Stage IB Cervical Carcinoma Research Articles

Human papillomavirus genotyping by a polymerase chain reaction-based genechip method in cervical carcinoma treated with neoadjuvant chemotherapy plus radical surgery

The aim of this study was to evaluate the accuracy of human papillomavirus (HPV) genotyping by a polymerase chain reaction (PCR)-based genechip method and to determine the prognostic value of HPV genotype in bulky stage IB or IIA cervical carcinoma treated with neoadjuvant chemotherapy (NAC) and radical surgery. A total of 149 patients had adequate tissue for the study. The SPF1/GP6+ primers were used to amplify a 184 bp fragment. The amplimers were submitted for direct sequencing and hybridization with a genechip using revert-blot detection of 39 types of HPV DNA in a single reaction. Two runs of PCR with respective hybridization were performed for each tumor. The complete concordance of HPV genotyping was 80.5% (120/149) of the paired genechip results. The kappa coefficient was 0.634 (P< 0.0001). HPV DNA sequences were detected in 100% of the specimens, among which 67.8% harbored single type and 32.2% contained multiple types. HPV-16 was detected in 98.7%, HPV-18 in 22.8%, HPV-31 in 0.7%, HPV-45 in 1.3%, HPV-52 in 2.0%, HPV-58 in 6.7%, HPV-59 in 4.7%, and HPV-67 in 0.7%. In multivariate analyses, the HPV genotype [HPV-18 or HPV-16 and HPV-18 only versus all others: relative risk (RR), 2.33; 95% CI, 1.17–4.64;P= 0.016] and pre-NAC tumor size (>5 versus ≤5 cm: RR, 2.25; 95% CI, 1.13–4.48;P= 0.021) were significantly related to overall survival. This PCR-based genechip method is sensitive and reproducible for HPV genotyping. The association of HPV-18 or HPV-16 and HPV-18 with poor outcome in cervical carcinoma treated with NAC plus radical surgery is confirmed.

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

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. 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. 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. 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.

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

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

First case of a centropelvic recurrence after radical trachelectomy: literature review and implications for the preoperative selection of patients

Background. To report the first case of a centropelvic recurrence in a patient who underwent a radical trachelectomy (RT) for a stage IB1 cervical carcinoma. Case. A 32-year-old woman presented with a stage IB1 adenocarcinoma that was treated by radical trachelectomy. The tumor measured 21 × 20 mm. Minimal lymphatic space involvement was observed close to the tumor associated with 30 negative nodes and free margins. The upper free margin measured only 5 mm. Twenty-six months after the surgical procedure, the patient became pregnant. Clinical examination and pap smears were normal 2 months prior. During the first trimester, ultrasonography depicted a suspicious lesion in the bladder. Abdomino-pelvic magnetic resonance imaging (MRI) demonstrated a suspicious 20-mm tumor in the bladder associated with suspicious common iliac nodes. Cystoscopy and biopsies were carried out which confirmed recurrent disease. The patient received external radiation therapy combined with concomitant chemotherapy. Conclusions. More data are required to establish what is the safety distance between the tumor and the uterine transection. A distance of 5 mm or less is likely to be too limited for radical trachelectomy to be accepted as treatment for cervical cancer.

Uterine perforation at the time of brachytherapy for carcinoma of the cervix

Objective The reported incidence of uterine perforation by tandems at the time of vaginal brachytherapy for management of cervical cancer ranges from 1.75% to 10% per application. The potential ramifications of afterloading a tandem that is outside the uterine cavity within the pelvis are sufficiently severe, in terms of bowel injury, that a reliable means of determining tandem positioning at the time of placement is essential. Methods We examined a representative patient that underwent tandem placement for Federation Internationale of Gynecologic Oncologist (FIGO) stage Ib1 cervical Squamous Cell Carcinoma (SCCA). The information provided by conventional radiographic assessment and clinical impression was not helpful in ultimately determining tandem placement. Results Direct endoscopic visualization provided accurate and irrefutable evidence of tandem location and positioning prior to leaving the operating room. Conclusion A variety of techniques have been described to assist in accurate placement of the uterine tandem prior to afterloading, when utilizing definitive chemoradiation in the management of cervical carcinoma. These include postoperative plain films or computerized tomography, versus intraoperative transabdominal or transrectal ultrasound guidance at the time of placement. Postoperative techniques that confirm perforation necessitate a second visit to the operating room, a second general anesthetic, as well as a treatment delay that may impact negatively upon central control rates in the long term. Intraoperative techniques have their limitations as well, particularly in the obese patient. With difficult or questionable insertions, direct endoscopic evaluation at the time of tandem insertion is the only means of knowing definitively the location of the tandem prior to leaving the operating room.

Radiation therapy with and without extrafascial hysterectomy for bulky stage IB cervical carcinoma: a randomized trial of the Gynecologic Oncology Group☆

Objective To evaluate, in a randomized clinical trial, the role of adjuvant hysterectomy after standardized radiation in improving progression-free survival and survival for patients with “bulky” stage IB cervical cancer. Methods A total of 256 eligible patients with exophytic or “barrel” shaped tumors measuring ≥4 cm were randomized to either external and intracavitary irradiation (RT, N = 124) or attenuated irradiation followed by extrafascial hysterectomy (RT + HYST, N = 132). Twenty-five percent of patients had tumors with a maximum diameter of ≥7 cm. Results Tumor size was the most pronounced prognostic factor followed by performance status 2 and age at diagnosis. Hysterectomy did not increase the frequency of reported grade 3 and 4 adverse effects (both groups, 10%). The majority of these adverse effects were from the gastrointestinal or genitourinary tracts exclusively. There was a lower cumulative incidence of local relapse in the RT + HYST group (at 5 years, 27% vs. 14%). There were no statistical differences in outcomes between regimens except for the adjusted comparison of progression-free survival, although all indicated a lower risk in the adjuvant hysterectomy regimen (unadjusted relative risk [URR] of progression, 0.77, P = 0.07; URR of death, P = 0.26, both one tail). Conclusion Overall, there was no clinically important benefit with the use of extrafascial hysterectomy. However, there is good evidence to suggest that patients with 4-, 5-, and 6-cm tumors may have benefitted from extrafascial hysterectomy (URR of progression; 0.58; URR of death, 0.60).

Prognostic value of age and histologic type in neoadjuvant chemotherapy plus radical surgery for bulky (≥4 cm) stage IB and IIA cervical carcinoma

The purpose of this study was to investigate pretreatment variables related to prognosis and to evaluate long-term outcome in patients with bulky early-stage cervical carcinoma who were enrolled into a protocol treatment of neoadjuvant chemotherapy (NAC) followed by radical surgery. Between 1988 and 1999, 162 women with previously untreated bulky (≥4 cm) stage IB or IIA carcinoma of the uterine cervix registered to receive cisplatin, vincristine, and bleomycin for three cycles followed by radical hysterectomy and pelvic lymphadenectomy, were enrolled into this study. The 5-year relapse-free (RFS) and overall survival (OS) rates of the whole series were 65% and 69%, respectively. In multivariate analyses, age (< 35 vs. ≥ 35-year-old: relative risk [RR], 2.06; 95% confidence interval [CI], 1.02–4.14; P = 0.043) and histologic type (adeno-adenosquamous vs. squamous carcinoma: RR, 2.60; 95% CI, 1.26–5.39; P = 0.010) were independent variables associated with RFS, and age (< 35 vs. ≥ 35-year-old: RR, 2.53; 95% CI, 1.24–5.14; P = 0.010) and pre-NAC tumor size (> 5 vs. = 5 cm: RR, 2.06; 95% CI, 1.09–3.90; P = 0.027) were significantly related to OS. Narrowing down patient selection to squamous carcinoma and age older than 35 years with stratification of tumor size (break point of 5 cm) is recommended in future trials involving cisplatin-based NAC plus radical surgery.

Detecting Cytokeratin 19 mRNA in the Peripheral Blood Cells of Cervical Cancer Patients and Its Clinical–Pathological Correlation

Objective. The aim of this study was to study the presence of cytokeratin 19 (CK19)-expressing cancer cells in the blood of preoperative patients with FIGO stage Ib and IIb cervical cancers who received radical hysterectomy and to investigate the cells' clinical significance.Methods. CK19 mRNA in the blood cells of the patients was detected preoperatively by a newly designed nested reverse transcriptase–polymerase chain reaction, which excluded pseudogenes a and b, performed on 84 patients with stage Ib and IIb cervical carcinoma. Possible correlations between clinicopathological factors were then analyzed.Results. The sensitivity of this assay was 1 CK19-mRNA-positive cell per 106 peripheral blood mononuclear cells. Results showed that 21.4% of the 84 patients with cervical carcinoma had CK19-mRNA-positive cells in the blood, in comparison with 5.7% of the 35 patients with benign gynecological tumors and 0% of the 28 healthy controls (P = 0.037 and 0.006, respectively). The positive tests in the cervical cancer patients were not associated with prognostic factors including stage, pelvic lymph node metastasis, pathological types, bulky tumor size (≥4 cm), differentiation, parametrial extension, lymphovascular space involvement, deep stromal invasion, or age.Conclusions. This study revealed the presence of circulating CK19-expressing cancer cells in the blood of patients with untreated early-stage cervical carcinomas, indicating that cervical cancer disseminated early. The survival effect of this phenomenon must be clarified. This detection assay provides an early checkpoint in the multistep process for developing metastasis in cervical cancer patients.

Pathologic complete remission after preoperative intracavitary radiotherapy of cervical cancer stage Ib and IIa is a strong prognostic factor for long-term survival: analysis of the Radiumhemmet data 1989-1991.

The purpose of this study was to evaluate the treatment results of preoperative brachytherapy and the prognostic value of pathologic complete remission after preoperative intracavitary irradiation in patients with stage Ib and IIa cervical carcinoma in relation to recurrence rate and survival. The clinical records of 185 patients with stage Ib (129 patients) and IIa (56 patients) cervical carcinoma, consecutively admitted to Radiumhemmet from January 1989 to December 1991 were reviewed. The median follow-up time was 71 months. In 121 patients the treatment consisted of uterovaginal intracavitary irradiation, according to the Stockholm technique, followed by surgery. Tumor remission assessed in the surgical specimen was classified as pathologic complete remission (pCR) if no microscopic tumor was found or incomplete pathologic remission (non-pCR) if microscopic residual tumor was found. Postoperative external beam radiation was added to cases with metastases in pelvic nodes or residual tumor in the resection margins. The disease-specific 5-year survival was 87% and 75% for stage Ib and IIa, respectively, for the patient population treated with preoperative intracavitary radiotherapy and surgery. After intracavitary radiation, 79% of the patients obtained pCR of the primary tumor. Five-year survival in those with pCR was 95%, compared with 46% in those with non-pCR (P < 0.0001). Patients with pCR and no lymph node metastases had a 98% 5-year survival as compared to a 5-year survival of 64% in patients with non-pCR and node negativity (P < 0.0001). Locoregional relapses were diagnosed in 2% of the patients with pCR compared to 54% in patients with non-pCR (P < 0.0001). Multivariate analysis revealed non-pCR (RR = 6.42) and node positivity (RR = 4.59) as nonfavorable factors for survival, while tumor size was not found to be of independent significance for survival. Pathologic complete remission after intracavitary irradiation is a strong favorable prognostic factor in node-negative patients. The combination of preoperative intracavitary radiotherapy and surgery results in a high cure rate and aids in identifying patients at risk for relapse who might be subject to adjuvant therapy.

Lymph node metastasis as a prognostic factor in patients with cervical cancer

Objectives: To elucidate the prognostic significance of the number and level of the involvement of lymph node metastases(LNM) in patients with early cervix cancer. Materials and Methods: Radical hysterectomy and bilateral pelvic lymphadenectomy were done on 366 patients diagnosed with cervical carcinoma stages ⅠB and ⅡA from june 1985 to June 1994 at Chonnam National University Hospital, Kwangju, Korea. Survival analysis was performed using the Kaplan-Meier estimator. Results: The 5 year survival rate in 296 patients without LNM was 95% versus 78% in 70 patients with LNM(p＜0.01). In 56 patients (80%) with single LNM, the 5-year survival rate was 85% versus 50% in 14 patients (20%) with multiple LNM (p＜0.01). The 5-year survival rate in the 7 patients (10%) with extrapelvic LNM (in the common iliac or paraaortic nodes) was 20%. The 5-year survival rate of the 63 patients (90%) with LNM below the level of the common iliac nodes was 84.6%. The difference was statistically significant (p＜0.01). There was no involvement of the common iliac or paraaortic lymph nodes without pelvic node involvement. Conclusions: These figures suggest that the number and site of positive nodes are more important prognostic factor than the existence of nodal metastasis. Although we need a randomized prospective study, it might be expected that the 5-year survival rates of those patients with one positive pelvic node can be improved up to the level of those without nodal metastasis without postoperative adjuvant radiation and/or chemotherapy.

Altered CD44 Variant 6 Expression in FIGO Stage IB Cervical Carcinoma

Objective. CD44 is an adhesion molecule which plays an important role in metastatic cascade by mediating tumor cell interaction with the endothelium and the subendothelial matrix. In this study CD44v6 expression was immunohistochemically investigated on 88 uterine cervical cancers. Correlation between expression and prognostic variables and the survival was examined.Methods. Eighty-eight patients with stage IB disease, treated primarily with surgery, were examined histopathologically and immunohistochemically. CD44v6 expressions of tumoral tissue and the nonneoplastic tissue nearby were examined using antiCD44v6 monoclonal antibody. CD44v6 expression was compared to the known clinicopathologic prognostic variables and survival of patients.Results. Nonneoplastic epithelium of the sections showed CD44v6 expression predominantly in basal and parabasal layers at least in traces. CD44v6 overexpression in neoplastic islands was evaluated as “general,” “basal” (only in the basal portion of neoplastic islands), and “nonbasal” (also in the central portion of the neoplastic islands) separately. When expression and prognostic variables were compared, CD44v6 non-basal expression was found to be significant in nonsquamous cancers, when the tumor diameter was greater than 3 cm and in the tumors that showed recurrences. Univariate survival analysis with the Kaplan–Meier method showed that only the age of the patient is significantly correlated with disease-free survival. Interestingly when the same analysis was done for 5-year overall survival, diameter of the primary tumor, depth of cervical stromal invasion, existence and number of lymph node involvement, positivity for general CD44v6 expression, and positivity for nonbasal expression were found to be statistically significant. Furthermore multivariate analysis with Cox regression showed that nonbasal CD44v6 expression and lymph node involvement are independent variables for 5-year overall survival.Conclusion. These results indicate that CD44v6 expression is associated with some of the important clinicopathologic prognostic variables and appears to be a predictor of advanced pathological–surgical stage of early clinical stage cervical carcinoma. CD44v6 nonbasal expression is significantly correlated with overall survival.

Prognostic value of nm23 expression in stage IB1 cervical carcinoma.

The purpose of this retrospective study was to evaluate the patterns of nm23 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare nm23 expression with clinicopathological findings and to assess its prognostic value. Twenty-seven patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of nm23 was studied immunohistochemically, followed by amplification and direct sequencing of exons 4 and 5 of the nm23 gene. Overexpression of nm23 was detected in 18.5% of the tumors and low expression was seen in 33.3%, while negative expression was found in 48.1% of the tumors. Deep cervical stromal invasion (> or =1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when nm23 overexpression was observed (p = 0.0063). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessel, squamous cell carcinoma (> or =2 ng/ml) and nm23 overexpression had a significantly lower recurrence-free survival rate of the patients. None of the above factors was significant according to multivariate analysis. There were no mutations in exons 4 and 5 of the nm23 gene in stage IB1 squamous cell carcinoma of the uterine cervix. This study suggests that expression of nm23 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.

The histopathological predictor factors in the recurrence of cervical carcinoma stage IB - IIA after radical hysterectomy

The aim of this study is to know the incidence of cervical carcinoma stage IB - IIA recurrence after radical hysterectomy and the histopathologic factors which are related to it. This was a retrospective cohort study involving 68 patients with recurrence cervical carcinoma stage IB - IIA who underwent radical hysterectomy, However, there were only 58 cases which fulfilled the study citeria, and therefore were evaluated histopathologically. The histopathologic evaluation consisted of differentiation, inflammatory reaction, lymph-vascular permeation, invasion to the vagina incision margin, and to endometrium, lymph nodes metastasis, and the depth of stromal invasion. The incidence of the cervical carcinoma stage IB-IIA recurrence 2 years after radical hysterectomy was 30.8% (21 out of 68 cases). The recurrence occurred in nine (75%) out of 12 cases with lymph node metastasis, compared to 10 (21.7%) out of 46 cases without lymph node metastasis (P = 0.0004). In addition, eight out of 11 adenosquamous carcinoma cases had recurrence (p = 0.01). There was only one out of the 12 cases with the depth of stromal invasion of &lt; 5 mm that had recurrence compared to 18 out of 45 cases with stromal invasion of &gt; 5 mm (P = 0.02). The clinical factors such as parity, staging, size of the tumor were not statistically significant. The other pathologic factors such as differentiation, inflammatory reaction, and parametrial, vagina incision margin and endometrial invasion were not statistically signifcant. The incidence of the recurrence of cervical carcinoma within 2 years after hysterectomy was related to the pathological risk factors i.e. lymph node metastasis, adenosquamous cell carcinoma and the depth of stromal invasion. (Med J Indones 2001; 10: 79-83) Keyword: risk factor, cervical cancer

CD44 Isoform 6 (CD44v6) Is a Prognostic Indicator of the Response to Neoadjuvant Chemotherapy in Cervical Carcinoma

Objective. Theclinical efficacy of neoadjuvant chemotherapy (NAC) in distinct groups of cervical cancer patients has been well documented, but parameters at the cellular level regulating the different responsiveness to this treatment have not been adequately explored.Method. A series of 21 patients with stage Ib and IIa bulky cervical carcinomas were treated by preoperative NAC with three courses of cisplatin, epirubicin, etoposide, and bleomycin prior to radical hysterectomy, and subsequently followed up for a mean of 52.3 months. Biopsies taken prior to NAC and operative specimens were subjected to immunohistochemical (IHC) staining for α-catenin, β-catenin, E-cadherin, and CD44 isoform 6 (CD44v6), to uncover the role of adhesion molecules as determinants of the response to NAC and disease outcome.Results. Seven of the twenty-one (33.3%) women died of the disease; adenosquamous (n = 4 cases) histology (RR 4.50, 95% CI 1.85–10.68) and lymph node involvement (RR 6.00, 95% CI 0.42–85.26) were significant determinants of nonsurvival. All 21 carcinomas were human papillomavirus DNA positive. The factors predicting the response to NAC in univariate analysis were: CD44v6 expression in the pre-NAC and post-NAC samples (P = 0.00056 and P = 0.00336, respectively). In multiple logistic regression analysis, the factors with independent predictive value for response to NAC were CD44v6 expression prior to (P = 0.0099) and after (P = 0.0470) NAC. In univariate survival analysis, the most significant (P < 0.001) predictors of recurrence-free survival (RFS) were age and number of lymph nodes removed. In multivariate survival analysis, the independent predictor for RFS was only histological type (P = 0.0064). Overall survival (OS) was predicted in a Cox model by recurrence (P = 0.0033), CD44v6 expression after NAC (P = 0.013), and patient's age (P = 0.039).Conclusions. These data indicate that CD44v6 is involved in the response to NAC, and eventually in disease outcome. This implicates that the assessment of CD44v6 expression might help in selecting patients who are likely to respond to NAC, i.e., women with significantly reduced CD44v6 expression in their tumors before treatment. Noteworthy, the response to NAC did not predict a favorable disease outcome.

Cervical Carcinoma Recurring in an Abdominal Wall Incision

Incisional recurrence of carcinoma of the uterine cervix is very rare. We report two patients who developed recurrence in the abdominal wall incision after hysterectomy. The first patient was aged 60 years and had a FIGO Stage IB1 cervical carcinoma treated initially by Wertheim's hysterectomy and postoperative radiotherapy. Nine months after surgery she developed recurrence on the abdominal scar, which was outside the radiation portal. She was treated with electron beam radiation therapy. The second patient developed an incisional recurrence 23 months after surgery and was treated by wide excision of the mass followed by radiotherapy. A survey of the literature identified 12 reported cases to date (eight squamous cell carcinoma and four adenocarcinoma).

The role of radical surgery followed by adjuvant therapy for high-risk early-stage cervical carcinoma patients with pelvic lymph node metastasis

Objectives: To identify a subgroup of high-risk node-positive patients in early-stage cervical cancers and to determine the role of radical hysterectomy followed by adjuvant therapy to these patients. Study design: We conducted a retrospective review of 482 surgically-treated patients of clinical stage Ib and IIa cervical carcinoma from July 1986 to December 1994 at Kaohsiung Chang Gung Memorial Hospital. Of these, 96 patients had pelvic lymph node metastases. Clinicopathological variables, including the level of pretreatment squamous cell carcinoma antigen (SCC-Ag), DNA flow cytometry analysis, and the use of different adjuvant therapies were studied. Results: Disease-free survival was significantly worse among patients with S-phase fraction greater than 20% and pretreatment SCC-Ag level above 5 ng/ml. Utilizing these significant variables, we identified two distinct risk groups. Those patients without any of the risk variables were categorized as the low-risk group. Those patients with either one or both risk variables were categorized as the high-risk group. Five-year disease-free survival rates were 74% in the low-risk group and 43% in the high-risk group, ( P=0.034). Disease recurred in 30.2% of the low-risk patients and 45.3% of the high-risk patients. No survival advantages were found by using different adjuvant therapies. Conclusions: Radical hysterectomy should not be attempted if either the pretreatment SCC-Ag level is above 5 ng/ml or S-phase fraction of the tumor greater than 20% due to its limited value despite applying aggressive postoperative adjuvant therapy.

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.

Prognostic Value of p53 Expression in Stage IB1 Cervical Carcinoma

The purpose of this retrospective study was to evaluate the patterns of p53 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare p53 expression with clinicopathological findings, and to assess its prognostic value. 27 patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of p53 was studied immunohistochemically. Overexpression of p53 was detected in 33.3% of the tumors, low expression was seen in 11.1%, and negative expression was found in 55.6%. Deep cervical stromal invasion (≧1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when p53 overexpression was observed (p = 0.0315). Univariate analysis revealed that tumor size (2–3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessels, squamous cell carcinoma antigen (≧2 ng/ml), and p53 overexpression had a significantly lower recurrence-free survival rate. None of these above factors obtained significance in the multivariate analysis. This study suggests that expression of p53 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.

Cervical conization to radical hysterectomy interval: does it matter?

Objective: To determine whether a difference in perioperative morbidity exists for different waiting periods between cervical conization and radical hysterectomy.Study design: Between January 1992 and September 1999, 225 type II or type III radical hysterectomies were performed at Parkland Memorial Hospital for stage IA2, stage IB, or stage IIA cervical carcinoma. Thirty women underwent radical hysterectomy after having a loop electrical excision procedure or cold knife conization. Estimated blood loss, intraoperative complication, blood transfusion, febrile morbidity, hospital re-admission, and postoperative complications were ascertained. These data were stratified according to the time interval between cervical conization and radical hysterectomy: 1–7 days, 8–28 days, and greater than 28 days. ANOVA was used for statistical analysis.Results: Our study population included 30 women, 7 of which underwent loop electrical procedure, and 23 underwent cold knife conization prior to radical hysterectomy. Fifteen percent, 25%, and 60% underwent cervical procedure prior to radical hysterectomy at less than 1 week, 1–4 weeks, and greater than 4 weeks, respectively. There was no statistically significant difference in estimated blood loss, intraoperative complication, operative time, blood transfusion, febrile morbidity, hospital re-admission, or postoperative complication. There was a statistically significantly longer hospital stay between the 1–4 weeks interval group and the others (P = 0.0008).Conclusions: Our data suggest that it is safe to perform radical hysterectomy at any point in time after a cervical conization; however, the operative interval of 1–4 weeks appears to lengthen the duration of hospital stay.

The role of pretreatment squamous cell carcinoma antigen in predicting nodal metastasis in early stage cervical cancer.

To evaluate whether the presence of pelvic lymph node metastasis can be predicted by pretreatment squamous cell carcinoma antigen (SCC-Ag) levels in early stage squamous cervical carcinoma. Between 1994 and 1998, 284 patients with stage Ib and IIa cervical squamous cell carcinoma undergoing radical hysterectomy had preoperative SCC-Ag determination. The correlation between clinicopathological findings on SCC-Ag levels were examined. The Mann-Whitney U test was used to statistically analyze differences between node positive and negative patients. Multiple regression analysis and a multiple logistic model were employed to examine the effect of clinicopathological findings on SCC-Ag levels. Of the 284 patients, 56 patients were found to have nodal metastasis. Median serum levels and 90% ranges of SCC-Ag were 0.74 microg/l (0.5-7.8) in the 228 nodal negative patients and 4.33 microg/l (0.5-48.5) in the 56 nodal positive patients (p<0.001). Lymph node metastasis and tumor size were found to have a significant impact on SCC-Ag levels. Around 86% of the patients with SCC-Ag levels below 8 microg/l showed no nodal metastasis, while about 65% of the patients with serum levels above 8 microg/l exhibited nodal metastasis. Multivariate analyses confirmed that only lymph node metastasis had a significant impact on the SCC-Ag levels exceeding 8 microg/l. For predicting nodal metastasis preoperatively, SCC-Ag levels greater than 8 microg/ l can be considered a high-risk zone for nodal metastasis.