Infertility treatment after conservative management of borderline ovarian tumors

BACKGROUND: Young patients with ovarian tumors of low malignant potential usually undergo conservative surgery because of the excellent prognosis of these tumors. Patients wishing to conceive after diagnosis occasionally require ovulation induction, but data regarding the safety of assisted reproductive technologies in this situation remains anecdotal. The current study analyzes the outcome of a group of patients who received infertility treatment after the conservative management of borderline ovarian tumors. METHODS: The clinical and pathologic records of 104 patients with a borderline tumor of the ovary who were treated and followed over a 20-year period (1979--1999) were reviewed. Forty-three patients who underwent conservative management were the subjects of the current study. RESULTS: Follow-up was available for 95% of the patients, giving a total of 270 women-years of follow-up. Nine of the 43 patients developed a local recurrence, 8 of which occurred in patients with serous tumors. Five of these 9 patients underwent cystectomy only at the time of recurrence, and all were without evidence of disease at a mean follow-up of 75 months (range, 25--93 months). Nineteen patients delivered a total of 25 healthy children after diagnosis of a borderline ovarian tumor; 7 of these patients were treated with in vitro fertilization (IVF) after diagnosis. Four of these patients developed a recurrence, two patients before the IVF treatment and two patients after the IVF treatment. The latter two patients were without evidence of disease at the time of last follow-up (15 months and 26 months, respectively, after the recurrence). CONCLUSIONS: The results of the current study suggest that ovulation induction may be considered after the diagnosis of a borderline ovarian tumor. Recurrences were observed in two of seven patients, all of which remained histologically borderline.     

Epidemiology of borderline ovarian tumors

Ovarian tumors of low malignant potential, often termed "borderline tumors," have been defined as those that have some but not all of the morphologic features of malignancy (i.e., they are not invasive). With the use of data obtained by the western Washington population-based Cancer Surveillance System for 1975-83, the incidence of serous and mucinous borderline epithelial ovarian tumors was analyzed, as well as the survival of women who developed them. The incidence of borderline tumors increased with increasing age, although at a pace somewhat slower than that of malignant ovarian tumors. There was an upward trend in the incidence of borderline tumors starting in the late 1970's, a trend not present for malignant tumors. Only 12% of borderline tumors were not confined to the ovary, as opposed to 40% of malignant Grade I and 73% of other malignant ovarian neoplasms. At 5 years following diagnosis, the survival of women with borderline tumors was 93% that of the general female population. This percentage varied little by stage or histologic type. Given the reduced survival of women with these ovarian tumors and the lack of a sharp histologic distinction between borderline and Grade I malignant lesions, it is recommended that borderline ovarian tumors be routinely ascertained by population-based cancer registries.     

Controversies in borderline ovarian tumors

Borderline ovarian tumors (BOTs) represent about 15% to 20% of all ovarian malignancies and differ from invasive ovarian cancers (IOCs) by many characters. Historically, standard management of BOT is peritoneal washing cytology, hysterectomy, bilateral salpingo-oophorectomy, omentectomy, complete peritoneal resection of macroscopic lesions; in case of mucinous BOTs, appendectomy should be performed. Because BOTs are often diagnosed at earlier stage, in younger age women and have better prognosis, higher survival rate than IOCs, fertility-sparing surgery is one of the option to preserve childbearing capacity. The study of such conservative surgery is being released, and still controversial. After surgery, pregnancy and ovarian induction followed by in vitro fertilization are also significant issues. In surgery, laparoscopic technique can be used by a gynecologic oncology surgeon. So far postoperative chemotherapy, radiotherapy and hormone therapy are not recommended. We will discuss controversial issues of BOTs on this review and present the outline of the management of BOTs.     

Clinical management of borderline ovarian tumors

Borderline ovarian tumors (BOTs) are epithelial tumors of the ovaries characterized by cellular proliferation and nuclear atypia but without an infiltrative growth pattern. As they frequently affect younger patients the clinical management is complicated by considerations such as preserving fertility and reducing postoperative morbidity. Over the past several decades surgical therapy has shifted from a radical approach to more conservative treatment. There are various modes of surgery applied to the patients. All these developments have to be considered from an oncologic standpoint as BOTs represent a potentially malignant disease. Oncologic safety, as well as patients’ desires and expectations, have to be balanced to reach the most appropriate treatment for BOTs. For this reason current literature will be discussed in this review to give a thorough overview of this topic and to develop recommendations for the surgical management of these patients. Open questions will be identified to elaborate the need for future surveys and research.     

卵巢交界性肿瘤210例临床分析

目的探讨卵巢交界性肿瘤（BOT）患者的临床病理学特点及复发相关危险因素。方法回顾性分析山西省肿瘤医院2001年1月至2015年12月收治的210例BOT患者的临床资料。结果210例BOT患者平均年龄为（41±16）岁,68.1%（143/210）的患者为ⅠA期,31.9%（67/210）的患者〉ⅠA期;术后23例复发,复发率为11.3%（23/204）。单因素分析结果显示,在不同年龄（P=0.007）、临床分期（P=0.009）、是否微乳头型（P=0.024）及手术方式（P=0.025）分组中,BOT患者的复发率差异有统计学意义。多因素logistic回归分析结果显示,微乳头型（OR=0.153,95% CI 0.044~0.535）、年龄≤40岁（OR=0.245,95% CI 0.088~0.686）、分期晚（OR=3.502,95% CI 1.360~9.020）是BOT患者复发的危险因素。结论BOT主要发生在育龄期女性,临床分期相对较早,预后良好;年龄≤40岁、分期〉ⅠA期及微乳头型患者易复发。     

卵巢交界性上皮性肿瘤36例临床分析

目的：探讨卵巢交界性上皮肿瘤的临床特征和治疗方法。方法：收集江西省妇幼保健院2003年至2007年36例卵巢交界性上皮性肿瘤患者临床资料,运用SPSS 11．5软件进行临床和病理统计分析。结果：发病年龄平均37．9岁,粘液性17例（47．2％）,浆液性16例（44．5％）,子宫内膜样2例（5．5％）,透明细胞1例（2．8％）。34例患者行手术治疗,其中Ⅰ期28例（82．4％）,Ⅲ期5例（14．7％）均为浆液性,治疗后1例（2．9％,Ⅰ期）浆液性复发。治疗方法以手术为主,21例于术后补充TP或PAc方案化疗,Ⅱ期与Ⅲ期患者均辅以化疗。结论：卵巢交界性上皮性肿瘤顶后良好,手术是其有效的治疗手段,对临床Ⅰa期,尤其需保留生育功能者,保守性手术较安全有效。浆液性外生性乳头状交界瘤多伴有腹膜种植,应行分期手术。CA125是监测卵巢非黏液性肿瘤复发及进展的有效指标。     

卵巢交界性上皮性肿瘤36例临床分析

目的:探讨卵巢交界性上皮肿瘤的临床特征和治疗方法.方法:收集江西省妇幼保健院2003年至2007年36例卵巢交界性上皮性肿瘤患者临床资料,运用SPSS 11.5软件进行临床和病理统计分析.结果:发病年龄平均37.9岁,粘液性17例(47.2% ),浆液性16例(44.5% ),子宫内膜样2例(5.5%),透明细胞1例(2.8%).34例患者行手术治疗,其中Ⅰ期28例(82.4%),Ⅲ期5例(14.7%)均为浆液性,治疗后1例(2.9% ,Ⅰ期)浆液性复发.治疗方法以手术为主,21例于术后补充TP或PAC方案化疗,Ⅱ期与Ⅲ期患者均辅以化疗.结论:卵巢交界性上皮性肿瘤预后良好,手术是其有效的治疗手段,对临床Ⅰa期,尤其需保留生育功能者,保守性手术较安全有效.浆液性外生性乳头状交界瘤多伴有腹膜种植,应行分期手术.CA125是监测卵巢非黏液性肿瘤复发及进展的有效指标.     

Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

Purpose

The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors.

Methods

In a population-based case–control study in Denmark, we included 554 women with invasive ovarian cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35–79 years. The analyses were performed in multiple logistic regression models.

Results

We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95 % CI 1.08–2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95 % CI 0.65–1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition.

Conclusion

Our results suggest that a history of PID is associated with an increased risk of ovarian borderline tumors, which may support the hypothesis that inflammation is an etiological factor. The lack of an association between previous PID and invasive ovarian cancer may indicate an etiological difference between ovarian borderline tumors and invasive ovarian cancer. However, an important limitation of the study is the use of self-reported PID.     

The current status of surgical staging of ovarian serous borderline tumors

BACKGROUND: The purpose of the current study was to evaluate the current practice of surgical staging of ovarian serous borderline tumors. METHODS: Women with a diagnosis of ovarian serous borderline tumors whose pathology slides were sent to the M. D. Anderson Cancer Center for second-opinion diagnostic consultation between 1990-1996 were identified. The original pathology reports and M. D. Anderson Cancer Center consultation reports of 255 cases were reviewed for the frequencies of frozen-section analyses and staging biopsies, biopsy results, the specialty of the surgeon, and hospital type. RESULTS: The majority (78%) of ovarian borderline tumors primarily were encountered and staged by general obstetrician-gynecologists. Overall, 66% of patients had at least 1 staging biopsy performed. Approximately 12% of subjects underwent complete surgical staging, defined as having biopsy samples taken from pelvic and abdominal peritoneum, omentum, and retroperitoneal lymph nodes. Gynecologic oncologists performed complete staging in 50% of cases, obstetrician-gynecologists performed complete staging in 9% of cases, and general surgeons performed complete staging in 0% cases. The overall frequency of a positive staging biopsy was 37%. Approximately 47% (80 of 169) of patients who underwent biopsies were upstaged as a result of positive biopsies, - with 41% (70 of 169) having extrapelvic spread. CONCLUSIONS: Currently, surgical staging for women with ovarian serous borderline tumors remains inadequate, although a significant proportion of patients who undergo staging are noted to have extrapelvic spread.     

Histologic distribution of borderline ovarian tumors worldwide: a systematic review

Objective

The histologic types of borderline ovarian tumors (BOTs) exhibit striking differences in clinical behavior and prognosis. Yet, there is no information available on the histologic distribution of BOTs according to geographic region. The purpose of this study was to systematically review this issue worldwide.

Methods

A comprehensive search of the literature was conducted using electronic databases. Studies were eligible if BOTs were investigated and the histologic distribution of the data was shown. The studies were grouped by geographic region and totaled by country.

Results

Of 487 potentially relevant studies, 51 met our inclusion criteria, as follows: 8 studies from North America (2 countries); 26 studies from Europe (14 countries); 7 studies from the Middle East (3 countries); and 10 studies from East Asia (5 countries). The histologic distribution of BOTs was considerably different in different parts of the world, but follows specific patterns. In general, serous-type BOTs were the predominantly identified histology in North America, the Middle East, and Europe, while mucinous-type BOTs predominated in East Asia.

Conclusion

Significant geographic variation is evident among BOT histology in different parts of the world. More research is needed to understand this phenomenon.     

Requirement for expert histopathological assessment of ovarian cancer and borderline tumors

The distinction between borderline ovarian tumours (BOT) and ovarian carcinoma is made by histopathological assessment. Of 64 patients managed according to institutional BOT protocols, 27 (42%) had been referred with a diagnosis of ovarian carcinoma that was subsequently changed to BOT following histopathological review. The 70% 6-year event-free survival of the patients with a revised diagnosis was not significantly different from those who were referred with a diagnosis of BOT. This change in diagnosis is important as it avoids the need for chemotherapy for most patients and results in patients receiving appropriate information concerning prognosis. Interestingly, 24 patients (38.1%) reported a family history of epithelial cancer, a finding that has not been reported previously. Campaign     

Survival among women with borderline ovarian tumors and ovarian carcinoma: a population-based analysis

BACKGROUND: Serous and mucinous ovarian tumors of low malignant potential (LMP-S and LMP-M, respectively) are noninvasive tumors that portend excellent survival when confined to the ovary. Comparison of the survival for women with LMP tumors staged as distant with women who have carcinoma may have important implications for diagnostic terminology and clinical management. METHODS: The authors compared relative survival rates among patients diagnosed with ovarian tumors during the period 1988-1999 (with follow-up through 2000) by histologic type, disease stage, tumor grade (for carcinomas), and patient age, using data from the Surveillance, Epidemiology, and End Results Program. RESULTS: The overall relative survival rate at 10 years (+/- 1.96 standard errors) was 96.9% +/- 2.3% for women with LMP-S tumors, 30.4% +/- 1.7% for women with serous carcinoma (CA-S); 94.0% +/- 3.1% for women with LMP-M tumors, and 64.7% +/- 3.4% for women with mucinous carcinoma (CA-M). The survival rate at 10 years for women with distant-stage LMP-S tumors was 89.9% +/- 5.3%, compared with 96.1% +/- 8.6% for women with well differentiated, localized CA-S. The survival rate for women with distant-stage LMP-M tumors at 5 years was 85.5% +/- 9.0%, compared with 95.5% +/- 3.4% for women with well differentiated, localized CA-M (data for 10 years were limited). Mucinous ovarian neoplasms were associated with an excess of second malignancies of the digestive tract. CONCLUSIONS: Relative survival among women with distant-stage LMP tumors was not 100% and resembled the survival of women who had carcinoma exhibiting favorable prognostic features (localized stage). Future studies of women with high-stage LMP tumors are required to clarify the pathogenesis of extraovarian lesions and their implications for management and prognosis.     

Plasma alpha-L-fucosidase activity and the risk of borderline epithelial ovarian tumors

The authors obtained venous blood samples from 106 female residents of western Washington in whom serous and mucinous borderline ovarian tumors had been diagnosed between 1980 and 1985 ("cases") and from a randomly selected telephone sample of 134 control women from the same counties. Mean activity in plasma of alpha-L-fucosidase was slightly higher in cases (334 units/ml) compared to controls (306 units/ml). The risk for a serous borderline tumor was virtually the same for women in all four quartiles of alpha-L-fucosidase activity. Women in the three lowest quartiles of activity were at 50-70% the risk of women in the highest quartile for the development of a mucinous tumor, but within these three quartiles there was no trend of decreasing risk with decreasing activity. These results suggest that for most women plasma alpha-L-fucosidase activity has little or no bearing on the risk of borderline ovarian tumors. Whether such an association exists in women genetically predisposed to these tumors could not be assessed.     

Hormone therapy and ovarian borderline tumors: a national cohort study

Purpose  

Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.     

保守性手术对交界性卵巢肿瘤预后及生育功能的影响

目的；研究首次行保守手术后交界性卵巢肿瘤（BOT）患者的生育功能和疾病结局。方法：对自1990年1月－2000年5月在我院住院43例符合筛选条件的BOT患者行问卷调查及回顾性病例分析，采用SAS软件包对数据进行处理。结果：43例病人中，41例病人完成问卷调查，26例为浆液性交界性卵巢肿瘤（SBOT）；17例为粘液性交界性卵巢肿瘤（MBOT），平均随访时间是63个月，术后无肿瘤复发29例，肿瘤复发14例（包括1例死于肿瘤复发，1例死于其它疾病），平均复发时间是术后39．3个月。卵巢肿瘤剥除术后肿瘤复发率58．3％（7／12），而卵巢切除术后肿瘤复发率22．6％（7／31），两者差异有显著性（Fisher精确概率P＝0．0351），但保守手术后肿瘤复发死亡率并不高于根治性手术（P＝0．64），术后24例有生育愿望的妇女，12例获得妊娠，妊娠年龄范围23－34岁，平均25岁，结论：保守手术可作为BOT患者的一种治疗选择；尽管术后肿瘤复发率较高（33％，14／43），尤其是行卵巢肿瘤剥除术的病人，但肿瘤复发死亡率并未增加；术后有妊娠愿望者能够再次妊娠并分娩正常后代。     

Epidemiologic features of borderline ovarian tumors in California: a population-based study

Purpose

Borderline ovarian tumors (BOT) became no longer reportable in 2001, and few registries still collect information on these still poorly understood tumors. This study’s objective was to describe epidemiologic features, trends, and survival of BOTs compared with those of low-grade (LG) and high-grade (HG) epithelial ovarian cancer (EOC) in the large and diverse population of California.

Methods

Data from the California Cancer Registry were used to examine demographic and tumor characteristics among women diagnosed with BOT (n = 9,786), LG-EOC (n = 3,656), and HG-EOC (n = 40,611) from 1988 to 2010. Annual percent changes in BOT and LG-EOC incidence rates were estimated using Joinpoint regression; 5-year relative survival was calculated for both BOTs and LG-EOCs by age, race/ethnicity, and histology.

Results

Age-adjusted incidence rates of BOT in 2009 were 3.1, 2.3, 2.2, and 1.4 per 100,000 among whites, Latinas, African Americans, and Asian/Pacific Islanders, respectively. Incidence rates for LG-EOC decreased by 2.2 % per year; rates for BOT increased by 7.3 % per year until 1993, remained unchanged until 2006, and seemed to decline thereafter. Compared with LG-EOCs, BOTs were diagnosed in higher frequency among Latinas, at younger age, and were more likely to affect only one ovary. Overall, 5-year relative survival for BOT was 98.9 %; among women diagnosed with stage IV BOT, survival was 77.1 %.

Conclusions

In this study, differences between BOTs and LG-EOCs were marked but varied substantially by histologic subtype and were far less dramatic than differences between BOTs and HG-EOCs. Findings underscore the importance of understanding these enigmatic tumors.     

Peritoneal implants of ovarian serous borderline tumors. Histologic features and prognosis

The clinicopathologic features of 56 cases of ovarian serous borderline tumors (SBT) associated with peritoneal implants were reviewed. Data from 368 person-years of follow-up (median follow-up, 6.0 years) were analyzed to investigate the possibility that the histologic features of implants of this type of tumor may correlate with the prognosis. Eighty-five percent of the 56 patients were clinically free of tumor at the time of death or at last contact. Thirteen percent of the patients died of tumor, and one patient (2%) was alive with widespread progressive tumor. The product-limit estimate of the probability of death from tumor (+/- standard error) was 4% (+/- 3%) at 5 years and 23% (+/- 9%) at 10 years. The following three histologic features of the implants correlated with an adverse prognosis: (1) invasion (P = 0.0004), (2) severe cytologic atypia in both invasive and noninvasive implants (P = 0.0008) and in noninvasive implants alone (P = 0.02), and (3) the presence of mitotic activity in both types of implants (P = 0.02) and in noninvasive implants alone (P = 0.02). The only other feature that correlated with the prognosis was the presence of residual tumor postoperatively as assessed by the surgeon (P = 0.01). The product-limit estimate of death of tumor in patients with at least one of these four adverse prognostic factors was 56% (+/- 20%) at 10 years. Whether or not the patients received radiation therapy, chemotherapy, or both had no statistically significant effect on the outcome. These data and the results of a stratified analysis suggest that patients may benefit from additional therapy if adverse prognostic factors are present, especially invasiveness or severe cytologic atypia. It is unlikely that additional therapy is necessary in patients without adverse prognostic features, because no deaths occurred in this group.     

Contemporary treatment of gastrointestinal stromal tumors

Great revolutionary changes have occurred in the diagnosis and treatment of gastrointestinal stromal tumor(GIST) due to the discovery and development of molecularly targeted therapy with imatinib and sunitinib, which have led to publication of several clinical guidelines for GIST. However, despite enhanced understanding of the clinical and molecular nature of GIST, there are many problems still remain. In this paper, I will focus on three GIST issues of great interest including: 1) laparoscopic surgery for GIST and gastrointestinal submucosal tumors; 2)multidisciplinary treatments for GIST, such as adjuvant therapy, neoadjuvant therapy, surgery during imatinib treatment, and surgery for focally imatinib-resistant GIST; and 3)the diagnosis and treatment of imatinib-resistant GIST.