Shinichiro Minobe

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.

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.

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.

Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer

Objective The aim of this study was to clarify the clinical significance of isolated tumor cells (ITCs) or micrometastasis (MM) in regional lymph nodes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II endometrial cancer. Methods In this study, a series of 63 patients with FIGO stage I to II were included, who had at least one of the following risk factors for recurrence: G3 endometrioid/serous/clear cell adenocarcinomas, deep myometrial invasion, cervical involvement, lympho-vascular space invasion, and positive peritoneal cytology. These cases were classified as intermediate-risk endometrial cancer. Ultrastaging by multiple slicing, staining with hematoxylin and eosin and cytokeratin, and microscopic examination was performed on regional lymph nodes that had been diagnosed as negative for metastases. Results Among 61 patients in whom paraffin-embedded block was available, ITC/MM was identified in nine patients (14.8%). Deep myometrial invasion was significantly associated with ITC/MM (p=0.028). ITC/MM was an independent risk factor for extrapelvic recurrence (hazard ratio, 17.9; 95% confidence interval [CI], 1.4 to 232.2). The 8-year overall survival (OS) and recurrence-free survival (RFS) rates were more than 20% lower in the ITC/MM group than in the node-negative group (OS, 71.4% vs. 91.9%; RFS, 55.6% vs. 84.0%), which were statistically not significant (OS, p=0.074; RFS, p=0.066). Time to recurrence tended to be longer in the ITC/MM group than in the node-negative group (median, 49 months vs. 16.5 months; p=0.080). Conclusions It remains unclear whether ITC/MM have an adverse influence on prognosis of intermediate-risk endometrial cancer. A multicenter cooperative study is needed to clarify the clinical significance of ITC/MM.

Initial failure site according to primary treatment with or without para-aortic lymphadenectomy in endometrial cancer

OBJECTIVE The objective of this study was to compare the initial failure sites in patients with endometrial cancer who underwent surgical treatment including pelvic lymphadenectomy with or without para-aortic lymphadenectomy. METHODS A retrospective chart review was carried out for 657 endometrial cancer patients with no residual disease after initial treatments including lymphadenectomy at two tertiary centers between 1987 and 2004. Surgical treatment at one institute included pelvic lymphadenectomy (PLX) without para-aortic lymphadenectomy (PALX), while surgical treatment including PLX+PALX was routinely performed at the other institute. We identified patients with recurrence and evaluated initial failure sites. Rates of recurrence in the respective sites were compared according to the type of lymphadenectomy. RESULTS Of the 657 patients, 103 (15.7%) suffered recurrence. There was no significant difference between the rate of intrapelvic recurrence in the PLX alone group and that in the PLX+PALX group (4.7% vs. 2.9%, p=0.22). The rate of extrapelvic recurrence in the PLX alone group was significantly higher than that in the PLX+PALX group (16.1% vs. 6.2%, p<0.0001), and the rate of para-aortic node (PAN) recurrence in the PLX alone group was also significantly higher than that in the PLX+PALX group (5.1% vs. 0.6%, p=0.0004). In the analysis of patients who received adjuvant chemotherapy, the rate of PAN recurrence in the PLX alone group was significantly higher than that in the PLX+PALX group (9.5% vs. 1.3%, p=0.0036). CONCLUSION PAN recurrence was a failure pattern peculiar to the PLX alone group. Adjuvant chemotherapy might not be able to replace surgical removal as a treatment for metastatic lymph nodes.

A validation study of the new revised FIGO staging system to estimate prognosis for patients with stage IIIC endometrial cancer

OBJECTIVE The aim of this study was to validate the role of the new FIGO staging system for estimating prognosis for patients with stage IIIC endometrial cancer. METHODS A total of 93 cases with stage IIIC were entered in this study and classified into three groups: one group of patients who underwent pelvic lymphadenectomy (PLX) and para-aortic lymphadenectomy (PALX) and who were for positive for pelvic node metastasis (PLNM) and negative for para-aortic node metastasis (PANM) (Group 1), one group of patients who underwent PLX alone and were positive for PLNM (Group 2) and one group of patients who underwent PLX and PALX and were positive for PANM (Group 3). Information on clinicopathologic findings and treatments was obtained from medical charts. Cox regression analysis was used to select prognostic factors. RESULTS The 5-years survival rates were 89.3% in Group 1, 46.5% in Group 2 and 59.9% in Group 3. The overall survival rate in Group 1 was significantly better than that in Group 2 (p=0.0001) and Group 3 (p=0.0016). No significant difference in overall survival was found between Group 2 and Group 3. Age, number of metastatic lymph nodes, type of lymphadenectomy and type of adjuvant therapy were significantly and independently related to overall survival. Only when patients received PALX, PANM was a prognostic risk factor. CONCLUSION Sub-classification of stage IIIC would be functional for estimating prognosis in the revised FIGO staging system. Systematic lymphadenectomy including PALX has therapeutic significance for patients with stage IIIC endometrial cancer. Prognosis of patients with stage IIIC endometrial cancer would depend much more on application of lymphadenectomy including PALX than nodal status.

Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy: a retrospective analysis in a Japanese cohort

Objective Concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer. We studied prognostic factors for patients treated with CCRT. Methods We retrospectively reviewed records of 85 consecutive patients with cervical cancer who were treated with CCRT between 2002 and 2011, with external beam radiation therapy, intracavitary brachytherapy, and platinum-based chemotherapy. Survival data were analyzed with Kaplan-Meier methods and Cox proportional hazard models. Results Of the 85 patients, 69 patients (81%) had International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease; 25 patients (29%) had pelvic lymph node enlargement (based on magnetic resonance imaging), and 64 patients (75%) achieved clinical remission following treatment. Median maximum tumor diameter was 5.5 cm. The 3- and 5-year overall survival rates were 60.3% and 55.5%, respectively. Cox regression analysis showed tumor diameter >6 cm (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2 to 4.6), pelvic lymph node enlargement (HR, 2.2; 95% CI, 1.1 to 4.5), and distant metastasis (HR, 10.0; 95% CI, 3.7 to 27.0) were significantly and independently related to poor outcomes. Conclusion New treatment strategies should be considered for locally advanced cervical cancers with tumors >6 cm and radiologically enlarged pelvic lymph nodes.

Previous conization on patient eligibility of sentinel lymph node detection for early invasive cervical cancer.

Objective: Sentinel lymph node (SLN) detection has been accepted as a common strategy to preserve the quality of life of the patients with gynecologic cancers. However, the feasibility of SLN detection after conization is not yet clarified. Accuracy of SLN after conization was evaluated. Methods: Eighteen cases with prior conization (cone group) and 32 cases without conization (noncone group), all of which belonged to IB1 except 1 case in IA stage, underwent SLN detection. Systemic pelvic and para-aortic lymphadenectomy was coincidently performed for the estimation of negative and positive predictive values. Results: Detection rate in which at least unilateral nodes were identified or bilaterally identified was 100% and 72.2% in the cone group, 90.6% and 71.9% in the noncone group, respectively. The average number of the detected SLN was 2.4 in the cone group and 2.1 in the noncone group. Negative and positive predictive value was 100% in both groups. On the distribution of sentinel node stations, most of the detected nodes were internal iliac and obturator node in both groups. Less frequent detection was observed in superficial common iliac node (5.4% in the cone group, 3.1% in the noncone group), external iliac node (2.7% and 9.5%), and parauterine artery node (5.4% and 1.6%). In both groups, no other lymph nodes were identified as SLN except 1 case in the cone group with the node in cardinal ligament. Conclusions: No significant difference was observed on detection rate, predictive value, and the distribution of sentinel node between the cone and noncone groups. Sentinel lymph node detection after conization can be performed with a certain reliability.

Incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes in intermediate- and high-risk endometrial cancer

OBJECTIVE The aim of this study was to elucidate the incidence of metastasis in circumflex iliac nodes distal to the external iliac nodes (CINDEIN), which are also called suprainguinal nodes, in intermediate- and high-risk endometrial cancer. Removal of these nodes needs to be discussed from the viewpoint of patients quality of life because removal of CINDEIN is strongly related to lower extremity lymphedema. METHODS A retrospective chart review was carried out for 508 patients with intermediate- and high-risk endometrial cancer who were included in this study. We identified patients with lymph node metastasis. Lymph node sites were classified into four groups: (1) CINDEIN, (2) external iliac nodes, (3) Group A consisting of circumflex iliac nodes to the distal obturator nodes, internal iliac nodes, obturator nodes, cardinal ligament nodes (including deep obturator nodes), and sacral nodes, and (4) Group B consisting of common iliac nodes and para-aortic nodes. Logistic regression analysis was used to select risk factors for CINDEIN metastasis. RESULTS In an analysis of 508 patients with intermediate- and high-risk disease, CINDEIN metastasis was found in fourteen (2.8%) of the patients. Multivariate analysis confirmed that high-risk histology (OR=5.7, 95% CI=1.2-16.1) and Group A node metastasis (OR=9.7, 95% CI=2.9-31.4) were independent risk factors for CINDEIN metastasis. None of the patients with G1 endometrioid adenocarcinoma had CINDEIN metastasis. Three (2.5%) of the patients with G2 endometrioid adenocarcinoma had CINDEIN metastasis and all of these three patients had other pelvic node metastasis. CONCLUSION Removal of CINDEIN can be eliminated in patients with G1 endometrial cancer and patients with G2 endometrial cancer who have no pelvic node metastasis.