Tıp Fakültesi / Faculty of Medicine

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    Survival Associated with Extent of Radical Hysterectomy in Early-Stage Cervical Cancer: A Subanalysis of the Surveillance in Cervical Cancer (SCCAN) Collaborative Study
    (2023) Bizzarri, Nicolo; Querleu, Denis; Dostalek, Lukas; van Lonkhuijzen, Luc R. C. W.; Giannarelli, Diana; Lopez, Aldo; Salehi, Sahar; Ayhan, Ali; Kim, Sarah H.; Ortiz, David Isla; Klat, Jaroslav; Landoni, Fabio; Pareja, Rene; Manchanda, Ranjit; Kostun, Jan; Ramirez, Pedro T.; Meydanli, Mehmet M.; Odetto, Diego; Laky, Rene; Zapardiel, Ignacio; Weinberger, Vit; Dos Reis, Ricardo; Anchora, Luigi Pedone; Amaro, Karina; Akilli, Huseyin; Abu Rustum, Nadeem R.; Salcedo Hernandez, Rosa A.; Javurkova, Veronika; Mom, Constantijne H.; Scambia, Giovanni; Falconer, Henrik; Cibula, David; 37336255
    BACKGROUND: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer.OBJECTIVE: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence.STUDY DESIGN: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy.RESULTS: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter <= 20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70).CONCLUSION: For tumors <= 20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve sparing radical hysterectomy after propensity score match analysis.
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    Fertility Sparing in Uterine Sarcomas: Single Center Experience of 13 Patients
    (2019) Tunc, Mehmet; Tohma, Yusuf Aytac; Sahin, Han Ifi; Akilli, Huseyin; Karakas, Latife Atasoy; Altundag, Ozden; Haberal, Ali; Ayhan, Ali; https://orcid.org/0000-0001-9418-4733; https://orcid.org/0000-0002-5240-8441; https://orcid.org/0000-0001-7369-5470; https://orcid.org/0000-0003-0197-6622; https://orcid.org/0000-0002-1486-7209; AAE-6482-2021; AAX-3230-2020; AEY-5060-2022; W-9219-2019; AAI-9331-2021; AAJ-5802-2021
    Purpose of Investigation: The feasibility and safety of conservative surgery is not well defined for fertility sparing approach for uterine sarcoma due to very low incidence and poor prognosis. The authors present their experience regarding fertility preservation for uterine sarcoma. Materials and Methods: A total of 13 patients with uterine sarcoma were included in this retrospective case study; endometrial stromal sarcoma (ESS) (n=6) and leiomyosarcoma (LMS) (n=7). Patients data, including clinicopathological characteristics and prognostic information were extracted from medical records. Excision of mass and reconstruction of uterus was performed for fertility sparing in all patients and staging surgery (bilateral pelvic and para-aortic lymphadenectomy +/- omentectomy) as performed for five cases (one ESS case and four LMS cases). Results: The median size of the mass was 8.5 (range: 1-22) cm. Median follow-up time was 54 (range 13-142) months. Recurrence rate was 69.2% (9/13). The mean relapse interval was 30.69 months. Four patients died and all of them was diagnosed with LMS. Four pregnancies (37%) were recorded. Two of them occurred with assisted reproductive technologies (intracytoplasmic sperm injection), the other two pregnancies were spontaneous, and all of them had a cesarean delivery. Conclusion: Patients should be informed about prognosis of uterine sarcomas and risk of fertility preserving approach. Close follow-up is obligatory and complementary surgery should be performed after completion of fertility due to high recurrence rate and poor prognosis especially with LMS.
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    Possible Impact of Immunosuppressive Therapy Regimens on Histopathologic Outcomes of Abnormal Uterine Bleeding in Solid-Organ Transplant Recipients
    (2018) Tohma, Yusuf Aytac; Akilli, Huseyin; Kirnap, Mahir; Haberal, Asuman Nihan; Akyel, Dilan; Zengin, Hatice Yagmur; Zeyneloglu, Hulusi Bulent; Kuscu, Esra; Ayhan, Ali; Haberal, Mehmet; https://orcid.org/0000-0001-9418-4733; https://orcid.org/0000-0002-5240-8441; https://orcid.org/0000-0001-9852-9911; https://orcid.org/0000-0002-9855-2449; https://orcid.org/0000-0002-0289-2642; https://orcid.org/0000-0002-3462-7632; 29851156; AAE-6482-2021; AAX-3230-2020; AAH-9198-2019; AAK-4587-2021; ABA-3224-2021; B-6487-2009; AAJ-8097-2021
    Background: In this study, we aimed to determine the frequency of histopathologic outcomes of solid-organ transplantation in women with abnormal uterine bleeding (AUB) receiving immunosuppressive therapies. Methods: This is a retrospective study including a single-center experience. Data were extracted from hospital records, and solid-organ transplant recipients who were diagnosed with AUB were included. Results: Fifty-five of these patients were renal transplant recipients (79.7%), and 14 were liver transplant recipients (20.3%). Histopathologic examination showed various histopathologic patterns of endometrium in patients with AUB consisting of normal histopathologic findings of endometrium in 31 patients (48.4%); 29 hormonal imbalance during proliferative and secretory phases of menstrual cycle and two atrophic endometrium. Endometrial hyperplasia without atypia was observed in 11 patients (17.2%). Polyp was seen in 22 patients (34.4%); 21 endometrial polyp and one endocervical polyp. There were significant differences in terms of histopathologic findings among the three groups of patients according to different immunosuppressive regimens (P = .029). There was no endometrial hyperplasia in women receiving sirolimus-based immunosuppressive regimens. Moreover, there was no endometrial hyperplasia in the liver transplant recipient group. Conclusions: Sirolimus-based immunosuppressive regimens may be administered to patients who have risk factors for endometrial precancerous lesions, such as endometrial hyperplasia. However, additional well-designed, large-scale studies are warranted to confirm our findings.
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    Effect of Increased Number of Neoadjuvant Chemotherapy Cycles on Tumor Resectability and Pathologic Response in Advanced Stage Epithelial Ovarian Cancer
    (2018) Akilli, Huseyin; Rahatli, Samed; Tohma, Yusuf Aytac; Karakas, Latife Atasoy; Altundag, Ozden; Ayhan, Ali; 0000-0002-5240-8441; 0000-0003-3163-7429; 0000-0001-9418-4733; 0000-0003-0197-6622; AAX-3230-2020; AAJ-3047-2021; AAE-6482-2021; AEY-5060-2022; W-9219-2019; AAJ-5802-2021
    Purpose: To identify the significance of the number of neoadjuvant chemotherapy (NACT) cycles on pathologic response and to define relationship between multiple cycles of NACT and the timing of interval debulking surgery (IDS) in epithelial ovarian cancer (EOC) patients. Methods: This retrospective case-control study was carried out at the Baskent University in Ankara between 2007 and 2017. We reviewed 62 patients with advanced stage (IIIC-IV) EOC who received NACT in other institutes and operated in our clinic. On the basis of the number of NACT cycles, patients were divided into 2 groups: group 1 received 3 cycles and group 2 received 4 to 6 cycles.The influence of the number of NACT cycles on complete pathologic response, lymph node involvement, overall survival (OS), progression free survival (PFS), platinum resistance and residual tumor were evaluated. Results: The median OS was 44.4 +/- 4.8 months and 48.8 +/- 4.49 months for group 1 and group 2 respectively (p=0.122). PFS was 19.3 +/- 3.75 months in group 1 and 24.3 +/- 4.67 months in group 2 (p=0.84). Tumor morphology according to lymph node involvement, no visible tumor and complete pathologic response were similar for both groups (p=0.49, p=0.79 and p=0.6 respectively). Pathological absence of residual disease were 13.6% vs 7.5% for group 1 and group 2 respectively (p=0.6) and complete pathologic response rate was 6/62 (9.67%). Platinum resistance developed in 4(18.2%) patients and 18(45%) patients in group 1 and 2 respectively (p=0.031). Complete resection rates were similar for both groups (p=0.9). After multivariate survival analyses, complete resection remained significant (p=0.000, odds ratio/ OR 2.28 [1.41-3.701]), and was independent of age, platinum resistance and number of NACT cycles. Complete resection rates were almost equal in each groups, (68.2% [15/22] and 67.5% [27/40] for group 1 and group 2 respectively (p=0.9)). Conclusions: Our data suggests that giving more than 3 cycles of NACT is unnecessary because increased number of cycles did not change the resectability and complete pathologic response, while it increased platinum resistance. Moreover OS and PFS remained similar.
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    Post-Recurrence Survival In Patients With Cervical Cancer
    (2022) Cibula, David; Dostalek, Lukas; Jarkovsky, Jiri; Mom, Constantijne H.; Lopez, Aldo; Falconer, Henrik; Scambia, Giovanni; Ayhan, Ali; Kim, Sarah H.; Isla Ortiz, David; Klat, Jaroslav; Obermair, Andreas; Di Martino, Giampaolo; Klat, Jaroslav; Obermair, Andreas; Di Martino, Giampaolo; Pareja, Rene; Manchanda, Ranjit; Kos'un, Jan; dos Reis, Ricardo; Meydanli, Mehmet Mutlu; Odetto, Diego; Laky, Rene; Zapardiel, Ignacio; Weinberger, Vit; Benesova, Klara; Borcinova, Martina; Cardenas, Fernando; Wallin, Emelie; Borcinova, Martina; Cardenas, Fernando; Wallin, Emelie; Anchora, Luigi Pedone; Akilli, Huseyin; Abu-Rustum, Nadeem R.; Barquet-Munoz, Salim Abraham; Javurkova, Veronika; Fischerova, Daniela; van Lonkhuijzen, Luc R. C. W.; https://orcid.org/0000-0002-5240-8441; 34955236; AAX-3230-2020
    Background. Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. Methods. Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. Results. The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. Conclusions. We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.
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    OPEC Study: An International Multicenter Study Of Ovarian Preservation In Endometrial Cancers
    (2022) Akgor, Utku; Ayhan, Ali; Shushkevich, Alexander; Ozdal, Bulent; Angelou, Kyveli; Akbayir, Ozgur; Kaidarova, Dilyara; Ulrikh, Elena; Stepanyan, Artem; Ortac, Firat; Aliyev, Shamistan; Ozgul, Nejat; Taranenka, Siarhei; Haberal, Ali; Salman, Coskun; Seyhan, Alper; Selcuk, Ilker; Haidopoulos, Dimitrios; Akilli, Huseyin; Bolatbekova, Raikhan; Alaverdyan, Areg; Taskin, Salih; Murshudova, Sabina; Batur, Meltem; Berlev, Igor; Gultekin, Murat; https://orcid.org/0000-0002-5240-8441; 35323994; AAX-3230-2020
    Objective To evaluate the feasibility and oncological safety of ovarian preservation in early stage endometrial adenocarcinoma (EC) patients aged 40 and below. Methods A total of 11 institutions from eight countries participated in the study. 169 of 5898 patients aged <= 40 years were eligible for the study. Patients with EC treated between March 2007 and January 2019 were retrospectively assessed. Results The median duration of follow-up after EC diagnosis was 59 months (4-187). Among 169 participants, ovarian preservation surgery (OPS) was performed in 54 (31.9%), and BSO was performed in 115 (68.1%) patients. Although patients younger than 30 years of age were more likely to have OPS than patients aged 30 to 40 years (20.4% vs. 9.6%, P = 0.021), there was no significant difference by the mean age. There were no other relevant baseline differences between OPS and BSO groups. The Kaplan-Meier analysis revealed no difference in either the overall survival (P = 0.955) or recurrence-free survival (P = 0.068) among patients who underwent OPS, and BSO. Conclusion OPS appears to be safe without having any adverse impact on survival in women aged <= 40 years with FIGO Stage I EC.
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    Survival In Recurrent Ovarian Cancer Patients Before And After The Bevacizumab Era: An Observational Single-Centre Study
    (2022) Akilli, Huseyin; Rahatli, Samed; Aliyeva, Khayala; Altundag, Ozden; Kuscu, Ulku Esra; Ayhan, Ali; https://orcid.org/0000-0002-5240-8441; https://orcid.org/0000-0003-0197-6622; 35260031; AAX-3230-2020; W-9219-2019
    A retrospective observational study was carried out in Baskent University School of Medicine, Ankara, Turkey. Recurrent ovarian cancer patients treated between 2007 and 2017 were divided into two groups according to their bevacizumab status. The primary endpoints were overall survival (OS) and safety. Three hundred and ninety-six patients enrolled in this study, 200 (50.5%) received bevacizumab while 196 (49.5%) patients never received bevacizumab. The median follow-up time was 48.2 and 47.6 months, respectively. The 5-year OS was 61% and 46%, respectively (p=.007). In multivariate analysis, only platinum-sensitivity (HR: 3.75, 95% CI: 3.0-5.32; p<.001) was identified as independent prognostic factors. In subgroup analyses according to platinum status, bevacizumab did not affect the 5 year OS in platinum sensitive patients (64% versus 68% p=.28) but increased survival in platinum resistant patients (36% versus 44%, p=.00). The rate of grade III-IV haematologic toxicities was 13.7% in the bevacizumab group and 11% in the other group (p=.6).Impact Statement What is already known on this subject? Bevacizumab increases the progression-free survival in platinum-sensitive and resistant recurrent ovarian cancer patients without changing overall survival. What do the results of this study add? Bevacizumab did not affect OS in platinum sensitive recurrent ovarian cancer patients however improved OS in platinum resistant patients with mild toxicity. What are the implications of these findings for clinical practice and/or further research? This study emphasised the crucial role of bevacizumab in the treatment of recurrent ovarian cancer patients.
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    Hyperthermic intraperitoneal chemotherapy in the treatment of recurrent ovarian cancer: When, and for whom?
    (2023) Ayhan, Ali; Akilli, Huseyin; Abasiyanik, Mehmet Ali; Taskiran, Cagatay; https://orcid.org/0000-0002-5741-8489; 36264620
    Objective The aim of this study is to evaluate the progression-free survival (PFS) of recurrent ovarian cancer (ROC) patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). Materials and Methods ROC patients who underwent cytoreductive surgery plus HIPEC between 2015 and 2021 were retrospectively evaluated. Patients' demographic information and clinicopathological characteristics including cancer type, histology, platinum status, presence of ascites, type of surgery, complications, chemotherapy history, and disease progression were documented. PFS was calculated using the Kaplan-Meier method. Results A total of 104 patients with ROC were included. The median age was 57 years and the median follow-up time was 15 months (range: 5-69 months). In Cox regression multivariate analyses, platinum resistance (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.91-5.76, p = 0.00), more than one relapse prior HIPEC (HR: 2.81, 95% CI: 1.65-4.87, p = 0.024), and presence of ascites (HR: 1.88, 95% CI: 1.08-3.26, p = 0.00) were found to be negative prognostic factors for PFS. In subgroup analyses of patients with the first recurrence, the median PFS was 21 months for platinum-sensitive patients and 6 months for platinum-resistant patients (p = 0.032). Conclusion HIPEC at the time of first platinum-sensitive relapse may lead to favorable PFS in the treatment ROC. However, HIPEC as salvage treatment even with R0 cytoreductive surgery does not seem effective.
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    Is the extent of lymphadenectomy a prognostic factor in International Federation of Gynecology and Obstetrics stage II endometrioid endometrial cancer?
    (2021) Cuylan, Zeliha Firat; Akilli, Huseyin; Gungorduk, Kemal; Demirkiran, Fuat; Oz, Murat; Salman, Mehmet Coskun; Sozen, Hamdullah; Celik, Husnu; Gokcu, Mehmet; Bese, Tugan; Meydanli, Mehmet Mutlu; Ozgul, Nejat; Topuz, Samet; Kuscu, Esra; Kuru, Oguzhan; Gokmen, Sibel; Gultekin, Murat; Ayhan, Ali; 33426779
    Aim This study aimed to evaluate the prognostic significance of adequate lymph node dissection (LND) (>= 10 pelvic lymph nodes (LNs) and >= 5 paraaortic LNs removed) in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrioid endometrial cancer (EEC). Methods A multicenter department database review was performed to identify patients who had been operated and diagnosed with stage II EEC at seven centers in Turkey retrospectively. Demographic, clinicopathological, and survival data were collected and analyzed. Results We identified 284 women with stage II EEC. There were 170 (59.9%) patients in the adequate lymph node dissection (LND) group and 114 (40.1%) in the inadequate LND group. The 5-year overall survival (OS) rate of the inadequate LND group was significantly lower than that of the adequate LND group (84.1% vs. 89.1%, respectively; p = 0.028). In multivariate analysis, presence of lymphovascular space invasion (LVSI) (hazard ratio [HR]: 2.39, 95% confidence interval [CI]: 1.23-4.63; p = 0.009), age >= 60 (HR: 3.30, 95% CI: 1.65-6.57; p = 0.001], and absence of adjuvant therapy (HR: 2.74, 95% CI: 1.40-5.35; p = 0.003) remained as independent risk factors for decreased 5-year disease-free survival (DFS). Inadequate LND (HR: 2.34, 95% CI: 1.18-4.63; p < 0.001), age >= 60 (HR: 2.67, 95% CI: 1.25-5.72; p = 0.011), and absence of adjuvant therapy (HR: 4.95, 95% CI: 2.28-10.73; p < 0.001) were independent prognostic factors for decreased 5-year OS in multivariate analysis. Conclusion Adequate LND and adjuvant therapy were significant for the improvement of outcomes in FIGO stage II EEC patients. Furthermore, LVSI was associated with worse 5-year DFS rate in stage II EEC.
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    Prognostic Value of the Number of the Metastatic Lymph Nodes in Locally Early-Stage Cervical Cancer: Squamous Cell Carcinoma Versus Non-Squamous Cell Carcinoma
    (2021) Aslan, Koray; Haberal, Ali; Akilli, Huseyin; Meydanli, Mehmet Mutlu; Ayhan, Ali; 0000-0002-5240-8441; 33772630; AAX-3230-2020
    Purpose To clarify the prognostic value of the number of metastatic lymph nodes (mLNs) in squamous and non-squamous histologies among women with node-positive cervical cancer. Methods One hundred ninety-one node-positive cervical cancer patients who had undergone radical hysterectomy plus systematic pelvic and para-aortic lymphadenectomy followed by concurrent radiochemotherapy were retrospectively reviewed. The prognostic value of the number of mLNs was investigated in squamous cell carcinoma (SCC) v (n = 148) and non-SCC (n = 43) histologies separately with univariate log-rank test and multivariate Cox regression analyses. Results In SCC cohort, mLNs > 2 was significantly associated with decreased 5-year disease-free survival (DFS) [hazard ratio (HR) = 2.06; 95% confidence interval (CI) 1.03-4.09; p = 0.03) and overall survival (OS) (HR = 2.35, 95% CI 1.11-4.99; p = 0.02). However mLNs > 2 had no significant impact on 5-year DFS and 5-year OS rates in non-SCC cohort (p = 0.94 and p = 0.94, respectively). We stratified the entire study population as SCC with mLNs <= 2, SCC with mLNs > 2, and non-SCC groups. Thereafter, we compared survival outcomes. The non-SCC group had worse 5-year OS (46.8% vs. 85.3%, respectively; p < 0.001) and 5-year DFS rates (31.6% vs. 82.2%, respectively; p < 0.001) when compared to those of the SCC group with mLNs <= 2. However, the non-SCC group and the SCC group with mLNs > 2 had similar 5-year OS (46.8% vs. 65.5%, respectively; p = 0.16) and 5-year DFS rates (31.6% vs. 57.5%, respectively; p = 0.06). Conclusion Node-positive cervical cancer patients who have non-SCC histology as well as those who have SCC histology with mLNs > 2 seem to have worse survival outcomes when compared to women who have SCC histology with mLNs <= 2.