A comparison of prognoses of FIGO stage IB adenocarcinoma and squamous cell carcinoma

OBJECTIVES: The objective of this study was to compare clinical and pathologic variables and prognosis of FIGO stage IB adenocarcinoma and squamous cell carcinoma of uterine cervix. METHODS: A retrospective review was performed of 521 patients with stage IB squamous cell carcinoma and adenocarcinoma of cervix who treated primarily by type 3 hysterectomy and pelvic and/or para-aortic lymphadenectomy at Hacettepe University Hospitals between 1980 and 1997. RESULTS: Age, tumor size, grade, depth of invasion, lymph node metastasis, parametrial, vaginal, and lymphvascular space involvement (LVSI) were not different between two cell types except number of the lymph nodes involved. Metastasis to three or more lymph nodes was significantly higher in adenocarcinoma. Overall and disease-free survival were 87.7%, 84.0% versus 86.4%, 83.1% for squamous cell carcinoma and adenocarcinoma, respectively (P > 0.05). The rate and site of recurrence were not different between two cell types. Multivariate analysis of disease-free and overall survival revealed independent prognostic factors as tumor size, LVSI, number of involved lymph node, and vaginal involvement. CONCLUSION: Prognosis of FIGO stage IB cervical cancer patients who were treated by primarily radical surgery was found to be same for those with adenocarcinoma and squamous cell carcinoma.     

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in uterine cervical cancer patients with high-risk factors

OBJECTIVES: To determine whether concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy is better than CCRT alone in the management of FIGO stage bulky IB and IIB uterine cervical cancer. METHODS: Two hundred and five FIGO stage bulky IB and IIB patients with squamous cell carcinoma of the uterine cervix treated with CCRT were divided into 2 groups: (1) CCRT alone (n=103, Group A) and (2) CCRT plus adjuvant chemotherapy (n=102, Group B), and treatment outcomes were retrospectively compared between the two patient groups. RESULTS: Only 63% of patients received all three planned cycles of adjuvant chemotherapy, while 16% received only one cycle because of increased treatment-related morbidity or other causes. There were no treatment-related deaths. Although 37 patients experienced failures after completion of treatment, no significant differences were found in patterns of local and regional failures between the two groups. The incidence of distant metastasis, including para-aortic or supraclavicular lymph node metastases, was not reduced in patients of Group B (8% in Group A vs. 7% in Group B). Overall five-year actuarial survival rates for Group A and Group B patients were 85% vs. 80%, and five-year disease-free survival rates were 83% vs. 78%, respectively. CONCLUSIONS: Our data failed to show discernable therapeutic advantage of adjuvant chemotherapy with given after CCRT for the management of FIGO stage bulky IB and IIB uterine cervical cancer patients. A future clinical trial will be necessary to test the clinical efficacy of the adjuvant treatment using newly developed agents in uterine cervical cancer patients.     

Prognostic factors in FIGO stage IB cervical cancer without lymph node metastasis and the role of adjuvant radiotherapy after radical hysterectomy

OBJECTIVES: The aim of this study was to evaluate the clinical and pathologic prognostic variables for disease free survival, overall survival and the role of adjuvant radiotherapy in FIGO stage IB cervical carcinoma without lymph node metastasis. METHODS: A retrospective review was performed of 393 patients with lymph node negative stage IB cervical cancer treated by type 3 hysterectomy and pelvic lymphadenectomy at the Hacettepe University Hospitals between 1980 and 1997. RESULTS: The disease free survival and overall survival were 87.6 and 91.0%, respectively. In univariate analysis, tumor size, depth of invasion, vaginal involvement, lympho-vascular space involvement (LVSI) and adjuvant radiotherapy were found significant in disease free survival. Overall survival was affected by tumor size, LVSI, vaginal involvement and adjuvant radiotherapy. Tumor size, LVSI and vaginal involvement were found as independent prognostic factors for overall and disease free survival in multivariate analysis. Disease free survival, recurrence rate and site did not differ between patients underwent radical surgery and radical surgery plus radiotherapy. CONCLUSION: Tumor size, LVSI and vaginal involvement were independent prognostic factors in lymph node negative FIGO stage IB cervical cancer. Adjuvant radiotherapy in stage IB cervical cancer patients with negative nodes provides no survival advantage or better local tumoral control.     

Lymphocyte-infiltrated FIGO Stage IIB squamous cell carcinoma of the cervix is a prominent factor for disease-free survival.

BACKGROUND: The data of histopathological factors affecting prognosis of patients with FIGO Stage IIB squamous cell carcinomas of the cervix are rarely known. The purpose of this study was to evaluate the histopathological factors rendering therapeutic failure in patients with FIGO Stage IIB. METHODS: Survival and prognostic factors were analyzed in 83 patients with FIGO stage IIB squamous cell carcinoma of the cervix treated with radical hysterectomy and retroperitoneal lymphadenectomy between 1980 and 1989. The relapse-free and overall survival rate was 61.4%. RESULTS: Univariate analysis demonstrated that the degree of lymphoreticular cells infiltrating the cervix, lymph node metastases, barrel shape of the cervix, lymph-vascular space invasion, more than three lymph nodes involved, and bulky tumor size (i.e. tumor size larger than 4 cm) were of prognostic significance in disease-free survival. However, pronounced lymphoreticular cells infiltrating the cervical cancer was the only independent factor to disease-free survival in patients with FIGO stage IIB squamous cell carcinoma treated with radical hysterectomy and retroperitoneal lymph node dissection using multivariate analysis. CONCLUSIONS: We concluded that the immune function of the host might play a crucial role in the process of anti-neoplasm even if local advanced carcinoma of the cervix is noted. Individual therapies may very well have limited efficacy based on the patient's tumor or the inherent host response. How to strengthen the power of the host's immune system may offer another thinking process to treat such a subgroup of patients. More studies are required.     

High-risk group in node-positive patients with stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation

OBJECTIVE: The goal of this study was to identify risk factors in patients with node-positive stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy with pelvic lymph node dissection and postoperative irradiation. METHODS: Two hundred forty-two patients with FIGO stage IB, IIA, and IIB cervical carcinoma underwent radical hysterectomy with pelvic lymph node dissection; pathological analysis of the surgical specimen showed positive lymph nodes in 59 patients. These 59 patients were further treated with postoperative radiotherapy. Eighteen patients were in stage IB, 4 in stage IIA, and 37 in stage IIB. Histological tumor type, tumor size, lymph-vascular space invasion, parametrium infiltration, number of positive nodes, and involvement of common iliac nodes were assessed for correlation with cancer recurrence. RESULTS: When all these variables were assessed in the Cox proportional regression analysis, parametrium infiltration (P = 0. 0199) and number of positive nodes (two or more nodes) (P = 0.0483) revealed the factor correlating significantly with disease-specific survival. Based on these two factors, node-positive patients could be divided into low-risk (n = 11), intermediate-risk (n = 29), and high-risk (n = 19) groups. The 5-year disease-specific survival for the low-risk group was 100% which was significantly better than the 39.1% for the high-risk group (P = 0.0012). CONCLUSION: For patients in the high-risk group, it may be worthwhile to consider new strategies to improve survival.     

Stromal invasion of the cervix can be excluded from the criteria for using adjuvant radiotherapy following radical surgery for patients with cervical cancer

BACKGROUND: Regarding complications of radiotherapy, the indications for adjuvant radiotherapy should be restricted. We conducted the present study to determine whether deep stromal invasion of the cervix could be excluded from the criteria used to identify patients for this treatment surgery. METHODS: This study included 115 patients with FIGO stage Ib to IIb cervical cancer who underwent radical hysterectomy and pelvic lymph node dissection. Patients had the following tumors: 61 nonkeratinizing squamous cell carcinoma, 21 keratinizing squamous cell carcinoma, 26 adenocarcinoma, and 7 adenosquamous cell carcinoma. Our study criteria for using adjuvant radiotherapy included positive lymph node involvement, a compromised surgical margin, or parametrial extension. Deep stromal invasion of the cervix was excluded from the criteria in this study. RESULTS: Seventy-two of the 115 patients (62.6%) underwent radical surgery only and all were alive. The remaining 43 patients received a complete course of external irradiation following radical surgery. The estimated 5-year survival rate is 100% for patients with stage Ib, 93.3% for stage IIa, and 52.7% for stage IIb. Fifty-five patients (47.8%) had deep stromal invasion. The prognosis for patients with deep stromal invasion was significantly worse than that for patients without deep stromal invasion (5-year survival rate, 69.8% vs. 98.0%). However, 21 patients (18.3%) with deep stromal invasion, but without positive lymph node involvement, compromised surgical margin, or parametrial extension, were alive without recurrence. Multivariate analysis showed that lymph node involvement and parametrial extension were independent prognostic factors, but that deep stromal invasion was not. CONCLUSION: Deep stromal invasion of the cervix can be excluded from the list of criteria for selecting patients with cervical cancer who would benefit from adjuvant radiotherapy following radical surgery.     

Residual pelvic lymph node involvement after concomitant chemoradiation for locally advanced cervical cancer

OBJECTIVE: Concomitant chemoradiation (and brachytherapy) has become the standard treatment for locally advanced cervical cancers (FIGO stage IB2 to IVA). Adjuvant surgery is optional. The aim of this study was to evaluate the rate of residual positive pelvic lymph nodes after chemoradiation. METHODS: From February 1988 to August 2004, 113 patients with locally advanced cervical cancer have been treated by chemoradiation followed by an adjuvant surgery with a pelvic lymphadenectomy performed (study group). A para-aortic lymphadenectomy had also been performed in 85 of them. RESULTS: The mean age of the patients was 48.4 years (27-74). FIGO stage was: IB2 in 17.7% (20/113), II in 44.2% (50/113), III in 21.2% (24/113) and IVA in 16.8% of the patients (19/113). The mean number of removed nodes was 11.5 (median 11) in pelvic, and 7.5 (median 7) in para-aortic basins. A pelvic lymph node involvement was present in 15.9% (18/113) of the patients after chemoradiation. In 11 patients, only one node was positive. 11.7% (10/85) of the patients had a para-aortic lymph node involvement. A residual pelvic lymph node disease has been observed in 6.3% (4/63) of the cases with no residual cervical disease (or microscopic) versus 26.5% (13/49) of the cases with macroscopic residual cervical tumor (P = 0.003). CONCLUSIONS: Our experience shows that a pelvic lymph node involvement persists in about 16% of the patients after chemoradiation. We can make the assumption that performing a pelvic lymphadenectomy along with the removal of the primary tumor after chemoradiation could reduce the rate of latero-pelvic recurrences, whatever the para-aortic lymph node status.     

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.     

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.     

Para-aortic node sampling in small (3-cm or less) stage IB invasive cervical cancer.

Only 2 of 125 patients with FIGO stage IB invasive squamous or adenocarcinoma of the cervix 3 cm or less in diameter who underwent exploration for radical hysterectomy, bilateral pelvic lymphadenectomy, and para-aortic node sampling had metastases to the para-aortic nodes. No patient had gross para-aortic nodal involvement, and both patients with microscopic para-aortic nodal metastases had grossly positive pelvic nodal involvement. Para-aortic node sampling in patients with small stage IB cervical cancers undergoing radical hysterectomy may be restricted to patients with suspicious pelvic or para-aortic nodes.     

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.     

早期宫颈鳞癌患者盆腔淋巴结转移的相关因素分析

目的:探讨早期宫颈鳞状细胞癌患者盆腔淋巴结转移的危险因素。方法:回顾分析152例行手术治疗的ⅠB~ⅡA期宫颈鳞癌患者的临床资料,分析患者的年龄、临床分期、肿瘤细胞分化程度、宫颈间质浸润深度、肿瘤直径大小、脉管癌栓、术前血清宫颈鳞状上皮抗原(SCC-Ag)水平、治疗前血浆纤维蛋白原(FⅠB)水平及D-二聚体水平9个指标与盆腔淋巴结转移的关系。结果:152例ⅠB~ⅡA期宫颈鳞癌患者中20例存在盆腔淋巴结转移(13.16%)。单因素分析结果显示,宫颈间质浸润深度、肿瘤直径、脉管癌栓、术前血清SCC-Ag水平及血浆FⅠB水平与盆腔淋巴结转移有关,差异有统计学意义(P0.05);淋巴结阳性患者的血浆D-二聚体水平高于阴性患者,但差异无统计学意义(P0.05)。多因素分析结果显示,脉管癌栓、术前血清SCC-Ag及血浆FⅠB水平与盆腔淋巴结转移相关,差异有统计学意义(P0.05)。结论:脉管癌栓、术前血清SCC-Ag水平及治疗前血浆FⅠB水平是ⅠB~ⅡA期宫颈鳞癌患者盆腔淋巴结转移的独立危险因素,而术前D-二聚体水平与盆腔淋巴结转移之间的关系,尚需进一步研究。     

局部晚期宫颈癌100例淋巴结转移特点及临床分析

目的：探索局部晚期（ⅠB2/ⅡA2期）宫颈癌的淋巴结转移特点及新辅助化疗对预后及并发症发生率的影响。方法：回顾性分析2008年1月-2016年12月南京医科大学第一附属医院收治的424例ⅠA2～ⅡA2期宫颈鳞癌或腺癌患者的临床资料,随访每位患者的生存情况,比较局部晚期宫颈癌患者淋巴结转移情况及新辅助化疗和直接手术患者在手术并发症及预后方面的差异。结果：共424例宫颈癌患者纳入研究,100例局部晚期宫颈癌患者中有68例直接行根治性手术治疗,32例先行1～2次介入或静脉新辅助化疗后行宫颈癌根治术,术后病理提示盆腔淋巴结转移者20例,没有发现腹主动脉旁淋巴结转移。单因素分析提示深肌层浸润、淋巴脉管间隙浸润（lymph vascular space invasion,LVSI）与淋巴结转移相关（P＜0.05）;组织学类型、分化程度、是否行新辅助化疗与淋巴结转移无关（P＞0.05）。将有统计学意义的单因素进行Logistic回归分析显示,LVSI为淋巴结转移的独立危险因素（P＜0.05）。新辅助化疗组淋巴结转移率为22.2％,手术组则为17.2％,2组比较差异无统计学意义（P＞0.05）。总生存期及无瘤生存期方面,局部晚期宫颈癌明显低于早期者。新辅助化疗组的术后感染发生率较低,手术时间和腹腔引流管留置时间较短,但2组差异无统计学意义（P＞0.05）,而术中输尿管支架置入率、输血率、其他相邻脏器损伤的发生率2组相似。结论：局部晚期宫颈癌预后较早期差,淋巴结转移率明显高于早期,盆腔淋巴结转移主要与LVSI及深肌层浸润有关。新辅助化疗对局部晚期宫颈癌的影响尚不明确,也没有证据证明新辅助化疗影响盆腔淋巴结转移的检出率,在手术相关并发症的发生率方面还需更大样本或多中心的研究。     

Re-classification of uterine cervical cancer cases treated with radical hysterectomy based on the 2018 FIGO staging system

ObjectiveWe re-classified patients with stage IB–II disease (based on the 2008 system) and compared the outcomes with those obtained after using the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system.Materials and methodsWe reviewed the data of 154 patients with cervical cancer who underwent radical hysterectomy at our hospital during 2006–2016. Pathological, histological, and radiographic data were used to re-classify the cases based on the 2018 FIGO system. We compared these outcomes to those obtained after using the 2008 FIGO assignments. Overall survival (OS) was calculated from primary therapy initiation until death or the last follow-up examination.ResultsThe histological types were squamous cell carcinoma (108 cases) and others (46 cases). The 2008 FIGO system assignments were stage IB1, IB2, IIA1, IIA2, and IIB (87, 27, seven, five, and 28 patients, respectively). The new 2018 FIGO system assignments were stage IB1, IB2, IB3, IIA1, IIA2, IIB, and IIIC1 (52, 26, 16, six, three, 21, and 30 patients, respectively). Re-classification to stage IIIC1 disease was observed for previously assigned stage IB1, IB2, IIA1, IIA2, and IIB cases (10, seven, two, two, and nine cases, respectively). The median OS durations based on the 2018 FIGO system were 71.7, 61.1, and 62.3 months for patients with stage IB1, IB2, and IB3 (p = 0.04) disease, respectively. The new stage IB3/IIA2/IIB cases had longer OS than the old stage IB2/IIA2/IIB cases. A positive computed tomography (CT) finding of nodal involvement was observed in 37% of cases with pathological confirmation of pelvic lymph node (LN) involvement. Using CT to identify pelvic LN metastasis had a sensitivity of 37% and specificity of 93%.ConclusionThe 2018 FIGO staging system for cervical cancer after radical hysterectomy showed a better ability to differentiate survival outcomes. However, the image evaluation method should be reconsidered.     

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.     

Evaluation of the Prognostic Significance of nm23/NDP Kinase Protein Expression in Cervical Carcinoma: An Immunohistochemical Study

The objective of this study was to evaluate the prognostic significance of immunohistochemical staining for nm23/nucleoside diphosphate (NDP) kinase in cervical carcinoma. A retrospective analysis of 176 patients with cervical carcinoma FIGO stage IB treated with radical hysterectomy and pelvic lymphadenectomy from 1987 to 1990 was conducted. Immunohistochemical staining using the polyclonal nm23-H1/NDP kinase A antibody was correlated to various histopathological and morphological characteristics (tumor size, histologic type, grade of differentiation, vessel invasion, invasion into parametria, and lymph node metastasis) and relapse-free survival. For controls, sections were obtained from 10 hysterectomy specimens with normal cervical epithelium. Staining for nm23/NDP kinase was observed in 90% of control cases and in 70.5% of cases of cervical carcinoma, more frequent in squamous and adenosquamous cell carcinoma than in adenocarcinoma and more frequent in poorly differentiated than in more highly differentiated tumors. There were no differences related to size of tumor or invasion into vessels or parametria or occurrence of lymph node metastasis. The relapse-free survival was lower for patients with squamous cell and adenosquamous tumors with positive immunostaining for nm23/NDP kinase than for those with negative tumors when evaluated in univariate analysis. In multivariate analysis with tumor size, vessel invasion, invasion into parametria, grade of differentiation, and lymph node metastasis included, this difference was no longer significant. In patients with adenocarcinoma no difference was found. In conclusion, we did not find immunostaining for nm23/NDP kinase to be a useful indicator for prognosis in cancer of the uterine cervix.     

Accuracy of frozen section examination of pelvic lymph nodes in patients with FIGO stage IB1 to IIB cervical cancer

OBJECTIVE: We evaluated the accuracy of intraoperative frozen section histology of pelvic lymph nodes in patients with FIGO stage IB1 to IIB cervical cancer. METHODS: A total of 96 patients with cervical cancer FIGO stage IB1 to IIB had surgery including systematic pelvic or pelvic and paraaortic lymphadenectomy and intraoperative frozen section examination of pelvic lymph nodes at our department between January 1997 and October 2001. The results of frozen section were compared with those of final histology. RESULTS: A total of 1044 pelvic lymph nodes underwent intraoperative frozen section examination and node metastases were found in 29 patients (30%). Final histopathology yielded a total of 5042 lymph nodes and identified an additional seven patients with node metastases for a false negative rate of 19%. The specificity and the positive predictive value of frozen section examination were 100%; the negative predictive value was 90% (60/67). CONCLUSION: The diagnostic accuracy of frozen section analysis of pelvic lymph nodes should be considered when intraoperative decisions are based on its results.     

Application of tumor markers CEA, TPA, and SCC-Ag in patients with low-risk FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix

OBJECTIVE: The aim of this study was to determine the potential clinical utility of tumor markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) in patients with FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix with low-risk clinicopathologic factors (negative lymph node metastasis, no lymphovascular space involvement, no bulky tumor size, no parametrial invasion, no deep stromal invasion, and well-differentiated cellular histology). METHODS: A retrospective study was performed on 558 patients with FIGO stage IB-IIA and pathology-proven invasive squamous cell carcinoma of the uterine cervix, treated at the Veterans General Hospital, Taipei, between December 1986 and November 1990. Serum specimens were drawn before operation. A total of 140 assessable patients were enrolled into the study (including 109 stage IB patients and 31 stage IIA patients; all patients had no clinicopathologic risk factors and had at least one tumor marker datum). Survival curves were constructed according to the Kaplan-Meier method and survival curves were compared using the log-rank test. RESULTS: In univariate analysis of survival, CEA, TPA, and SCC-Ag all have roles in the prediction of prognosis. In Cox proportional hazards model using CEA, TPA, and SCC-Ag as covariates, TPA demonstrated the most significant risk factor (P = 0.031). CONCLUSIONS: We concluded that preoperative evaluation of serum TPA might be of great value in the prediction of survival of patients without any clinicopathologic risk factors and this special group of patients should be paid much attention in the follow-up period. From this study, preoperative elevation of TPA defines a group of otherwise low-risk invasive cervical cancer patients who are at high risk for recurrence. Adjuvant therapy might be necessary for this special subset of patients. A prospective study with a larger sample should be conducted to prove this particular finding.     

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.     

Pattern of invasion is of prognostic value in surgically treated cervical cancer patients

OBJECTIVES: Different patterns of invasion (representing different grades of tumor cell dissociation) are associated with prognostic outcome in cancer. We evaluated the prognostic value of different patterns of invasion (PI) in cervical carcinomas (CX). METHODS: Six hundred eleven surgically treated CX (FIGO IB to IIB) were re-evaluated histologically regarding the PI, using a three-level scoring system. Closed PI was defined as cohesive growth with well-delineated (pushing) borders. In finger-like PI the tumor grows in solid cords/trabecles. Highly dissociative growth in small groups or single cells was defined as spray-like PI. Types of PI were correlated to tumor stage, histo-morphologic factors and prognostic outcome. RESULTS: Sixty percent of the tumors showed a spray-like PI, 30% a finger-like PI and only 7.4% were of the closed type. Spray-like PI showed a significant correlation with advanced stage disease, lymphovascular space involvement, poorly differentiated tumors and pelvic lymph node metastases. Spray-like PI was accompanied by a reduced 5-year overall survival when compared to the finger-like and closed PI (68.7% vs. 80.9% vs. 88.5%; P=0.0004). The prognostic impact of the PI disappeared in node-positive patients (P=0.06) but persisted in patients without pelvic lymph node disease (P=0.03). In multivariate analysis, using COX regression model, the PI represented as independent prognostic factor. CONCLUSIONS: Spray-like PI (i.e., highest degree of tumor cell dissociation) is associated with advanced tumor stages, increased rate of recurrency and a reduced overall survival. In separate analysis of patients with and without lymph node metastases, the impact of PI persisted only in node-negative cases as a prognostic factor.