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.     

Sentinel lymphatic mapping among women with early-stage cervical cancer: A systematic review

The presence of pelvic lymph node metastases is without doubt the most significant prognostic factor that determines recurrences and survival of women with early-stage cervical cancer. To avoid the underdiagnosis of lymph node metastasis, pelvic lymphadenectomy procedure is routinely performed with radical hysterectomy procedure. However, the pelvic lymphadenectomy procedure may not be necessary in most of these women due to the relatively low incidence of pelvic lymph node metastasis. The removal of large numbers of pelvic lymph nodes could also render non-metastatic irreversible damages for these women, including vessel, nerve, or ureteral injuries; formation of lymphocysts; and lymphedema. Over the past decades, the concept of sentinel lymph node biopsy has emerged as a popular and widespread surgical technique for the evaluation of the pelvic lymph node status in gynecologic malignancies. The histological status of sentinel lymph node should be representative for all other lymph nodes in the regional drainage area. If metastasis is non-existent in the sentinel lymph node, the likelihood of metastatic spread in the remaining regional lymph nodes is very low. Further lymphadenectomy is therefore not necessary for a patient with negative sentinel lymph nodes. Since the uterine cervix has several lymphatic drainage pathways, it is a challenging task to assess the distribution pattern of sentinel lymph nodes in women with early-stage cervical cancer. This review article will adapt the methodology proposed in these studies to systematically review sentinel lymphatic mapping among women with early-stage cervical cancer.     

Early ovarian cancer: Is there a role for systematic pelvic and para-aortic lymphadenectomy?

Baiocchi G, Raspagliesi F, Grosso G, Fontanelli R, Cobellis L, di Re E, di Re F. Early ovarian cancer: Is there a role for systematic pelvis and para-aortic lymphadenectomy? Int J Gynecol Cancer 1998; 8 : 103–108.
In order to focus on the incidence and the clinical significance of lymphatic spread in patients with cancer apparently confined to the ovaries, we present our 20 year experience in a large series of patients with early ovarian cancer who had systematic pelvic and para-aortic lymphadenectomy. A retrospective study of 280 consecutive patients is presented. Systematic pelvic and para-aortic lymphadenectomy was performed in 205 cases (73.2%). Selective sampling and node biopsy were performed in 30 (10.7%) and 7 (2.5%), respectively. Node metastases were found in 32/242 patients (13.2%). The incidence of metastatic nodes was significantly higher in patients with serous adenocarcinomas and/or poorly-differentiated tumors. When few nodes were involved (1–3) lymphatic spread was most ipsilateral to the tumor. Even though the retrospective nature of the study has to be considered, univariate analysis revealed statistically significant differences in 5-year survival based on FIGO stage, histology, grade of differentiation, and node status. By contrast, using multivariate analysis, none of these risk factors was an independent variable for predicting long-term survival. However, node status closely approached the statistically significant level ( P = 0.06). Only prospective and randomized studies can clarify the role of lymphadenectomy in early ovarian cancer. However, while awaiting these results, this surgical procedure should be a part of a research protocol.     

Incidence of metastasis in the circumflex iliac nodes distal to the external iliac nodes in ovarian cancer

Objective

The circumflex iliac nodes distal to the external iliac nodes (CINDEINs) are included in the regional lymph nodes that are commonly dissected during systematic lymphadenectomy for ovarian cancer. Because in recent years CINDEIN dissection has been reported as a significant risk factor for postoperative lower limb lymphedema, we investigated the validity of omitting the CINDEIN dissection by evaluating the distribution pattern of positive lymph nodes in ovarian cancer, in order to improve postoperative quality of life (QOL).

Methods

We performed a retrospective chart review of 142 patients with ovarian cancer who had undergone systematic lymphadenectomy between 1995 and 2010. We assessed the distribution pattern of lymph node metastasis and the presence of CINDEIN metastasis according to the pT classification (pT1, pT2, and pT3).

Results

Of the 142 patients, 71, 21, and 50 were classified into pT1, pT2, and pT3, respectively. The lymph nodes most frequently involved were the para-aortic lymph nodes superior to the mesenteric artery (14%), followed by the obturator nodes (11%), the internal iliac nodes (9.4%), and the common iliac nodes (7.4%). Although the frequency of CINDEIN metastasis was 5.3% (6 of 114 cases with CINDEIN dissection), no metastasis to the CINDEINs was observed in pT1 patients.

Conclusions

It may be acceptable to omit CINDEIN dissection during surgery for pT1 ovarian cancer in view of postoperative QOL.     

Lymph node metastasis in stage I epithelial ovarian cancer

OBJECTIVES: A relatively high incidence of para-aortic and pelvic lymph node metastasis is found in epithelial ovarian cancer. This paper investigates the clinicomorphological features of intra-abdominal stage I epithelial ovarian cancer that may predict the occurrence of lymph node metastasis and the prognosis of patients in whom lymph node metastases are identified. METHODS: From November 1988 to December 1997 we performed systematic para-aortic and pelvic lymphadenectomy as primary surgery in 47 patients with intra-abdominal stage I epithelial ovarian cancer. The incidence of lymph node metastasis in these patients and the clinicomorphological features of the patients with lymph node involvement were examined. RESULTS: Five patients (10.6%) were metastasis positive (IC: four; IA: one), of whom four had serous adenocarcinoma. Serous adenocarcinoma was associated with a significantly higher incidence of metastases than other histological types (P < 0.05). The number of positive lymph nodes was one in four patients and two in one patient, and the metastatic sites ranged from the para-aortic to the suprainguinal lymph nodes. All five metastasis-positive patients were alive and disease free at the time of this report (survival 28-85 months: median 59 months). CONCLUSION: This clinical study suggests that serous adenocarcinoma carries a high risk of lymph node metastasis, requiring systematic lymphadenectomy for accurate staging in intra-abdominal stage I epithelial ovarian cancer.     

Retrograde Lymphatic Spread: A Likely Route for Metastatic Ovarian Cancers of Gastrointestinal Origin

In order to outline the pathways of gastrointestinal malignancies metastasizing to the ovaries, we reviewed 103 cases of metastatic ovarian tumors, and also performed para-aortic lymph node sampling on 11 patients at operation for metastatic ovarian tumors. Of the 103 patients, 74% (26/35) with gastric cancer and 67% (45/67) with colorectal cancer had lymph node metastasis at or before the diagnosis of ovarian tumor. Intraperitoneal metastases presented in 49 and 42% of patients with gastric and with colorectal cancers, respectively. Twenty-three percent of gastric cancer patients and 25% of colorectal cancer patients presented with both lymph node and intraperitoneal metastases. The ovary was the first or among the early metastatic organs diagnosed in 51 of the 53 patients with metachronous ovarian metastases. Only 4 patients with colorectal cancer and none with gastric cancer showed parenchymal organ metastases. These 4 patients also showed intraperitoneal lesions, and 3 of these 4 patients had node metastasis. Among the 11 patients who underwent prospective para-aortic lymph node sampling during operation for the ovarian tumors, only 1 had enlarged para-aortic nodes depicted by computed tomography, 2 had grossly enlarged (≥1.5 cm) para-aortic lymph nodes noted at surgery, and 6 of the 7 patients with gastric cancer and all 3 with colorectal cancer had metastatic nodes histologically. Among the 58 nodes taken from these patients, 67% showed metastatic foci. We concluded that lymph node metastasis is frequently seen in patients with metastatic ovarian tumors of gastrointestinal origin, and hypothesized that retrograde lymphatic spread is a likely route for the metastases.     

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.     

Lymph node involvement in primary carcinoma of the fallopian tube

Although the bad prognosis of primary fallopian tube carcinoma has been mostly ascribed to early lymphogenous dissemination, precise information regarding the characteristics of retroperitoneal spread are still missing. Our study was designed to evaluate the incidence and clinical significance of lymph node metastases in 33 patients with primary carcinoma of the fallopian tube. During primary surgery nine patients (27%) were submitted to systematic pelvic and para-aortic lymphadenectomy, whereas 24 received lymph node sampling. The clinicopathologic characteristics of the patients (intraperitoneal spread, grading, peritoneal cytology, depth of tubal infiltration and residual disease after primary surgery) were compared with lymphnodal status.
Overall 15 patients (45%) had positive nodes, that is, invaded by tumor; whereas 18 (55%) showed no lymphatic spread. Six patients (40%) had exclusively positive para-aortic lymph nodes; five (33%) had only tumor metastases in pelvic lymph nodes, three (20%) manifested simultaneously pelvic and para-aortic spread, and one patient with pure primary squamous cell carcinoma had a massive groin node metastasis as presenting sign of the tumor. The rate of lymphogenous metastases was not significantly related to progressive intra-abdominal dissemination, histologic grade or depth of tubal infiltration. On the other hand, the presence of residual disease after primary surgery and positive peritoneal cytology significantly increased the risk of nodal metastases. Patients with lymph node metastasis had a significantly ( P = 0.02) worse prognosis compared with patients without nodal involvement (median survival 39 vs 58 months).
Considering the high incidence of lymph node metastasis, correct staging of tubal carcinoma should include a thorough surgical evaluation of both pelvic and para-aortic lymph nodes. The role of systematic lymph node dissection in the treatment of tubal carcinoma remains controversial.     

Pelvic and aortic lymph node metastasis in epithelial ovarian cancer

OBJECTIVE: The appropriate management of advanced ovarian cancer has been controversial in recent years. There are no adequate data about the importance of lymphadenectomy and the appropriate sites for lymph node assessment. We sought to evaluate the distribution, size, and number of pelvic and aortic lymph node metastases in patients with epithelial ovarian carcinoma. METHODS: Retrospective chart review of 116 patients with stage IIIC or IV epithelial ovarian carcinoma treated at Mayo Clinic who underwent systematic bilateral pelvic and aortic lymphadenectomy between 1996 and 2000. RESULTS: Eighty-six (78%) of 110 patients who underwent pelvic lymphadenectomy were found to have nodal metastases in 422 (16%) of 2705 pelvic nodes that were removed. Eighty-four (84%) of 100 patients had documented aortic lymph node metastases in 456 (35%) of 1313 aortic nodes that were removed. Fifty-five (59%) of 94 patients had bilateral metastatic pelvic and aortic lymph nodes and bilateral aortic lymphadenectomy was conducted in 53 (72%) of 74 patients. The most representative group for detection of nodal metastases was the aortic group (83%) followed by the external iliac group (59%) and the obturator nodes (53%). There was no significant difference between the mean size of positive (1.8 cm) and negative nodes (1.6 cm). Thirty-seven patients had unilateral tumor, and 1 patient (7%) had contralateral node metastasis. CONCLUSION: The incidence of positive nodes bilaterally and positive high aortic nodes indicates the need for bilateral pelvic and aortic node dissection (extending above the inferior mesenteric artery) in all patients regardless of laterality of the primary tumor.     

盆腹腔淋巴取样术在子宫内膜癌手术中的临床意义

目的探讨盆腹腔淋巴取样术在子宫内膜癌的临床意义。方法分析2000年1月-2007年12月上海同济大学附属第一妇婴保健院手术治疗的213例子宫内膜癌患者,其中,86例行盆腹腔淋巴取样术,127例行淋巴结切除术。手术方式根据手术切除淋巴结的情况分为两组。①取样组：淋巴取样术,筋膜外全子宫双附件切除/次广泛子宫切除术＋盆腔/腹主动脉旁淋巴结取样术86例;②切除组：次广泛/广泛子宫切除术＋盆腔淋巴结切除/腹主动脉旁淋巴结切除术127例。结果取样组：切除淋巴结中位数18枚,淋巴结的转移10例。切除组：切除淋巴结中位数32枚,淋巴结转移11例。5年生存率分别为94.2%和94.5%。取样组无病发症发生,淋巴结切除组中有9例,分别是1例术中大出血（〉2000ml）,淋巴囊肿感染6例,淋巴漏2例。结论在子宫内膜癌中淋巴结取样术可准确了解淋巴结的转移情况,适宜手术分期,并不影响生存率,是避免过度手术减少并发症发生的有效方法。     

Contralateral pelvic and aortic lymph node metastasis in clinical stage I epithelial ovarian cancer.

Bilateral pelvic and aortic node lymphadenectomy is recommended for clinically localized unilateral epithelial ovarian adenocarcinoma (International Federation of Gynecologists and Obstetricians stage IA). The laterality of nodal metastasis in clinical stage I disease is rarely documented in the literature. Some authors have reported that ipsilateral node dissection is adequate for staging. A patient with contralateral pelvic and aortic lymph node metastasis and clinical stage I epithelial ovarian adenocarcinoma is presented. Pathologic findings were consistent with contralateral-only lymph node metastasis. This case illustrates the importance of bilateral lymph node sampling for appropriate staging of clinically localized epithelial ovarian cancer.     

Value of lymph node assessment in ovarian cancer: Status of the art at the end of the second millennium

Abstract. di Re F, Baiocchi G. Value of lymph node assessment in ovarian cancer: Status of the art at the end of the second millennium.
Available data on the incidence and the clinical value of lymph node assessment in ovarian cancer are reported. In early ovarian cancer, positive nodes are found in 4–25% of patients. Serous adenocarcinoma and poorly differentiated tumors are characterized by the highest incidence of node metastases. Five-year survival for stage IIIC disease with only retroperitoneal spread is clearly better than for stage IIIC with intraperitoneal dissemination. In advanced ovarian cancer, the rate of node involvement ranges from 55 to 75%. The percentage of positive nodes is significantly related to the amount of residual tumor after cytoreductive surgery, and node status seems to be an important prognostic factor for survival. Although data from retrospective studies advocate a therapeutic effect for systematic lymphadenectomy, results from prospective randomized trials are warranted. After chemotherapy a high percentage of patients (range, 25–77%) are found to have metastatic nodes. In particular, at second-look laparotomy, positive nodes are detected in 17–40% of patients who have no intraperitoneal disease.     

Inguinal lymph node metastasis as the only manifestation of lymphatic spread in ovarian cancer: A case report

OBJECTIVE: Inguinal metastasis is a rare manifestation of ovarian cancer. Autopsy studies have reported inguinal metastasis in 0-3% of patients with advanced disease. CASE REPORT: We describe a 43-year-old patient with ovarian cancer limited to the adnexa who had an isolated metastasis in an enlarged inguinal lymph node. The patient underwent total abdominal hysterectomy, omentectomy, pelvic and paraaortic lymphadenectomy, and excision of the enlarged inguinal lymph node. All 78 pelvic and 40 paraaortic lymph nodes were negative. CONCLUSION: This case demonstrates that early isolated distant lymph node metastasis, although rare, can occur in patients with ovarian cancer and may be a presenting symptom.     

Lymph node metastasis in stage I ovarian cancer]

One hundred and sixteen cases of stage I Ovarian cancer from nine hospitals in all the China during Sept. 1982-April 1991 were investigated for their lymph node metastasis. There were 70 epithelial tumors, 36 malignant germ cell tumors, 8 from gonadal stroma and 2 undifferentiated. In 89 patients the ovarian tumor was confined to one ovary (stage Ia); in 6 cases both ovaries were involved (stage Ib); 21 cases was documented stage Ic. Systemic lymphadenectomy covering all pelvic groups of node together with aortic lymph node accomplished in 82 cases. In the remaining 34 cases only pelvic lymph node dissection was performed. There was 10.3 percent incidence of lymphatic metastasis in this series. The most common lesion was serous cystadenocarcinoma. All patients were follow-up for at least half year. The mortality rate in patients without lymph node metastasis was 2.8%, but 8.3% for those with lymph node metastasis. The clinical significance of retroperitoneal lymphadenectomy in early ovarian cancer was discussed.     

Risk of lymph node metastases in patients with ovarian cancer

AIM: The aim of this study was the assessment of incidence of the lymph node spread in patients with ovarian cancer. Additionally, some of clinical and histopathology factors, as well as patients age were analyzed in relation with lymph nodes metastases. MATERIAL AND METHOD: Based on 112 operations performed in patients with ovarian cancer FIGO stage I-IV, analysis of pelvic and paraaortic lymph node metastasis was carried out. In this group only in 70 patients paraaortic lymph nodes were removed. The rest of patients underwent pelvic lymphadenectomy only because of poor general condition or very intensive cytoreductive surgery. Statistical analysis was provided using unvaried regression test and Pearson test. RESULTS: In early stages of ovarian cancer (I and II) the percent of patients with involved lymph nodes was 17.4 and in advanced stages 37.9. Strong correlation between involvement of pelvic and paraaortic lymph nodes was seen. The most frequent localization of lymph node metastases was the site around intercrossing of left renal vein and aorta. It should be stressed that in 8 cases isolated paraaortic metastases were seen. Risk factors of lymph node metastases were clinical stage, tumor grade and age of patients. Clear cell carcinoma and mixed carcinoma had also prognostic significance. CONCLUSION: This analysis proved that incidence of lymph node metastases was high even in early stage, and therefore lymphadenectomy should be an integral part of standard surgical procedures in patients with ovarian cancer.     

Sentinel lymph node in endometrial cancer: an overview

The role of complete pelvic and para-aortic lymphadenectomy in early endometrial cancer remains controversial in gynecologic oncology. Sentinel lymph node detection is an alternative to assess lymphatic spread in several solid tumors. The authors review the literature related to the detection of sentinel lymph node in endometrial cancer, the techniques employed, and its results and feasibility. The authors review reported case series of endometrial cancer in which the sentinel lymph node biopsy was performed. A systematic literature review was conducted using the PubMed database. Different techniques were used considering lymphatic imaging mapping (colorimetric, isotopic, and fluorescence procedures) and injection site (subserous, hysteroscopic, and cervical). Detection rates of sentinel lymph node were heterogeneous, varying between 44 and 100 % with false-negative rates between 0 and 33 %. Although technically demanding, hysteroscopy approach was associated with the highest detection rate. The largest trials showed a good detection rate with cervical injection, a more reproducible procedure. The laparoscopic route improved the results. Immunohistochemistry staining improved the micrometastasis detection in sentinel lymph node. Cost-effectiveness of systematic lymphadenectomy compared with sentinel lymph node procedure and its value on adjuvant therapies as well as a standardized reproducible and reliable technique must be assessed.     

Anatomical and pathological study of retroperitoneal nodes in endometrial cancer

Benedetti-Panici P, Maneschi F, Cutillo G, D'Andrea G, Manci N, Rabitti C, Scambia G, Mancuso S. Anatomical and pathological study of retroperitoneal nodes in endometrial cancer. Int J Gynecol Cancer 1998; 8 : 322–327.
To assess the patterns of lymphatic spread in endometrial carcinoma, data from 91 endometrial cancer patients (surgical FIGO stage I: 59; II: 12; III–IV: 20) who underwent systematic pelvic and aortic lymphadenectomy were analyzed. The median number of nodes removed was 27 aortic (range 15–57) and 31 pelvic (range 20–68) nodes. Positive nodes were found in 16 patients (18%), seven having pelvic, one aortic, and eight both pelvic and aortic metastasis. The median number of positive nodes was three (range 1–29) aortic and two (range 1–18) pelvic nodes. Isolated pelvic node metastasis was observed in seven patients and aortic metastasis in one patient.
Pre-paracaval, pre-paraortic and intercavoaortic, with superficial obturator, external iliac and common iliac were the node groups most frequently involved. These nodes may be considered primarily invaded by the tumor. The higher prevalence of pelvic with respect to aortic metastasis, and the low risk of isolated aortic spread, suggest that endometrial cancer spreads preferentially to the pelvic area. Multivariate analysis showed that depth of myoinvasion and adnexal metastasis were independent factors predicting the risk of lymphatic spread. The risk of aortic spread was also predicted by the pelvic node status. These data may be useful for tailoring lymphadenectomy.     

Laparoscopic identification of sentinel lymph node in treatment of invasive cervical cancer

The fundamental prognostic factor in treatment of early cervical cancer is the state of regional lymph nodes. If the first lymphatic node is involved by cancer, the other ones may be affected; otherwise if the first one is free of metastatic cells, the others should not be involved by cancer either. Detection and removal of the lymphatic node called the sentinel lymph node permit to avoid radical lymphadenectomy which is connected with many severe complications. We reported a technique of identification of the sentinel lymph node during laparoscopic radical hysterectomy with pelvic lymphadenectomy in treatment of early invasive cervical cancer with presentation of case history. Identification of sentinel node with its histopathology examination may be essential in women with cervical cancer and potentially identifies women in whom lymph node dissection can be avoided. Laparoscopic lymphadenectomy seems to be equally effective and less invasive in comparison to traditional technique.     

预测子宫内膜癌患者腹主动脉旁淋巴结转移方法的研究进展

子宫内膜癌是妇科常见恶性肿瘤之一,发病率逐年上升。淋巴结转移为子宫内膜癌患者的主要转移途径,其中盆腔淋巴结转移较为常见,腹主动脉旁淋巴结转移较为少见。但存在腹主动脉旁淋巴结转移的患者预后相对较差。腹主动脉旁淋巴结转移情况可以通过术前、术中相关方法进行预测。预测子宫内膜癌患者是否存在腹主动脉旁淋巴结转移方法的研究近年来发展迅速,但目前尚无预测方法的统一标准。综合分析患者的病理、血清学和影像学检查方法对腹主动脉旁淋巴结转移的预测价值,对指导临床决策,避免不必要的腹主动脉旁淋巴结切除术,减少不良反应,降低手术费用以及选择合适的术后辅助治疗显得尤为重要。     

The relation of intraabdominal findings and retroperitoneal lymph node metastasis in the epithelial ovarian cancer patients

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