Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy

BACKGROUND: The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy. METHODS: A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors. RESULTS: Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively. CONCLUSIONS: LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.     

Postoperative pelvic radiotherapy for cervical cancer patients with positive parametrial invasion

OBJECTIVE: To evaluate patterns of failure in cervical cancer patients with histopathologic parametrial invasion treated with postoperative pelvic radiation therapy. METHODS: Records of 117 stages IB-IIB cervical cancer patients with parametrial invasion treated with postoperative radiation therapy from 1985 to 2002 were retrospectively reviewed. Patients were divided into two groups based on status of pelvic lymph nodes. Patterns of recurrence and prognosis by status of pelvic lymph nodes were statistically analyzed. RESULTS: Status of pelvic lymph nodes had significant impact on both recurrence and survival. Extrapelvic recurrence was observed in 23 of 66 node-positive patients compared with 6 of 51 node-negative patients (P = 0.005). Of 66 patients with a positive pelvic lymph node, 18 developed visceral metastases, whereas only three visceral metastases were noted in the 51 node-negative patients (P = 0.003). Five-year overall survival in node-positive and -negative patients was 52% and 89%, respectively (P = 0.0005). Corresponding rates for recurrence-free survival were 44% and 83%, respectively (P = 0.0002). The correlation between nodal metastasis and prognosis was enhanced when node-positive patients were stratified into two groups based on number of positive nodes (n = 1 and n > or = 2). Five-year recurrence-free survival rates for patients with negative, one positive, and two or more positive nodes were 83%, 61%, and 31%, respectively (P = 0.0001). CONCLUSIONS: Extrapelvic recurrence was uncommon in node-negative patients with parametrial invasion. These findings do not support use of systemic therapy for cervical cancer patients with parametrial invasion if pelvic lymph node metastasis is negative.     

子宫颈鳞癌Ⅰb～Ⅱa期患者预后预测系统的建立及其临床意义

目的分析子宫颈鳞癌Ⅰb~Ⅱa期患者的预后影响因素并建立预后预测系统,以探讨其在指导术后辅助治疗中的作用。方法回顾性分析接受手术治疗的306例Ⅰb~Ⅱa期宫颈鳞癌患者的临床病理资料,对影响其预后的因素进行单因素和多因素分析。结果306例患者的5年生存率为78 1%。单因素分析结果显示,与其预后有关的因素为淋巴结转移、病理分化程度、肿瘤直径、宫旁组织浸润、深肌层浸润和脉管内瘤栓(P<0 05);多因素分析结果显示,淋巴结转移、深肌层浸润、宫旁组织浸润是影响其预后的独立危险因素(P<0 05)。根据危险因素的不同建立预后预测系统,即将患者分为低危组、中危组和高危组3组,其5年生存率分别为90 3%、83 9%和43 1%。低危组(无危险因素或仅宫旁组织浸润)局部复发的发生率仅为2 2%;中危组(深肌层浸润或合并有宫旁组织浸润)局部复发的发生率为13 5%,远处转移的发生率为1 3%, 局部复发合并远处转移的发生率为0 6%;高危组(淋巴结转移或合并其他危险因素)局部复发和远处转移的发生率分别为25 9%和48 3%,局部复发合并远处转移的发生率为10 3%。结论淋巴结转移、深肌层浸润、宫旁组织浸润是影响Ⅰb~Ⅱa期宫颈鳞癌患者预后的独立因素;根据预后影响因素建立的预后预测系统有助于指导术后辅助治疗。     

The prognostic factors for patients with early cervical cancer treated by radical hysterectomy and postoperative radiotherapy

PURPOSE: This study was undertaken to evaluate the efficacy of postoperative radiotherapy (post-OP RT) and to investigate the prognostic factors for early-stage cervical cancer patients who were treated by radical surgery, and the pathological findings suggested a relatively high risk of relapse with surgery alone. MATERIALS AND METHODS: From January 1990 to December 1995, 222 patients with stage IB-IIA cervical cancer, treated by radical surgery and a full course of post-OP RT, were included in this study. The indications for post-OP RT were based on pathological findings, including lymph node metastasis, positive surgical margins, parametrial extension, lymphovascular permeation, and invasion of more than two-thirds of the cervical wall thickness. The radiation dose of external beam was 44-45 Gy to the whole pelvis and 50-54 Gy to the true pelvis. One hundred seventy-two patients also received intravaginal brachytherapy as a local boost. The minimal follow-up period was 2 years. RESULTS: The actuarial 5-year overall and disease-specific survival rates for all patients were 76 and 82%, respectively. The tumor control rate within the pelvis reached 94%, and distant metastasis was the major cause of treatment failure. Univariate analysis of clinical and pathological parameters revealed that clinical stage, bulky tumor size, positive lymph nodes, parametrial extension, and histologic type were significant prognostic factors. After multivariate analysis, only positive lymph nodes (P = 0.01), bulky tumor size (P = 0.02), and parametrial extension (P = 0.05) independently influenced the disease-specific survival (DSS). For patients with lymph node metastasis, the number and location of the nodal involvement significantly affected the prognosis. The 5-year DSS for patients with no, one, and more than one lymph node metastasis were 87, 84, and 61% (P = 0.0001), respectively. Patients with upper pelvic lymph node metastasis had a higher incidence of distant metastasis (50% vs 16% in lower pelvic node group, P = 0.03). In the subgroup of single lower pelvic nodal metastasis, the prognosis was similar to that of patients without lymph node involvement (5-year DSS 85% vs 87%, P = 0.71). CONCLUSION: Our results indicate that post-OP RT can achieve very good local control in stage IB-IIA cervical cancer patients whose pathological findings show risk features for relapse after radical surgery. The prognostic factors for treatment failure identified in this study can be used as selection criteria for clinical trials to test the effects of other adjuvant treatments, such as chemotherapy. Patients with a single lower pelvic lymph node metastasis have a relatively good prognosis and may not need adjuvant treatment beyond radiation therapy.     

盆腔淋巴清扫术对子宫内膜癌预后的影响

目的　探讨子宫内膜癌盆腔淋巴转移的相关因素及盆腔淋巴清扫术对子宫内膜癌预后的影响。方法　选择 1981年 1月至 2 0 0 2年 12月行子宫内膜癌盆腔淋巴清扫术患者 90例 ,淋巴结取样活检术患者 12例 ,分析这 10 2例患者淋巴转移与各临床病理指标的关系。随机选取同期未行淋巴清扫术的 90例患者作为对照与行淋巴清扫术的 90例患者进行比较 ,寿命表法计算两者的生存率。结果　 10 2例患者中 ,低分化、深肌层浸润、宫颈浸润、腹腔冲洗液细胞学检查阳性、附件浸润、远处转移者 ,盆腔淋巴转移的发生率升高 ,分别为 46%、42 %、44%、52 %、75%、10 0 %。盆腔淋巴转移患者的 5年累计生存率 (3 7% )低于无淋巴转移者 (89% ,P <0 0 1)。 90例行盆腔淋巴清扫术患者与对照者的 5年累计生存率分别为 78%和 72 % ,两者比较 ,差异无显著性 (P >0 0 5)。COX逐步回归分析显示 ,盆腔淋巴清扫术不是影响患者预后的独立因素。结论　低分化、深肌层浸润、宫颈浸润、腹腔冲洗液细胞学检查阳性、附件浸润、远处转移是子宫内膜癌盆腔淋巴转移的高危因素 ,有盆腔淋巴转移的患者预后差 ,但盆腔淋巴清扫术并不改善患者预后     

卵巢癌腹主动脉旁淋巴结清除术与生存率的关系

目的:探讨上皮性卵巢癌患者行腹主动脉旁淋巴结清除术与其生存预后的关系。方法:回顾分析卵巢癌肿瘤细胞减灭术的80例患者,将其中行腹主动脉旁淋巴结(PAN)+盆腔淋巴结(PLN)清除术分为A组(30例),仅行PLN清除术者分为B组(50例),分析PAN清除与患者生存预后的相关性。结果:行卵巢肿瘤细胞减灭术的80例患者中,32例(40.0%)发生淋巴结转移。A组中19例发生淋巴结转移,其中仅PAN阳性7例,仅PLN阳性3例,PAN和PLN均阳性9例;B组中13例发生PLN转移。A与B组患者的淋巴结转移与临床分期、肿瘤细胞分化程度和组织学类型显著相关(P0.05)。A组中淋巴结转移部位以PAN最多16例,其余依次为髂内、闭孔、髂总、腹股沟及髂外淋巴结。A组患者的3年、5年生存率分别为77.9%和46.7%,均高于B组(69.0%和39.2%),但无显著差异(P0.05)。A与B组患者中转移至PLN者的3年生存率分别是68.5%和41.4%,5年生存率是49.7%和26.4%,两组比较差异显著(P=0.044)。A组患者中淋巴结阳性与阴性患者3年生存率分别为43.5%和72.7%,5年生存率是27.2%和58.5%,差异显著(P=0.048)。Cox模型单因素分析提示,淋巴结状态对患者的生存率有影响(P0.01),而且是死亡风险因素。结论:腹主动脉旁淋巴结的清除对改善卵巢癌患者预后起着重要作用。     

Pattern of lymph node metastasis and the optimal extent of pelvic lymphadenectomy in FIGO stage IB cervical cancer

AIM: To evaluate the distribution pattern of lymph node metastasis and to determine the optimal extent of pelvic lymphadenectomy (LA) in FIGO stage IB cervical cancer. METHODS: The medical records of 187 patients with FIGO stage IB cervical cancer from March 1996 to December 2002 were reviewed retrospectively. The distribution pattern and risk factors of lymph node metastases were analyzed in 31 patients with lymph node metastases confirmed surgically. One hundred patients, who underwent type III hysterectomy with pelvic LA but did not receive any adjuvant treatment, were analyzed to evaluate whether the extent of LA affected the prognosis of FIGO stage IB cervical cancer. Type I LA included the external iliac nodes, hypogastric nodes, obturator nodes, and parametrial nodes. Type II LA included the pelvic nodes described in type I LA, the common iliac nodes, gluteal nodes, deep inguinal nodes and sometimes the presacral nodes. RESULTS: Solitary lymph node metastasis confined to one node group was seen in the obturator, external iliac or hypogastric lymph nodes. All patients with lymph node metastases at multiple sites had metastasis in at least one of these lymph-node groups. There was no significant difference in disease-free survival and overall survival in patients without pathologic high-risk factors according to the type of pelvic LA. CONCLUSION: The extent of LA should be adjusted to reduce complications and not to affect adversely the prognosis of FIGO stage IB cervical cancer patients without pathologic high-risk factors.     

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.     

淋巴结转移的Ⅰb 1～Ⅱb期子宫颈癌患者手术后的综合治疗及预后分析

目的研究淋巴结转移的Ⅰb1～Ⅱb期宫颈癌患者广泛性子宫切除加盆腔淋巴结切除术后综合治疗的方式和预后。方法选取1990年1月至2003年6月复旦大学附属肿瘤医院接受手术治疗的Ⅰb1～Ⅱb期淋巴结转移的宫颈癌患者215例。所有患者均接受了广泛性子宫切除加盆腔淋巴结切除术。根据术后治疗情况将患者分为4组：放疗加化疗组（107例）、放疗组（45例）、化疗组（22例）和无辅助治疗组（41例）。通过比较4组患者的临床病理资料,对患者预后及可能影响预后的有关因素进行分析。结果放疗加化疗组、化疗组、放疗组和无辅助治疗组患者的3年无瘤生存率分别为60．7％、53．5％、47．4％和36．0％,放疗加化疗组患者的3年无瘤生存率显著高于无辅助治疗组,两组比较,差异有统计学意义（P=0．001）,而化疗组、放疗组的3年无瘤生存率分别与无辅助治疗组比较,差异无统计学意义（P值分别为0．060和0．159）。放疗加化疗组、化疗组、放疗组和无辅助治疗组患者的盆腔复发率分别为7．5％、22．7％、26．7％和34．1％,远处转移率分别为16．8％、18．2％、15．6％和22．0％,复发合并转移率分别为4．7％、0、4．4％和7．3％。放疗加化疗组盆腔复发率显著低于其余3组,与其余3组比较,差异有统计学意义（P〈0．01）,而远处转移率、复发合并转移率与其余3组比较,差异无统计学意义（P〉0．05）。多因素分析显示,肿瘤直径、病理类型、淋巴结转移数目和术后辅助治疗是影响淋巴结转移的宫颈癌患者预后的重要因素（P〈0．05）。结论淋巴结转移的宫颈癌患者根治性手术后辅助放、化疗能提高3年无瘤生存率,降低盆腔复发率。     

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. METHODS: The preoperative serum levels of squamous cell carcinoma antigen (SCC), cancer antigens CA125 and CA19-9 were assayed simultaneously in 103 patients with stages IB to IIB cervical SCC undergoing radical hysterectomy. The cut-off values of SCC, CA125, and CA19-9 in this study were 1.5 ng/ml, 35 U/ml, and 37 U/ml, respectively. The relation between preoperative tumor marker levels and histopathologic prognostic factors including lymph node metastasis and patient survival was studied. RESULTS: Preoperative serum SCC, CA125, and CA19-9 levels were significantly related to the FIGO stage. In addition, serum SCC and CA125 levels were significantly related to tumor diameter, depth of cervical stromal invasion, lymph-vascular space invasion, and lymph node metastasis. We subsequently created a double-tumor-marker (DTM) index, which incorporated the number of positive markers of SCC and CA125. The DTM index was strongly related to the number of positive pelvic lymph nodes (p = 0.0002) and to the site of positive nodes (none vs. pelvic only vs. common iliac/paraaortic) (p = 0.0005). Probability of lymph node metastasis according to the DTM index = 0, 1, and 2 was 6/48 (12.5%), 14/45 (31.1%), and 8/10 (80.0%), respectively. The rate of common iliac/paraaortic node metastasis according to the DTM index = 0, 1, and 2 was 1/48 (2.1%), 2/45 (4.4%), and 3/10 (30.0%), respectively. By logistic regression analysis, it was shown that the DTM index and tumor diameter were independently related to lymph node metastasis. Using multivariate Cox regression analysis including singly determined serum SCC and CA125 levels, clinical stage (IB/IIA vs. IIB), tumor diameter ( 4 cm), parametrial invasion, lymph node metastasis, and the DTM index, the DTM index was found to be the most important prognostic factor (p = 0.0005). However, when the sites of positive nodes were included in the multivariate analysis, only the sites of positive nodes (p = 0.0008) and parametrial invasion (p = 0.041) showed independent prognostic significance. CONCLUSION: Combination assay of pretreatment serum SCC and CA125 levels seems to be useful in estimating lymph node status and the prognosis for patients with cervical SCC in a preoperative setting.     

Significance of pathologic patterns of pelvic lymph node metastases in endometrial cancer

OBJECTIVE: The aim of this study was to correlate the pathologic characteristics of pelvic lymph node metastases with survival, recurrence, and patterns of recurrence in endometrial cancer. METHODS: Sixty patients with epithelial endometrial cancer and pelvic node metastasis were managed surgically between 1984 and 1993 at the Mayo Clinic. The mean number of nodes harvested was 16.7 and the mean number of nodes positive was 3.0. Mean follow-up was 45.5 months. The pathologic patterns of lymph node metastases were characterized. RESULTS: Outcome was related to pathologic patterns of pelvic node metastasis. Both diameter of lymph node metastasis (P < 0.01) and capsular integrity (P < or = 0.01) influenced 5-year disease-related survival and 5-year progression-free survival. The percentage of biopsied pelvic lymph nodes harboring metastatic disease and the proportion of the involved lymph nodes occupied by tumor significantly influenced death rates and recurrence rates (P < 0.05). The immune response and the absolute number of positive pelvic nodes did not impact recurrence or survival. The above characteristics of pelvic node metastasis correlated also with patterns of recurrence. Regression analysis indicated that capsular integrity (RR = 2.97; P = 0.005) and proportion of positive pelvic nodes biopsied (RR = 3.84; P = 0.01) were significant predictors of recurrence, whereas diameter of metastasis (RR = 3.68; P = 0.02) and proportion of positive pelvic nodes biopsied (RR = 4.04; P = 0.02) were most predictive of survival. CONCLUSIONS: The pathologic patterns of pelvic node metastasis appear to be significantly related to survival, recurrence, and patterns of recurrence.     

宫颈小细胞癌与非小细胞癌临床特征及预后的对比研究

目的:对比性研究宫颈小细胞癌(SCCC)与宫颈非小细胞癌在发病特点、临床特征、治疗方案、预后情况等方面的差异,并探究影响其预后的因素。方法:回顾性分析2003年5月至2015年6月四川大学华西第二医院收治的宫颈小细胞癌患者63例(SCCC组)和根据诊断时间及相近的FIGO分期配对的宫颈非小细胞癌(鳞癌、腺癌)患者60例(对照组)的临床病理资料及生存情况,采用Pearson卡方检验或Fisher确切概率法比较两组临床特征、治疗方案等方面的差异,Kaplan-Meier方法比较两组总体生存率及无病生存率的差异,单因素和多因素分析影响SCCC预后的因素。结果:(1)SCCC组患者初诊的中位年龄较对照组年轻(40岁vs 44岁,P=0.001),淋巴结转移率、宫旁浸润率、脉管累及率及手术切缘阳性率也均显著高于对照组(P0.05)。而在临床症状、肿块大小、诊断分期、术前治疗、术后治疗等方面比较两者差异均无统计学意义(P0.05)。(2)生存分析中,SCCC组的累积5年生存率(29.2%)与累积5年无瘤生存率(26.6%),显著低于对照组(分别为82.6%、76.7%),差异有统计学意义(P0.05)。(3)在影响SCCC预后的多因素COX多元回归分析结果显示,有淋巴结转移是影响患者5年总生存率和5年无瘤生存率的独立危险因素(HR=4.784、3.067,P0.05)。肿块直径≥4 cm是影响5年总生存率的独立危险因素(HR=3.610,P0.05)和FIGO分期(ⅠB2以上)是影响无瘤生存率的独立危险因素(HR=2.793,P0.05)。结论:SCCC患者更年轻,其临床症状、病灶外观、治疗方案等和宫颈非小细胞癌相似,但淋巴结转移率、脉管累及率、宫旁浸润率及手术切缘阳性率均显著高于宫颈非小细胞癌,预后极差。影响SCCC患者预后的主要因素为有无淋巴结转移、FIGO分期、肿块直径。     

早期子宫颈癌脉管间隙及宫旁浸润危险因素1245例分析

目的:探讨子宫颈癌淋巴脉管间隙浸润(lymph-vascular space invasion,LVSI)及宫旁浸润与其他临床病理因素的关系。方法:回顾性分析2009年1月至2019年1月期间于西安交通大学第一附属医院妇科接受手术治疗1245例早期子宫颈癌患者的临床资料,分别根据是否LVSI及宫旁浸润分为LVSI组、无LVSI组和宫旁浸润组、无宫旁浸润组,采用单因素和多因素Logistic回归分析脉管及宫旁浸润危险因素。结果:1245例LVSI率14.1%(175/1245),宫旁浸润率1.85%(23/1245)。单因素分析显示LVSI的发生与病灶类型、病理类型、肿瘤细胞分化程度、子宫颈浸润深度、淋巴转移、切缘阳性、宫旁浸润比较,差异有统计学意义(P<0.05)。根据淋巴转移情况分层分析发现,在淋巴未转移组LVSI的发生率与年龄、病灶类型、病理类型、子宫颈浸润深度比较,差异有统计学意义(P均<0.05)。Logistic回归分析显示病灶类型为内生型、病理为鳞癌、子宫颈深肌层浸润和淋巴转移相较于非内生型、非鳞癌、子宫颈浸润浅肌层、无淋巴转移早期子宫颈癌患者是发生LVSI的独立危险因素(OR>1,P<0.05)。单因素分析显示宫旁浸润与病灶类型、子宫颈浸润深度、累及阴道、累及宫体下段、切缘阳性、淋巴转移、LVSI有关(P<0.05)。Logistic回归分析示病灶类型为内生型、累及宫体下段、淋巴转移相较于非内生型、未累及宫体下段、无淋巴转移的早期子宫颈癌患者是发生宫旁浸润的独立危险因素(OR>1,P<0.05)。结论:子宫颈深肌层浸润、淋巴结转移、内生型的子宫颈鳞癌患者更可能发生LVSI;病灶类型为内生型、累及宫体下段、淋巴转移的患者更可能发生宫旁浸润。     

Results of postoperative radiotherapy for clinical stage Ib uterine cervical carcinoma with evidence of microscopic involvement of surgical margin, parametrium and/or lymph node metastasis.

From January 1979 to September 1985, a total of 125 patients preoperatively staged as International Federation of Gynecology and Obstetrics (FIGO) Ib uterine cervical carcinoma were proven to have either microscopic involvement of the surgical margin, parametrium and/or regional lymph node metastasis histopathologically after radical hysterectomy and pelvic lymphadenectomy. All of these patients were treated postoperatively with radiotherapy because of the above indications. Based on indications of postoperative radiotherapy, patients were divided into 3 major subgroups according to the microscopic involvement: group A patients (50) with microscopic evidence of regional lymph node metastasis only; group B patients (59) with microscopic evidence of parametrial involvement; and group C patients (16) with microscopic infiltration of the surgical margin involving the vaginal cuff. All patients were treated with external irradiation using a Cobalt-60 teletherapy machine. The overall actuarial 5-year survival rate was 62% with a 77% 5-year survival rate for group A, a 50% rate for group B and a 75% rate for group C. Further analysis of the prognostic factors revealed that those with regional lymph node involvement of 4 or less had a better chance of survival than those with lymph node involvement of more than 4. Also those with poorly differentiated squamous cell carcinoma had a lower 5-year survival rate than those with moderately or well-differentiated squamous cell carcinoma. Univariate analysis revealed that hemoglobin values, age, and the time interval from surgery to radiotherapy were not significant prognostic factors.     

Uterine body invasion of carcinoma of the uterine cervix as seen from surgical specimens

To estimate the actual states of uterine body invasion of carcinoma of the uterine cervix, 301 radically hysterectomized specimens were reviewed histologically. Incidence of uterine body invasion was 21.6% in all cases (65 cases out of 301), 7.8% in stage Ib, 25.5% in stage IIa, and 38.2% in stage IIb. Most of the positive invasion cases had spread to other surrounding tissues. Vaginal wall was invaded in 58.5% of all positive cases, parametrial infiltration was recognized in 87.7%, and pelvic lymph node metastasis was seen in 52.3%. On the contrary, in negative cases these were 33.9, 19.1, and 15.7%, respectively. There was a higher incidence of the L type of Imai's CPL classification among positive cases of uterine body invasion than among negative cases (81.5% vs 38.1%). When cervical cancer spread into the uterine body, peritoneal carcinomatosis and distant metastasis increased. Thus the outcome of patients with positive invasion was, naturally, poor. Patients with negative invasion had a 5-year survival rate of 92.4%, compared to 53.8% in patients with positive uterine body invasion. These results suggest that uterine body invasion of carcinoma of the uterine cervix is an important prognostic factor and treatment should be modified in such cases.     

Lymph node pathway in the spread of endometrial carcinoma

OBJECTIVE: To elucidate the sentinel nodes of endometrial carcinoma, the spread pathway was clarified. The correlation between lymph node spread and other clinicopathological variables was also analyzed. METHODS: Dissected lymph node samples in 342 patients who underwent pelvic and selective paraaortic lymphadenectomy were reviewed. Pelvic and paraaortic node (PLN and PAN) status was compared with clinicopathological parameters. RESULTS: Lymph node metastasis was demonstrated in 52 patients, including 46 cases with PLN metastasis and six patients with independent PAN metastasis. The metastatic sites were most frequent in the obturator and internal iliac nodes. Eleven of 49 patients who underwent PAN dissection were positive for metastasis. Sixteen of 23 cases with parametrial metastasis also metastasized in the retroperitoneal lymph node. CONCLUSION: The lymph node spread pathway in endometrial carcinoma consists of a major route via the obturator node or internal iliac node with or without parametrial involvement, and rarely a direct PAN pathway.     

The case for completing the lymphadenectomy when positive lymph nodes are found during radical hysterectomy for cervical carcinoma

BACKGROUND: In the present study we report on the results of a retrospective study on the effect on survival of the pelvic lymphadenectomy in a group of 294 patients with stage Ia2-IIa cervical carcinoma treated by radical hysterectomy from 1984 through 1996 at the Leiden University Medical Center. METHODS: Lymphadenectomy was called 'complete' when lymph node bearing tissue had been removed from 5 or 6 lymph node stations and 'not-complete' when this was the case in 1-4 stations. RESULTS: A radical hysterectomy was carried out in 294 patients. In 63 patients positive lymph nodes were found. Patients with positive nodes showed poorer 5 year survival: 64.5% compared to 90% in patients with negative nodes. In the univariate analysis the following factors were found to affect the presence of node metastases in a statistically significant way: age, tumor size, depth of infiltration, vaso-invasion, surgical margins, parametrial infiltration, stage and place of referral. In 63 patients with positive nodes, a complete lymphadenectomy was carried out in 23 patients, and in 40 patients the procedure was incomplete. All 63 patients were treated by adjuvant radiation therapy; those with complete lymphadenectomy had significantly less recurrences (25%) compared to those with incomplete lymphadenectomy (56%): the relative risk (RR) was 2.9 (95% ci: 1.3-6.7), p=0.012. After adjustment for other prognostic factors including tumor size, depth of infiltration and parametrial involvement, the complete lymphadenectomy showed an independent effect on disease free survival: RR= 3.2 (95% ci: 1.3-7.7), p=0.011. Prognostic factors were not significantly different for patients with complete or incomplete lymphadenectomy. CONCLUSIONS: From the results of this study, although retrospective and non randomized, it can be concluded that to complete removal of lymph nodes in combination with radical hysterectomy seems to have a beneficial effect on prognosis in case of positive nodes. The policy of aborting the procedure when lymph node metastases are found in frozen section should be questioned.     

Surgical pathologic factors in patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection: association with administration of adjuvant radiotherapy and effect on survival

PURPOSE OF INVESTIGATION: To identify surgical pathologic factors that best correlate with administration of adjuvant radiotherapy and best predict survival in early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection (RHND). METHODS: Data from the files of 126 patients with cervical carcinoma treated by RHND at the Soroka Medical Center from 1962 through 2005 were analyzed. RESULTS: Fifty-four percent of the patients received postoperative adjuvant radiotherapy. In a univariate analysis, each of the following factors: positive pelvic lymph nodes, lower uterine segment involvement, lymph vascular space involvement, penetration > or = 50% of the cervical wall, grade 2+3, parametrial and/or paracervical involvement, vaginal margin involvement, non-squamous histologic type, tumor size > or = 3 cm and Stage IB2 + IIA was significantly associated with administration of radiotherapy. In a multivariate analysis, positiviy of pelvic lymph nodes was persistently the most significant factor associated with administration of radiotherapy. The 5-year survival rate was 82.6% overall. In a univariate analysis, a significant worsening in survival was demonstrated with positivity of pelvic lymph nodes and positivity of lymph vascular space involvement. In a "better fit" model of multivariate analysis, pelvic lymph node status was the strongest and the only significant predictor of survival. CONCLUSIONS: In patients with early-stage cervical carcinoma treated with radical hysterectomy and pelvic lymph node dissection, pelvic lymph node status is the strongest factor affecting administration of adjuvant radiotherapy and the most significant predictor of survival.     

Do the pelvic lymph nodes predict the parametrial status in cervical cancer stages IB–IIA?

The aim of this study was to determine whether the pelvic lymph nodes would predict the parametrial status in patients with cervical cancer stages IB1-IIA submitted to radical surgery and pelvic lymphadenectomy. To this end, we evaluated the relationship between positive and negative pelvic lymph nodes and their parametria. Our final purpose was to use this information to recommend the tailoring of the parametrial resection according to the status of pelvic lymph nodes to decrease the morbidity related with radical paratrectomy. From January 1996 to December 2001, 107 consecutive patients with cervical cancer stages IB1 and IIA were primarily treated by radical hysterectomy type III with systematic pelvic lymphadenectomy in a prospective study. Parametria were studied in two sections: the first included the tissue adjacent to the cervix, and the second the distal 2/3. Lymph nodes were routinary processed. Twenty-two patients (20.6%) had positive pelvic nodes and 16 patients (14.9%) had parametrial involvement, mostly by direct extension. Eight patients with positive pelvic nodes (36.4%) had parametrial involvement, whereas among 85 patients with negative pelvic nodes only eight patients (9.4%) had parametrial involvement (P < 0.001), most in internal parametria (62.5%). The sensitivity of pelvic lymph nodes for parametrial involvement was 50% and the positive predictive value was 36.4%, whereas the specificity was 84.6%; and the negative predictive value 90.6%. In the group of negative pelvic lymph nodes, only two patients (2.3%) had parametrial involvement beyond internal parametria. The univariated and multivariated analysis of prognostic factors was always significant but without a significant independent factor for positive parametria. Pelvic lymph nodes appear as good predictors of parametrial status, especially in node-negative patients, and could be used to decrease the paratrectomy in radical surgery.     

Clear cell carcinoma of the uterine cervix: pathology and prognosis in surgically treated stage IB-IIB disease in women not exposed in utero to diethylstilbestrol

OBJECTIVE: The purpose of this research was to compare the clinical behavior, pathology findings, and prognosis of surgically treated FIGO stage IB-IIB clear cell carcinomas of the cervix with those of squamous cell carcinomas and non-clear cell adenocarcinomas. METHODS: Fifteen patients with clear cell adenocarcinomas of the cervix (8 FIGO stage IB, 7 FIGO stage IIB) were reviewed. The control group consisted of 444 squamous cell carcinomas and 59 non-clear cell adenocarcinomas. None of the patients had a history of in utero exposure to diethylstilbestrol. All patients underwent radical abdominal hysterectomy with systematic pelvic lymphadenectomy. All specimens were processed as serial giant frontal sections. The mean follow-up in the clear cell group was 83 (13-182) months. Statistical analysis was done with contingency tables, chi(2) tests, and Fisher's exact test. RESULTS: Twelve of the fifteen clear cell carcinomas (80%) were endophytic and tended toward deep cervical infiltration. Clear cell carcinomas extended to the uterine corpus significantly more often than squamous cell and non-clear cell adenocarcarcinomas (P < 0.001). The rates of parametrial involvement and pelvic lymph node involvement were 40 and 47%, respectively. Four patients (27%), all with positive pelvic nodes, developed recurrences an average of 14 (4-48) months after initial therapy. The extrapelvic sites of relapse were the lung, liver, and bone. Clear cell carcinomas had a worse 5-year survival rate (67%) than squamous cell carcinomas (80%) and non-clear cell adenocarcinomas (77%) but this was not statistically significant (P = 0.6). No significant differences were seen for age, growth pattern, parametrial and vaginal involvement, parametrial and pelvic lymph node metastases, frequency of recurrent disease, and time to first recurrence. CONCLUSION: The clinicopathologic findings and prognosis of surgically treated patients with stage IB-IIB clear cell carcinomas without exposure to diethylstilbestrol in utero are similar to those of patients with squamous cell carcinomas and non-clear cell adenocarcinomas.