Isolated full-thickness cervical stromal invasion warrants post-hysterectomy pelvic radiotherapy in FIGO stages IB-IIA uterine cervical carcinoma

OBJECTIVE: To evaluate the potential benefit of postoperative radiotherapy (PORT) in women with isolated full-thickness cervical stromal invasion (FTSI) as an unfavorable pathological finding after radical hysterectomy and pelvic lymph node dissection (PLND) in FIGO stages IB-IIA cervical carcinoma. METHODS: A total of 1868 patients with stages IB-IIA cervical carcinoma underwent radical hysterectomy and PLND between January 1982 and December 2002. Seventy-four of these patients had isolated FTSI without any other unfavorable pathological finding, such as lymph node metastasis, microscopic parametrial involvement, involved resection margin, lympho-vascular space invasion, or large clinical tumor diameter (>4 cm). Forty-one of these patients had no adjuvant treatment (S group) and 33 received PORT (PORT group). Patients with isolated FTSI who received chemotherapy were excluded. Treatment outcomes in the PORT and S groups were compared. RESULTS: Ten-year disease-free survival (DFS) and pelvic-failure-free survival (PFFS) of S group vs. PORT group were 73.2% vs. 92.4% (P=0.038) and 79.8% vs. 97.0% (P=0.044), respectively. According to a Cox proportional hazards model developed by forward, stepwise regression incorporating all prognostic variables, only PORT was marginally significant for DFS (RR 0.234; 95% CI 0.051-1.067; P=0.061) and significant for PFFS (RR 0.055; 95% CI 0.005-0.620; P=0.019). A grade 4 late complication developed in two patients (6%) in PORT group. CONCLUSION: PORT administered to patients with isolated FTSI after radical hysterectomy and PLND improves pelvic control in FIGO stages IB-IIA cervical carcinoma with acceptable morbidity.     

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 possible use of colour flow Doppler in planning treatment in early invasive carcinoma of the cervix.

OBJECTIVE: To investigate the pathological significance of intra-tumoural blood flow signals detected by colour Doppler ultrasound and their association with angiogenesis in cervical carcinoma. DESIGN: A prospective cross-sectional study. SETTING: University hospital. POPULATION: One hundred and four women with Stage IB-IIA cervical carcinoma. METHODS: All women underwent radical hysterectomy and pelvic lymph node dissection. Transvaginal colour Doppler ultrasound was performed before surgery to search for arterial blood flow signals within the tumours. Tumours with a measurable intra-tumoural resistance index were defined as tumour with detectable blood flow and the others as tumour with undetectable blood flow. The microvessel density of the excised tumour was assessed immunohistochemically. The women's clinical and pathologic data were recorded. RESULTS: There were 60 tumours (58%) exhibiting detectable intra-tumoural blood flow signals. Tumours with detectable blood flow were larger, had deeper cervical stromal invasion, a higher incidence of parametrial invasion and pelvic lymph node metastases, and a higher microvessel density, when compared with those without detectable blood flow. Cervical cancers with deep cervical stromal invasion, parametrial invasion, and pelvic lymph node metastasis had higher microvessel density than those with superficial stromal invasion, no parametrial invasion, or no lymph node metastasis. Microvessel density correlated well with lymph node metastases and parametrial invasion by multiple regression analysis, while intra-tumoural blood signals only showed correlation with parametrial invasion. In the prediction of pelvic lymph node metastases and parametrial invasion, colour flow Doppler had a sensitivity of 0.80 and specificity of 0.48 in predicting lymph node metastases, and sensitivity of 0.91 and specificity of 0.57 in predicting parametrial invasion. CONCLUSIONS: The characteristics of blood flow signals in cervical carcinoma detected by colour Doppler ultrasound are associated with tumour angiogenesis and could reflect the likelihood of parametrial invasion and lymph node metastases in cervical carcinoma. The intra-tumoural blood flow signals might be used as a screening test in predicting parametrial invasion and pelvic lymph node metastases. These findings may be helpful in planning treatment for women with Stage I and II cervical carcinoma.     

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.     

A prospective surgical pathological study of stage I squamous carcinoma of the cervix: A Gynecologic Oncology Group study

Thirty-three institutions collaborating in the Gynecologic Oncology Group gathered surgical and pathological data on 1125 patients with primary, previously untreated, histologically confirmed stage I cervical carcinoma with more than 3 mm of invasion who were selected to undergo radical hysterectomy and paraaortic and pelvic lymphadenectomy. Of the 940 eligible, evaluable patients, 732 had squamous carcinoma. Of the study group, 87 (12%) did not undergo radical hysterectomy because of gross disease beyond the uterus or microscopic aortic node involvement documented at exploratory laparotomy. Among the 645 patients undergoing pelvic and paraaortic lymphadenectomy and radical hysterectomy, five risk factors were significantly associated with microscopic pelvic lymph node metastasis: depth of invasion (P = 0.0001), parametrial involvement (P = 0.0001), capillary-lymphatic space invasion (P = 0.0001), tumor grade (P = 0.01), and gross versus occult primary tumor (P = 0.009). The factors identified as independent risk factors for pelvic lymph node metastasis by multivariate analysis were capillary-lymphatic space involvement (P less than 0.0001), depth of invasion (P less than 0.0001), parametrial involvement (P = 0.0005), and age (P = 0.02). The model was used to predict the chance of a patient having nodal metastasis for any combination of risk factors.     

Value of preoperative serum CA125 in early-stage adenocarcinoma of the uterine cervix without pelvic lymph node metastasis

OBJECTIVE: This investigation attempted to clarify the value of preoperative serum CA125 in predicting histopathological prognostic factors for early-stage cervical adenocarcinoma without lymph node metastasis. METHODS: This study initially surveyed 163 patients with clinical stage Ib or IIa cervical adenocarcinoma treated with radical hysterectomy and pelvic lymphadenectomy. Of the 163 patients, 116 had preoperative serum CA125 levels, and 14 had pelvic lymph node metastasis. The investigation group comprised 102 lymph node-negative patients. RESULTS: A cutoff value of 26 U/ml was obtained after the discriminant function analysis for identifying patients with positive lymph vascular space invasion (LVSI) or depth of stromal invasion > or =2/3 thickness. Multivariate analysis revealed that among the preoperative clinicopathological variables, including age, tumor size, parametrial invasion, and CA125 level, raised CA125 most significantly influenced the assessment of the LVSI (P = 0.040) and depth of cervical stromal invasion (P = 0.002). CONCLUSIONS: In early-stage cervical adenocarcinoma with negative pelvic lymph node metastasis, preoperative serum CA125 levels at the cutoff value of 26 U/ml impacted the determination of the poor histopathological prognostic factors.     

Prognostic factors in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy

OBJECTIVE: The purpose of the present study was to identify prognostic factors and recurrent patterns in pathologic parametrium-positive patients with stage IB-IIB cervical cancers treated by radical surgery and adjuvant therapy. METHODS: The patient population consisted of 84 individuals presenting with stage IB-IIB cervical cancers and histologically proven parametrial invasion. All these patients were treated postoperatively with adjuvant external whole pelvic irradiation, combination chemotherapy, or chemoradiotherapy. RESULTS: The 5-year disease-free survival rate was found to be 67.2% and 5-year overall survival rate, 75.4%. Multivariate analysis revealed that vaginal invasion (p=0.0008), lymph node metastasis (p=0.002), and non-squamous histology (p=0.010) were independent indicators of the disease-free survival rates and that the vaginal invasion (p=0.009) and lymph node metastasis (p=0.011) were independent prognostic factors for the overall survival rates. The 5-year overall survival rate was approximately 90% for patients without these risk factors. Disease recurrence was observed in 26 patients (31.0%) with a median time of 16.5 months (range, 5-59 months) from the surgery. Hematogenous recurrences, including those in the lung, liver, and bone, were significantly higher in patients with non-squamous cell carcinomas (p=0.008). Distant lymph node recurrences were significantly higher in patients with positive pelvic lymph node and vaginal invasion (p=0.004 and p=0.023, respectively). Pelvic recurrences were significantly higher in patients with vaginal invasion (p=0.026). CONCLUSIONS: Vaginal invasion and lymph node metastasis are independent indicators for disease-free and overall survival rates in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy. The survival rate is excellent in the patients without these risk factors. Hematogenous recurrence may be evident in patients with non-squamous cell carcinomas.     

How important is removal of the parametrium at surgery for carcinoma of the cervix?

OBJECTIVES: The aims of this study were (1) to determine the incidence and factors predictive for pathologic parametrial involvement in clinical stage IA1/2 and IB1 cervical cancer after radical surgery and (2) to identify a population at low risk for pathologic parametrial involvement. METHODS: All patient information was collected prospectively and extracted from a cervical cancer radical surgery database. Selection criteria for surgery were generally based upon tumor size, with the cutoff for surgery between 3 and 4 cm. Parametrial involvement (PI) was defined as either positive parametrial lymph nodes (PMLN) or malignant cells in the parametrial tissue (PT) (including lymphovascular channels) by either contiguous or discontiguous spread. Statistical analysis included the chi2 test, the Wilcoxon rank test, and the Mantel-Haentzel test. RESULTS: Between July 1984 and January 2000, 842 patients underwent radical surgery for clinical stage IA1/2 and IB1 cervical cancer at our center. Forty-nine patients (6%) had positive pelvic lymph nodes. Thirty-three patients (4%) had pathologic PI, 8 in the PMLN and 25 in the PT (none had both). PI was associated with older age (42 vs 40 years, P < 0.04), larger tumor size (2.2 vs 1.8 cm, P < 0.04), higher incidence of capillary-lymphatic space invasion (85% vs 45%, P = 0.0004), tumor grades 2 and 3 (95% vs 65%, P = 0.001), greater depth of invasion (18.0 vs 5.0 mm, P < 0.001), and pelvic lymph node metastases (44% vs 5%, P < 0.0001). The incidence of PI in patients with tumor size < or =2 cm, negative pelvic lymph nodes, and depth of invasion < or =10 mm was 0.6%. CONCLUSION: Pathologic parametrial involvement in clinical stage IA1/2 and /IB1 cervical cancer is uncommon. Acknowledging that almost all patients with pelvic lymph node metastases and a high proportion of patients with tumor invasion >10 mm will receive adjuvant radiation regardless of the radicality of surgery, a population at low risk for pathologic parametrial involvement can be identified. These patients are worthy of consideration for studies of less radical surgery performed in conjunction with pelvic lymphadenectomy.     

早期宫颈癌淋巴结转移规律的临床研究

Objective?To study the risk factors and patterns of pelvic lymph node metastasis in early cervical cancer, which provide a basis for selective lymph node dissection and postoperative individualized clinical target volume (CTV) outlining. Methods?The clinical data of 7 472 patients with early-stage (ⅠA1~ⅡA2) cervical cancer who underwent radical cervical cancer surgery admitted to Hunan Cancer Hospital from January 2009 to December 2015 were retrospectively analyzed. Results?The rate of pelvic lymph node metastasis in 7 472 patients was 12.93%, and the rate of closed lymph node metastasis accounted for 66.37%. Closed lymph node metastasis was correlated with lymph node metastasis in other regions of the pelvis (χ2=919.478, P<0.001). Among patients with lymph node metastasis, the metastasis rates of lymph nodes with local, skip, and continuous metastasis were 47.72%, 26.92%, and 25.36%, respectively. The mode of lymph node metastasis in early-stage cervical cancer was highly correlated with the type of pathology, lymph vascular space invasion(LVSI) and depth of cervical muscle infiltration (χ2=13.339, P<0.01; χ2=11.365, P<0.01; χ2=16.616, P<0.001). In addition, χ2 test showed that age, tumor grade, tumor size, clinical stage, pathological type, LVSI, deep myometrial infiltration of the cervix, and intrauterine involvement were independent influencing factors of pelvic lymph node metastasis (P<0.001); logistic regression analysis showed that age, pathological type, LVSI, deep myometrial infiltration of the cervix, intrauterine involvement, and tumor grade were independent factors of pelvic lymph node metastasis (P<0.01). Conclusion?The metastasis pattern and risk factors of early cervical cancer can guide the scope of lymph node dissection and the outline of CTV in postoperative personalized radiotherapy target area.     

术前SCC-Ag对早期宫颈鳞癌盆腔淋巴结转移预测价值研究

目的 探索鳞状细胞癌抗原(SCC-Ag)对宫颈鳞癌盆腔淋巴结转移的预测价值.方法 回顾性分析2007年1月至2017年1月于南充市中心医院接受初始治疗为根治性手术的603例早期宫颈鳞癌患者.统计学比较其临床病理特征,并采用Logistic回归分析影响盆腔淋巴结转移的危险因素,绘制ROC曲线确定SCC-Ag 预测盆腔淋巴...     

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.     

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.     

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.     

HPV status in sentinel nodes might be a prognostic factor in cervical cancer

OBJECTIVE: Although there have been studies that focused on the correlation between the HPV presence of pelvic lymph nodes and pathological metastasis in patients with cervical cancer, the biologic role of HPV DNA in lymph nodes still remains uncertain. We performed this study to investigate the correlation between the sentinel-node HPV status and pelvic lymph node metastasis in patients with cervical cancer. The patients were followed up for 3 years to evaluate the clinical role of HPV in sentinel nodes as a prognostic factor. METHODS: From August 2001 to July 2003, 57 patients affected by stages IB-IIA cervical cancer had sentinel-node biopsies performed during radical hysterectomy and pelvic and paraaortic lymphadenectomy. Each detected sentinel node was divided into two parts. One part of them was submitted for frozen section examination and the other was submitted for HPV typing by oligonucleotide microarray. After follow-up, we analyzed the outcome of the patients with respect to the influence of sentinel-node HPV. RESULTS: Sentinel nodes were identified in all patients. A total of 79 nodes from 57 patients were detected as sentinel nodes. Metastasis in the sentinel nodes were found in 10 patients (17.6%) by frozen section and 11 patients by pathologic examination. The results of sentinel lymph node frozen biopsy were statistically significant for predicting the metastasis of the pelvic lymph nodes (P<0.05), but showed one false-negative case. HPV DNA was detected in the cervical cancer lesions of 55 patients (96.5%) and 80.0% (44/55) of them were found to have HPV DNA in the sentinel nodes as well. HPV DNA was detected in sentinel nodes of 10 patients among 11 patients with lymph node metastasis. Disease recurred in five patients and one of them did not show pelvic lymph node metastasis at surgery. But, all of these patients had HPV in sentinel nodes. The combination of sentinel-node frozen biopsy and HPV typing showed a negative predictive value of 100% in predicting non-metastasis of lymph node and no recurrence of disease. CONCLUSION: Our results suggested the possibility that sentinel-node HPV typing could play a supportive role to reduce the false-negative rate of the sentinel-node biopsy. All of five patients with recurrence had HPV infection in the sentinel nodes. Absence of HPV in sentinel nodes showed reliable negative predictive value for lymph node metastasis and recurrence. Additional study will be needed to confirm the clinical application of the sentinel-node procedure and to determine whether there is a correlation of HPV status of sentinel nodes to lymph node metastasis and recurrence in cervical cancer patients.     

Surgically-treated early cervical cancer: Prognostic factors and the significance of depth of tumor invasion

Hellebrekers BWJ, Zwinderman AH, Kenter GG, Peters AAW, Snijders-Keilholz A, Graziosi GCM, Fleuren GJ, Trimbos JB. Surgically-treated early cervical cancer: Prognostic factors and the significance of depth of tumor invasion. Int J Gynecol Cancer 1999; 9: 212–219.
The objectives of this study were to scrutinize surgical features and analyze local tumor parameters of early cervical cancer to identify patients at-risk for recurrent disease. Three hundred eight patients who underwent radical hysterectomy and pelvic lymphadenectomy between 1984 and 1997 were studied retrospectively. All radical hysterectomies were performed in a referral oncology center, and treatment policies and operating staff were the same during the study period. Operating time gradually decreased significantly during the study period from an average of 270 min to an average of 187 min ( P < 0.0001), and blood loss during surgery also decreased continually from 1515 ml to 1071 ml ( P < 0.0001). Postoperative radiation treatment was given to 119 patients (40%). The overall five-year survival rate was 83%, 91% for those with negative, and 53% for those with positive pelvic nodes. Univariate analysis showed that lymph node status, parametrial involvement, status of the surgical margins, capillary lymphatic space involvement, tumor size and depth of invasion were all significantly related to the occurrence of recurrent disease. Multivariate analysis revealed that lymph node involvement (hazard ratio 4.4), parametrial involvement, tumor size and depth of invasion were independent factors of prognostic significance for disease-free survival. It was concluded that the local control of cervical tumors infiltrating > 10 mm (hazard ratio 5.1) might be improved by adjuvant radiotherapy, even in the absence of lymph node metastasis, parametrial involvement or affected surgical margins.     

Histopathological factors influencing pelvic lymph node metastases in two or more sites in patients with cervical carcinoma undergoing radical hysterectomy.

BACKGROUND: Lymph node metastasis has been one of the strongest prognostic factors in patients with cervical cancer. In order to select patients with high risk for recurrence, a relationship between status of lymph node and other histopathological parameters was investigated in the patients treated with radical hysterectomy with pelvic lymph adnectomy. METHODS: Of 483 patients undergoing radical hysterectomy with pelvic lymph adnectomy, 309 had stage Ib disease, 62 stage IIa, and 112 stage IIb. RESULTS: Pelvic lymph node metastasis(PLNM) was positive in 98 patients (20%). Of those positive patients, 51(56%) had metastasis in one site, 25 (26%) in two sites, and 22 (22%) in three or more sites. There was a significant difference in survival between patients with metastasis in one or no sites and those in two or more sites (p<0.0001). There was a relationship between PLNM in more than two sites and histological parameters such as histologic subtype, longitudinal diameter of cervical lesion, degree of stromal invasion, depth of stromal invasion, lymph-vascular space invasion, parametrial invasion, and corpus invasion. All of these parameters except for histologic subtype were significantly correlated with the number of positive lymph node sites. Multivariate analysis revealed that among these parameters, longitudinal diameter of the cervical lesion, parametrial invasion, and lymph-vascular space invasion were independently significantly correlated with PLNM in two or more sites. CONCLUSIONS: From these results, patients having these three histopathological parameters could be considered as those with extensive disease distribution.     

Maylard incision for radical hysterectomy and pelvic and para-aortic lymph node dissection

Angioli R, Koechli OR, Sevin B-U. Maylard incision for radical hysterectomy and pelvic and para-aortic lymph node dissection. Int J Gynecol Cancer 1998; 8 : 274–278.
Although the transverse, muscle-splitting technique for abdominal incision (Maylard incision) has been described for radical hysterectomy and for lymph node dissection of the pelvis and para-aortic area, the adequacy of the procedure performed through this incision has not been assessed. From 1991 to 1994, 205 patients underwent radical hysterectomy with pelvic lymph node (PLN) and para-aortic lymph node (PALN) dissection at the Division of Gynecologic Oncology, Jackson Memorial Hospital/University of Miami School of Medicine. Twenty-four patients with cervical cancer stage IB-IIA underwent radical hysterectomy, pelvic lymph node and para-aortic lymph node dissection through a Maylard incision. Three patients had panniculectomy performed at the same time. Duration of surgery, estimated blood loss, number of pelvic and para-aortic lymph nodes removed and duration of hospital stay were within acceptable ranges. Postoperative and intraoperative complications were minimal. Excellent cosmetic results were obtained. In conclusion, the Maylard incision offers good exposure to the pelvic and para-aortic area for lymph node dissection, good cosmetic result, and can be performed in association with abdominoplasty. Complications are similar to those observed with a vertical skin incision. This type of incision should be considered in selected young patients with early cervical cancer and in obese patients desiring abdominoplasty.     

Rethinking the use of radiation and chemotherapy after radical hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy Oncology Group trial

OBJECTIVE: To retrospectively analyze data from a previously reported randomized trial of either pelvic radiation (RT) or RT + chemotherapy (CT) in patients undergoing radical hysterectomy and pelvic lymphadenectomy with positive pelvic lymph nodes, parametrial involvement, or surgical margins; to explore associations between RT + CT; and to investigate histopathologic and clinical factors which might be predictive of recurrence. METHODS: Histopathologic sections from biopsies and hysterectomies and clinical data were reviewed from patients with stage IA2, IB, or IIA cervical cancer treated with RT or RT + CT (cisplatin 70 mg/m2 plus fluorouracil 1000 mg/m2 every 3 weeks for four cycles). A univariate analysis was performed because the relatively small sample size limited the interpretation of a multivariate analysis. RESULTS: Of the 268 enrolled women, 243 (RT = 116; RT + CT = 127) were evaluable. The beneficial effect of adjuvant CT was not strongly associated with patient age, histological type, or tumor grade. The prognostic significance of histological type, tumor size, number of positive nodes, and parametrial extension in the RT group was less apparent when CT was added. The absolute improvement in 5-year survival for adjuvant CT in patients with tumors < or =2 cm was only 5% (77% versus 82%), while for those with tumors >2 cm it was 19% (58% versus 77%). Similarly, the absolute 5-year survival benefit was less evident among patients with one nodal metastasis (79% versus 83%) than when at least two nodes were positive (55% versus 75%). CONCLUSIONS: In this exploratory, hypothesis-generating analysis, adding CT to RT after radical hysterectomy, appears to provide a smaller absolute benefit when only one node is positive or when the tumor size is < 2 cm. Further study of the role of CT after radical hysterectomy in patients with a low risk of recurrence may be warranted.     

Missing association between telomerase activity and clinicopathological features in patients with early stage carcinoma of the cervix

OBJECTIVES: This study was undertaken to evaluate the association between the telomerase activity in the tumor and clinicopathological findings in patients with stage IB-IIA (FIGO) carcinoma of the cervix. METHODS: Thirty-eight patients with carcinoma of the cervix submitted to radical hysterectomy were prospectively from January 1998 to November 2001. Samples from the tumor were taken and analyzed by the telomerase PCR-TRAP-ELISA kit. Clinicopathological characteristics such as age, stage, tumor size, grade of differentiation, lymphatic vascular space invasion (LVSI), parametrial involvement and status of pelvic lymph nodes were also recorded. RESULTS: Patient's mean age was 49.3+/-1.99 years (29-76 years). The clinical stage (FIGO) was IB in 35 patients (92.1%) and IIA in 3 patients (7.9%). The histological classification identified squamous cell carcinoma in 33 patients (86.8%) and adenocarcinoma in 5 patients (13.2%). There was no association between age, clinical stage, histological classification, tumor size, grade of differentiation and presence of LVSI with tumoral telomerase activity. The telomerase activity was not associated with the presence of vaginal involvement (P=0.349), parametrium involvement (P=0.916), pelvic lymph node metastasis (P=0.988) or tumoral recurrence (P=0.328) in patients with carcinoma of the cervix. CONCLUSIONS: Telomerase activity in the tumor is not associated with clinicopathological findings or tumor recurrence in patients with early stage cervical carcinoma.     

Outcomes of abandoned radical hysterectomy in patients with stages IB–IIA cervical cancer found to have positive nodes during the operation

The objective of this study was to evaluate the outcomes of stages IB-IIA cervical cancer patients whose radical hysterectomy (RH) was abandoned for positive pelvic nodes detected during the operation compared with those found to have positive nodes after the operation. Among 242 patients with planned RH and pelvic lymphadenectomy (RHPL) for stages IB-IIA cervical cancer, 23 (9.5%) had grossly positive nodes. RH was abandoned, and complete pelvic lymphadenectomy was performed. Of these 23 patients, 22 received adjuvant chemoradiation, and the remaining 1 received adjuvant radiation. Four patients with positive para-aortic nodes were additionally treated with extended-field irradiation. When compared with 35 patients whose positive nodes were detected after the operation, there were significant differences regarding number of positive nodes and number of patients receiving extended-field irradiation. Complications in both groups were not significantly different, but the 2-year disease-free survival was significantly lower in the abandoned RH group compared with that of the RHPL group (58.5% versus 93.5%, P= 0.01). In conclusion, the survival of stages IB-IIA cervical cancer patients whose RH was abandoned for grossly positive pelvic nodes was significantly worse than that of patients whose node metastasis was identified after the operation. This is because the abandoned RH group had worse prognostic factors.