Role of appendectomy in predicting lymph node metastases in patients with ovarian cancer

OBJECTIVE: The aim of this study was to assess the diagnostic accuracy of appendectomy in predicting lymph node metastases in women undergoing cytoreductive procedures for ovarian cancer. STUDY DESIGN: In 127 consecutive patients with ovarian carcinoma appendectomy was performed in 30 patients over a period of 5 years. Eight of them were found to have metastases to the appendix. Pelvic and paraaortic lymphadenectomy was performed in 34 patients, in 24 of them the appendix was removed during primary surgery. RESULTS: Among 19 patients without metastases to the appendix the lymph nodes were positive in five cases (26.3%) and among five patients with metastases to the appendix the lymph nodes were positive in four cases (80.0%), which is not a significant difference. Evaluation of the appendiceal metastases as a predictor of lymph node metastases in patients with ovarian cancer gives a sensitivity of 44%, a specificity of 93%, a positive predictive value of 80%, a negative predictive value of 74% and an accuracy of 75%. CONCLUSION: The possibility of predicting retroperitoneal lymph node metastases in ovarian cancer on the basis of histological examination of the appendix is limited.     

Aortic lymph node metastases in early ovarian cancer

Aortic node biopsies performed in 26 patients with Stage I ovarian cancer revealed 5 with metastases. All were associated with virulent tumors of the undifferentiated anaplastic or embryonal cell type. The 19 per cent incidence of lymphatic metastasis in this area stresses the need for evaluation of the aortic node chain in patients with early delimited ovarian cancer.     

Retroperitoneal lymph node metastasis in patients with ovarian cancer

From 1979 to 1987 retroperitoneal lymph node dissection was performed at the Tokyo University Hospital in 41 cases (pelvic lymph node biopsy was done in 4 cases, pelvic lymphadenectomy in 23 cases, pelvic and paraaortic lymphadenectomy up to the renal vessels in 14 cases) of Stage Ia to IV ovarian cancer following cytoreductive surgery. The incidence of retroperitoneal positive nodes was 11.1% (2/18) in Stage I, 50.0% (5/10) in Stage II, 50.0% (5/10) in Stage III and 0% (0/3) in Stage IV (FIGO criteria without considering the pathologic findings of retroperitoneal lymph nodes). The positive rate of lymph node involvement in Stage II and Stage III was significantly higher than that in Stage I. The tumors involving both ovaries were more likely to metastasize to retroperitoneal lymph nodes. Enlargement of tumors and increased ascites were not the risk factors of retroperitoneal lymph node metastasis. These data suggest that the occurrence of retroperitoneal lymphatic spread in ovarian cancer is comparable to that in uterine cancer and increased by involvement of both ovaries and extension to other pelvic tissues.     

卵巢癌相关成纤维细胞与卵巢癌淋巴结转移的关系

目的:探讨肿瘤相关成纤维细胞(CAFs)与卵巢癌临床病理学特征特别是淋巴结转移的关系,研究CAFs在卵巢癌淋巴管生成和淋巴管内皮细胞(LEC)增殖迁移中的作用。方法:免疫组化法检测、计算机图像处理软件分析71例卵巢癌组织间质中α-平滑肌肌动蛋白(α-SMA)阳性面积百分比,以此代表卵巢癌CAFs的数量。用D2-40标记淋巴管内皮细胞,检测淋巴管密度(LVD)。EdU标记法和Transwell迁移实验检测与CAFs共培养前后淋巴管内皮细胞增殖和迁移情况。结果:卵巢癌有淋巴结转移组间质中CAFs百分比明显高于无淋巴结转移组(P=0.024),分别为(29.39±4.32)%和(22.56±6.78)%。卵巢癌间质CAFs数量与淋巴管密度呈正相关(r=0.504,P=0.0003)。与卵巢癌成纤维细胞共培养后,淋巴管内皮细胞增殖增多2.8倍(P<0.0001),迁移增多5.2倍(P<0.0001)。结论:卵巢癌间质成纤维细胞可能通过促进淋巴管内皮细胞增殖、迁移和淋巴管生成,参与卵巢癌的进展和淋巴结的转移。     

Pattern and clinical predictors of lymph node metastases in epithelial ovarian cancer

Para-aortic lymphadenectomy is part of staging in early epithelial ovarian cancer (EOC) and could be part of therapy in advanced EOC. However, only a minority of patients receive therapy according to guidelines or have attendance to a specialized unit. We analyzed pattern of lymphatic spread of EOC and evaluated if clinical factors and intraoperative findings reliably could predict lymph node involvement, in order to evaluate if patients could be identified in whom lymphadenectomy could be omitted and who should not be referred to a center with capacity of performing extensive gynecological operations. Retrospective analysis was carried out of all patients with EOC who had systematic pelvic and para-aortic lymphadenectomy during primary cytoreductive surgery. One hundred ninety-five patients underwent systematic pelvic and para-aortic lymphadenectomy. Histologic lymph node metastases were found in 53%. The highest frequency was found in the upper left para-aortic region (32% of all patients) and between vena cava inferior and abdominal aorta (36%). Neither intraoperative clinical diagnosis nor frozen section of pelvic nodes could reliably predict para-aortic lymph node metastasis. The pathologic diagnosis of the pelvic nodes, if used as diagnostic tool for para-aortic lymph nodes, showed a sensitivity of only 50% in ovarian cancer confined to the pelvis and 73% in more advanced disease. We could not detect any intraoperative tool that could reliably predict pathologic status of para-aortic lymph nodes. Systematic pelvic and para-aortic lymphadenectomy remains part of staging in EOC. Patients with EOC should be offered the opportunity to receive state-of-the-art treatment including surgery.     

Biological markers in pT1 and pT2 ovarian cancer with lymph node metastases

OBJECTIVE: A relatively high incidence of pelvic and paraaortic lymph node metastases is found in patients with pT1 and pT2 ovarian cancer. This paper investigates the clinicomorphological parameters and the expression of various biological markers in these tumors in order to define possible risk factors for lymphatic dissemination. METHODS: In a retrospective study we identified 51 patients with pT1 and pT2 ovarian cancer. All patients underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and systemic pelvic +/- paraaortal lymphadenectomy. The incidence of lymph node metastases in these patients and the clinicomorphological parameters of their tumors were examined. Immunohistochemistry was used to determine the expression levels of the cell proliferation marker Ki-67, the cell adhesion molecules CD44s and CD44v6, and the oncoprotein HER2/neu of the tumors and their respective lymph node metastases. RESULTS: Lymph node involvement was found in 5 of 26 patients with pT1 ovarian cancer and in 6 of 25 patients with pT2 ovarian cancer. Serous adenocarcinoma was associated with a significantly higher incidence of lymph node metastases than other histological types (chi(2) = 4.7, P = 0.03). No correlation was found between tumor grade and the lymph node status. High Ki-67 expression was significantly correlated with spread to the lymph nodes (chi(2) = 4.2, P = 0.04), whereas expression of CD44s, CD44v6, and HER2/neu was not related to the lymph node status. Survival analyses showed no difference in disease-free and overall survival in patients with lymph node metastases compared to those without lymph node metastases. No association was seen among histological type, tumor grade, and immunohistochemically detected Ki-67, CD44s, CD44v6, and HER2/neu expression on the one hand and disease-free and overall survival on the other hand. CONCLUSIONS: Our data suggest that in early stage ovarian cancer the serous histological type and tumors showing a high Ki-67 expression carry a high risk of lymph node metastases. With respect to prognosis our data showed a minor role for Ki-67, CD44s, CD44v6, and HER2/neu expression and the occurrence of lymph node metastases in pT1 and pT2 ovarian cancer.     

Prognostic value of lymph node ratio in patients with advanced epithelial ovarian cancer

ObjectiveLymph node status is an established prognostic factor in epithelial ovarian cancer (EOC). Lymph node ratio (number of positive LN/number of resected LN) reflects both qualitative and quantitative lymph node spread as well as surgical effort and extent of disease. We evaluated whether LNR is a more precise prognostic factor than conventional lymph node status in patients with EOC.MethodsThe present retrospective study includes 809 patients with EOC, who underwent primary cytoreductive surgery between 2000–2013. Clinico-pathological parameters and survival data were extracted from a prospectively maintained tumor registry database. The optimal cut-off point for LNR was calculated by using Martingale residuals. Survival analyses were calculated using Kaplan–Meier method and Cox regression models.ResultsLymphadenectomy was performed in 693 (85.7%) out of 809 patients. Median number of removed LN was 64 (IQR 25–75%: 39–84). LNR of 0.25 was identified as the optimal prognostic cut-off value. The estimated 5-year-OS rates were 69.3% for patients with node-negative EOC compared to 33.1% for patients with any lymph node metastasis (p < 0.001). The estimated 5-year-OS rates were 42.5% for patients with LNR ≤ 0.25, and 18.0% for patients with LNR > 0.25 (p < 0.001). Additionally in multivariate analysis LNR > 0.25 was approved to be an independent prognostic factor for overall survival (adjusted HR 1.44, 95% CI 1.04–2.00; p = 0.028).ConclusionLNR more precisely predicts overall survival than conventional lymph node status in EOC patients undergoing primary debulking surgery.     

Debulking of pelvic and para-aortic lymph node metastases in ovarian cancer with the cavitron ultrasonic surgical aspirator

Six patients with metastatic ovarian cancer with extensive involvement of the pelvic and/or para-aortic lymph nodes underwent surgical debulking with the Cavitron Ultrasonic Surgical Aspirator. Intraoperative and postoperative morbidity was minimal. It is suggested that this technique may be used for cytoreductive surgery in combination with standard surgical techniques.     

单中心559例卵巢癌患者淋巴结转移的危险因素分析与淋巴结切除术临床决策探讨#br#

【Abstract】?Objective?To review the data of patients with ovarian cancer, analyze the related factors of pelvic lymph node metastasis (PLNM) and para-aortic lymph node metastasis (PALNM), and establish a predictive model, so as to provide suggestions for clinical practice. Methods?The clinicopathological data of 559 patients with ovarian cancer treated in Chinese PLA General Hospital from January 2014 to January 2019 were retrospectively analyzed. The risk factors affecting PLNM and PALNM were analyzed by univariate and logistic regression, and the prediction model was established. Results?Among 559 ovarian cancer patients, pelvic lymph node metastasis was found in 205 cases (36.67%) and abdominal para-aortic lymph node metastasis in 117 cases (20.93%). The independent risk factors affecting PLNM were bilateral lesions (OR=2.278, 95%CI: 1.433~3.621), pelvic metastases (OR=1.801, 95%CI: 1.154~2.810), and abdominal metastases (OR=4.177, 95%CI: 2.597~6.717) and appendiceal metastasis (OR=2.332, 95%CI: 1.389~3.915); The independent risk factors affecting PALNM were appendiceal metastasis (OR=2.324, 95%CI: 1.383~3.906) and PLNM (OR=7.629, 95%CI: 4.615~12.610). Age (≥55 years) (OR=0.566, 95%CI: 0.350~0.915) was the protective factor. The ROC curve AUC of PLNM and PALNM was 0.803 (95%CI: 0.767~0.840) and 0.793 (95%CI: 0.745~0.841), respectively. Conclusion?Bilateral lesions, pelvic metastases, intraperitoneal metastases and appendiceal metastases were independent risk factors for PLNM in ovarian cancer patients. Appendiceal metastasis and PLNM were independent risk factors for PALNM, and age (≥55 years) was the protective factor.     

An evaluation of chemotherapy in patients with cancer of the cervix and lymph node metastases

During the past twelve years, out of the 288 cervical cancer patients who had lymph node involvement, the recurrence rate in the lymph node, was 26.6% if one or two nodes were involved and 50.8% if three or more nodes were involved (P<0.0001). The recurrence rate of patients who received eight intravenous treatments (at monthly intervals) of multi-agent chemotherapy was lower than those who did not receive treatment. Of patients with one or two positive lymph nodes, 114 received treatment while 50 did not; their respective recurrence rates were 19.3% and 42.0%, a statistically significant difference (P<0.025). Of patients with three or more positive lymph nodes, 97 received treatment and 27 did not, their respective recurrence rates, were 46% and 66% (P=0.30) and the difference is not statistically significant. It would seem that multi-agent chemotherapy may reduce the recurrence rate in patients with cancer of the cervix and positive lymph nodes.AbbreviationCX CA Cervival cancer     

Pretherapeutic scalene lymph node biopsy in ovarian cancer

To study scalene lymph node involvement in ovarian cancer, 37 patients with this disease underwent pretherapeutic open sampling of the left scalene fat tissue. Only 1 patient had a palpable supraclavicular mass. Positive scalene nodes were found in 7 (22%) of 32 patients with stage III or IV disease. Three of four patients with positive scalene nodes also had both positive pelvic and positive paraaortic nodes; one patient with stage IV disease had negative pelvic and paraaortic nodes. Demonstration of scalene node involvement per se currently does not alter the management of patients with ovarian cancer, although patients with occult involvement of the scalene nodes could be considered ineligible for intraperitoneal chemotherapy.     

Flow cytometric analysis of lymph node metastases in advanced ovarian cancer: Clinical and biologic significance

OBJECTIVE: This study was undertaken to evaluate the deoxyribonucleic acid content and S-phase fraction in advanced epithelial ovarian carcinomas to determine whether lymph node metastases are biologically distinct from peritoneal sites of metastases.STUDY DESIGN: Thirty-five patients with stage III or IV epithelial ovarian cancer who had undergone complete pelvic and paraaortic lymphadenectomy had representative samples from the primary ovarian tumor, peritoneal metastases, and lymph node metastases analyzed by flow cytometry for deoxyribonucleic acid nuclear content and S-phase fraction.RESULTS: Diploid cell lines are found in metastatic lymph nodes (52%) significantly more frequently than in peritoneal metastases (25%, p < 0.02) or in primary ovarian tumors (26%, p < 0.001). The ploidy category frequency distribution of peritoneal metastases mirrors that found in the primary tumor, and both are significantly different from the ploidy category frequency distribution found in metastatic lymph nodes. Heterogeneity among sites is common, being identified in 54% of patients. Peritoneal metastases are more likely to be concordant with the primary tumor (69%) than are lymph node metastases (39%, p < 0.001). Mean S-phase fraction did not differ overall by site but was significantly different between diploid and aneuploid samples by site. Diploid lymph node metastases were found to have the lowest mean S-phase fraction (7.2% ± 3.3%), and aneuploid lymph node metastases had the highest mean S-phase fraction (22.3% ± 10.2%). Diploidy of the primary tumor is a positive predictor of long-term survival. Tumoral heterogeneity and lymph node metastases are not related to survival in this group of patients who underwent therapeutic pelvic and aortic lymphadenectomy.CONCLUSIONS: A high proportion of tumor deposits found in metastatic lymph nodes are diploid with a low S-phase fraction. Therapeutic pelvic and aortic lymph node dissection removes disease that, on the basis of flow cytometric characteristics, may be predicted to be resistant to chemotherapy and radiation therapy. (Am J Obstet Gynecol 1997;176:1319-27.)     

Incidence of lymph node and ovarian metastases in leiomyosarcoma of the uterus

OBJECTIVE: The purpose of this study was to determine the incidence of lymph node and ovarian metastases in newly diagnosed uterine leiomyosarcoma (LMS), and to describe possible predictive factors. METHODS: We used our prospectively acquired databases to identify 275 consecutive patients with uterine LMS treated from 7/82 to 12/01. Patients were included if there was clear documentation of lymph nodes and/or ovarian tissue in the pathologic reports. Clinical data were extracted from electronic medical records. Statistical analysis using the Fisher exact test was used to determine prognostic factors. RESULTS: There were 108 patients (39.2%) identified in whom an oophorectomy and 37 patients (13.5%) in whom lymph node sampling was performed as part of the initial surgical management of uterine LMS. Bilateral oophorectomy was performed in 102 (94.4%) of the 108 patients. The median numbers of pelvic, para-aortic, and total lymph nodes acquired were 5 (range, 1-27), 3 (range, 1-9), and 6 (range, 1-34), respectively. Ovarian metastases were found in 4 (3.9%) out of 108 patients. Two (2.8%) of the 71 patients with disease confined to the uterus and/or cervix (stage I/II) and 2 (5.4%) of the 37 patients with gross extrauterine disease had ovarian metastases (P = 0.43). Positive lymph nodes were seen in 3 (8.1%) of 37 patients. No patients with stage I/II disease had positive lymph nodes (P = 0.015). None of the factors analyzed predicted for metastases to the ovary. Only the presence or absence of gross extrauterine disease correlated with lymph node metastasis. In addition, all three of these cases had clinically suspicious (enlarged) lymph nodes. CONCLUSIONS: The incidence of ovarian and lymph node metastases in uterine LMS is very low and is most commonly associated with extrauterine disease. Lymph node dissection for uterine LMS should be reserved for patients with clinically suspicious nodes.     

Bulky lymph node resection in patients with recurrent epithelial ovarian cancer: impact of surgery

The aim of this study was to evaluate the role of systematic lymphadenectomy, feasibility, complications rate, and outcome in epithelial ovarian cancer (EOC) patients with recurrent bulky lymph node disease. A prospective observational study of EOC patients with pelvic/aortic lymph node relapse was conducted between January 1995 and June 2005. After a clinical and laparoscopic staging, secondary cytoreduction, including systematic lymphadenectomy, were performed. The eligibility criteria were as follows: disease-free interval > or =6 months, radiographic finding suggestive of bulky lymph node recurrence, and patients' consent to be treated with chemotherapy. Forty-eight EOC patients with lymph node relapse were recruited. Twenty-nine patients were amenable to cytoreductive surgery. Postoperatively, all patients received adjuvant treatment. The median numbers of resected aortic and pelvic nodes were 15 (2-32) and 17 (8-47), respectively. The median numbers of resected aortic and pelvic positive lymph nodes were 4 (1-18) and 3 (1-17), respectively. The mean size of bulky nodes was 3.3 cm. Four patients (14%) experienced one severe complication. No treatment-related deaths were observed. After a median follow-up of 26 months, among cytoreduced patients, 18 women were alive with no evidence of disease, nine were alive with disease. Among the 11 patients not amenable to surgery, five women were alive with persistent disease, six patients died of disease, at a median follow-up of 18 months. Estimated 5-year overall survival and disease-free interval for operated women were 87% and 31%, respectively. In conclusion, patients with bulky lymph node relapse can benefit from systematic lymphadenectomy in terms of survival. The procedure is feasible with an acceptable morbidity rate.     

Therapy of paraaortic lymph node metastases of cervix cancer

Report about 52 patients with uterine cervical carcinoma and lymphographically positive paraaortic lymph nodes. 30 of these patients have been irradiated, 22 not. Survival times of these two groups did not differ significantly. Reasons for this result have been discussed. A more invasive diagnosis in curable cases is proposed.