence of lymphovascular space invasion were not affected by cell type. CONCLUSION: Aggressive cell types significantly increase the adnexial and lymph node metastasis in endometrial cancer.