Endometrial cancer

Endometrial carcinoma is the most common gynaecological malignancy in the Western world. The standard management of endometrial carcinoma is total hysterectomy and bilateral salpingo-oophorectomy with or without pelvic and para-aortic lymph-node dissection. Increasingly, endometrial cancer is being diagnosed in younger women in whom preserving fertility may be an important consideration when deciding optimal management. Conservative management of endometrial carcinoma may be a therapeutic option in carefully selected women with well-differentiated endometrial cancer in the absence of any myometrial invasion or adnexal disease seen on imaging. The biggest concern with conservative management of endometrial carcinoma is disease progression while on treatment or after initial response to medical treatment. Women opting for conservative management should be aware that hormonal therapy is not the standard form of management. Potential adverse outcomes should be taken into consideration.     

Analysis of vaginal recurrences in stage I endometrial adenocarcinoma

OBJECTIVE: To determine the risk of vaginal recurrence in Stage 1 endometrial cancer and treatment morbidity associated with different therapeutic approaches MATERIAL AND METHODS: Between 1995 and 2005, 341 patients with clinical Stage I endometrial cancer were treated at Istanbul Medical Faculty. One hundred and forty-four women were included in this study as the follow-ups and records were complete. The patients with no myometrial invasion received no further therapy following hysterectomy. When there was superficial myometrial invasion postoperative vaginal vault radiation was used, and if deep myometrial invasion was present, external pelvic radiation was given. RESULTS: Overall 5-year survival rate for all patients with Stage I disease was 80%. Nine patients (6.25%) developed recurrent disease, three of whom had vaginal recurrences. All three vaginal recurrences were small and diagnosed at routine follow-up exam within 51 months of primary therapy. CONCLUSION: This selective treatment protocol for patients with Stage I endometrial cancer avoided radiation entirely in 38% of the patients while achieving a very low rate of vaginal recurrence and good overall survival.     

High-dose rate brachytherapy for Stage I/II papillary serous or clear cell endometrial cancer

OBJECTIVE: To determine the efficacy of high-dose rate brachytherapy as adjuvant treatment for Stage I/II papillary serous or clear cell endometrial cancer. METHODS: A retrospective study of all patients with Stage I/II papillary serous or clear cell endometrial cancer treated with high-dose rate brachytherapy between 1995 and 2001 was performed. Following surgical staging, which included hysterectomy with pelvic and aortic lymphadenectomy, all patients without extrauterine disease were treated with high-dose rate brachytherapy and followed for recurrence. The locations of recurrences were noted and were classified as local or distant. RESULTS: Three (13%) recurrences occurred among 24 patients with Stage I/II papillary serous or clear cell carcinoma. The risk of recurrence was similar for papillary serous and clear cell cancer (12% vs. 12%). Local control was achieved in 96%. The risk of recurrence for those with no myometrial invasion, less than 1/2, or more than 1/2 myometrial invasion was 0%, 10%, and 50%, respectively (P < 0.04). Two of the three recurrences were distant and all patients with recurrence died despite additional treatment. CONCLUSIONS: High-dose rate brachytherapy (HDR) as the sole adjuvant treatment of Stage I/II papillary serous or clear cell carcinoma is associated with a 13% risk of recurrence. Although local control with HDR is excellent, the risk of distant recurrence is increased with deep myometrial invasion. High-dose rate brachytherapy is adequate for Stage IA cases, but more aggressive treatment combining chemotherapy with HDR should be evaluated for more advanced Stage I/II cases.     

Microvessel density index as a prognostic factor in a low histological differentiation stage of endometrial carcinoma

OBJECTIVE: Angiogenesis in malignant tumors is a prognostic factor associated with tumor growth and metastasis. Studies of angiogenesis in breast, prostate and lung cancer showed that neovascularisation correlates with likelihood of metastasis and recurrence. Our study was to evaluate microvessel density as a prognostic factor in endometrial cancer. METHODS: Between 1995-1999, 58 women were treated for endometrial carcinoma. The primary treatment consisted of total abdominal hysterectomy, bilateral salpingoophorectomy and pelvic lymphadenectomy. The microscopic examination of paraffin blocks showed the areas of the deepest myometrial invasion. The microvessels within the invasive cancer were highlighted by means of immuno-cytochemical staining to detect CD-31 antigen. RESULTS: Microvessel count was related to likelihood of recurrence. We found statistically significant differences between patients who died after operation and patients with nonrecurrence process. All patients were in the same stage and grade of endometrial carcinoma. CONCLUSION: Microvessel density index seems to be an important factor for planing postoperation treatment in endometrial carcinoma.     

Prevention of vaginal recurrence of stage I endometrial adenocarcinoma with postoperative vaginal radiation

From 1975 to 1982 a prospective study was conducted at Roswell Park in 68 patients (group 1) for surgical stage I endometrial cancer, grade 1 or 2, and less than 50% myometrial invasion. These patients were treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal radium. With median follow-up of 4.8 years, there has not been a single vaginal recurrence. This treatment plan was based on a prospective study at the same institute from 1958 to 1967, which compared patients with stage I endometrial cancer treated by hysterectomy alone, preoperative radium followed by hysterectomy, and hysterectomy followed by postoperative radium. In addition, 19 patients (group 2) were evaluated as to their initial treatment after their referral to Roswell Park with vaginal recurrence after surgical treatment for stage I endometrial cancer. None of these patients were treated initially with postoperative vaginal radium after hysterectomy. Based on the zero incidence of vaginal recurrence in 117 patients with FIGO stage I endometrial cancer, the estimated five-year survival rate of 97.2% for the group 1 patients, and the actuarial five-year survival of 95% in the 1958 to 1967 prospective study, it is concluded that primary surgery should be followed by postoperative vaginal radium (cesium) in those patients with stage I endometrial cancer, grade 1 or 2, with less than 50% myometrial invasion.     

Endometrial carcinoma remaining after term pregnancy following conservative treatment with medroxyprogesterone acetate

BACKGROUND: Successful pregnancies after conservative progestin treatment to young women with endometrial carcinoma have recently been reported. However, it is not known for certain whether the lesion is completely eradicated in such patients. We present a case of residual endometrial carcinoma after term pregnancy which had been treated conservatively before the pregnancy began. CASE: A 28-year-old woman with endometrial carcinoma received conservative treatment with high-dose medroxyprogesterone acetate (MPA) and then conceived. After delivery at term, atypical cells were found in the endometrial curettage specimen. A hysterectomy was performed 6 months after delivery and revealed the presence of a small focus of intramucosal, grade 1, endometrioid-type adenocarcinoma. Immunohistochemically, the tumor cells were positive for estrogen and progesterone receptors. CONCLUSION: We concluded that while MPA treatment had been effective, it had not completely eradicated the carcinomatous lesion, which remained during and after the term pregnancy.     

Papillary serous adenocarcinoma of the endometrium: a clinicopathologic study of 19 cases.

Survival in 19 patients with papillary serous adenocarcinoma of the endometrium treated at the University of Vermont during the period 1960-1987 was significantly worse than that for 360 patients with other types of endometrial cancer. Deaths were associated with extrauterine spread and deep myometrial invasion detected at the time of surgery. Two patients without myometrial invasion and with extrauterine spread who also died may have developed synchronous peritoneal serous carcinoma.     

Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.     

Ovarian metastasis in a nulliparous woman with endometrial adenocarcinoma failing conservative hormonal treatment

BACKGROUND: There have been several reports about successful fertility-preserving treatment of endometrial carcinoma with subsequent pregnancy. However, conservative hormonal treatment for early-stage endometrial cancer still entails some risk. CASE: We present a 36-year-old nulliparous woman, initially diagnosed as clinical stage IA, grade 1 endometrial adenocarcinoma, receiving 6-month conservative treatment with remission achieved at 4 months from diagnosis. Recurrence at the endometrium was documented at the end of treatment. She underwent a definitive surgery including total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. The final pathology revealed well-differentiated endometrioid adenocarcinoma with inner one-third myometrial invasion and right ovarian metastasis. CONCLUSION: This case report signals a warning that negative preoperative imaging studies are not reassuring for a relapsing low-grade, early-stage endometrial carcinoma failing conservative treatment.     

Survival of women with surgical stage II endometrial cancer.

OBJECTIVE: The aim of this study was to report survival and determine prognostic factors and results of therapy in women with surgical stage II endometrial cancer. METHODS: Forty-eight consecutive women with surgical stage II endometrial cancer treated at the University of Vermont between March 1984 and March 1998 were reviewed. Patients' characteristics, surgical procedure, postoperative treatment and its complications, and tumor recurrence and its treatment were recorded. In addition, a formal review of their pathological material for confirmation of the diagnosis was performed. RESULTS: The median duration of follow-up was 6.2 years. Three patients (6.3%) had tumor recurrence and two (4.2%) died of their disease. The estimated 5-year overall survival and disease-free survivals were 92.1% (SE = 5.5%, 95% confidence interval: 81.3, 100%) and 89.9% (SE = 5.8%, 95% confidence interval: 78.5%, 100%), respectively. None of the patients treated by total abdominal hysterectomy followed by both whole pelvic and vaginal cuff radiation therapy (the main line of treatment for patients in whom cervical involvement was diagnosed following hysterectomy, n = 20) or by radical hysterectomy (the main line of treatment for patients in whom cervical involvement was known before hysterectomy, n = 11) had tumor recurrence. Three of 17 (17.6%) patients treated with total abdominal hysterectomy followed by either whole pelvic (n = 13) or vaginal cuff (n = 4) radiation therapy had tumor recurrence. The difference between those two groups was statistically significant (0/31 versus 3/17, P = 0.02). There was no difference in survival among women with stage IIA and IIB or women who underwent radical abdominal hysterectomy and those who underwent total abdominal hysterectomy with postoperative pelvic and vaginal cuff radiation. Morbidity secondary to therapy was mild. Age, depth of myometrial invasion, tumor histology, and grade were not significantly related to recurrence. CONCLUSIONS: Survival of women with surgical stage II endometrial cancer is excellent especially among those treated with total abdominal hysterectomy followed by both pelvic and vaginal cuff radiotherapy or by radical abdominal hysterectomy.     

晚期子宫内膜癌患者的治疗及预后分析

目的 探讨晚期(Ⅲ～Ⅳ期)子宫内膜癌的治疗方法及预后影响因素.方法 选择1996年1月至2006年12月间收治的晚期子宫内膜癌患者118例,对其治疗方法及预后影响因素进行回顾性分析,患者随访至2007年12月,平均随访26个月.结果 随访期内,共33例患者死亡,占28.0%;25例患者术后出现疾病进展,占21.2%.Ⅲ、Ⅳ期患者的3年总生存率分别为78.3%和39.4%,子宫内膜样腺癌和非子宫内膜样腺癌患者的3年总生存率分别为69.3%和42.0%,分别比较,差异均有统计学意义(P<0.05).4例仅有腹水细胞学检查阳性的Ⅲa期患者,术后未行辅助治疗,现已平均随访16个月均无瘤生存.单因素分析显示,手术病理分期、病理类型、肌层浸润深度、病理分级、后腹膜淋巴结切除术(包括盆腔淋巴结切除或加腹主动脉旁淋巴结切除术)和术后辅助联合放化疗与预后明显相关(P<0.05).多因素分析显示,手术病理分期和肌层浸润深度与预后明显相关(P<0.05).对不同治疗方式分析显示,行后腹膜淋巴结切除术患者的预后明显优于未行该手术者(P<0.05);术后残留灶直径≤1 cm患者的预后明显优于残留灶直径>1 cm者(P<0.05);术后行辅助联合放化疗患者的预后明显优于未行联合放化疗和仅行放疗或化疗者(P<0.05).结论 手术病理分期和肌层浸润深度是影响晚期子宫内膜癌患者预后的独立的危险因素.治疗应在满意的肿瘤细胞减灭术和后腹膜淋巴结切除术的基础上,除仪腹水细胞学检查阳性的Ⅲa期患者外,术后均应辅以联合放化疗,以改善患者的预后.     

The role of MRI in the conservative management of endometrial cancer

BACKGROUND: Young patients with endometrial cancer who desire to preserve their fertility often decline hysterectomy in favor of conservative progestin therapy. Proper candidates should have disease confined to the uterus and a well-differentiated tumor. One of the evolving techniques to evaluate the extent of the disease and myometrial or cervical invasion is magnetic resonance imaging (MRI). CASE: A young patient with early-stage endometrial cancer initially declined surgery and was treated with megestrol. MRI suggested myoinvasion, and the patient consented to surgical staging. The final pathology revealed no residual carcinoma. CONCLUSIONS: The accuracy of MRI in detecting myoinvasion is limited, and as such results should be interpreted with caution when this information is used in counseling a young patient regarding surgical staging for endometrial cancer.     

Endometrial carcinoma. Clinical and pathological correlations with survival and surgical treatment

From 1978 to 1985 a total of 151 patients were treated for endometrial carcinoma. Of these, 25 patients underwent extrafascial abdominal hysterectomy and pelvic lymphadenectomy, 25 were treated according to Wertheim procedure and pelvic lymphadenectomy and 32 underwent intrafascial abdominal hysterectomy; 62 women underwent vaginal surgery, 7 of whom according to Shauta. A correlation between the degree of myometrial invasion, histological grading, hystological type and stage of the tumor showed no statistically significant difference. The 5-year actuarial survival rate was found to be 76.5%. A comparison between survival and age of patients showed a significant difference in the survival (p less than .01) of the group less than 55 years as compared to the older age group. As far as the surgical treatment instituted is concerned, no statistical difference in survival was found between patients operated vaginally and those operated abdominally (p greater than .05). The site of recurrences were then analyzed in 22 patients, 50% were local recurrences, and the remaining distant metastases. Of these only one patient was cured and is still free of disease 5 years after recurrence. The criteria used to select patients for vaginal surgery are also indicated.     

Adjuvant radiation therapy is not necessary in the management of endometrial carcinoma stage I, low-risk cases

In an attempt to create uniform nationwide guidelines for the management of all stages of endometrial carcinoma, and to limit the use of adjuvant radiation therapy in stage I disease to high-risk patients only, a protocol was developed by the Danish Endometrial Cancer group (DEMCA). From September 1986 through August 1988, 1214 women in Denmark with newly diagnosed carcinoma of the endometrium have been treated according to this protocol. This figure represents all endometrial carcinomas diagnosed in Denmark during this 2-year period. The primary treatment was total abdominal hysterectomy and bilateral salpingo-oophorectomy and no preoperative radiation therapy was delivered. In 1039 cases no macroscopic residual tumor and/or microscopic tumor tissue in the resection margins was found following surgery. Based on surgery and histopathology, these patients were classified as: P-stage I low-risk (grade 1 & 2 and 50% myometrial invasion), P-stage I high-risk (grade 1 & 2 and> 50% myometrial invasion, and grade 3), P-stage II and P-stage III (Group 1). Distribution was as follows: P-I low-risk 641 patients, P-I high-risk 235, P-II 105 and P-III (Group 1) 58 patients. No postoperative radiation therapy was given to P-I low-risk cases. P-I high-risk, P-II, and P-III (Group 1) cases received external radiation therapy. Recurrence rate at 68–92 months follow-up was 45/641 (7%) in P-I low-risk, 36/235 (15%) in P-I high-risk, 30/105 (29%) in P-II, and 27/58 (47%) in P-III (Group 1) cases. Fifteen of 17 vaginal recurrences in P-I low-risk cases were salvaged (mean observation time 61 months).     

Concurrent endometrial carcinoma following hysterectomy for atypical endometrial hyperplasia

Objective

To evaluate the prevalence of concurrent endometrial carcinoma in women diagnosed with atypical endometrial hyperplasia (AEH) by endometrial biopsy.

Study design

We retrospectively analyzed the medical records of 126 patients who underwent hysterectomies for AEH diagnosed by endometrial biopsy from 1999 to 2008. AEH was initially diagnosed by dilatation and curettage (98 cases) or endometrial biopsy with a Z-sampler (24 cases). The remaining four cases were diagnosed by hysteroscopic polypectomy. The results of the endometrial biopsies were graded on an ordinal scale and were compared with pathologic features obtained at the hysterectomy.

Results

In patients preoperatively diagnosed with AEH by biopsy, hysterectomy specimens revealed a rate of simple or complex endometrial hyperplasia without atypia of 27% with AEH and normal proliferative phases found in 54.7 and 7.9% of specimens, respectively. The incidence of endometrial carcinoma was considerably high (13/126, 10.3%). Eleven of 13 cases were confined to the endometrium and the remaining two were located at the adenomyosis without myometrial invasion. All patients with endometrial carcinoma displayed coexisting atypical complex hyperplasia following hysterectomy.

Conclusions

Biopsy specimens showing AEH, particularly atypical complex hyperplasia, are associated with a risk of coexisting endometrial carcinoma. When considering management strategies for women with a biopsy diagnosis of AEH, clinicians should take into account the considerable rate of concurrent endometrial cancer and the discrepancy with pathologic diagnosis. Treatment modalities may differ depending on population as the rates of concurrent endometrial cancer with AEH and myometrial invasion vary by geographical location.     

早期子宫内膜癌保留生育功能的治疗

手术治疗仍是治疗子宫内膜癌（包括重度不典型增生）的标准方法。虽然可取得良好的治疗效果，但术后患者会丧失生育能力，这会对患者的生存质量和社会-心理状态造成严重影响。该文以近期FIGO肿瘤报告和NCCN最新版指南为基础，总结了子宫内膜癌保留生育功能治疗方法的进展和我院的治疗经验。     

Stage I endometrial carcinoma: a review of 140 patients primarily treated by surgery only

One hundred patients with stage Ia and 40 patients with stage Ib endometrial carcinoma had hysterectomy and bilateral salpingo-oophorectomy performed as the only primary treatment. Sixty-two percent of the patients had well-differentiated tumors, 31% moderately differentiated, and 7% undifferentiated tumors. Information on myometrial invasion was not available. The overall 5-year survival was 0.92 and the 5-year survival by tumor grade 0.96, 0.90, and 0.80 for patients with grade 1, 2, and 3 tumors, respectively. Survival rates decreased significantly with increased tumor dedifferentiation. Prognosis was not affected by enlargement of the uterine cavity or by higher patient age. Of 7 cases of isolated vaginal or pelvic recurrence, 4 could by controlled by irradiation therapy. These results compared to reported results of combined therapy suggest, that in well-differentiated cases-the majority of stage I endometrial cancers-combined therapy of surgery and irradiation presents no advantage over simple hysterectomy.     

Abnormal cervical cytology: a risk factor for endometrial cancer recurrence

The objective of this study was to evaluate the relationship between cervical cytology, histologic type, and risk of endometrial cancer recurrence. We performed a retrospective study of patients undergoing surgery for endometrial carcinoma. Risk factors for recurrence including histology, tumor grade, nodal status, myometrial invasion, peritoneal washings, stage, and cervical cytology were assessed. Abnormal cervical cytology was defined as the presence of any endometrial cells on Pap smear. Papillary serous and clear cell carcinomas were considered high-risk histologies. Univariate and multivariate analyses of risk factors for recurrence were performed. Thirty-nine (9%) patients developed recurrent endometrial cancer. More patients with abnormal Pap smears recurred (12% versus 4%, P < 0.05). For endometrioid adenocarcinoma, abnormal cervical cytology occurred in 61% and 7% recurred, while with high-risk histologies, 84% had abnormal cervical cytology and 19% recurred (P < 0.05). Other significant predictors of recurrence on univariate analysis were myometrial invasion, nodal status, washings, stage, and histology. On multivariate analysis, only nodal status remained a significant predictor of recurrence. Abnormal cervical cytology is associated with increased risk of endometrial cancer recurrence. Abnormal cervical cytology occurs more frequently in high-risk histologies, which are known to have a higher risk of recurrence. On multivariate analysis, only nodal spread remains a significant predictor of recurrence.     

Influence of body mass index on clinicopathologic features, surgical morbidity and outcome in patients with endometrial cancer

Aim

To examine the influence of obesity on the patient characteristics and clinicopathologic features of endometrial cancer, and to find how treatment and prognosis were affected by obesity in women with endometrial cancer.

Methods

The data of 370 consecutive women operated for endometrial cancer were retrospectively reviewed. Patients were divided into three categories as <25, 25–29.9 and ≥30 according to BMI. All patients underwent primary surgical treatment including total abdominal hysterectomy, bilateral oophorectomy and peritoneal cytology. Pelvic lymphadenectomy was carried out for all patients except for those with no myometrial invasion regardless of the tumor grade or for whom it was technically impossible. Paraaortic lymphadenectomy was performed when pre- and intraoperative assessments suggested non-endometrioid or grade 3 endometrioid cancer, >50?% myometrial invasion and cervical involvement.

Results

Patients with a BMI (body mass index) of <25 were significantly younger. Patients with a BMI of ≥30 were statistically less likely to have >50?% myometrial invasion and more likely to have stage I disease. There were no significant differences in the incidences of positive pelvic and paraaortic lymph nodes and tumor grades between the three groups. Also, there were no differences in surgery type, the mean of removed pelvic and paraaortic lymph node number, hospital stay, blood loss and complications between the groups. The patients with a BMI of ≥30 had significantly longer operating time. There were no statistically significant differences in recurrences, the median number of months at recurrence or the site of recurrence between the three groups, as well as the 5-year overall and disease-free survival of patients. Multivariate proportional hazard models identified stage III and IV disease as significant covariates for mortality rates, while stage III and IV disease, hypertension and pelvic irradiation were identified as significant covariates for recurrence rates.

Conclusion

Positive peritoneal cytology, deep myometrial invasion and stage II–IV endometrial cancer were significantly more common in patients with a BMI of <25. There were no significant differences in tumor grade, surgical technique, surgical morbidity or adjuvant radiotherapy between the BMI groups. Recurrence and cancer-related mortality rates were not affected by the BMI.     

Small cell neuroendocrine carcinoma of the endometrium: A clinicopathologic study of six cases

ObjectivesPrimary small cell carcinoma of the endometrium is a rare disease that can only be diagnosed at an advanced stage, and thus has a poor prognosis. In this study, the clinicopathologic characteristics of endometrial small cell carcinoma are described and the survival outcomes are discussed.Materials and methodsThe data from six patients from a single medical institution who were diagnosed with endometrial small cell carcinoma in the past 20 years were retrospectively reviewed.ResultsThe median age of the six patients was 60 years. Vaginal bleeding was the most common symptom. All six patients underwent complete staging surgery, including hysterectomy, bilateral salpingoophorectomy, and systematic lymphadenectomy. Three of the patients were diagnosed with early stage disease, [International Federation of Gynecology and Obstetrics (FIGO) stage I or II], and the other three were in an advanced stage (FIGO stage III). Pathologically, deep myometrial invasion was observed in five (83.3%) of the patients, and lymphovascular invasion in six. As adjuvant therapy, four (66.7%) patients received platinum-based chemotherapy and one (16.7%) underwent concurrent chemoradiotherapy. During the median follow-up period of 16.2 months, recurrence developed in four patients (66.7%). There were disseminated recurrences on the peritoneum and lymph nodes in two cases, and distant metastasis to the brain in the other two cases. The median time to recurrence was 7.5 months (range, 315 months). One patient died of disease.ConclusionSmall cell carcinoma of the endometrium shows an aggressive clinical behavior, such as a disseminated disease and distant metastasis within a short time to recurrence. Initial active management with complete surgical resection and systemic chemotherapy might improve outcomes, although further large studies should be done to confirm this.