Prognostic significance of morphology of tumor and retroperitoneal lymph nodes in epithelial carcinoma of the ovary: I. Correlation with lymph node metastasis

The prognostic indices based on a morphologic study of tumor and retroperitoneal lymph nodes in 63 patients with epithelial carcinoma of the ovary are reported. The purpose of the study was to identify those variables most frequently related to nodal involvement. The cases in the series consisted of 11 Stage I, 10 Stage II, 34 Stage III, and 8 Stage IV. Histologic distribution was 60.4% serous type, 11.1% mucinous, 6.3% endometrioid, 6.3% clear cell and 15.9% unclassified. All patients had maximal surgery and selective biopsy of para-aortic and pelvic lymph nodes. The results showed statistically significant variables associated with nodal metastasis in both primary tumor and regional lymph nodes. The indices in primary tumor were grade of tumor, vascular invasion, lymphocytic infiltration, and stromal fibrosis; those in lymph node were type of lymph node reaction, sinus histiocytosis, and fibroblastic proliferation. The nodes with lymphocyte depletion were associated with nodal spread in 81.3% of cases. It is concluded that morphologic study of tumor and lymph node could identify prognostic factors predicting regional nodal metastasis in ovarian carcinoma.     

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.     

Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential

A comprehensive understanding of retroperitoneal lymphatic involvement is lacking in tumors of low malignant potential. This study was undertaken to evaluate retroperitoneal lymphatic involvement in patients with ovarian tumors of low malignant potential. One hundred seventy-one patients were diagnosed with epithelial ovarian tumors of low malignant potential between 1979 and 1989. Thirty-four (20%) of these patients underwent surgical staging which included lymph node sampling. The stage distribution was Stage I in 17 patients (50%), Stage II in 4 patients (12%), and Stage III in 13 patients (38%). The histology of the tumors was serous in 26 patients (76%), mucinous in 7 patients (21%), and seromucinous in 1 patient (3%). The incidence of retroperitoneal lymphatic involvement was 21%. The occurrence of positive pelvic and para-aortic nodes was 17 and 18%, respectively. Patients with localized intraperitoneal disease were upstaged in 22% of the cases based on retroperitoneal lymphatic involvement. Four of twenty-one patients (19%) with intraperitoneal disease confined to the ovary and two of six patients (33%) with intraperitoneal disease confined to the pelvis were upstaged to Stage III as a result of retroperitoneal lymphatic disease. Although the nodal status of patients did not significantly affect survival, those patients with localized intraperitoneal disease and nodal involvement had a higher incidence of recurrence which was statistically significant (P = 0.025). Accordingly, retroperitoneal lymph node sampling at the time of initial laparotomy may provide valuable prognostic information regarding recurrence in patients with tumors of low malignant potential.     

Survival of ovarian carcinoma with or without lymph node metastasis

Because of the limited number of reports concerning the influence of retroperitoneal lymph node metastasis upon survival in patients with ovarian carcinoma, a prospective study was conducted between December 1975 and December 1982 to provide such information. This series consisted of 75 unselected patients with epithelial carcinoma of the ovary in all stages. Thirty-three patients had tumor-positive nodes and 42 had negative nodes. The two groups were compared with regard to stage of disease, grade of tumor, histology of tumor, residual disease after initial operation, finding at second-look laparotomy, and survival. All had initial maximal surgery and biopsy of para-aortic and pelvic nodes: most received postoperative chemotherapy. Follow-up was from 36 months to 10 years. Patients with positive nodes preferentially had more advanced disease (Stage III and IV). Grade 3 tumor, papillary serous cystadenocarcinoma, residual disease greater than 2%, low rate of second-look laparotomy, and death. Patients with negative nodes were connected with earlier disease (Stage I and II), nonserous tumor, minimal residual disease, high rate of second-look laparotomy, and survival. No patient with isolated nodal metastasis to pelvic or para-aortic survived. Only 18.2% with concomitant para-aortic and pelvic node involvements are currently alive, opposed to 64.3% with negative node. The results indicate that tumor-positive nodes in ovarian carcinoma are a poor prognostic factor and current combination chemotherapy is not effective. Alternative treatment for these patients should be considered.     

Lymph node metastasis in ovarian cancer: difference between serous and non-serous primary tumors

OBJECTIVE: To investigate the lymph node sites most susceptible to involvement relative to primary tumor histology in ovarian cancer. METHODS: The locations of metastatic lymph nodes were investigated in 208 patients with primary ovarian cancer who underwent systemic lymphadenectomy covering both the pelvic and para-aortic regions. RESULTS: Lymph node metastasis was present in 12.8% (20/156) of patients with stage I (pT1M0), 48.6% (18/37) with stage II (pT2M0), and 60% (9/15) with stage III (pT3M0) disease, thus in 22.6% (47/208) of all study patients. Isolated para-aortic nodal involvement was present in 23.3% (14/60) of patients with serous tumor and 4.1% (6/148) of those with non-serous tumor (P = 0.00002). In an analysis of 35 positive nodes from 25 patients with up to 3 positive nodes, 86.4% (19/22) of metastatic lymph nodes from patients with serous tumor were found in the para-aortic region, with 14 positive nodes located above the inferior mesenteric artery (IMA) and 5 below it, whereas metastasis to para-aortic lymph nodes accounted for 53.8% (7/13) of metastatic lymph nodes from patients with non-serous tumor (P = 0.0334). CONCLUSIONS: The locations of metastatic lymph nodes in ovarian cancer depend upon the histologic type of the primary cancer. In cases of serous tumor, the para-aortic region, particularly above the IMA, is the prime site for the earliest lymph node metastasis. However, the likelihood of pelvic node involvement is almost equal to that of para-aortic node involvement in cases of non-serous tumor.     

Patterns of pelvic and paraaortic lymph node involvement in ovarian cancer

One hundred eighty patients with ovarian cancer underwent complete pelvic lymphadenectomy (n = 75) or pelvic and paraaortic lymphadenectomy (n = 105). Twenty-one patients underwent a preoperative biopsy of the scalene lymph nodes. The incidence of positive lymph nodes was 24% in stage I (n = 37), 50% in stage II (n = 14), 74% in stage III (n = 114), and 73% in stage IV (n = 15). Of the 105 patients who underwent pelvic and paraaortic lymphadenectomy, 13 (12%) had positive pelvic and negative paraaortic nodes and 10 (9%) had positive paraaortic and negative pelvic nodes. Positive scalene nodes were found in four patients (19%) later shown to have stage IV disease. One hundred forty patients were studied for number of involved nodes and node groups, size of nodal metastases, residual tumor, and survival. Of the 81 patients with positive nodes, most had only one or two positive node groups or one to three positive individual nodes. A few patients had seven to eight involved node groups with up to 44 positive nodes. Greater numbers of positive nodes were found in stage III than stage IV. The size of the largest nodal metastasis was not related to the clinical stage or survival, but did correlate with the number of positive nodes. Stage III patients with no residual tumor had a significantly lower rate of lymph node involvement than those with tumor residual (P less than 0.01). Actuarial 5-year survival rates of patients with stage III disease and no, one, or more than one positive nodes were 69, 58, and 28%, respectively.     

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.     

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.     

Lymph node spread in stage III or IV primary peritoneal serous papillary carcinoma

BACKGROUND: The aim of this study was to determine the rates and topography of pelvic and para-aortic nodal involvement in patients with stage III or IV primary peritoneal serous papillary carcinoma (PSPC). METHODS: Retrospective review of 19 women who underwent a systematic bilateral pelvic and para-aortic lymphadenectomy. RESULTS: The overall frequency of lymph node involvement was 63% (12/19). Eighteen patients underwent complete resection of peritoneal disease. Only 4 patients underwent this procedure as part of their initial surgery (before chemotherapy). The frequency of pelvic and para-aortic metastases was 58% (11/19) and 58% (11/19), respectively. When para-aortic nodes were involved, the left para-aortic chain above the level of the inferior mesenteric artery was the site most frequently involved (72%). The event-free survival of the 18 patients without macroscopic disease at the end of debulking surgery was significantly correlated with the nodal status. None of the patients with positive nodes developed recurrent disease in abdominal nodes. CONCLUSIONS: The rate of nodal involvement in patients with PSPC is high. The topography of nodal spread is similar to that of ovarian cancer. Lymphadenectomy has a prognostic value.     

Significance of Lymph Node Sampling in Epithelial Carcinoma of the Ovary

From 1979 to 1984, 127 patients operated on for ovarian cancer underwent pelvic, para-aortic, or pelvic and para-aortic lymph node sampling. Forty-seven patients proved to be stage I (14 IA and 33 IC), 14 were stage II (3 IIA, 8 IIB, and 3 IIC), 58 were stage III (7 IIIA, 13 IIIB, and 38 IIIC), and 8 were stage IV. Positive lymph nodes were found in 4.2% of patients at stage I, 35.7% at stage II, 41.3% at stage III, and 87.5% at stage IV. With regard to grading, positive lymph nodes were found in 4.4% of G1, in 21.6% of G2, and in 49.1% of G3. A significant increase in survival (P= 0.04) was found for patients classified as stage IIIC only according to lymph node involvement compared to patients in peritoneal stage IIIC with positive lymph nodes (3-year survival: 46% vs 12%). A small increase in survival was observed for N− patients compared to N+ patients, at both stage III and IV, even with same residual tumor size, but the difference is not statistically significant. All other things being equal, because the prevalence of lymph node positivity depends closely on the number of lymph nodes removed and examined (OR = 3.9 for >10 lymph nodes removed compared to 1–5 lymph nodes removed), lymph node sampling does not seem to be a reliable method for evaluating the retroperitoneal status. With regard to the therapeutic role of systematic lymphadenectomy, few data in literature are available and, most important, are not derived from experimental studies. Probably, only randomized studies with a large number of patients will provide useful answers.     

Analysis of clinicopathologic factors predicting para-aortic lymph node metastasis in endometrial cancer

The purposes of this study were to compare the relationships between para-aortic lymph node metastasis and various clinicopathologic factors to evaluate whether para-aortic lymph node dissection is necessary when treating endometrial cancer. A retrospective study was performed on 841 patients with endometrial cancer, who underwent the initial surgery at the Keio University Hospital. Clinicopathologic factors related to para-aortic lymph node metastasis significant on a univariate analysis were analyzed in a multivariate fashion using a logistic model. According to the multivariate analysis, the clinicopathologic factor most strongly related to the existence of para-aortic lymph node metastasis was positive pelvic lymph node metastasis (P < 0.01). Among the 155 patients who underwent pelvic and para-aortic lymph node dissection, the difference of 5-year overall survival by the presence of retroperitoneal lymph node metastasis was examined by Kaplan-Meier method. The prognosis was poor even if para-aortic lymph node dissection was performed in cases of positive para-aortic lymph node metastasis. In conclusion, when deciding whether to perform para-aortic lymph node dissection in patients with endometrial cancer, it is necessary to consider the pelvic lymph nodal status. If there is no pelvic lymph node metastasis, it could not be necessary to perform para-aortic lymph node dissection.     

Prognostic significance of morphology of tumor and retroperitoneal lymph nodes in epithelial carcinoma of the ovary: II. Correlation with survival

Correlation between prognostic indices derived from morphologic studies of retroperitoneal lymph nodes as well as primary tumor and survival in 39 patients with epithelial carcinoma of the ovary is reported. All had maximal surgery, adjuvant chemotherapy, and were followed for more than 2 years. A selective biopsy of pelvic and para-aortic lymph nodes was performed during the staging laparotomy in all instances. The chemotherapeutic regimen was a combination of Adriamycin, cis-platinum, and Cytoxan in a majority of cases.Prognostic indices, which showed positive correlation with survival, were cancer involvement, type of lymph node reaction, sinus histiocytosis, and fibroblastic proliferation in the regional lymph nodes; tumor grade, lymphocytic infiltration, stromal fibrosis, and histologic type in primary tumor; and stage of disease. Unfavorable factors for survival were nodal metastasis, lymphocytic depletion in abdominal nodes, and Grade 3 tumor. Clinical implications of our findings are discussed.     

Ovarian serous borderline epithelial tumors with multiple retroperitoneal nodal involvement: metastasis or malignant transformation of epithelial glandular inclusions?

One of four patients who underwent lymph node excision at exploration for ovarian serous borderline epithelial tumor (OSBT) at Baystate Medical Center was found to have FIGO Stage III C lesion associated with extensive ovarian external (surface) papillary growth, peritoneal implants in the omentum and cul-de-sac, and involvement of multiple pelvic and periaortic lymph nodes by the tumor. Histologically, the lymph nodes showed an admixture of endosalpingeal glandular inclusions with neoplastic tissue identical to the ovarian tumor. The exact histogenesis and the prognostic significance of the nodal involvement by OSBT are still not fully understood. Although there is a small number of reported cases of lymph node involvement associated with OSBT, they are described as examples of nodal metastases or independent primary foci of malignant transformation. This paper presents an interesting association of OSBT with extensive pelvic and periaortic nodal involvement and reviews the relevant literature.     

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.     

化疗对晚期卵巢、输卵管及腹膜浆液性癌淋巴结转移的临床疗效(附70例临床分析)

目的:探讨化疗对晚期卵巢、输卵管及腹膜浆液性癌腹膜后淋巴结转移的临床疗效。方法:将晚期卵巢、输卵管及腹膜浆液性癌70例患者,根据淋巴结切除术与化疗的先后顺序分为2组:A组21例,化疗后行淋巴结切除术。B组49例,淋巴结切除术后化疗。比较2组患者的一般情况、治疗方案及淋巴结转移情况。结果:2组患者的年龄,肿瘤分期分级,治疗前的肿瘤标记物,切除淋巴结的数量等均无显著性差异(P>0.05)。初治时A组患者盆腹腔黏连及转移重于B组;初次手术A组进行满意的肿瘤细胞减灭术的几率明显低于B组(0%vs73.47%,P<0.05)。化疗后A组患者淋巴结转移率低于B组(38.10%vs49.00%,P>0.05),腹主动脉旁淋巴结为肿瘤最常侵犯的淋巴结。A组行TC(泰素/紫杉醇+伯尔定/卡铂)或TP(泰素/紫杉醇+顺铂)方案化疗的患者淋巴转移率低于行CAP(顺铂+阿霉素+环磷酰胺)方案的患者(33.33%vs50%,P=0.045)。结论:化疗对卵巢、输卵管及腹膜浆液性癌淋巴结转移有一定的疗效。初治时不能进行淋巴结切除的患者可考虑先行化疗后再次手术切除淋巴结。     

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.     

Retroperitoneal lymph node metastases in Stage I carcinoma of the endometrium: Correlation with risk factors

The present study was undertaken in patients with Stage I carcinoma of the endometrium to correlate risk factors and the prevalence of retroperitoneal lymph node metastases. From January 1975 to April 1983, 202 patients with Stage I disease had initial therapy at the Long Island Jewish-Hillside Medical Center, New Hyde Park, New York. Among these patients, 74 who had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and selective lymph node biopsy without preoperative radiation were included in the study. Results indicate that risk factors associated with nodal metastasis were Grade 3 tumor (42.1%), papillary adenocarcinoma (28.6%), deep myometrial invasion (42.9%), surface extent of tumor growth greater than of the endometrial cavity (31.8%), and a diffuse pattern of tumor growth (17.2%). In Stage 1 endometrial cancer with any of the above 5 risk factors, it is urged that a selective biopsy of para-aortic and pelvic nodes during hysterectomy should be performed.     

Pelvic lymphadenectomy in operative treatment of ovarian cancer

From the end of 1979 to September, 1985, radical pelvic lymphadenectomy was performed at the Graz Clinic in 123 cases of Stages IA to IV ovarian cancer following maximum debulking procedure. In 97 patients lymphadenectomy was done primarily. In 26 it was performed during a follow-up operation to chemotherapy. The frequency of pelvic node involvement was 61.8% in the total material and 78.0% in 82 cases of Stage III disease only; 75.0% positive nodes were found in Stage III after chemotherapy. Aortic nodes were positive in 41.4%, but only when pelvic nodes were also positive. The 5-year actuarial survival rate for Stage III disease was 53.0% after pelvic lymphadenectomy compared with 13.0% without. In cases with negative nodes the survival rate was 74.7%; with positive nodes the survival rate was 45.9%.     

Incidence of subclinical metastasis in stage I and II ovarian carcinoma

The incidence of unsuspected metastasis to the diaphgram, retroperitoneal lymph nodes, and omentum as well as malignant cytologic peritoneal washings in women with presumed localized ovarian cancer is presented. Of the women with presumed Stage I ovarian cancer, from our clinical experience and those reported in the literature, 11.3% were found to have diaphragmatic metastases, 13.3% had aortic lymph node metastases, 8.1% had pelvic lymph node metastases, 3.2% had omental metastases, and 32.9% had malignant peritoneal washings. In Stage II ovarian cancer, 23% were found to have diaphgragmatic metastases, 10.0% had aortic lymph node metastases, 0% had omental metastases, and 12.5% had malignant peritoneal washings.     

Is it necessary to do retroperitoneal evaluation in borderline epithelial ovarian tumors?

Objective Borderline epithelial ovarian tumors have good prognosis without any adjuvant therapy. The advantage of aggressive surgical staging, especially retroperitoneal lymph node sampling is questionable in patients with borderline ovarian tumors. We designed this study to evaluate the necessity of retroperitoneal pelvic and para-aortic lymph node dissection in the treatment of borderline epithelial ovarian tumors. Study design From 1998 to 2007, 57 women who were diagnosed with borderline epithelial ovarian tumor in our hospital were prospectively accrued and evaluated; 27 of them (47.3%) had full surgical staging procedure including para-aortic and pelvic node dissection. Student’s t-test was used to compare follow-up times. Results Median follow-up time was 54.6 (12–96) months for all patients in the study. There was one recurrence of disease, which was in the complete staging group. Follow-up times of patients were not statistically different between lymph node evaluated and non-evaluated groups (p = 0.10). We did not find any metastasis in lymph nodes in 27 women who had complete surgical staging procedure. Conclusion Patients with borderline epithelial tumors who had full surgical staging procedure do not have survival advantage over those who had no lymph node evaluation and yet were patients with malignant ovarian tumors.