Diagnostic hysteroscopy and risk of peritoneal dissemination of tumor cells

Questions have been raised about the safety of diagnostic hysteroscopy preceding surgical treatment of endometrial carcinoma. Several studies showed that the risk of a positive cytology among patients presenting endometrial adenocarcinoma was increased after diagnostic hysteroscopy, suggesting a peritoneal dissemination of tumor cells due to the exploration. We studied this hypothesis on the basis of a systematic review of the scientific data. Five studies fulfilling inclusion criteria have been selected and have been introduced into a fixed model of meta-analysis. On a total of 756 studied patients, 79 presented a positive peritoneal cytology. The diagnostic hysteroscopy did not increase significantly the risk of abdominal dissemination of tumor cells, the peritoneal cytology being positive among 38 patients in the group having undergone this intervention vs 41 patients in the control group (OR = 1,64; 95% CI: 0,96-2,80). In conclusion, no formal evidence is currently available concerning the role of diagnostic hysteroscopy on the frequency of peritoneal dissemination of tumor cells, or on the vital prognosis of the patients presenting with endometrial carcinoma. From the data available, there is not any reason to avoid diagnostic hysteroscopy in the initial workup of endometrial cancer.     

Positive peritoneal cytology in endometrial cancer: enhancement of other prognostic indicators

OBJECTIVE: The goal of this study was to investigate the prognostic significance of positive peritoneal cytology in endometrial cancer. METHODS: A clinicocytopathological study was performed in 534 patients with endometrial cancer to assess the prognostic value of positive peritoneal cytology. The study population was divided into three groups: a low-risk group (disease limited to the uterus, grade 1, and depth of invasion < or =1/2), a moderate-risk group (disease limited to the uterus, grade 2 or 3, and/or depth of invasion >1/2), and a high-risk group (extrauterine disease). In each group, disease-free survival was compared in the patients who were positive or negative for malignant cells. RESULTS: The overall incidence of positive peritoneal cytology was 22.3% (119/534). The 5-year disease-free survival of patients positive or negative for malignant cells was 98.1% versus 100% in the low-risk group (n = 250), 77.5% versus 91.3% in the moderate-risk group (n = 211), and 42.9% versus 72.1% in the high-risk group (n = 73). A significant difference was noted in the moderate-risk (P = 0.044) and high-risk (P = 0.015) groups, but not in the low-risk group (P = 0.56). CONCLUSIONS: Positive peritoneal cytology is not a negative prognostic indicator itself, but it potentiates other prognostic indicators for endometrial cancer. Our findings also suggest that patients with positive peritoneal cytology in the absence of other adverse prognostic factors do not need upstaging.     

宫腔镜检查对Ⅱ型子宫内膜癌患者腹腔细胞学结果及预后的影响

目的:研究宫腔镜检查对Ⅱ型子宫内膜癌患者腹腔细胞学结果及预后的影响,探讨其用于Ⅱ型子宫内膜癌术前诊断的安全性。方法:回顾分析2001年6月至2010年6月在我院接受手术治疗且术后确诊为Ⅱ型子宫内膜癌的84例患者的临床病理资料。根据其术前诊断方式,分为宫腔镜检查组(32例)和传统诊刮组(52例)。比较两组患者的临床病理特点和腹腔细胞学检查阳性率,评价宫腔镜检查对Ⅱ型子宫内膜癌癌细胞腹腔播散的影响;分析术前不同诊断方式对Ⅱ型子宫内膜癌患者预后的影响。结果:两组患者的年龄、病理类型、临床分期、肌层浸润、累及附件及淋巴转移及治疗方式等比较,差异均无统计学意义(P0.05)。宫腔镜诊刮组与传统诊刮组的腹水细胞学检查阳性率分别为37.5%(12/32)和17.3%(9/52),差异有统计学意义(χ~2=4.308,P=0.036)。宫腔镜检查组与传统诊刮组患者的5年总生存率(OS)分别为56.8%和69.2%,5年无进展生存率(PFS)分别为50.7%和67.9%;两组患者的总生存率曲线和无进展生存曲线分别比较,差异均无统计学意义(P=0.329;P=0.424)。结论:宫腔镜检查用于Ⅱ型子宫内膜癌的诊断,可增加癌细胞腹腔播散的风险,但对其长期生存可能无影响。     

Impact of hysteroscopy on disease-free survival in clinically stage I endometrial cancer patients

Abstract. Obermair A, Geramou M, Gücer F, Denison U, Graf AH, Kapshammer E, Medl M, Rosen A, Wierrani F, Neunteufel W, Frech I, Preyer O, Speiser P, Kainz C. Impact of hysteroscopy on disease-free survival in clinically stage I endometrial cancer patients.
Recent data strongly suggest tumor cell dissemination of endometrial carcinoma cells in the course of fluid hysteroscopy. In patients who had endometrial cancer which was (except for peritoneal cytology) confined to the uterus, the disease-free survival (DFS) of 135 patients who underwent hysteroscopy prior to staging laparotomy was compared with the DFS of 127 patients without hysteroscopy. After a median follow-up of 23 months, 10 patients experienced tumor recurrence. Although there was a trend towards a higher incidence of positive peritoneal cytology at laparotomy in patients who underwent hysteroscopy, this difference did not achieve statistical significance ( P = 0.47). For 5 years, the DFS was 92.4% in patients with hysteroscopy and 84.7% in patients without hysteroscopy before laparotomy (log-rank, P = 0.782). Our data therefore suggest a similar short-term DFS in endometrial cancer patients with and without hysteroscopy prior to laparotomy.     

The prognostic significance of positive peritoneal cytology and adnexal/serosal metastasis in stage IIIA endometrial cancer

OBJECTIVE: The clinical significance and optimal management of patients with stage IIIA endometrial cancer are controversial. We sought to determine whether recurrence and survival of patients with stage IIIA endometrial cancer differ with surgical pathologic findings (positive peritoneal cytology versus positive adnexae or serosa) and adjuvant treatment. METHODS: Retrospective single institution analysis of patients surgically staged for IIIA endometrial cancer at Duke University Medical Center from 1973 to 2002. Stage IIIA patients were stratified into positive cytology alone (group IIIA1, n=37) and positive adnexae or uterine serosa (group IIIA2, n=20). Comparison was made with previously reported group of 467 patients with surgical stage I/II disease. Recurrence and survival were analyzed using Kaplan-Meier estimations and Cox proportional hazards model. RESULTS: Mean age of 57 patients with stage IIIA endometrial cancer was 63. Adjuvant therapies were administered to 89% patients (74% radiotherapy, 4% chemotherapy, 19% progestins). Five-year overall (OS) and recurrence-free disease-specific survival (RFDSS) were 64% and 76%, respectively. Survival was similar comparing IIIA1 (62%) and IIIA2 (68%, p=0.999). RFDSS by adjuvant therapy was: external beam radiotherapy 89% (n=10), intraperitoneal P32 84% (n=21), progestins 78% (n=9), none 75% (n=6). 61% recurrences included extrapelvic component. In multivariable analysis of stage I-IIIA patients (n=517), positive cytology but not adnexal/serosal metastasis was predictive of death (HR 1.70, 95% CI 1.06-2.73) and disease recurrence (HR 1.70, 95% CI 1.07-2.71). CONCLUSION: Among patients with stage IIIA endometrial cancer, metastasis to adnexae or serosa does not appear to confer worse prognosis than positive cytology alone. Positive cytology is an independent predictor of prognosis among patients with stage I-IIIA endometrial cancer. While optimal adjuvant therapy for these groups remains unclear, recurrence patterns suggest that systemic therapies are appropriate.     

宫腔镜手术中子宫内膜细胞腹腔播散的研究

目的 探讨宫腔镜手术中子宫内膜细胞腹腔播散的特点及其影响因素.方法 收集121例行宫腹腔镜联合手术的患者宫腔镜手术前后腹腔冲洗液,进行离心与细胞固定,分别在显微镜下观察腹腔冲洗液中细胞种类的变化及子宫内膜细胞阳性率的差异,根据宫腔镜手术后腹腔冲洗液中是否存在子宫内膜细胞分为阳性组和阴性组,比较两组的宫腔镜手术时间、膨宫压力、灌流液用量和子宫内膜状态等因素对子宫内膜细胞腹腔播散的影响.结果 宫腔镜手术后,腹腔冲洗液中子宫内膜细胞阳性者62例(51.2%,62/121),术前腹腔冲洗液子宫内膜细胞阳性者46例(38.0%,46/121),两者比较,差异有统计学意义(P=0.020);阳性组平均手术时间为(38±16)min,阴性组为(27±13)min,两组比较,差异有统计学意义(P=0.003);两组患者术中灌流液用量、膨宫压力、子宫内膜状态等比较,差异均无统计学意义(P＞0.05).结论 宫腔镜手术能够造成子宫内膜细胞的腹腔播散;在设定膨宫压力下,子宫内膜细胞的腹腔播散与宫腔镜手术时间有关.     

Hysteroscopic dissemination of endometrial carcinoma using carbon dioxide and normal saline: a retrospective study

OBJECTIVE: The aim of this study was to compare the likelihood of disseminating endometrial carcinoma cells into the peritoneal cavity by hysteroscopic examination using carbon dioxide (CO(2)) or normal saline (NS) as the distension medium. METHODS: A retrospective study of 162 consecutive patients with endometrial carcinoma treated at a university teaching hospital from 1994 to 1999 was undertaken. All patients had a hysteroscopic examination, using either CO(2) or NS as the distension medium, as part of the investigation for abnormal uterine bleeding or in determining whether the uterine cervix was invaded by tumor. Peritoneal fluid for cytology was collected immediately upon entry into the abdominal cavity. Positive peritoneal cytology was considered the primary statistical endpoint. RESULTS: Among 162 patients, 39 cases were excluded from the study because of macroscopic intraperitoneal diseases (n = 32) or pathology other than endometrioid adenocarcinoma (n = 7). Another 3 cases were excluded because both distension mediums had been used in the hysteroscopy. Analysis was therefore based on the data of 120 patients. There was no statistically significant difference between the two groups of patients undergoing hysteroscopy using either CO(2) (n = 70) or NS (n = 50) with regard to age, pathologic stage, International Federation of Gynecology and Obstetrics grading, myometrial invasion, tumor size, cervical involvement, nodal involvement, and 2-year progression-free survival. However, there was a mean of 13.0 plus minus 5.0 days (range 3-21 days) time gap between laparotomy for definitive surgery and CO(2) hysteroscopy compared to immediate laparotomy after NS hysteroscopy (P < 0.001). Positive peritoneal cytology was noticed in 8 (6.7%) patients of which 7 were in the NS group and 1 was in the CO(2) group. Positive cytology was significantly more common among patients after hysteroscopy using NS than CO(2) (14.0% versus 1.4%, odds ratio = 11.2, 95% confidence interval = 1.3-94.5, P = 0.009). The presence of positive peritoneal cytology was not associated with age, tumor grade, tumor size, myometrial invasion, cervical involvement, or nodal metastasis. All 8 patients with positive cytology received no additional treatment and are disease free at 12 to 34 months of follow-up. CONCLUSIONS: Our data suggested that endometrial malignant cells were introduced into the peritoneal cavity during hysteroscopy and might be more likely after the use of NS rather than CO(2). This report emphasizes the need for prospective evaluation for further clarification of this hypothesis. The clinical significance of the dissemination awaits the long-term follow-up of these patients.     

宫腔镜检查诊断子宫内膜癌的价值及与腹腔冲洗液阳性的关系探讨

目的:探讨宫腔镜检查对子宫内膜癌的诊断价值,以及是否增加腹腔冲洗液细胞学阳性率。方法:回顾性分析在本院行手术治疗后病理检查确诊为子宫内膜癌患者113例的临床资料,其中术前行单纯分段诊断性刮宫71例(分段诊刮组),行宫腔镜检查后再行分段诊刮42例(宫腔镜组)。比较两组手术前后的诊断、组织学分级、组织学类型符合率,腹腔冲洗液细胞学的阳性率,并同时分析组织学类型、组织学分级、肌层浸润深度、病灶分布、附件转移等与腹腔冲洗液细胞学的关系。结果:宫腔镜组42例患者,病理诊断符合率97.62%(41/42),高于分段诊刮组的病理诊断符合率83.10%(59/71),差异有统计学意义(P<0.05)。宫腔镜组腹腔冲洗液阳性率28.57%(12/42),高于分段诊刮组的阳性率25.35%(18/71),但两组比较差异无统计学意义(P>0.05)。113例子宫内膜癌患者腹腔冲洗液阳性与宫腔病灶范围大小有关(P<0.05),与附件转移、子宫肌层浸润深度、组织学类型、组织学分级无关(P>0.05)。结论:宫腔镜检查诊断子宫内膜癌准确性优于单纯分段诊刮,并且不增加腹腔冲洗液阳性率。腹腔冲洗液阳性率与宫腔病灶范围大小有关。     

宫腔镜辅助下分段诊断性刮宫术在诊断子宫内膜癌中的应用

目的 探讨宫腔镜辅助下分段诊断性刮宫（诊刮）术诊断子宫内膜癌的临床应用价值。方法 子宫内膜癌患者156例,分为单纯分段诊刮（A）组93例,及宫腔镜辅助下的分段诊刮（B）组63例,比较两组术前诊断子宫内膜癌的准确率。结果 A组手术病理分期与临床分期相比,期别提高的百分率为34％（31／92）,期别降低的百分率为15％（14／92）,对宫颈受累估计的准确率为75％（68／91）,腹腔洗液细胞学阳性率为32％（23／71）;B组分别为43％（27／63）,3％（2／63）,90％（56／62）和35％（18／51）。两组间手术病理分期与临床发期相比期别提高的百分率及腹腔洗液细胞学阳性率比较,差异无显著性（P＞0．05）;而两组间手术病理分期与临床发期相比期别降低的百分率及对宫颈受累估计的准确率比较,差异有显著性（P＜0．05）。结论 宫腔镜以确切了解子宫内膜癌患者宫颈受累情况,提高了在其辅助下分段诊辞术前诊断子宫内膜的准确率,且不增加患者腹腔洗液细胞学检查的阳性率。     

Does diagnostic hysteroscopy in patients with stage I endometrial carcinoma cause positive peritoneal washings?

OBJECTIVES: Previous studies have shown that positive peritoneal washings may adversely affect cancer survival rates and that hysteroscopy is associated with a higher risk of positive washings in patients with endometrial carcinoma. Our aim was to assess if diagnostic hysteroscopy increases the risk of positive peritoneal washings in patients with endometrial cancer and affects the prognosis after surgery. STUDY DESIGN: Retrospective cohort study. The medical records of 50 consecutive patients with endometrial carcinoma, diagnosed with hysteroscopy and tissue sampling and treated by abdominal hysterectomy with bilateral salpingo-oophorectomy and peritoneal washings were reviewed. RESULTS: Of the 43 patients with endometrial carcinoma FIGO stage I, none had positive peritoneal washings (95%CI: 0-8.2%). The mean interval between hysteroscopy and surgery was 33.5 days. The 5-year disease-specific survival rate was 91.8%, the 5-year recurrence-free survival rate was 85.4%. CONCLUSIONS: Diagnostic hysteroscopy had no adverse effect on the incidence of positive peritoneal washings or on prognosis in stage I endometrial cancer patients.     

Lymphotoxin-alpha polymorphisms and the risk of endometrial cancer in Japanese subjects

OBJECTIVE: To test the association of endometrial cancer with the lymphotoxin-alpha (LTalpha) C804A and A252G polymorphisms, a hospital-based incident case-control study was performed in Japanese subjects. METHODS: The cases comprised 110 endometrial cancer patients, and the controls were 220 age-matched cancer-free females. RESULTS: The LTalpha C804A and A252G polymorphisms were in complete linkage disequilibrium. We performed conditional logistic regression analysis adjusted for age, which revealed that the LTalpha 252AG and 804CA variant genotypes were associated with a significantly reduced risk of endometrial cancer (OR=0.51, 95% CI=0.31-0.86, P=0.011). Being homozygous of the LTalpha 252G and 804A alleles was not associated with the risk of endometrial cancer. However, the presence of at least one variant LTalpha allele was associated with a significantly lower risk of endometrial cancer (OR=0.54, 95% CI=0.33-0.87, P=0.012). After adjusting for potential confounders (body mass index, age at menarche, parity, hypertension, diabetes mellitus, family history of endometrial cancer, hormone replacement therapy, smoking status, and alcohol consumption), the risk of endometrial cancer was significantly lower both in carriers of one variant allele and in carriers of either one or two of the variant alleles (OR=0.47, 95% CI=0.26-0.85, P=0.017; OR=0.50, 95% CI=0.28-0.89, P=0.019; respectively). CONCLUSION: The results suggest that these LTalpha polymorphisms play an important role in the tumorigenesis of endometrial cancer.     

The prognostic significance of peritoneal cytology for stage I endometrial cancer

A retrospective study of 567 patients treated for surgical stage I endometrial cancer was undertaken to resolve the controversy over the significance of malignant peritoneal cytology findings in early-stage disease. Twenty-eight women (4.9%) had peritoneal cytology positive for malignant cells. Comparisons were made between the groups with positive and negative cytology. Subgroups used in analysis included stage according to the International Federation of Gynecology and Obstetrics, treatment regimen, histology, grade, depth of myometrial invasion, and cervical Papanicolaou smear results. Cervical smear status was the only subgroup in which a statistically significant difference was found, with the positive peritoneal cytology patients having a higher incidence of positive Papanicolaou smears (P = .01). Forty-nine women (8.6%) developed recurrent tumor, 7% of the negative-cytology group and 32% of the positive-cytology group (P = .0002). The progression-free survival rate was lowered significantly by positive peritoneal cytology (P less than .0001); patients with negative peritoneal cytology had a significantly better 5-year survival rate, 96 versus 84% (P = .0001). When multivariate analysis was performed on the 477 cases that had no missing values, peritoneal cytology remained significant for both survival rate (P = .01) and progression-free interval (P = .002). Positive peritoneal cytology is a poor prognostic factor for patients with surgical stage I endometrial cancer.     

Prospective self-controlled study on prevention of hysteroscopic dissemination in endometrial carcinoma

Patients diagnosed to have endometrial carcinoma without prior hysteroscopic examination were recruited from March 2000 to August 2003. Normal saline was used to distend the uterine cavity during the hysteroscopic examination to look for endocervical spread before the definitive surgical treatment. We performed laparotomy, clamped both fallopian tubes, and collected peritoneal washing before the hysteroscopic examination was performed. Peritoneal washing was collected once more after the hysteroscopic examination. Hysteroscopic assessment was performed in 103 patients. Of them, 10 patients were excluded from the study due to previous history of tubal sterilization or blockage. The final analysis was confined to 93 patients. Positive peritoneal cytology was found in 10 (10.8%) patients and this finding was significantly related to the tumor grading (P = 0.023), adnexal involvement (P = 0.003), cervical invasion (P = 0.01), and the presence of peritoneal seedlings (P = 0.001). In five of the 10 patients with positive peritoneal cytology before the hysteroscopic examination, malignant cells could also be recovered in the peritoneal washing collected after the hysteroscopic examination. For patients with negative peritoneal cytology before hysteroscopy, none exhibited positive peritoneal cytology after the procedure. Our data suggested that complete occlusion of both fallopian tubes can effectively prevent the dissemination of endometrial malignant cells into the peritoneal cavity during hysteroscopy.     

子宫内膜癌患者腹腔细胞学阳性的临床意义及对预后的影响

目的 探讨子宫内膜癌患者腹腔细胞学阳性的临床意义及对预后的影响.方法 对1996年1月至2008年12月复旦大学附属肿瘤医院收治的315例子宫内膜癌患者的临床病理资料进行回顾性分析,所有患者均行手术治疗,且均行术中腹水或腹腔冲洗液细胞学检查.对与腹腔细胞学阳性相关的因素,采用相关分析法进行分析;对影响子宫内膜癌患者预后的因素,采用log-rank检验进行单因素分析,采用Cox回归法进行多因素分析.结果 (1)315例子宫内膜癌患者中,30例(9.5%)患者腹腔细胞学阳性.腹腔细胞学阳性与多个子官内高危因素包括病理类型(P=0.013)、手术病理分期(P=0.000)、肌层浸润(P=0.012)、脉管浸润(P=0.012),以及多个子宫外转移危险因素包括子宫浆膜层侵犯(P=0.004)、宫颈受累(P=0.016)、附件转移(P=0.000)和大网膜转移(P=0.000)明显相关,而与病理分级(P=0.152)、淋巴结转移(P=0.066)无明显相关性.(2)315例子宫内膜癌患者的3年总生存率和3年无疾病进展生存率分别为93.0%和85.5%.单因素分析显示,腹腔细胞学阳性及不同手术病理分期、病理类型、肌层浸润深度、病理分级和脉管浸润是影响子宫内膜癌患者预后的危险因素(P＜0.05);多因素分析显示,手术病理分期、肌层浸润深度是影响子宫内膜癌患者预后的独立危险因素(P＜0.05).30例腹腔细胞学阳性患者中,无高危因素患者的3年生存率和3年无疾病进展生存率均显著高于有高危因素者(P＜0.05);进一步分析显示,腹腔细胞学阳性是影响晚期(Ⅲ～Ⅳ期)子官内膜癌患者预后的独立危险因素(P=0.006).结论 腹腔细胞学阳性与多个子宫内高危因素和子宫外转移危险因素密切相关,是影响晚期子宫内膜癌患者预后的独立危险因素.因此,腹水细胞学检查应继续作为全面分期手术的步骤之一,并将结果单独进行报告,是十分有必要的.

Abstract：

Objective To evaluate the clinical significance of positive peritoneal cytology in patients with endometrial cancer.Methods The records of 315 patients with endometrial cancer who were operated at Cancer Hospital, Fudan University between January 1996 and December 2008 were reviewed.Peritoneal cytology were performed and diagnosed in all patients.Factors related with peritoneal cytology were analyzed by correlation analysis.Log-rank test and Cox regression test was used for the analysis of prognosis,respectively.Results (1) Peritoneal cytology were positive in 30 (9.5%) patients.Positive peritoneal cytology was associated with pathological subtype ( P = 0.013 ), stage ( P = 0.000 ), myometrial invasion ( P =0.012), lymph-vascular space invasion ( P = 0.012 ), serosal involvement ( P = 0.004 ), cervical involvement ( P = 0.016), adnexal involvement ( P = 0.000), and omental involvement ( P = 0.000), with no association with grade ( P = 0.152 ) and lymph node metastasis ( P = 0.066 ).( 2 ) Three-year overall survival (OS) and progression-free survival(PFS) were 93.0% and 85.5% ,respectively.Positive peritoneal cytology, surgical stage, pathological subtype, myometrial invasion, grade, and lymph-vascular space invasion were significantly associated with worse prognosis by univariate analysis ( P ＜ 0.05 ), while only surgical-pathology stage and myometrial invasion were independent prognostic factors by multivariate analysis ( P ＜ 0.05 ).For 30 cases with positive peritoneal cytology, the patients with no high risk factors shown significantly prognoses better than those with any risk factors.The results shown that for patients with late stage (stage Ⅲ - Ⅳ ) endometrial cancer with positive peritoneal cytology was significantly associated with the worse OS and PFS by multivariate analysis ( P = 0.006).Conclusions Positive peritoneal cytology was associated with serosal involvement, cervical involvement, adnexal involvement, omental involvement, and late stage.Therefore, peritoneal cytology should be performed and reported separately as a part of full surgical staging procedure.     

Diagnosis of endometrial cancer by hysteroscopy does not increase the risk for microscopic extrauterine spread in early-stage disease

The purpose of this study was to determine whether women with endometrial cancer have a higher incidence of microscopic extrauterine spread in early-stage disease when diagnosed by hysteroscopy compared with being diagnosed by dilatation and curettage (D&C) or endometrial biopsy (Pipelle). We retrospectively reviewed the medical records of 110 patients who had undergone surgical staging for endometrial cancer from January 1997 to December 2003. They all had a preoperative histological diagnosis of endometrial carcinoma without evidence of extrauterine disease. Diagnosis was made by hysteroscopy in 64 patients (58.2%), by D&C in 17 (15.5%), and by endometrial biopsy using a Pipelle device in 29 (26.3%). The groups were compared for known prognostic factors for microscopic extrauterine spread, including age, grade, stage, and vascular space involvement, and did not differ in these parameters. Microscopic intraperitoneal disease and positive peritoneal cytology were considered the primary endpoints of this analysis. Peritoneal cytology was positive in three of 110 (2.7%) patients. The presence of positive peritoneal cytology was not associated with hysteroscopy as the diagnostic procedure. We conclude that diagnosis of endometrial cancer by hysteroscopy does not increase the risk of microscopic intraperitoneal spread compared with diagnosis by D&C or endometrial biopsy (Pipelle).     

The value of preoperative platelet count in the prediction of cervical involvement and poor prognostic variables in patients with endometrial carcinoma

OBJECTIVE(S): To evaluate the relationship between preoperative platelet counts and prognostic factors extensively, among endometrial cancer patients, especially with respect to cervical involvement. METHODS: One-hundred fifty-five patients with endometrial carcinoma, who underwent surgery as the initial treatment consisting peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, systematic pelvic-paraaortic lymphadenectomy, and omentectomy were retrospectively analyzed. RESULTS: There were no differences with respect to age, histological type (endometrioid vs. non-endometrioid), depth of myometrial invasion, peritoneal cytology, LVSI, and lymphatic metastasis. However, advanced stage (stages III and IV), poorly differentiated tumor grade (grade 3), the presence of cervical and adnexal involvements were associated with significantly higher median preoperative platelet counts. Accepting 325.000/microl platelet count as a threshold value, multivariate analysis revealed cervical involvement (P=0.008; OR=1.84, 95% CI:1.17-2.89) and presence of high grade histology (P=0.014; OR=2.23, 95% CI:1.18-4.23, for grade 3 disease) to be significantly associated with higher platelet count. At a cut-off value of 326.000/microl, 42.3% sensitivity and 82.8% specificity for the prediction of cervical involvement was observed under receiver operator characteristic curve method. CONCLUSION(S): Higher preoperative platelet counts, even in conditions with normal range (150.000-400.000/microl), may reflect poor prognostic factors such as cervical involvement and high grade among patients with endometrial carcinoma. Also, the higher platelet count should be taken into consideration for the necessity of radical hysterectomy.     

Office hysteroscopy and the risk of microscopic extrauterine spread in endometrial cancer

OBJECTIVE: The aim of this study was to evaluate the incidence of tumor cell dissemination according to diagnostic modality in patients with endometrial cancer. METHODS: A retrospective study was conducted on 146 patients with endometrial cancer in whom one of the following diagnostic methods was performed: dilation and curettage (D&C, n=122) or office hysteroscopy (HSC, n=24). No selection or randomization of patients was applied to the groups. The presence of suspicious or positive peritoneal cytology as well as adnexal or abdominal metastases was considered the endpoint of this analysis. RESULTS: Suspicious or positive peritoneal cytology was present in two patients (1.6%) after D&C and in three patients (12.5%) after HSC (chi2=4.2455; p<0.05). Adnexal metastases were present in 10 (8.2%) patients after D&C and in 1 patient (4.2%) after HSC (chi2=0.0680; p>0.05). Metastases to abdominal cavity were found in 3 (2.5%) patients after D&C and in 1 patient after HSC (chi2=0.0464; p>0.05). Lymph node metastases were found in 7 patients (5.7%) after D&C and in 2 patients (8.3%) after HSC (chi2=0.0004; p>0.05). After complete histopathological analysis, upstaging due to positive peritoneal cytology and adnexal or abdominal metastases was necessary in 11 patients (9.0%) from the D&C group and in 3 patients (12.5%) from the HSC group, but the difference was not significant (chi2=0.2227; p>0.05). CONCLUSIONS: These data show that diagnostic HSC significantly increases the risk of positive peritoneal cytology, but not the risk of adnexal, abdominal or retroperitoneal lymph node metastases in patients with EC.     

Does fluid hysteroscopy increase the stage or worsen the prognosis in patients with endometrial cancer? A randomized controlled trial

OBJECTIVE: To determine whether fluid hysteroscopic directed biopsies, in patients with endometrial cancer upstages the tumor and worsens the prognosis. STUDY DESIGN: Between January 1996 and September 2001, a total of 62 consecutive patients with endometrial cancer, treated at our institution, were randomized 3:2 to have or not to have a fluid hysteroscopic biopsy just prior to surgery. A total of 38 patients underwent a hysteroscopy after the induction of anesthesia. All patients had pelvic washings performed, followed by a hysterectomy, bilateral salpingooforectomy and pelvic +/- para-aortic lymph node dissections. Only stages I and II endometrioid type tumors or stage IIIa, secondary to positive pelvic washings, were included in the study. Eight patients in the hysteroscopy group and four patients in the control group were excluded for various reasons. Patients received post-operative radiation therapy depending on the surgical-pathological risk factors. The median follow up was 34 months. Fisher's Exact Test was performed to compare differences between the hysteroscopic (n = 30) and the control (n = 20) groups. RESULTS: We found three patients (10%) with positive washings in the hysteroscopic group compared to one (5%) among the controls (P = 0.64), with a statistical power of <20%. If the differences would persist, we would need 588 patients in each arm to obtain a power of 80%, and reach definitive conclusions. The Odds Ratio (OR) of performing a hysteroscopy and upstaging the tumor in this study was: 2.1 95% CI (0.20-21.09). Prognostic variables were compared between both groups and no differences were observed. All patients but one (dead due to intercurrent disease), were alive and with no evidence of disease at the completion of the study. CONCLUSIONS: Fluid hysteroscopy and directed biopsies may have a small risk of upstaging early endometrial cancers, but does not seem to influence prognosis.     

High incidence of positive peritoneal cytology in low-risk endometrial cancer treated by laparoscopically assisted vaginal hysterectomy

OBJECTIVE: Laparoscopically assisted vaginal hysterectomy (LAVH) has evolved into an alternative form of surgical management in the treatment of low-risk endometrial cancer. The purpose of this study was to determine whether low-risk endometrial cancer patients are subject to a higher incidence of positive peritoneal cytology when treated with LAVH compared to total abdominal hysterectomy (TAH). METHODS: We retrospectively reviewed the medical records of patients with low-risk endometrial cancer (grade 1--2 endometrioid type with no evidence of extrauterine spread or grade 3 with <50% myometrial invasion (MI), no cervical or adnexal involvement, and negative lymph nodes when sampled) treated at Memorial Sloan-Kettering Cancer Center from January 1993 to September 1999. We compared 131 patients treated with LAVH to 246 controls who underwent TAH. The two groups were compared for known prognostic factors including grade, MI, vascular space involvement, and lower uterine segment extension. RESULTS: The mean age of patients who underwent LAVH (61 years) was similar to that of the controls (62 years). Fourteen (10.3%) of the patients treated with LAVH had positive peritoneal cytology compared to only 7 (2.8%) of the control population. Factors including FIGO grade, myometrial invasion, and preoperative hysteroscopy did not influence the final results. When stratifying for these factors, the odds ratios of having positive peritoneal washings in those patients treated by LAVH were 5.2, 5.2, and 3.7, respectively. CONCLUSION: Treatment of low-risk endometrial cancer by LAVH is associated with a significantly higher incidence of positive peritoneal cytology. This may be due to the retrograde dissemination of cancer cells into the peritoneal cavity during uterine manipulation. The clinical significance of these findings is yet to be determined.     

Hysteroscopic Morcellation in Endometrial Cancer Diagnosis: Increased Risk?

Study ObjectiveOperative hysteroscopy requires elevated intrauterine pressures, which could lead to the spread of malignant cells into the peritoneal cavity. Currently, there is a paucity of data analyzing clinical outcomes in endometrial cancer after hysteroscopic morcellation with newer equipment. In this study, we sought to determine whether there are increased rates of positive peritoneal cytology, lymphovascular space invasion, or surgical upstaging in patients undergoing hysteroscopic morcellation compared with alternative endometrial biopsy methods.DesignA retrospective chart review of patients from 2013–2018 was performed. The exclusion criteria included biopsy at outside institution, stage IV endometrial cancer known before biopsy, and missing data regarding biopsy method and histology. Peritoneal cytology results, lymphovascular space invasion, and surgical staging were compared by method of biopsy and histology using chi-square and Kruskal-Wallis tests.SettingThe patients included in this study were accrued from the Karmanos Cancer Insittute in Detroit, Michigan.PatientsA total of 289 patients met the inclusion criteria: 184 patients were classified as low-grade (Fédération Internationale de Gynécologie et d'Obstétrique grades 1 and 2) and 105 as high-grade (Fédération Internationale de Gynécologie et d'Obstétrique grade 3, serous, clear cell, and carcinosarcoma) endometrial cancer.InterventionsFifty-three patients (18%) underwent hysteroscopy with morcellation. Alternative biopsy methods included hysteroscopy without morcellation, n = 81 (28%); endometrial biopsy, n = 112 (38.7%); and dilation and curettage, n = 43 (15%).Measurements and Main ResultsPositive peritoneal cytology was noted in 34 cases (12%) and negative cytology in 165 (57%). Cytology was not performed in 90 cases (31%). When comparing outcomes by histologic subtypes, no difference was seen in peritoneal cytology (p = .704 and .727 for low grade and high grade, respectively), stage (p = .773 and .053 for low grade and high grade, respectively) or lymphovascular space invasion (p = .400 and .142 for low grade and high grade, respectively).ConclusionOur study demonstrates that hysteroscopy with morcellation is a safe diagnostic method for low- and high-grade endometrial pathologic conditions and does not lead to increased dissemination of malignant cells, lymphovascular space invasion, or upstaging of patients.