High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion

OBJECTIVE: The enzymes cyclooxygenase (COX)-1 and -2 are necessary for the synthesis of prostaglandins. COX-2 is usually absent in normal cells and is upregulated and expressed as a product of the "immediate early" gene during inflammatory processes. In previous studies, the expression of COX-2 has been shown to be induced by proinflammatory cytokines, and suggestions have been made that overexpression of COX-2 suppresses apoptosis and is directly related to tumor growth. We have attempted to determine a relationship between tumor invasion and metastasis of uterine cervical cancer and COX and apoptosis by comparing the protein expression of apoptosis, COX-1, and COX-2 in tumor tissues. METHODS: The subjects were 36 patients who were FIGO stage IB uterine cervical cancer patients who underwent surgery at Ajou University Hospital. There were 12 cases with lymph node or parametrial involvement. All tissues were subjected to immunohistochemical staining for COX-1, -2, and TUNEL method for apoptosis detection, and the following results were obtained. RESULTS: Tumor tissues confirmed by cytokeratin were separated into tumor surface, tumor stroma, and invasion site portions, in which decreased apoptosis was observed in the invasion sites. COX-2 expression was observed in all tumor tissues and was especially strong in the tumor invasion site. Therefore, it is suggested that COX-2 expression may suppress cell apoptosis at the tumor invasion site. When COX-2 expression was investigated according to the groups with regard to the presence of lymph node or parametrial involvement, there was a statistically significant (Mann-Whitney U test) COX-2 expression difference in the tumor invasion site (P value = 0.040) and the tumor stroma (P value = 0. 028). CONCLUSIONS: In surgically treated stage IB cervical cancer patients, COX-2 was significantly expressed when lymph node or parametrial involvement was present. These results suggest that the expression of COX-2 in stage IB cervical cancer may downregulate apoptotic processes and thus enhance tumor invasion and metastasis.     

淋巴结阳性率在ⅠB～ⅡA期宫颈癌患者中的临床意义

目的:研究淋巴结阳性比率(LNR)对IB~IIA期宫颈癌患者无进展生存期(PFS)及总生存期(OS)的影响。方法:回顾分析2010年1月~2015年12月我院收治的102例经根治性子宫切除±双侧卵巢切除+盆腔淋巴结清扫±腹主动脉淋巴结清扫术的淋巴结转移阳性的102例IB~IIA期宫颈癌患者的临床资料。采用单因素和多因素分析LNR、分期、病理类型、组织学分级、肿瘤大小、辅助治疗对PFS及OS的影响。结果:单因素分析显示,LNR、分期对PFS、OS有显著影响。多因素分析显示,LNR10%的患者PFS更差(HR=0.151,P=0.047,95%CI为0.023~0.974);而LNR10%患者的OS与LNR≤10%者比较,差异无统计学意义。结论:LNR可以作为判断IB~IIA期宫颈癌患者PFS的一项独立危险因素。     

Isolated para-aortic node involvement in stage IB/II cervical carcinoma

The aim of this report was to describe exceptional cases of patients treated for stage Ib and II cervical carcinoma with isolated para-aortic node involvement and to deduce therapeutic implications. Between 1985 and 1998, 491 women with stage IB or II cervical carcinoma underwent radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy. Five patients had para-aortic metastatic nodes but no external iliac, obturator or common iliac node involvement. These five patients had a tumor size >3 cm. According to these cases, in patients with bulky cervical carcinoma systematic complete lymphadenectomy should be performed in order to avoid misdiagnosis of para-aortic node involvement.     

The significance of peritoneal cytology in stage IB cervical cancer.

OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to evaluate its usefulness in the management of patients with early-stage cervical cancer. METHODS: Peritoneal cytology was studied in 273 women undergoing primary surgical exploration for International Federation of Gynecology and Obstetrics stage IB cancer of the cervix. Charts were reviewed retrospectively for clinicopathologic data concerning tumor size, cell type, lymph node status, and outcome. RESULTS: Cytology was positive in four women, three of whom had enlarged pelvic or para-aortic lymph nodes or intraperitoneal disease. There was no association between tumor histology or tumor size and peritoneal cytology. CONCLUSION: The incidence of positive peritoneal cytology in early-stage cervical cancer is low, and the prognostic significance of positive cytology is overshadowed by other risk factors more obvious at surgery. The routine collection of cytologic specimens at laparotomy should be abandoned in this setting.     

Postoperative radiotherapy in stage IB squamous cell cervical cancer

OBJECTIVE: The purpose of the study was to evaluate postoperative whole pelvic radiation for high-risk patients with FIGO Stage IB cervical cancer. METHODS: One hundred and forty-eight patients with Stage IB squamous cell carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy. The low-risk group included patients without unfavorable prognostic factors who were treated only by surgery. The high-risk group included women with pelvic node metastases, with positive or close surgical margins, clinical tumor size > 4.0 cm, depth of stromal invasion > 1/3 the cervical wall, grade 3 tumor and presence of lymphovascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks after surgery. RESULTS: Seventy patients (47.3%) were low risk and 78 patients (52.7%) were high risk. Locoregional recurrences were diagnosed in nine cases (12.8%) in the surgery group and in 11 patients (14.1%) assigned to radiotherapy. The incidence of distant metastases was 2.8% in the surgery group and 6.4% in the surgery and radiotherapy group. Overall survival at five years was 88.6% in the low-risk group and 84.7% in the high-risk group. CONCLUSION: Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, thus emphasizing the value of whole pelvic radiation in patients with unfavorable prognostic factors in Stage IB cervical cancer.     

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.     

Surgical treatment of lymph node metastases in stage IB cervical cancer. The laterally extended parametrectomy (LEP) procedure: experience with a 5 year follow-up

Introduction

In 2003, we published our preliminary experience with the use of an operative technique (laterally extended parametrectomy, the LEP procedure) without adjuvant therapy, in the treatment of 29 stage IB, cervical cancer patients with pelvic lymph node metastases. In our present paper, by an extended recruiting period, with a completed 5 year follow up, we studied the outcome of LEP operations, used with the same indications.

Methods

In 70 out of 106 LEP-Wertheim operated patients, no adjuvant treatment was used. In 36 patients, where histology suggested tumor spread beyond the threshold of our surgery, adjuvant chemo-radiotherapy was advised. 5 year follow up was completed (without any patient lost for follow up) for the whole cohort of patients.

Results

In 70 patients treated by LEP procedure alone, the overall 5-year survival was 91.4%. For those 36 patients, who were excluded due to disease spread above study criteria, 5 year survival was 44%. Complications in 10% of the cases necessitated a second operation. Apart from transient hyper continence and one case of permanent incontinence, no severe quality of life consequence of the operation was observed.

Conclusions

Our results suggest that in two-thirds of pelvic lymph node positive, stage IB cervical cancer cases surgery alone could provide equal or better survival (without the toxicity of chemo-radiotherapy), than any kind of multimodality treatment alternatives. LEP procedure should be considered a treatment option for stage IB cervical cancer patients with pelvic lymph node metastases.     

Prognostic significance of single versus multiple lymph node metastases in cervical carcinoma stage IB

From January 1, 1970, to December 31, 1985, 51 patients with stage IB (FIGO) carcinoma of the cervix with lymph node metastases were treated at the University Hospital, Groningen, The Netherlands. The survival rate was 54% and the average duration of follow-up was 78 months (range 47-132). Important clinical variables for survival were investigated retrospectively: the survival rate in patients with a single lymph node metastasis (with tumor confined to the node itself) (n = 23) appeared to be much better than that of patients with multiple node involvement and/or single nodes with extranodular tumor infiltration (n = 28); survival was 85 and 24%, respectively (P less than 0.001). The same applied to patients with only occult lymph node involvement: the survival rate in patients with occult involvement of the hypogastric, external iliac, or obturator nodes was 87% in 19 patients with a single metastasis and 53% in 15 patients with multiple node involvement (P less than 0.02). The survival rate in 8 patients with adenomatous histological components was 42%. In 42 patients with squamous cell carcinoma, the survival rate was 56%. This difference was not statistically significant. Treatment complications and the effect of treatment on the site of recurrence were investigated.     

Factors associated with parametrial involvement in stage IB1 cervical cancer and identification of patients suitable for less radical surgery

Objective

The purpose of the present study was to determine possible factors associated with parametrial spread in patients with stage IB1 cervical cancer and define parameters associated with a low risk for parametrial spread, in order to identify candidates for less radical surgery.

Patients and methods

We retrospectively reviewed 200 patients with stage IB1 cervical cancer who had undergone radical hysterectomy (class III) and pelvic lymphadenectomy.

Results

Overall, 20 (10.0%) of the 200 patients revealed parametrial spread, of which 11 (55%) had only direct microscopic extension of the disease, 3 (15%) had only disease spread to parametrial lymph nodes, 1 (5%) had both direct microscopic extension and disease spread to parametrial lymph nodes, and 5 (25%) had only tumor emboli within the lymph vascular channels in the parametrial tissue. Elderly age, depth of invasion, tumor size, lymph vascular space invasion (LVSI), positive pelvic nodes, and ovarian metastasis were significantly associated with parametrial involvement. The multivariate analysis model included factors that could be determined by a cone biopsy and showed LVSI, deep stromal invasion, and elderly age to be the independent predictors of parametrial involvement. Ninety-one patients had a depth of invasion of ≤ 10 mm and no LVSI, of which only 1 (1.1%) had parametrial involvement. When patients aged ≤ 50 years were further stratified into those with a depth of invasion of ≤ 10 mm and no LVSI, parametrial involvement was found to be 0.0% (0/68).

Conclusion

Patients with a tumor depth of invasion of ≤ 10 mm, no LVSI, and aged ≤ 50 years, could be considered for less radical surgery such as modified radical hysterectomy or simple hysterectomy with pelvic lymphadenectomy.     

Ovarian metastasis in stage IB and II cervical adenocarcinoma.

We performed the present study to identify those patients with adenocarcinoma of the cervix in whom ovarian preservation might be acceptable. Between January 1971 and December 1996, 82 patients with International Federation of Gynecology and Obstetrics stage IB and II cervical adenocarcinoma and adenosquamous carcinoma, treated by radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, were identified. The mean age of the patients was 44.6 years (range 27-72). The incidence of ovarian metastasis was more frequent in stage II (19.0%) than in stage IB disease (2.5%), in which only 1 patient with apparent extrauterine disease at laparotomy had an ovarian metastasis. No patients with up to inner two-thirds of stromal invasion had ovarian metastasis; however, 5 of 24 patients with outer one-third stromal invasion (20.8%) and 4 of 20 with parametrial invasion (20.0%) had ovarian metastasis. A significantly higher incidence of ovarian metastasis was also observed in 5 of 20 cases with lymph node metastasis (25.0%) than in 4 of 62 patients without lymph node metastasis (6.5%). Multivariate analysis, however, found only deep stromal invasion to be an independent risk factor for ovarian metastasis. Although it would be reasonable to conserve normal-appearing ovaries in young women undergoing radical hysterectomy for treatment of stage IB cervical adenocarcinoma and adenosquamous carcinoma, gross intraoperative inspection of the radical hysterectomy specimen may identify deep cervical invasion or extrauterine spread in those who are at increased risk of ovarian metastases.     

Role of laterally extended parametrectomy in the surgical treatment of cervical cancer stage IB with lymph node metastases (summary of own and foreign experience)

We summarized the world experience as well as our experience in the surgical treatment of women with early cervical cancer stage IB with lymph node metastases, laterally extended parametrectomy was used. 62 women with IB stage cervical cancer who were with metastases of the pelvic lymph nodes were examined. The patients were followed for 20-120 months (median 56 months). 50 patients were alive and free from disease at the end of the researched period. We used the Kaplan-Meier 5 years cumulative proportion survival which was 82%. 8 complications were observed which necessitated a second operation. In 2 patients we had treatment-refractory incontinence. According to the foreign experience as well our experience the metastases in the pelvic lymph nodes can be treated by surgery alone without chemo and radiotherapy especially in the early stages cervical cancers. Additional research in this field will give more light and information in this field.     

Prevalence and prognostic significance of COX-2 expression in stage IB cervical cancer

OBJECTIVES: To evaluate the prevalence of cyclooxygenase-2 (COX-2), correlation with various clinicopathologic factors and prognostic significance of COX-2 in stage IB cervical cancer patients. METHODS: 89 paraffin-embedded specimens of patients with stage IB cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy at King Chulalongkorn Memorial Hospital during 1 January 1997-31 December 2002 and were stained with polyclonal goat antiserum against COX-2 using immunohistochemical method. Medical records were reviewed; clinicopathological variables were retrieved and used for analysis. RESULTS: The prevalence of positive COX-2 expression in stage IB cervical cancer in this study was 49.4%. Positive COX-2 expression in cervical adenocarcinoma was higher than squamous cell carcinoma (86.7% versus 40.6%, P < 0.05) and significantly expressed when lymph node metastasis was presented (100% versus 46.4%, P < 0.05). However, COX-2 expression was possibly associated with parametrial involvement (80% versus 47.6%, P > 0.05). There was no correlation between COX-2 expression and patient's age, tumor size, depth of stromal invasion and lymphovascular space invasion. Five-year disease free survival and 5-year overall survival in patients with positive COX-2 expression were 81% and 98% which were not differed from patients with negative COX-2 expression (92% and 95%, P > 0.05). CONCLUSIONS: Strong correlation was found in cervical adenocarcinoma and lymph node metastasis. However, COX-2 expression failed to demonstrate as a significant prognostic factor in stage IB cervical cancer.     

Neoadjuvant intraarterial infusion chemotherapy in patients with stage IB2-IIIB cervical cancer

OBJECTIVES: The purpose of this study was determine the effect of neoadjuvant intraarterial chemotherapy (NAIC) on the prognosis of patients with locally advanced cervical cancer. METHODS: From January 1992 to December 1997, 26 previously untreated patients with stage IB2-IIIB cervical cancer were enrolled in the study. NAIC was administered for more than two courses every 3 weeks using a combination of 17.5 mg/m(2) bleomycin, 7 mg/m(2) mitomycin-C, and 75 mg/m(2) cisplatin via the bilateral internal iliac artery. Pathologic findings were evaluated with histologic examinations of surgical specimens. A nonrandomized control group of 120 patients who underwent conventional treatment between 1980 and 1991 was used for comparison. RESULTS: Nineteen (73.1%) of the 26 patients responded to initial chemotherapy, permitting a radical hysterectomy with pelvic lymphadenectomy in 14 patients. The remaining 5 patients received radiotherapy. One of 7 nonresponders was able to undergo radical surgery. Pathologic complete responses were found in 4 of the 15 patients who underwent radical surgery. The incidence of lymph node metastasis, parametrial infiltration, and vascular space involvement in the 15 patients who received NAIC followed by radical surgery was significantly lower than that in the control group (13.3, 6.7, and 13.3% vs 54.2, 43.8, and 60.4%). The overall 5-year estimated survival rate was significantly higher for all 26 patients who received NAIC (80.0%) than for the control group (59.6%). In stage II and III, the 5-year survival rate for patients who received NAIC was significantly higher than that in the control group (83.3 and 77.8% vs 68.1 and 49.8%). CONCLUSIONS: These preliminary results suggest that NAIC is able to eliminate effectively the pathologic risk factors in the pelvic cavity, to improve the operability in patients with stage IIIB cervical cancer, considered inoperable, and to improve the prognosis of patients with locally advanced cervical cancer.     

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.     

Peritoneal cytology in patients with stage IB cervical cancer undergoing radical hysterectomy: limited value.

Peritoneal cytology, obtained at the start of planned radical hysterectomy in 200 consecutive patients with Stage IB cervical cancer, none of whom had intra-abdominal extension of disease, was positive in only one patient; this patient received no adjuvant treatment and remains disease-free at 48 months. Routine peritoneal cytology during radical hysterectomy adds little information for patient management and may be safely omitted.     

Umbilical metastases from a stage IB cervical cancer after laparoscopy: a case report.

The first reported case of laparoscopy site metastases from an unsuspected stage IB cervical cancer diagnosed during laparoscopy for endometriosis is presented. Implications of this clinical situation are discussed.     

Preoperative MRI criteria for trials on less radical surgery in Stage IB1 cervical cancer

Objective

The aim of this study is to identify a patient group with a low-risk of parametrial involvement (PMI) in Stage IB1 cervical cancer using preoperative magnetic resonance imaging (MRI) parameters.

Methods

In total, 190 Stage IB1 cervical cancer patients with clinically visible lesions who had undergone Type C2 radical hysterectomy and preoperative MRI were included in this study. Clinical records, pathology reports, and preoperative MRI findings were reviewed retrospectively.

Results

Of the 190 patients, 19 (10%) had pathologic PMI. The largest tumor diameter identified by MRI ranged from zero (no definite mass on the cervix) to 60 mm, with a median of 21 mm. Patients were identified as being either low-risk (tumor size ≤ 25 mm and no evidence of PMI, n = 127) or high-risk (tumor size > 25 mm and/or findings indicating PMI, n = 63) based on MRI parameters. The rate of pathologic PMI in low- and high-risk patients was 0.0% and 30.2%, respectively (P < 0.001). Five-year progression-free survival in low-risk patients was 95.9%, which is significantly better than the rate of 85.6% for patients in the high-risk group (P = 0.039).

Conclusions

Preoperative MRI parameters can help identify patients with a low-risk of PMI and, therefore, possible candidates for trials on less radical surgery.