Yukiharu Todo

Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis

BACKGROUND In response to findings that pelvic lymphadenectomy does not have any therapeutic benefit for endometrial cancer, we aimed to establish whether complete, systematic lymphadenectomy, including the para-aortic lymph nodes, should be part of surgical therapy for patients at intermediate and high risk of recurrence. METHODS We selected 671 patients with endometrial carcinoma who had been treated with complete, systematic pelvic lymphadenectomy (n=325 patients) or combined pelvic and para-aortic lymphadenectomy (n=346) at two tertiary centres in Japan (January, 1986-June, 2004). Patients at intermediate or high risk of recurrence were offered adjuvant radiotherapy or chemotherapy. The primary outcome measure was overall survival. FINDINGS Overall survival was significantly longer in the pelvic and para-aortic lymphadenectomy group than in the pelvic lymphadenectomy group (HR 0.53, 95% CI 0.38-0.76; p=0.0005). This association was also recorded in 407 patients at intermediate or high risk (p=0.0009), but overall survival was not related to lymphadenectomy type in low-risk patients. Multivariate analysis of prognostic factors showed that in patients with intermediate or high risk of recurrence, pelvic and para-aortic lymphadenectomy reduced the risk of death compared with pelvic lymphadenectomy (0.44, 0.30-0.64; p<0.0001). Analysis of 328 patients with intermediate or high risk who were treated with adjuvant radiotherapy or chemotherapy showed that patient survival improved with pelvic and para-aortic lymphadenectomy (0.48, 0.29-0.83; p=0.0049) and with adjuvant chemotherapy (0.59, 0.37-1.00; p=0.0465) independently of one another. INTERPRETATION Combined pelvic and para-aortic lymphadenectomy is recommended as treatment for patients with endometrial carcinoma of intermediate or high risk of recurrence. If a prospective randomised or comparative cohort study is planned to validate the therapeutic effect of lymphadenectomy, it should include both pelvic and para-aortic lymphadenectomy in patients of intermediate or high risk of recurrence. FUNDING Japanese Foundation for Multidisciplinary Treatment of Cancer, and the Japan Society for the Promotion of Science.

Risk factors for postoperative lower-extremity lymphedema in endometrial cancer survivors who had treatment including lymphadenectomy

OBJECTIVE The aim of this study was to determine the incidence rate of lower-extremity lymphedema after systematic lymphadenectomy in patients with uterine corpus malignancies and to elucidate risk factors for this type of lymphedema. METHODS A retrospective chart review was carried out for all patients with uterine corpus malignant tumor managed at Hokkaido Cancer Center between 1991 and 2007. Patients who did not undergo lymphadenectomy as a treatment or died of cancer/intercurrent disease were excluded from this study. All living patients included in this study had hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy and their medical records were reviewed. We identified patients with postoperative lower-extremity lymphedema (POLEL). Logistic regression analysis was used to select the risk factors for POLEL. RESULTS Of 286 patients evaluated, 103 (37.8%) had POLEL. Multivariate analysis confirmed that adjuvant radiation therapy (OR=5.2, 95% CI=2.1-12.7), resection of more than 31 lymph nodes (OR=2.6, 95% CI=1.4-4.9), and removal of circumflex iliac nodes to the distal external iliac nodes (CINDEIN) (OR=6.1, 95% CI=1.3-28.2) were independent risk factors for POLEL. CONCLUSION Adjuvant radiation therapy should be avoided in patients who undergo systematic lymphadenectomy if an alternative postoperative strategy is possible. Although reducing the number of resected lymph nodes is not appropriate from a therapeutical point of view, elimination of CINDEIN dissection may be helpful in reducing the incidence of POLEL. The clinical significance of CINDEIN dissection needs to be investigated by a randomized controlled trial.

Preoperative serum SCC, CA125, and CA19-9 levels and lymph node status in squamous cell carcinoma of the uterine cervix

Background.  We wanted to investigate the clinical usefulness of determining the pretreatment levels of multiple serum tumor markers in predicting lymph node status and the prognosis for patients with cervical carcinoma.

Prognostic significance of serous and clear cell adenocarcinoma in surgically staged endometrial carcinoma

Background. The serous adenocarcinoma (SA) and clear cell adenocarcinoma (CCA) of endometrium have been shown to be associated with high relapse rate and poor survival. It is not clear whether prognostic significance of these specific cell types of tumor is independent of retroperitoneal lymph node metastasis and other histopathologic prognostic factors in endometrial carcinoma.

A retrospective analysis of postoperative complications with or without para-aortic lymphadenectomy in endometrial cancer.

Introduction: Although para-aortic lymphadenectomy (PALX) has not been accepted as a standard treatment for patients with endometrial cancer, it is possible that systematic lymphadenectomy including PALX has therapeutic significance for patients with intermediate-/high-risk endometrial cancer. On the other hand, a consensus regarding the safety of PALX has not been reached. The aim of this study was to compare the incidence rates of postoperative complications after pelvic lymphadenectomy (PLX) with or without PALX in patients with uterine corpus cancer. Methods: A retrospective chart review was carried out for all patients with endometrial cancer treated at 2 tertiary centers between 1998 and 2004. Surgery at one institute included both PLX and PALX, whereas PLX alone was routinely performed at the other institute. A total of 142 patients underwent PLX + PALX and 138 patients underwent PLX alone. We evaluated postoperative complications including intraoperative injury, ileus, lymphedema, lymphocyst, and thrombosis. Results: There was no fatal accident associated with surgery. Lymphedema was the most frequent complication. Comparing the PLX + PALX group and the PLX group, there were no significant differences in the rate of cases of lymphedema (23.2% vs 28.3%), lymphocyst (9.2% vs 9.4%), and thrombosis (4.9% vs 2.2%). The rate of cases of mild/moderate ileus in the PLX + PALX group was significantly higher than that in the PLX group (10.5% vs 2.9%; P = 0.011). However, no significant difference in the rates of cases of severe ileus was found between the 2 groups (1.4% vs 0.7%). There were also no significant differences between the 2 groups in the rates of intraoperative organ injury (2.8% vs 2.2%) and secondary operation for postoperative complications (4.9% vs 4.3%). Conclusions: Para-aortic lymphadenectomy can be performed with an acceptable morbidity under the conditions in which it is performed by experienced surgeons, and measures to prevent complications are properly taken.

Treatment of cervical cancer with adjuvant chemotherapy versus adjuvant radiotherapy after radical hysterectomy and systematic lymphadenectomy

Aim:  To compare the clinical efficacy focused on post‐treatment morbidity between adjuvant chemotherapy (CT) and pelvic radiotherapy (RT) after radical hysterectomy for patients with cervical cancer.

Growing teratoma syndrome of the Ovary: A case report with FDG ‐PET findings

Growing teratoma syndrome (GTS) is defined as enlarging masses during or after chemotherapy for germ cell tumors, and containing only mature teratoma components. A surgical resection is important to confirm a diagnosis and thereby result in the resection of the most appropriate therapeutic management. GTS is a rare event in association with ovarian germ cell tumors. This report presents a case of a 36‐year‐old female treated surgically for GTS found during the follow‐up after chemotherapy and the primary surgical resection of a malignant immature teratoma. Those masses showed fluorodeoxyglucose positron emission tomography positivity and elevated serum CA19‐9 prior to the second operation. The histology revealed a mature teratoma. The patient has been disease free for 6 months after the second operation.

Para-aortic lymph node metastasis in relation to serum CA 125 levels and nuclear grade in endometrial carcinoma.

Background. To investigate the relationship between preoperative serum CA 125 levels and para‐aortic lymph node (PAN) metastasis as determined by systematic pelvic and para‐aortic lymph node dissection in endometrial carcinoma.

Clinical significance of tumor volume in endometrial cancer: A Japan–Korea cooperative study

OBJECTIVE The aim of this study was to elucidate the significance of tumor volume as a risk factor for predicting lymph node metastasis. METHODS We applied the tumor volume index to the data that were collected for 327 Korean patients with endometrial cancer who underwent preoperative assessment including magnetic resonance imaging (MRI) and subsequent surgery including systematic lymphadenectomy. The volume index, which we previously reported in the literature, was defined as the product of maximum longitudinal diameter along the uterine axis, maximum anteroposterior diameter in a sagittal section image, and maximum horizontal diameter in a horizontal section image according to MRI data, from 425 Japanese women with endometrial cancer. Relationships between lymph node metastasis and results of preoperative examinations including volume index were analyzed by logistic regression analysis. RESULTS The prevalence of affected lymph nodes was 14.2%. Multivariate analysis showed that high-grade histology assessed by endometrial biopsy [odds ratio (OR); 2.9, 95% confidence interval (CI): 1.4-6.4], volume index (OR; 2.4, 95% CI: 1.1-5.3), node enlargement assessed by MRI (OR; 4.2, 95% CI: 1.4-13.2), and high serum cancer antigen (CA)125 level (OR; 3.6, 95% CI: 1.6-8.1) were significantly and independently related to lymph node metastasis. When volume index was excluded from the analysis, myoinvasion assessed by MRI was an independent risk factor for lymph node metastasis as well as high-grade histology, node enlargement, and high serum CA125 level. CONCLUSION Volume index is compatible with myometrial invasion as a factor for predicting lymph node metastasis in endometrial cancer.

Ultrastaging of para-aortic lymph nodes in stage IIIC1 endometrial cancer: A preliminary report

OBJECTIVE The aim of this study was to determine the rate of occult metastasis, including isolated tumor cells, in para-aortic lymph nodes of patients with stage IIIC1 endometrial cancer who underwent pelvic and para-aortic lymphadenectomy. METHODS A series of 15 patients who had undergone combined pelvic and para-aortic lymphadenectomy during the period from 2004 to 2010 and who were diagnosed as being positive for pelvic node metastasis but negative for para-aortic node metastasis were included in this study. Ultra-staging by multiple slicing, staining with hematoxylin/eosin and cytokeratin, and microscopic inspection was performed on a total of 242 para-aortic lymph nodes. RESULTS Eleven (73.3%) of the 15 patients had occult para-aortic lymph node metastasis. Two patients (13.3%) had macrometastasis and nine patients (60.0%) had isolated tumor cells. Type 2 endometrial cancer tended to have a higher rate of occult metastasis than that of type 1 cancer (90% vs. 40%, P=0.07). The rate of occult para-aortic node metastasis was not related to the number of metastatic pelvic nodes. Five patients suffered recurrence in the lung or in the intraabdomen, but lymph node recurrence was not found in any case. CONCLUSION Patients with stage IIIC1 endometrial cancer have a potentially high rate of occult para-aortic node metastasis. Local treatment of the para-aortic region should be considered in patients with stage IIIC1 endometrial cancer until effective adjuvant therapy is established.