The Association of an Elevated Thrombocyte Count with Clinicopathological Prognostic Factors and Survival in Patients with Uterine Carcinosarcoma.

BACKGROUND: Uterine carcinosarcoma (UCS) is a rare tumor with a poor prognosis. An elevated thrombocyte count and thrombocytosis were found to be associated with poor prognosis in several gynecological tumors. Data regarding an elevated thrombocyte count and thrombocytosis, particularly in UCS, are scarce. OBJECTIVES: To assess the frequency of a preoperative elevated thrombocyte count and of thrombocytosis in UCS patients and their association with clinicopathological prognostic factors and survival. METHODS: The preoperative thrombocyte count of 29 consecutive verified USC patients diagnosed in our medical center from January 2000 to July 2015 was recorded, and clinicopathological data of these patients were abstracted from hospital files. RESULTS: Thrombocytosis was found in two patients (6.8 %) and both died of the disease. An elevated thrombocyte count was found in nine patients (31.0%). The percentage of patients with the poor prognostic factors who had a preoperative elevated thrombocyte count was not statistically different from those without these risk factors. The cumulative survival of patients with an elevated count was 22.1 months and that of those without an elevated count was 31.1 months. This difference was statistically not significant (P = 0.85). There was also no difference between the groups regarding the progression free survival. CONCLUSIONS: No association between an elevated thrombocyte count and prognosis was found. Larger studies are needed to clarify this issue.

Hysterscopic Resection of Premalignant and Malignant Endometrial Polyps: Is it a Safe Alternative to Hysterectomy?

STUDY OBJECTIVE: The standard treatment of endometrial cancer (EC) and complex atypical hyperplasia (CAH) is hysterectomy with or without adnexectomy. In the last decade several centers have attempted to perform hysteroscopic resection of malignant and premalignant polyps as an alternative to hysterectomy. In the present study we evaluated the safety of this procedure in regard to residual uterine pathology. DESIGN: Retrospective chart review (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Women (n = 1766) who underwent hysteroscopic polypectomy during the years 1998 to 2016. INTERVENTIONS: Patients with CAH and endometrioid type EC in the removed polyps who underwent hysterectomy were included in the study. Patients with nonendometrioid pathology were excluded. The operative and pathologic reports of the hysteroscopy and hysterectomy procedures were revised. MEASUREMENTS AND MAIN RESULTS: Forty-three women (2.4%) were diagnosed with premalignant and malignant polyps: 21 with EC and 22 with CAH. Thirty-four women (79.0%) underwent hysterectomy and were included in the study group. The median age was 62 years (range, 35-83). Most women (79.4%) presented with postmenopausal bleeding or menorrhagia. In 13 patients (38.2%) more than 1 polyp was removed. The median size of the polyps was 2 cm (range, 1-4). In 27 women there were no other visible endometrial findings during the hysteroscopy except for the removed polyp. However, in 24 women (88.9%) residual CAH or EC was present in the hysterectomy specimen, mostly (55.6%) as multifocal lesions. CONCLUSION: Our results indicate that hysteroscopic evaluation of the uterine cavity and polyp resection are not enough for the eradication of premalignant and malignant endometrial lesions. This alternative should be reserved for well-selected cases such as for fertility preservation and for patient with surgical risk factors that after the hysteroscopic polypectomy will receive further medical treatment.

Is there a revision needed of the current FIGO staging system?

The FIGO staging system has undergone many modifications since it first appeared in about the middle of the previous century. Due to the use of modern diagnostic tools, namely computed tomography, magnetic resonance imaging, positron emission tomography, sentinel lymph node biopsy and neoadjuvant chemotherapy, certain gynecological cancer cases cannot be allocated to a specific stage if one wishes to adhere strictly to FIGO requirements. In these circumstances such cases actually remain unstaged. This should prompt appropriate modifications of the current FIGO staging system so that it fulfills its aims.

The optimal angle of the mediolateral episiotomy at crowning of the head during labor.

INTRODUCTION AND HYPOTHESIS: The aim of the mediolateral episiotomy incision is to increase the diameter of the soft tissue of the vaginal outlet to facilitate birth and to prevent vaginal tears. Episiotomy angles that are too narrow and close to the midline increase the risk of obstetric anal sphincter injuries. In order to determine the optimal angle of the episiotomy, we assessed the changes in the angles of episiotomy lines marked during the first stage of labor and measured at the time of crowning of the head. METHODS: Incision lines for mediolateral episiotomy were marked on the perineal skin at angles of 30°, 45°, and 60° from the midline during the first stage of labor in women with a singleton pregnancy. The angles of the marked lines were measured at crowning of the head. Mediolateral episiotomy was performed only for obstetric indications. RESULTS: The study included 102 women with a singleton pregnancy. Of these women, 50 were primiparous and 52 were multiparous. All angles marked during the first stage of labor increased significantly (by more than 30°) at crowning of the head. Similar changes were observed in primiparous and multiparous women. CONCLUSIONS: The angle of the mediolateral episiotomy line was significantly greater at crowning of the head than when marked during the first stage of labor. To achieve the desired episiotomy angle, it is important to take into consideration the changes in mediolateral episiotomy angles that occur during labor.

Preoperative elevated platelet count and thrombocytosis in gynecologic malignancies.

PURPOSE: Platelets have multiple functions and they also play an important role in malignancies. Elevated platelet count and thrombocytosis at the time of diagnosis in patients with many solid tumors correlates with prognosis and is associated with poor survival. The aim of the following report is to review the literature concerning elevated platelet count and thrombocytosis in gynecologic malignancies. METHOD: A PubMed search of all English literature peer-reviewed publications was performed containing the terms elevated platelet count or thrombocytosis and vulvar cancer, cervical cancer, endometrial cancer, and ovarian cancer. All studies published until December 31, 2015, were included in the following review. RESULTS: A pretreatment elevated platelet count and thrombocytosis have been shown to be associated with a poor prognosis in many studies of gynecologic malignancies with the exception of vulvar carcinoma. CONCLUSION: Since elevated platelet count and thrombocytosis may be prevented by blocking thrombopoietic cytokines, their assessment may, in the future, be of therapeutic significance.

Gemcitabine-Induced Subacute Cutaneous Lupus Erythematosus: A Case Report.

Subacute cutaneous lupus erythematosus (SCLE) is a rare eruption related to several pharmacological and chemotherapy agents. We present a 63-year-old female with recurrent epithelial ovarian cancer who developed SCLE after administration of gemcitabine. Following discontinuation of gemcitabine and after oral steroid treatment, all skin lesions disappeared. In view of the extensive use of gemcitabine in recurrent ovarian cancer, it is important to be aware of the possibility of SCLE occurrence in these patients.

Review of Recommended Treatment of Uterine Carcinosarcoma.

Surgery is the primary treatment for uterine carcinosarcoma (UCS). Lymphadenectomy should be performed for staging purposes in tumors apparently confined to the uterus. Most studies found that lymphadenectomy is of therapeutic value. The therapeutic value of cytoreduction to no residual macroscopic disease in advanced UCS is based mostly on small retrospective uncontrolled studies. Postoperative adjuvant therapy should be considered for all stages of UCS. Adjuvant pelvic radiotherapy may reduce locoregional recurrences. However, this does not translate into improved overall survival since most recurrences are distant outside the irradiated field, and the survival rates remain poor, the 5-year overall survival being about 50%. Several adjuvant platin-based combination chemotherapy schedules such as cisplatin/ifosfamide, ifosfamide/paclitaxel, and paclitaxel/carboplatin have been found to be an effective mode of adjuvant treatment. Multimodal therapy (i.e., adjuvant chemotherapy plus radiotherapy) has also been shown to be effective. Most studies dealing with adjuvant treatment are retrospective and prospective randomized controlled trials (i.e., phase III studies) comparing that between the various adjuvant chemotherapy schedules and between them and multimodal treatment are lacking. Quality of life with the various treatment modalities needs also to be assessed. An effective targeted therapy has so far not been found. In spite of the multiple studies with regard to the treatment of UCS published during the last 15 years, the optimal management of UCS is still not established.

The Effect of Cyclooxygenase-2 Expression in Uterine Carcinosarcoma on Survival: A Reassessment Based on Mature Data.

OBJECTIVE: To reassess the effect cyclooxygenase-2 (COX-2) expression in carcinosarcoma on survival based on mature 5-year survival data. METHOD: A comparison of 5-year survival of 27 patients with carcinosarcoma according to the presence of COX-2 immunohistochemical staining and staining score was performed. RESULTS: The 5-year survival of those with positive and negative COX-2 staining was statistically not different. However, there was a clear trend for more favorable 5-year survival in patients with a high staining score than in those with a low score, and the difference was of borderline significance (38.5% vs 7.1%; P = 0.06). CONCLUSION: In view of the role of COX-2 in carcinogenesis, our finding that COX-2 expression may confer a better survival in patients with carcinosarcoma is intriguing. Larger studies are indicated to elucidate the effect of COX-2 expression on survival in patients with carcinosarcoma because this may have therapeutic implications.

The Significance of Normal Pretreatment Levels of CA125 (<35 U/mL) in Epithelial Ovarian Carcinoma.

OBJECTIVE: To assess the association between normal CA125 levels at diagnosis of epithelial ovarian carcinoma (EOC) with prognostic factors and with outcome. METHODS: The study group consisted of histologically confirmed EOC patients with normal pretreatment CA125 levels, and the controls consisted of EOC patients with elevated (≥35 U/mL) pretreatment CA125 levels, diagnosed and treated between 1995 and 2112. Study and control group patients fulfilled the following criteria: 1) their pretreatment CA125 levels were assessed; 2) they had full standard primary treatment, i.e. cytoreductive surgery and cisplatin-based chemotherapy; and 3) they were followed every 2-4 months during the first two years and every 4-6 months thereafter. RESULTS: Of 114 EOC patients who fulfilled the inclusion criteria, 22 (19.3%) had normal pretreatment CA125 levels. The control group consisted of the remaining 92 patients with ≥35 U/mL serum CA125 levels pretreatment. The proportion of patients with early-stage and low-grade disease, with optimal cytoreduction, and with platin-sensitive tumors was significantly higher in the study group than in the control group. The progression-free survival (PFS) and overall survival (OS) were significantly higher in the study group than in the control group on univariate analysis but not on multivariate analysis. CONCLUSION: It seems that a normal CA125 level at diagnosis in EOC may also be of prognostic significance for the individual patient.

Very late recurrence (after more than 20 years) of epithelial ovarian carcinoma: case report and literature review.

PURPOSE: To present a case of very late (more than 20 years) recurrence of epithelial ovarian carcinoma and to review the pertinent literature. We encountered a 50-year-old patient who, at the age of 22, underwent cytoreductive surgery and adjuvant chemotherapy for stage III serous ovarian carcinoma. She recurred after 28 years and underwent secondary surgery and chemotherapy. METHOD: A PubMed search of the English literature containing the following key words: ovarian cancer, late recurrence, late relapse, late metastasis was performed. RESULTS: Only five cases (including the present one) with recurrence after more than 20 years are so far on record. Of these, four patients were 33 years old or younger and had advanced stage at diagnosis. Time to recurrence ranged from 21 to 28 years. All patients had serous carcinoma and three had recurrence in lymph nodes. CONCLUSIONS: Very late recurrence is an extremely rare event and may result from either regrowth of dormant tumor cells or from development of a new cancer. Lifelong follow-up is critically important for ovarian cancer patients.

CA125 expression in the tissue of uterine leiomyosarcoma.

UNLABELLED: Background: Elevated serum levels of the epithelial marker CA125 are occasionally observed in leiomyosarcoma (LMS) patients. OBJECTIVES: To assess the immunohistochemical expression of this marker in the tissue of LMS. METHODS: The consecutive unselected records of all patients with LMS diagnosed during the period 1995-2012 were located and abstracted. After verification of the diagnosis, 4 µm unstained slides were prepared from each case for immunohistochemical staining for CA125. Sections of ovarian carcinoma known to express CA125 were used as positive controls. RESULTS: We located 17 LMS patients from the period under study. Bleeding was the presenting symptom in 9 patients; the diagnosis was established prior to treatment in 11 patients. The tumor was in an advanced stage in 6 patients, and in 7 unstaged patients it was grossly confined to the uterus. Ten patients died within 14 months after the diagnosis. Serum CA125 levels prior to treatment were assessed in only 8 patients and were above normal limits (> 35 U/ml) in 3 of them. Two of the three with elevated serum levels were in stage III, and the third was an unstaged apparent stage I patient. None of the LMS tissue specimens demonstrated immunohistochemical expression of CA125. CONCLUSIONS: CA125 was not immunohistochemically expressed in the tissue of any LMS tumors examined by us. The origin of elevated serum CA125 in some of these tumors is therefore not in its tissue and remains unknown.

Conservative fertility-sparing surgical treatment of invasive epithelial ovarian cancer: when is it acceptable?

The disadvantages of the reviewed studies dealing with fertility-sparing conservative surgery in EOC reported during the last 20 years are inherent in their retrospective nature. Many of the studies include a limited number of patients. The follow-up periods in these studies vary greatly and in some it is not indicated at all. Outcome is often given as the number of patients with recurrence or the number of patients alive at the end of follow-up and not as the probability of survival. The percentage of serous and mucinous carcinoma in stage I EOC in young patients is about equal. Yet, in many of the studies the rate of patients with mucinous carcinomas treated conservatively exceeds by far that of other histological types and is as high as 62-76%, while serous tumors comprise only a small proportion of the cases. In several studies the histological type is not given at all. An assessment of outcome according to histologic type of the tumor was not done in many of the studies, probably because of the limited number of patients. In some of the studies adjuvant chemotherapy was administered after conservative surgery. However, how this affected the outcome was not assessed. Nevertheless, it seems that the presented data indicate that fertility-sparing conservative surgery in stage IA grade 1 (and possibly grade 2) EOC does not significantly compromise survival and allows future fertility. Although favorable results have been reported in many studies that included conservatively treated patients with higher stage and grade, their number is too small to draw any conclusion.

The significance of the pattern of serum CA125 level ascent to above the normal range in epithelial ovarian, primary peritoneal and tubal carcinoma patients.

OBJECTIVE: A rise of the CA125 marker above the normal range during follow-up of ovarian, primary peritoneal and tubal carcinoma patients with a complete clinical response after initial treatment signifies recurrence. We assessed whether the pattern of CA125 ascent to above the normal range at recurrence is associated with outcome. METHODS: The records of all recurrent ovarian primary peritoneal and tubal carcinoma patients diagnosed during 1998-2007 were abstracted. Included were patients who fulfilled the following criteria: CA125 levels were ≥35 U/mL at diagnosis and at recurrence, they had full primary treatment with a complete clinical and radiographic response, were followed-up according to schedule, and had at least two CA125 results within the normal range during follow-up. Two patterns of CA125 ascent to above the normal range were compared: a gradual rise and an abrupt rise. RESULTS: 52 patients with recurrent disease who met the inclusion criteria were identified. The median progression free and overall survival were significantly longer in patients with a gradual than in those with an abrupt rise (22.96 vs 14.07; P=0.0014; and 44.37 vs. median not yet reach, respectively). Multivariate analysis showed that the pattern of CA125 ascent is an independent predictor of progression free and overall survival. CONCLUSIONS: Our data seem to indicate that at recurrence the pattern of ascent of serum CA125 levels to above the normal range in patients in complete clinical remission is of prognostic value.

Prognostic significance of rising serum CA-125 levels within the normal range in patients with epithelial ovarian, primary peritoneal, and tubal cancers, who, after initial treatment, had a complete clinical response.

OBJECTIVE: This study aimed to assess the ability of 3 criteria of rising CA-125 levels within the reference range to predict recurrence in patients with ovarian, primary peritoneal, and tubal carcinomas after complete clinical response to initial treatment. MATERIAL AND METHODS: Included were patients diagnosed during 1998 to 2008 who fulfilled the following criteria: CA-125 levels of 35 U/mL or greater at diagnosis and recurrence, full primary treatment with a complete clinical and radiographic response, follow-up according to schedule, and at least 2 CA-125 results within the reference range during follow-up. Three criteria of rising CA-125 values within the reference range were used for the prediction of recurrence: (1) an absolute increase of 5 U/mL or higher from the nadir value at completion of chemotherapy, (2) early signal of progressive disease criterion, and (3) a rise to an absolute level of 20 U/mL or greater. RESULTS: Of 82 patients who satisfied study inclusion criteria, 58 (70.7%) had disease recurrence. Early signal of progressive disease and a rise to an absolute level of 20 U/mL or greater were highly statistically significant predictors of disease recurrence (odds ratio, 12.62 [95% confidence interval, 2.71-58.7], P = 0.0012; and odds ratio, 6.7 [95% confidence interval, 2.18-20.54], P = 0.001, respectively) and preceded recurrence by a median of 3 and 3.3 months, respectively. CONCLUSIONS: Our data indicate that the early signal of progressive disease criterion and a single rise to an absolute level of 20 U/mL or greater within reference limits are highly predictive of clinical recurrence, although the latter is simpler to use. However, whether this is of practical clinical value remains to be proven.

The effect of hysterectomy on survival of patients with borderline ovarian tumors.

OBJECTIVE: The classically recommended surgical treatment of borderline ovarian tumors (BOTs) includes hysterectomy in addition to bilateral adnexectomy. Possible reasons for hysterectomy might be a high frequency of uterine involvement and its favorable effect on survival. The purpose of the present study was to assess the frequency of uterine involvement in patients with BOTs and the effect of hysterectomy on survival. METHODS: All incident cases of histological confirmed BOTs diagnosed in Israeli Jewish women between March 1 1994 and June 30 1999, were identified. Clinical and pathological characteristics were abstracted from medical records. Patients with tumors grossly confined to the ovaries (apparently stage I) were considered to have had surgical staging when at least hysterectomy, bilateral salpingooophorectomy, omentectomy and pelvic lymph node sampling were done. RESULTS: The study group comprised 225 patients. Hysterectomy was performed in 147 (65.31%) patients and uterine involvement was present in only 3 (2.0%) of them. The 13 year survival of the total group of patients was 85.8% and of those in apparent stage I, 88.5%. Among patients with tumors apparently confined to the ovaries, no significant survival difference was observed between unstaged and surgically staged patients. There was also no survival difference between the overall staged and unstaged patients and between patients in stages II-III who did and did not undergo hysterectomy. CONCLUSIONS: Our data indicate that the rate of uterine involvement in BOT is low and that hysterectomy does not favorably affect survival. The necessity of hysterectomy in BOT patients is questioned.

Neoadjuvant chemotherapy in ovarian, primary peritoneal and tubal carcinoma: can imaging results prior to interval debulking predict survival?

OBJECTIVE: To assess whether there is an association between improvement of computed tomography imaging results prior to interval debulking with survival in patients treated by neoadjuvant chemotherapy. METHODS: The clinical and outcome data of all advanced ovarian, primary peritoneal and tubal carcinoma patients who after diagnosis had neoadjuvant chemotherapy and underwent interval debulking during the period 2000-2010, were abstracted. Results of computed tomography imaging at diagnosis and prior to interval debulking were compared. Two parameters were assessed: the change of the size and number of abnormal findings and the change in the amount of ascites. CA-125 level response was also calculated. An assessment of progression free survival and of survival by the Kaplan-Meier method was made according to the change in computed tomography imaging results and according to response of CA-125 levels. RESULTS: The median progression free survival and the median survival of the 37 study group patients were 7.9 and 49.2 months respectively. No significant difference in progression free survival and survival was observed between patients with marked improvement in the computed tomography results and those with less desirable results (7.93 vs. 7.23 months respectively, p=0.89; 45.8% vs. 52.5% months respectively, p=0.95). There were also no statistically significant difference according to CA-125 level response. CONCLUSION: It seems that neither improvement in imaging results nor CA-125 level response can predict the survival of ovarian carcinoma patients prior to interval debulking after neoadjuvant chemotherapy.

Is removal of asymptomatic cervical polyps necessary?: histologic findings in asymptomatic Israeli Jewish women.

OBJECTIVE: : The purpose of the present study was to assess the frequency of abnormal histologic findings in polyps of asymptomatic Israeli Jewish women who are known to have a low incidence of cervical neoplasia. MATERIALS AND METHODS: : The medical records of Israeli Jewish women with histologically proven cervical polyps treated during 2005 to 2009 in 2 Maccabi Health Service clinics that specialize in cervical pathology and colposcopy were retrieved from a computerized database. The records of asymptomatic women who underwent polypectomy were reviewed, and demographic information, clinical information, and the presence of abnormal colposcopic patterns, cervical intraepithelial neoplasia (CIN), and malignancy were abstracted. RESULTS: : The study included 228 asymptomatic women with cervical polyps who underwent colposcopy. Their median age was 49 ± 10.9 years (range = 21-82 y). The highest percentage of patients was observed in the 40- to 49-year-old age group, was Israeli-born, and was married. The percentage of patients referred because of an abnormal cytology report (29.4%) was considerably higher than the percentage reported in Israeli Jewish women. Abnormal colposcopy patterns were seen in 9 polyps, and CIN was found in 6 of them. Despite the high frequency of abnormal cytologic smears, CIN 3 was detected in only 1 polyp (0.4 %). In none of the polyps was malignancy found. CONCLUSIONS: : The very low frequency of neoplasia in cervical polyps of asymptomatic patients seems to support the notion that there is no clear indication for polypectomy when cytology is normal.

Selected clinical characteristics of Israeli Jewish women with squamous cell carcinoma of the uterine cervix: a population-based study.

BACKGROUND: The age-standardized incidence rate of invasive cervical cancer in Israeli Jewish women is persistently low. Selected demographic characteristics of Israeli Jewish women with cervical squamous cell carcinoma (SCC) were reported recently. OBJECTIVES: To assess selected clinical characteristics of Israeli Jewish women with cervical SCC. METHODS: Included were all Israeli Jewish women with SCC diagnosed during the 3-year period 2002-2004. Data were obtained from the Israel National Cancer Registry and the Central Population Registry. Discharge summaries of the patients were reviewed and clinical data were abstracted. RESULTS: The study was based on 350 israeli Jewish women with histologically confirmed cervical SCC diagnosed during the 3-year study period. The median age of the patients was 50.3 years. The most common main complaint was discharge/bleeding (35.7%) and only a small percentage (7.4%) was diagnosed subsequent to an abnormal cytological smear. The rate of patients diagnosed in stage I was 47.7%. The overall absolute 5-year survival and survival in stage I rates were 70% and 83.8% respectively. The rate of Israeli born patients diagnosed in stage I and their overall absolute 5-year survival was significantly higher than in the other ethnic groups. CONCLUSIONS: Age, the most frequent main complaint, the percent of patients diagnosed in stage I and the 5-year survival (overall and in stage I) are similar to data in other countries. The survival rate of Israeli born women seems to be better than that of other ethnic groups.

Selected demographic characteristics of Israeli Jewish women with high-grade cervical intraepithelial neoplasia (CIN3): a population-based study.

PURPOSE: A population-based study of cervical intraepithelial neoplasia grade 3 (CIN3) has hitherto not been performed in Israel. The aim of the present study was to assess selected demographic characteristics of Israeli Jewish CIN3 patients in an attempt to identify the risk factors in this population. METHODS: All CIN3 patients diagnosed during 2002-2004 according to the Israel National Cancer Registry were included. Demographic and population data were obtained from the Central Population Registry and from the Israel Central Bureau of Statistics annual abstract reports. The age-standardized incidence rate (ASR) and rate ratios (RR) for each demographic category were calculated. RESULTS: The study comprised 1,108 CIN3 patients (mean age 38.4 years) yielding an ASR of 13.9/100.000. A significantly greater number of CIN3 in the 30-39-year (RR = 2.16) and 40-49-year (RR = 1.74) age groups were observed. The overall rate of single and married women was similar, that in widowed women significantly lower and divorced women significantly higher (RR = 2.37) than in the general population. The mean number of children was 1.7. The rate of patients with 5 + children was significantly higher only in the 30-39-year age group. RR varied with age within each demographic category. The rate of Israeli born was higher and that of other ethnic origins was similar to the population rates. No association between CIN3 and socioeconomic status was found. CONCLUSION: Greater CIN3 rates were observed in women of 30-49 years, divorced women and Israeli-born women. Great differences in RR between age groups within the demographic categories were observed.