Clear cell carcinoma of the uterine cervix; an unusual HPV-independent tumor: Clinicopathological features, PD-L1 expression, and mismatch repair protein deficiency status of 16 cases.

Objective: Endocervical clear cell carcinoma (c-CCC) is a rare and HPV-independent adenocarcinoma type of cervix. Being usually resistant to conventional chemotherapy. Immunotherapy has recently been added as a preferred regimen as a second-line treatment option for programed cell death-ligand 1 (PD-L1)-positive or mismatch repair (MMR) deficient cervical carcinomas. In this study, clinicopathological features, PD-L1 expression, and MMR deficiency status of c-CCCs were investigated. Materials and Methods: Sixteen c-CCC diagnosed cases were included in this study. PD-L1 expression was evaluated using two different PD-L1 clones (22C3 and SP263). MMR deficiency status of the cases was evaluated using four MMR proteins (MLH1, PMS2, MSH2, and MSH6). Results: Most of the c-CCC cases were presented as FIGO Stage I (68.75%). PD-L1 expression in either tumoral or tumor-infiltrating immune cells (TILs) was present in 62.5% (10/16) and 69% (11/16) of the 22C3 and SP263 clones, respectively. Most of the cases with high TIL density were also positive for PD-L1. The PD-L1 expression rate was less than 50% in most of the cases and 12.5% of the cases shared extensive PD-L1 staining. Overall, MMR deficiency was observed in 31.25% of the cases. Most of the MMR-deficient cases (80%) were PD-L1 positive. Conclusion: Although our study cohort is limited, we have shown that PD-L1 expression and MMR deficiency can be found in c-CCCs in variable degrees. These findings suggest that accompanying TIL density and MMR deficiency could be used as candidates for predicting PD-L1 positivity for c-CCCs. However, to indicate the clinical importance of these findings, objective treatment outcomes of cases treated with immunotherapy should be seen.

Survival impact of number of removed para-aortic lymph nodes in stage I epithelial ovarian cancer.

PURPOSE: The survival effect of presence or absence of lymphadenectomy in early-stage epithelial ovarian cancer (EOC) was priorly shown but the effect of number of removed lymph nodes kept in background. We aimed to evaluate the survival impact of number of removed lymph nodes and their localizations in stage I EOC. METHODS: This study included 182 patients. The best cut-off levels for number of pelvic and para-aortic lymph nodes (PaLN) were 24 and 10, respectively. Univariate and multivariate survival analyses were performed for these cut-offs and other prognostic factors. RESULTS: The median age of the patients was 49. The median number of removed pelvic and paraartic lymph nodes were 29 and 9, respectively. The median overall (OS) and progression-free survival (PFS) were 67 and 50 months, respectively. The 5-year OS rate was 89.6%. Recurrence occured in 24 (19.5%) patients. In univariate analyses tumor grade (p: 0.005), pelvic LN number (p: 0.041) and PaLN number (p: 0.004) were the factors that were significantly associated with PFS. Tumor grade and PaLN number were independently and significantly associated with PFS in multivariate analyses (p: 0.015 and p: 0.017, respectively). In OS analyses, age, tumor grade, presence of LVI, number of pelvic and PaLNs were the significantly associated factors (p < 0.05 for all). In multivariate analyses, age and PaLN number were independently and significantly associated with OS (p: 0.011 and p: 0.021, respectively). CONCLUSIONS: The number and localizations of removed lymph nodes may have a survival affect in stage I EOC. We also think that this study may constitute a kernel point for larger prospective series on lymph node number and lymphatic regions.

Prognostic impact of p16 and p53 gene expressions in stage 1a epithelial ovarian cancer.

OBJECTIVE: Epithelial ovarian cancer (EOC) is rarely detected at stage 1a. Most of the patients have a good prognosis and there are limited factors that affect their survival. In the present study, we evaluated the p16 and p53 gene expressions of stage 1a EOC patients. Prognostic effects of these gene expressions, as well as those of other factors on short term survival were analyzed. METHODS: Our study included 29 patients. The specimens of the ovary with cancer were stained for p16 and p53. Gene expressions and other prognostic factors were evaluated. RESULTS: The median age of the patients was 51 years (27-84). The mean numbers of dissected pelvic and paraaortic lymph nodes were 27 and 12, respectively. The mean follow-up time was 33.7±18.9 months. During this period, recurrence occurred in two patients. One of the patients had grade 2 mucinous carcinoma and died of the disease at month 12 after the recurrence occurred at month 7. The second patient had clear cell carcinoma and recurrence occurred at month 34. p16 and p53 gene expressions or other factors were not associated with overall survival (OS) or disease-free survival in the short term. The lower p16 positivity rate in the non-clear cell group was found to be statistically significant (P=0.003). Both p53 and p16 positivity rates were higher in the high-grade carcinoma. CONCLUSION: The levels of none of the common prognostic factors, including those of p16 and p53 gene expression, were associated with the progression-free survival or OS of stage 1a in the short term. Appropriate surgical staging and non-omission of subclinical metastases seem to be of central importance.

Relation of Preoperative and Postoperative Echocardiographic Parameters With Rejection and Mortality in Liver Transplant Patients.

OBJECTIVES: Survival in liver transplant after end-stage liver disease is associated with major cardiac functions. In a significant number of patients with end-stage liver disease, cardiac dysfunctions may be observed, which can include high-output heart failure, cardiac valve disease, and pulmonary venous and arterial hypertension. All of these affect perioperative survival. The aim of our study was to determine whether preoperative and postoperative echocardiographic parameters, specifically right heart-related tricuspid regurgitation, estimated systolic pulmonary arterial pressure, and tricuspid annular plane systolic excursion, are associated with rejection and mortality in liver transplant patients. MATERIALS AND METHODS: Adult patients (> 18 years old) who underwent liver transplant at our center between January 2011 and March 2017 were included in the study, with 64 patients retrospectively screened. The echocardiographic images that were taken immediately before and immediately after liver transplant were evaluated. The patients were divided into 2 groups according to rejection data and mortality. All parameters were analyzed for both variables. RESULTS: For the 24 patients with liver rejection and 40 patients without liver rejection, there were no statistically significant differences in terms of demographic data, echocardiographic parameters, and laboratory data. However, when patients were evaluated according to survival, there was a statistically significant difference between these 2 groups concerning the echocardiography parameters of systolic pulmonary arterial pressure (P = .005), tricuspid annular plane systolic excursion (P = .001), and postoperative right ventricular width (P = .01). CONCLUSIONS: Echocardiography, being a simple and easily accessible technique that is reliable in excluding pulmonary hypertension diagnosis, can be used as a guide in the evaluation of right ventricular function and tricuspid regurgitation, particularly in patients who are not hemodynamically stable before and after liver transplant.

A novel prediction method for lymph node involvement in endometrial cancer: machine learning.

OBJECTIVE: The necessity of lymphadenectomy and the prediction of lymph node involvement (LNI) in endometrial cancer (EC) have been hotly-debated questions in recent years. Machine learning is a broad field that can produce results and estimations. In this study we constructed prediction models for EC patients using the Naïve Bayes machine learning algorithm for LNI prediction. METHODS: The study assessed 762 patients with EC. Algorithm models were based on the following histopathological factors: V1: final histology; V2: presence of lymphovascular space invasion (LVSI); V3: grade; V4: tumor diameter; V5: depth of myometrial invasion (MI); V6: cervical glandular stromal invasion (CGSI); V7: tubal or ovarian involvement; and V8: pelvic LNI. Logistic regression analysis was also used to evaluate the independent factors affecting LNI. RESULTS: The mean age of patients was 59.1 years. LNI was detected in 102 (13.4%) patients. Para-aortic LNI (PaLNI) was detected in 54 (7.1%) patients, of which four patients had isolated PaLNI. The accuracy rate of the algorithm models was found to be between 84.2% and 88.9% and 85.0% and 97.6% for LNI and PaLNI, respectively. In multivariate analysis, the histologic type, LVSI, depth of MI, and CGSI were independently and significantly associated with LNI (p<0.001 for all). CONCLUSIONS: Machine learning may have a place in the decision tree for the management of EC. This is a preliminary report about the use of a new statistical technique. Larger studies with the addition of sentinel lymph node status, laboratory findings, or imaging results with machine learning algorithms may herald a new era in the management of EC.

Oncological and obstetric outcomes after fertility-sparing radical abdominal trachelectomy for early stage cervical cancer: a tertiary centre's 10 years' experience.

The aim of this study is to present our clinical experience about fertility-sparing procedures in early stage cervical cancer and its obstetrical and oncological outcomes. Between the years 2006 and 2016, a total of 22 early stage cervical cancer patients who underwent a fertility-sparing radical abdominal trachelectomy in our clinic were retrospectively analysed. The median age was 33 (range: 28-39) years. The median follow-up was 47 (range: 22-125) months. Five patients (22.7%) had Stage IA1, three patients had (13.6%) Stage IA2, and 14 patients (63.6%) had Stage IB1 disease. Only one patient had a recurrence. A pregnancy was obtained in five patients (22.7%) and one of them (20%) had a live birth. A pregnancy was obtained spontaneously in two patients (40%), whereas assisted reproductive techniques were used in three of the patients (60%). A miscarriage occurred in two patients (40%), and one of them was within the first trimester and the other was within the second trimester. Impact statement What is already known on the subject? Currently, the first-line treatment of early stage cervical cancer is surgery. However, a fertility-sparing trachelectomy is the most widely adopted approach in the reproductive aged patients who have a desire to be pregnant later. What does this study add? In the literature, there is a growing number of studies on this subject. However, it would take time to obtain adequate knowledge. We believe that our study would contribute to the existing data. What are the implication of these findings for clinical practice? This study is important as it indicates that a multidisciplinary approach is required to preserve fertility among gynaecologic oncologists and the outcomes would be reflected into the clinical practice. In addition, we believe that our study would pave the way for further studies regarding this subject among oncologists.

Possible impact of immunosuppressive therapy regimens on histopathologic outcomes of abnormal uterine bleeding in solid-organ transplant recipients.

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.

Is the presence of endometriosis associated with a survival benefit in pure ovarian clear cell carcinoma?

BACKGROUND: The purpose of this study was to compare the prognoses of women with pure ovarian clear cell carcinoma (OCCC) arising from endometriosis to those of women with pure OCCC not arising from endometriosis treated in the same manner. METHODS: A dual-institutional, retrospective database review was performed to identify patients with pure OCCC who were treated with maximal or optimal cytoreductive surgery (CRS) followed by paclitaxel/carboplatin chemotherapy between January 2006 and December 2016. Patients were divided into two groups according to the detection of cancer arising in endometriosis or not, on the basis of pathological findings. Demographic, clinicopathological, and survival data were collected, and prognosis was compared between the two groups. RESULTS: Ninety-three women who met the inclusion criteria were included. Of these patients, 48 (51.6%) were diagnosed with OCCC arising in endometriosis, while 45 (48.4%) had no concomitant endometriosis. OCCC arising in endometriosis was found more frequently in younger women and had a higher incidence of early stage disease when compared to OCCC patients without endometriosis. The 5-year overall survival (OS) rate of the patients with OCCC arising in endometriosis was found to be significantly longer than that of women who had OCCC without endometriosis (74.1 vs. 46.4%; p = 0.003). Although univariate analysis revealed the absence of endometriosis (p = 0.003) as a prognostic factor for decreased OS, the extent of CRS was identified as an independent prognostic factor for both recurrence-free survival (hazard ratio (HR) 8.7, 95% confidence interval (CI) 3.15-24.38; p < 0.001) and OS (HR 11.7, 95% CI 3.68-33.71; p < 0.001) on multivariate analysis. CONCLUSION: Our results suggest that endometriosis per se does not seem to affect the prognosis of pure OCCC.

Primary ovarian malignant melanoma arising in teratomatous component of mixed- germ cell tumor in a child: case report.

Primary ovarian malignant melanoma arising in teratomatous component of germ cell tumors is seen extremely rare with most reports being only of single cases and small series in reproductive aged woman and mostly from cystic teratoma, whereas information on pediatric presentation is sparse. This case is reported for being extremely rare tumor.

To what extent should we perform parametrectomy in FIGO stage IB cervical cancer?

OBJECTIVE: To demonstrate the histopathological basis of individually tailored less radical surgery concept in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer. MATERIAL AND METHODS: The study was performed in the gynaecologic oncology department of Baskent School of Medicine Hospital, Ankara, Turkey between January 1(st) 2008 and January 1(st) 2009. Cardinal and uterosacral ligaments were serially sectioned in an alternative approach, and were examined by a senior gynaecologic pathologist. Clinical and pathological features and findings in sections of uterine ligaments were recorded. Study data were analysed using the SPSS 17.0 program. RESULTS: Thirty-two out of 38 cases had squamous cell carcinoma (SCC) (84.2 %), and six had non-squamous cell tumours (15.8%). Four cases had microscopic (10.5 %) and one case had macroscopic (2.6 %) tumour extension in cardinal ligaments. Mean tumour-free cardinal ligament length was 16.8±7.39 mm. Presence of tumour invasion in cardinal ligaments correlated significantly with pelvic lymph node metastasis (p=0.02). No isolated tumour deposits were found in any of the cases in serial sections of the cardinal or uterosacral ligaments. CONCLUSION: This research was designed as a preliminary study. Future studies are needed to determine the optimal resection margins of the uterine ligaments in surgically treated stage IB cervical cancer. With continuing research and the development of newer surgical techniques, patients' quality of life will be optimised accordingly.

Does Aquaporin-1 expression have clinical significance in serous epithelial ovarian cancer?

OBJECTIVE: To assess the relationship between Aquaporin-1 (AQP1) expression and clinicopathological variables in serous epithelial ovarian cancer (EOC). MATERIAL AND METHODS: Serous EOC cases treated in our institution between January 2007 and December 2009 were included in the study. A semi-quantitative immunohistochemical method was used to determine AQP1 expression levels, intratumoral microvessel density (IMD) and AQP1/IMD ratios. The relationship between these parameters and clinicopathological variables were assessed. P values less than 0.05 was considered statistically significant. RESULTS: A total of 55 cases of serous EOC were included in the study. AQP1 was strongly expressed in the membranes of microvessels and small vessels within all tumor tissues. In a few cases, AQP1 expression was also observed in the membrane of interstitial cells and in individual tumor cells. A positive correlation was detected between preoperative CA125 levels and the expression of AQP1 (R: 0.277, p<0.05). AQP1 expression was similar between FIGO stage I-II and FIGO stage III-IV cases (p > 0.05). A significant relationship did not exist between AQP1 expression and FIGO stage, lymph node metastasis or ascites volume (p>0.05). CONCLUSION: In this study, AQP1 expression did not have a significant association with important clinicopathological variables in serous EOC. Future studies are needed to determine AQP1 expression in other histological types of EOC.

Pap smear findings in chronic renal failure patients compared with the normal population according to Bethesda 2001.

Dialysis remains the most common treatment for end-stage renal disease (ESRD). Although the increased risk of cancer after renal transplant is well documented, there is less certainty about the risk of cancer in patients treated only with dialysis. From 1997 to 2002, 262 ESRD patients received a Pap test at Baskent University. The smears of 149 patients who had ESRD for more than 9 months were compared with the smears of 150 otherwise healthy patients. All of the Pap smears were re-examined according to Bethesda 2001 criteria. The mean age of the patients was 42.88 years. Regarding micro-organisms, no statistically significant difference between the groups were observed. In 36 Pap smears, a shift in flora suggestive of bacterial vaginosis was detected. There were statistically significant differences between the groups. When age was considered as a marker of atrophy, atrophy in patients younger than 50 years was statistically different between the groups. Also, we determined that the shift in flora suggestive of bacterial vaginosis and atrophy in patients aged younger than 50 years did not depend on the length of hemodialysis. Of 13 patients (4.3%) who had epithelial cell abnormalities there were not statistically significant differences between the groups. In conclusion, according to our study, CRF seems not to be a predictive factor for cervical cancer. Shift in flora suggestive of bacterial vaginosis and atrophy in patients aged younger than 50 years might be the natural effects of uremia, and they appear not to be dependent on the length of the hemodialysis period.

VEGF, COX-2, and PCNA expression in renal cell carcinoma subtypes and their prognostic value.

OBJECTIVE: To evaluate the prognostic value of new markers such as VEGF (vascular endothelial growth factor), COX-2 (cyclooxygenase-2), and PCNA (proliferating cell nuclear antigen) and review their differences in expression by histological subtype in patients with renal cell carcinoma (RCC). METHODS: About 99 patients who underwent radical (n = 79) or partial nephrectomy (n = 20) were included in this study. Histopathological specimens from the subjects were retrospectively analyzed immunohistochemically for the presence of VEGF, COX-2, or PCNA. RESULTS: Mean staining ratios for VEGF, COX-2, and PCNA were 16.5, 16.8, and 31%, respectively. Correlations were evaluated among these three prognostic factors. There was no correlation between PCNA and VEGF (P = .068), but there were significant correlations between COX-2 and both PCNA and VEGF (P = .005 and P = .000, respectively). A significant correlation was found between the expression of VEGF and both pathologic stage and vascular invasion (P = .018 and P = .025, respectively). In addition, patients with conventional RCC had significantly lower VEGF and COX-2 levels than those with papillary RCC (P < .012). CONCLUSIONS: It is obvious that prognostic factors such as VEGF, COX-2, and PCNA may vary depending on histological subtype. The level of expression of these factors together with histological subtype may provide valuable predictive information about the outcome of treatment.